Patent Application
20200093505
The present disclosure is directed generally to systems and methods for treating patients having sympathetically mediated disease associated at least in part with augmented peripheral chemoreflex or heightened sympathetic activation by ablating at least one of a carotid body, two carotid bodies, and a nerve associated therewith.
It is known that an imbalance of the autonomic nervous system is associated with several disease states. Restoration of autonomic balance has been a target of several medical treatments including modalities such as pharmacological, device-based, and electrical stimulation. For example, beta blockers are a class of drugs used to reduce sympathetic activity to treat cardiac arrhythmias and hypertension; Gelfand and Levin (U.S. Pat. No. 7,162,303) describe a device-based treatment used to decrease renal sympathetic activity to treat heart failure, hypertension, and renal failure; Yun and Yuarn-Bor (U.S. Pat. Nos. 7,149,574; 7,363,076; 7,738,952) describe a method of restoring autonomic balance by increasing parasympathetic activity to treat disease associated with parasympathetic attrition; Kieval, Burns and Serdar (U.S. Pat. No. 8,060,206) describe an electrical pulse generator that stimulates a baroreceptor, increasing parasympathetic activity, in response to high blood pressure; Hlavka and Elliott (US 2010/0070004) describe an implantable electrical stimulator in communication with an afferent neural pathway of a carotid body chemoreceptor to control dyspnea via electrical neuromodulation. More recently, Carotid Body Ablation (CBA) has been conceived for treating sympathetically mediated diseases.
This disclosure is related to methods, devices, and systems for reducing afferent signaling between a peripheral chemoreceptor and the central nervous system. The disclosure includes methods, devices, and systems for directed energy ablation of a carotid body or its associated nerves. In particular, methods and devices for ablating tissue such as a carotid body, carotid septum or nerves associated with a carotid body that is proximate a vessel such as a vein or artery with an endovascular carotid body ablation (CBA) catheter having means for imaging and ablation.
The disclosure herein is related to systems, devices, and methods for carotid body ablation to treat patients having a sympathetically mediated disease (e.g., cardiac, renal, metabolic, or pulmonary disease such as hypertension, CHF, sleep apnea, sleep disordered breathing, diabetes, insulin resistance, asthma, COPD) at least partially resulting from augmented peripheral chemoreflex (e.g., peripheral chemoreceptor hypersensitivity, peripheral chemosensor hyperactivity) or heightened sympathetic activation. Carotid body ablation as used herein refers generally to completely or partially ablating one or both carotid bodies, carotid body nerves, intercarotid septums, or peripheral chemoreceptors. A main therapy pathway is a reduction of peripheral chemoreflex or reduction of afferent nerve signaling from a carotid body (CB), which results in a reduction of central sympathetic tone. Higher than normal chronic or intermittent activity of afferent carotid body nerves is considered enhanced chemoreflex for the purpose of this application regardless of its cause. Other important benefits such as increase of parasympathetic tone, vagal tone and specifically baroreflex and baroreceptor activity reduction of dyspnea, hyperventilation and breathing rate may be expected in some patients. Secondary to reduction of breathing rate additional increase of parasympathetic tone may be expected in some cases. Augmented peripheral chemoreflex (e.g., carotid body activation) leads to increases in sympathetic nervous system activity, which is in turn primarily responsible for the progression of chronic disease as well as debilitating symptoms and adverse events seen in the intended patient populations. Carotid bodies contain cells that are sensitive to oxygen and carbon dioxide. Carotid bodies also respond to blood flow, blood pH, blood glucose level and possibly other variables. Thus, carotid body ablation may be a treatment for patients, for example having hypertension, heart disease or diabetes, even if chemosensitive cells are not activated.
To inhibit or suppress a peripheral chemoreflex, anatomical targets for ablation (also referred to as targeted tissue, target ablation sites, or target sites) may include at least a portion of at least one carotid body, an aortic body, nerves associated with a peripheral chemoreceptor (e.g., carotid body nerves, carotid sinus nerve, carotid plexus), small blood vessels feeding a peripheral chemoreceptor, carotid body parenchyma, chemosensitive cells (e.g., glomus cells), tissue in a location where a carotid body is suspected to reside (e.g., a location based on pre-operative imaging or anatomical likelihood), an intercarotid septum, a portion of an intercarotid septum, a substantial part of an intercarotid septum or a combination thereof. As used herein, ablation of a carotid body may refer to ablation of any of these target ablation sites.
An intercarotid septum, which is also referred to herein as a carotid septum, is herein defined as a wedge or triangular segment of tissue with the following boundaries: a saddle of a carotid bifurcation defines a caudal aspect (i.e., an apex) of a carotid septum; facing walls of internal and external carotid arteries define two sides of the carotid septum; a cranial boundary of a carotid septum extends between these arteries and may be defined as cranial to a carotid body but caudal to any important non-target nerve structures (e.g., a hypoglossal nerve) that might be in the region, for example a cranial boundary may be about 10 mm to about 15 mm from the saddle of the carotid bifurcation; medial and lateral walls of the carotid septum are generally defined by planes approximately tangent to the internal and external carotid arteries; one of the planes is tangent to the lateral walls of the internal and external carotid arteries and the other plane is tangent to the medial walls of these arteries. An intercarotid septum is disposed between the medial and lateral walls. An intercarotid septum may contain, completely or partially, a carotid body and may be absent of important non-target structures such as a vagus nerve or sympathetic nerves or a hypoglossal nerve. An intercarotid septum may include some baroreceptors or baroreceptor nerves. An intercarotid septum may also include intercarotid plexus nerves, small blood vessels and fat. An intercarotid septum may be a target for ablation. Even if a carotid body or carotid body nerve cannot be easily identified visually to target specifically an intercarotid septum may be targeted with a high probability of ablating a carotid body and safely avoiding non-target nerves. Multiple ablations may be created within a carotid septum to cover an increased volume of tissue to increase a probability of ablating a carotid body. Multiple ablations may overlap or be discrete within a carotid septum.
Carotid body nerves are anatomically defined herein as carotid plexus nerves and carotid sinus nerves. Carotid body nerves are functionally defined herein as nerves that conduct information from a carotid body to a central nervous system. Carotid body nerves can be referred to herein as one or more nerves that are associated with the carotid body.
An ablation may be focused exclusively on targeted tissue, or be focused on the targeted tissue while safely ablating tissue proximate to the targeted tissue (e.g., to ensure the targeted tissue is ablated or as an approach to gain access to the targeted tissue). An ablation region may be as big as a peripheral chemoreceptor (e.g., carotid body or aortic body) itself, somewhat smaller, or bigger and can include one or more tissues surrounding the chemoreceptor such as blood vessels, adventitia, fascia, small blood vessels perfusing the chemoreceptor, and nerves connected to and innervating the glomus cells. An intercarotid plexus or carotid sinus nerve may be a target of ablation with an understanding that some baroreceptor nerves will be ablated together with carotid body nerves. Baroreceptors are distributed in the human arteries and have a high degree of redundancy.
Tissue may be ablated to inhibit or suppress a chemoreflex of only one of a patient's two carotid bodies. Other embodiments include ablating tissue to inhibit or suppress a chemoreflex of both of a patient's carotid bodies. In some embodiments an ablation is performed on a first carotid body, and an assessment is then performed to determine if the other carotid body should be ablated. For example, a therapeutic method may include ablation of one carotid body, measurement of resulting chemosensitivity, sympathetic activity, respiration or other parameter related to carotid body hyperactivity, and ablation of the second carotid body can be performed if desired to further reduce chemosensitivity following the unilateral ablation.
An embodiment of a therapy may substantially reduce chemoreflex without excessively reducing the baroreflex of the patient. The proposed ablation procedure may be targeted to substantially spare the carotid sinus, baroreceptors distributed in the walls of carotid arteries, particularly internal carotid arteries, and at least some of the carotid sinus nerves that conduct signals from said baroreceptors. For example, the baroreflex may be substantially spared by targeting a limited volume of ablated tissue possibly enclosing the carotid body, tissues containing a substantial number of carotid body nerves, tissues located in periadventitial space of a medial segment of a carotid bifurcation, or tissue located at the attachment of a carotid body to an artery. Said targeted ablation is enabled by visualization of the area or carotid body itself, for example by CT, CT angiography, MRI, ultrasound sonography, fluoroscopy, blood flow visualization, or injection of contrast, and positioning of an instrument in the carotid body or in close proximity while avoiding excessive damage (e.g., perforation, stenosis, thrombosis) to carotid arteries, baroreceptors, carotid sinus nerves or other important non-target nerves such as a vagus nerve or sympathetic nerves located primarily outside of the carotid septum. Thus imaging a carotid body before ablation may be instrumental in (a) selecting candidates if a carotid body is present, large enough and identified and (b) guiding therapy by providing a landmark map for an operator to guide an ablation instrument to the carotid septum, center of the carotid septum, carotid body nerves, the area of a blood vessel proximate to a carotid body, or to an area where carotid body itself or carotid body nerves may be anticipated. It may also help exclude patients in whom the carotid body is located substantially outside of the carotid septum in a position close to a vagus nerve, hypoglossal nerve, jugular vein or some other structure that can be endangered by ablation. In one embodiment only patients with a carotid body substantially located within the intercarotid septum are selected for ablation therapy.
An embodiment of a method of treatment may comprise only ablating one of the right and left carotid bodies. Compared to ablating both carotid bodies, this may reduce procedure time and cost and safety risk while resulting in a desired therapeutic effect. Furthermore, patients having only one accessible carotid body, for example due to vascular disease or abnormalities, may be candidates for a procedure. When performing a one-sided treatment there may be advantages of ablating the right side carotid body over the left. For example, the right side may be easier, faster, or safer to approach or may have a greater therapeutic effect than the left side.
Once a carotid body is ablated, removed or denervated, the carotid body function (e.g., carotid body chemoreflex) does not substantially return in humans, partly because in humans aortic chemoreceptors are considered undeveloped. To the contrary, once a carotid sinus baroreflex is removed it is generally compensated, after weeks or months, by the aortic or other arterial baroreceptor baroreflex. Thus, if both the carotid chemoreflex and baroreflex are removed or substantially reduced, for example by interruption of the carotid sinus nerve or intercarotid plexus nerves, the baroreflex may eventually be restored while the chemoreflex may not. The consequences of temporary removal or reduction of the baroreflex can be in some cases relatively severe and require hospitalization and management with drugs, but they generally are not life threatening, terminal or permanent. Thus, it is understood that while selective removal of carotid body chemoreflex with baroreflex preservation may be desired, it may not be absolutely necessary in some cases. Ablation:
The term “ablation” may refer to the act of altering a tissue to suppress or inhibit its biological function or ability to respond to stimulation permanently or for an extended period of time (e.g., greater than 3 weeks, greater than 6 months, greater than a year, for several years, or for the remainder of the patient's life). Selective denervation may involve, for example, interruption of afferent nerves from a carotid body while substantially preserving nerves from a carotid sinus, which conduct baroreceptor signals, and other adjacent nerves such as hypoglossal, laryngeal, and vagal nerves. Another example of selective denervation may involve interruption of a carotid sinus nerve, or intercarotid plexus which is in communication with both a carotid body and some baroreceptors wherein chemoreflex from the carotid body is reduced permanently or for an extended period of time (e.g., years) and baroreflex is substantially restored in a short period of time (e.g., days or weeks). As used herein, the term “ablate” or a derivative thereof refers to interventions that suppress or inhibit natural chemoreceptor or afferent nerve functioning, which is in contrast to electrically neuromodulating or reversibly deactivating and reactivating chemoreceptor functioning.
Carotid Body Ablation (“CBA”) as used herein refers to ablation of a target tissue wherein the desired effect is to reduce or remove the afferent neural signaling from a chemosensor (e.g., carotid body) or reducing a chemoreflex. Chemoreflex or afferent nerve activity cannot be directly measured in a practical way, thus indexes of chemoreflex such as chemosensitivity can sometimes be used instead. Chemoreflex reduction is generally indicated by a reduction of blood pressure, a reduction of an increase of ventilation and ventilation effort per unit of blood gas concentration, saturation or partial pressure change or by a reduction of central sympathetic nerve activity that can be measured indirectly. Sympathetic nerve activity can be assessed by reduction of blood pressure, measuring activity of peripheral nerves leading to muscles (MSNA), heart rate (HR), heart rate variability (HRV), production of hormones such as renin, epinephrine and angiotensin, and peripheral vascular resistance. All these parameters are measurable and can lead directly to the health improvements. In the case of CHF patients blood pH, blood PCO2, degree of hyperventilation and metabolic exercise test parameters such as peak VO2, and VE/VCO2 slope are also important. It is believed that patients with heightened chemoreflex have low VO2 and high VE/VCO2 slope (index of respiratory efficiency) as a result of, for example, tachypnea and low blood CO2. These parameters are also related to exercise limitations that further speed up a patient's status deterioration towards morbidity and death. It is understood that all these indexes are indirect and imperfect and intended to direct therapy to patients that are most likely to benefit or to acquire an indication of technical success of ablation rather than to prove an exact measurement of effect or guarantee a success. It has been observed that some tachyarrhythmias in cardiac patients are sympathetically mediated. Thus carotid body ablation may be instrumental in treating reversible atrial fibrillation and ventricular tachycardia.
Carotid body ablation may include methods and systems for the thermal ablation of tissue via thermal heating mechanisms. Thermal ablation may be achieved due to a direct effect on tissues and structures that are induced by the thermal stress. Additionally or alternatively, the thermal disruption may at least in part be due to alteration of vascular or peri-vascular structures (e.g., arteries, arterioles, capillaries or veins), which perfuse the carotid body and neural fibers surrounding and innervating the carotid body (e.g., nerves that transmit afferent information from carotid body chemoreceptors to the brain). Additionally or alternatively thermal disruption may be due to a healing process, fibrosis, or scarring of tissue following thermal injury, particularly when prevention of regrowth and regeneration of active tissue is desired. As used herein, thermal mechanisms for ablation may include both thermal necrosis or thermal injury or damage (e.g., via sustained heating, convective heating, resistive heating, or any combination thereof). Thermal heating mechanisms may include raising the temperature of target tissue, such as neural fibers, chemosensitive cells, all or a substantial number of carotid body cells, and small blood vessels perfusing the carotid body or its nerves, above a desired threshold, for example, above a body temperature of about 37° C. e.g., to achieve thermal injury or damage, or above a temperature of about 45° C. (e.g., above about 60° C.) to achieve thermal necrosis for a duration of time known to induce substantially irreversible ablation at the resulting temperature.
In addition to raising temperature during thermal ablation, a length of exposure to thermal stimuli may be specified to affect an extent or degree of efficacy of the thermal ablation. In some embodiments the length of exposure to thermal stimuli is between about 1 and about 60 seconds, such as between about 5 and about 30 seconds. In some embodiments the length of exposure to thermal stimuli can be, longer than or equal to about 30 seconds, or even longer than or equal to about 2 minutes. Furthermore, the length of exposure can be less than or equal to about 10 minutes, though this should not be construed as the upper limit of the exposure period. A temperature threshold, or thermal dosage, may be determined as a function of the duration of exposure to thermal stimuli. Additionally or alternatively, the length of exposure may be determined as a function of the desired temperature threshold. These and other parameters may be specified or calculated to achieve and control desired thermal ablation. Thermally-induced ablation may be achieved via indirect generation or application of thermal energy to the target tissue, such as neural fibers, chemosensitive cells, and all or a substantial number of carotid body cells, such as through application of high-intensity focused ultrasound (HIFU), partially focused ultrasound, or high intensity directed ultrasound, to the target neural fibers.
Carotid body ablation may comprise delivering an agent systemically and directing energy such as ultrasound energy to the carotid body or associated nerves to activate the agent causing impairment of the carotid body or associated nerves.
Additional and alternative methods and apparatuses may be utilized to achieve ablation.
Sonography can be instrumental in guiding both percutaneous and endovascular procedures. Sonography can be performed from the surface of the skin, such as the neck, from inside the vasculature, from inside vasculature via imaging transducers positioned in or on an ablation catheter, or from a natural orifice such as the esophagus.
A directed energy device as used herein refers to an elongate device with an energy emitter configured to emit energy, and wherein the device is configured to deliver directed energy into target tissue. In some embodiments the device includes a therapeutic ultrasound transducer (also referred to herein as an energy emitter), which can be in a distal region of the device. In methods of use, the device can be positioned in a patient's body proximate to a carotid body or an associated nerve(s) of the patient. The therapeutic ultrasound transducer is then activated and acoustic energy capable of thermally ablating tissue is delivered to the target tissue, ablating the target tissue, such as a carotid body. Directed energy can be expected generally to penetrate tissue in a way that causes volumic heating of a volume of tissue in the direction in which the energy is emitted. It is expected that as the distance from the emitter increases, the directed energy is deposited, converted into heat and deformation of tissue, and thus attenuated. There is a boundary or distance beyond which the directed energy will not penetrate in a biologically significant way because of attenuation in tissue. Volumic heating of target tissue, which occurs when using therapeutic ultrasound ablation energy as described herein, is different than conductive heating of tissue, which requires heating from the contact point, through intervening tissue, and to the target tissue. There may be, however, some degree of conductive heating that accompanies volumic heating. With directed energy, however, it is intended that volumic heating is the primary means by which the target tissue is heated. Additionally, directed energy such as therapeutic ultrasound energy does not require intimate contact with the target to be effectively delivered. Ultrasound can be transmitted through blood with approximately ten times lower absorption than in the carotid body area, for example, allowing the energy to be delivered without intimate vessel wall (e.g., carotid artery or jugular vein) contact, or even without serious regard to the distance from emitter to that wall. This can be important where a vessel wall is irregular or vulnerable.
Ultrasonic acoustic energy is produced by an ultrasonic transducer by electrically exciting the ultrasonic emitter, which is disposed on or about the elongate device (e.g., a catheter). In some embodiments ultrasonic transducers may be energized to produce directed acoustic energy from the transducer surface in a range from about 10 MHz to about 30 MHz. The transducer can be energized at a duty cycle, such as in the range from about 10% to about 100%. Focused ultrasound may have much higher energy densities localized to a small focal volume, but will typically use shorter exposure times or duty cycles. In the case of heating the tissue, the transducer will usually be energized under conditions that cause a temperature rise in the tissue to a tissue temperature of greater than about 45 degrees C. In such instances, it can be desirable to cool the luminal surface in which the elongate device is positioned, in order to reduce the risk of injury.
Embodiments of ultrasonic transducers for placement in a patient's body for ultrasonic ablation of a carotid body are described herein. Such ultrasound transducers may be employed in any carotid body ultrasound ablation device described herein. For example, any of the ultrasonic transducers herein may be incorporated in a carotid body ablation catheter having a deployable or expandable structure (e.g., a balloon, cage, basket, mesh, or coil) to position, align, and maintain stable position of the transducer in a vessel such as an external carotid artery or internal jugular vein.
It is generally desired to position the transducer with the emitter face surface pointing towards the target. The distal assembly containing the ultrasound transducer element of the ablation device may be guided in to place, for example in an external carotid artery, for instance, by using low intensity ultrasound Doppler guidance by the means of sensing blood flow in the internal carotid artery. The sample volume of the pulse wave Doppler along the ultrasound beam axis is adjustable in length and location. The location of the sample volume along the beam axis is preferably set to cover a range of about 2 to 15 mm (e.g., about 2 mm to 9 mm) from the transducer face. The ultrasound beam may be aligned with the aid of Doppler to cover a carotid body for ablation. Once the transducer is determined to be properly aligned, the carotid body and other desired target structures may be ablated using high intensity continuous wave, or high duty cycle (preferably greater than 30%) pulsed wave ultrasound. Pulsed ultrasound has advantage of cooling of the transducer and blood vessel by blood flow while the carotid septum more remote from the carotid blood flow continues to be heated. Ultrasound Doppler guidance and ultrasound ablation may be performed with the same transducer element, or alternatively with a separate transducer elements. Alternatively, the ultrasound transducer may consist of an annular array, for instance, a two-element array with a center disc for high intensity ablation and an outer ring for low intensity Doppler use.
The transducers herein may be configured to achieve thermal ablation with a maximum heating zone centered in tissue about 2 mm to 9 mm from the transducer face along the ultrasound beam axis. In some embodiments the transducer is configured to achieve thermal ablation with a maximum heating zone centered in tissue about 5 mm to about 8 mm from the transducer face. As set forth elsewhere herein, ablating in tissue this far from the transducer can allow for selective carotid body ablation while minimizing the risks associated with ablating other non-target tissue. Heating of tissue by endovascular ultrasound is affected by cooling by blood and by dissipation of mechanical energy of an ultrasonic beam in the tissue. The location of the maximum heating zone depends on the transducer design, specifically, the aperture size and frequency of operation, which defines the attenuation with distance and the shape of the ultrasound beam. In general, a higher frequency ultrasonic wave attenuates in a shorter distance as it travels though tissue and is absorbed. The maximum heating zone location may be fixed with a single element transducer. Alternatively, an ultrasound beam may be steered to a desired maximum heating zone location using phased array technology, acoustic lenses or geometrically focused transducers. The device may be designed to achieve a volume of ablated tissue of about 8 to 300 mm3 (e.g., about 154+/−146 mm3). The combination of delivered energy, shape, direction of the ultrasound beam, and application time sequence may determine the volume of ablated tissue. Energy delivery, e.g., power settings and mode of operation (e.g., pulsed wave vs. continuous application time sequence), may be used to enhance heating in a target location or zone and achieve repeatable target tissue temperature over time. In an example embodiment, for a transducer having a width of about 2 mm and length of about 4 mm, an ultrasound frequency of operation may be chosen to be about 10 to about 30 MHz, (e.g., 15 to 25 MHz). In some embodiments the ultrasound is delivered at a frequency of between about 10-25 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 10-20 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 10-15 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 15-30 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 15-25 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 15-20 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 20-30 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 20-25 MHz. In some embodiments the ultrasound is delivered at a frequency of between about 25-30 MHz.
The ultrasound transducer may be operated in the thickness resonance mode, i.e., the frequency of operation is substantially determined by the half wavelength thickness of the piezoelectric transducer element. The transducer element may be made of PZT-4 (Navy I) or PZT-8 (Navy III) type piezoceramic material or equivalent that exhibits low losses under high power driving conditions and may be incorporated in a piezocomposite structure. High intensity, high duty cycle, mode of operation may result in self-heating of the transducer element and surrounding structural elements. Therefore, the temperature of transducer or adjacent elements may be monitored with a temperature sensor (e.g., a thermocouple). If temperature is deemed to be too high, the transducer may be cooled down during use by a means of reducing duty cycle, or electrical power output into the transducer, or irrigation or circulating fluid cooling. Alternatively, transducer efficiency may be enhanced to reduce transducer self-heating by a means of electrical and acoustic impedance matching. For instance, the capacitive reactance of electrical transducer impedance may be cancelled or reduced by a means of inductive tuning. If the transducers perform imaging or Doppler sensing function the acoustic impedance, defined as a product of speed of sound and density, of commonly used piezoelectric materials is much higher than acoustic impedance of soft tissue (e.g., about 20×). Therefore, coupling of acoustic energy from the transducer element to soft tissue is poor. A means of improving coupling of acoustic energy may be to use a matching layer, or multiple matching layers, of about quarter wavelength thickness at the frequency of operation, on the transducer face between the transducer element and tissue. Theoretically, the acoustic impedance of a matching layer should be close to the geometric mean of that of the source, piezoelectric transducer element (about 30 MRayl), and load, soft tissue (about 1.5 MRayl). It is understood that some methods of improving acoustic efficiency may be relevant more to high-energy delivery and some more to imaging and Doppler sensing.
In some embodiments the effectiveness of a therapeutic high energy mode transducer operating in continuous mode at or near resonance frequency can be optimized by including a matching layer made of material with acoustical impedance lower than the acoustical impedance of soft tissue or water (about 1.5 MRyal) divided by a transducer mechanical quality factor (between 0 and 100 measured in water). A common means of improving power transfer between water and acoustically hard ceramic by insertion of a quarter wavelength matching layer is not applicable in the case of a planar transducer undergoing large displacement at resonance. A thin therapeutic matching layer can be constructed, for example, by bonding a thin layer of polyester, polyurethane, or polyimide polymer directly to an emitting surface of the ceramic transducer. Alternatively, a therapeutic matching layer can be constructed of polyvinylidene fluoride (PVDF), which may be used as an imaging element or multi-element imaging array directly attached to the surface of a therapeutic transducer. PVDF is a piezoelectric polymer with low acoustic impedance well suitable for ultrasound imaging. Deposition of PVDF on the emitting surface of a high impedance, hard, therapeutic ceramic may help to miniaturize the design and optimize power transmission in therapeutic mode and obtain an ultrasound imaging function in the same stack of transducer.
Alternatively a material with high acoustic impedance can be used to prevent spreading of energy in the direction other than target. Backing can be made of dense and high sound speed materials such as metals, for example stainless steel, that reflect acoustic energy. Generally transition or interface between materials with significantly different acoustic properties (e.g., speed of sound) will reflect acoustic energy.
Ultrasound Carotid Body Ablation from an Endovascular Catheter Positioned in a Vein
The disclosure herein includes embodiments in which an endovascular ultrasound ablation catheter is delivered to an internal jugular vein or one of its tributaries to direct ablative energy to a carotid septum. Trans-venous instruments can have an advantage over trans-arterial ones in that they have a lower risk of brain embolization. Additionally, a larger instrument can be used in trans-venous approaches.
One aspect of the disclosure is a method of carotid body ablation that includes introducing an elongate device such as a catheter into the venous system of the patient, advancing a distal end of the catheter into an internal jugular vein or one of its tributaries proximate to a carotid septum, wherein the distal region includes a directional emitter of high-energy ultrasound capable of delivering ablative acoustic energy, aligning the emitter with the carotid septum, and directing energy into the septum to ablate the target tissue (e.g., carotid body, tissue in the carotid septum, carotid body nerves).
Excitation frequencies in the range of about 10 to about 30 MHz, such as between about 10 MHz to about 20 MHz, can be expected to produce the desired effect, including sufficient depth of penetration of ablative energy and at the same time containment of the desired ablation zone. Cooling from blood flow within internal 90 and external 91 carotid arteries may assist containment of the ablative thermal energy, or ablation zone, in a carotid septum. Thus a heat distribution from an ablative ultrasound beam may be shaped additionally by inhomogeneous heat conduction of the area influenced by cooling blood flow and enhancing ultrasound induced heating related bio-effects in the target space between the internal carotid artery 90 and external carotid artery 91 (i.e. carotid septum 205). Due to high blood flow and consequent effective thermal cooling of blood vessels, ultrasound energy in the selected frequency range travels through the vessel walls and blood without significant biologic effects and therefore only the septum will be selectively heated. One aspect of this disclosure is a method of delivering high intensity ablative ultrasound towards the carotid septum while utilizing the cooling effects of the blood in the internal and external carotid arteries to selectively ablate only septal tissue. Some attenuation through scattering can be expected to reduce the posterior ultrasound effects and protect non-target structures behind the arteries. This principle can be classified as forming of a lesion using thermal heating by an ultrasound beam that is shaped in the tri-vessel space. In some embodiments the emitted ultrasound energy ablates septal tissue by increasing the temperature of the septal tissue to greater than about 45 degrees C., yet tissue outside of the septum remains less than about 45 degrees C. and is thus not ablated. Ablation is a function of temperature and time, and longer exposure to lower energy and temperature can also ablate tissue. This disclosure focuses mainly on temperature and includes treatments that last about 5 to about 60 seconds. The temperatures mentioned herein however shall not be interpreted as strict limitations.
Choice of ultrasound therapeutic parameters such as power, frequency, time and regime (e.g., pulsed or continuous) may ensure that an ultrasound beam does not ablate tissues deeper than about 15 mm (e.g., no deeper than about 9 mm) from the jugular vein. For the typical attenuation of ultrasound in muscle tissue of 1 dB/cm/MHz, the characteristic depth of unfocused ultrasound penetration in tissue is the inverse of attenuation coefficient divided by frequency. For example, at 10 MHz the characteristic penetration depth is 7.7 mm and at 20 MHz the characteristic penetration depth is 3.8 mm, which roughly corresponds to a one example of a range of target distances in a trans-jugular catheter configuration.
Directing the beam from a jugular vein 12 into the septum between two carotid branches benefits the shaping of the lesion by cooling effects from carotid arteries. As illustrated by
Directing and targeting an ultrasound ablation beam 232 at a target site such as a carotid septum 205 from within a jugular vein may be facilitated by detecting vasculature such as the common carotid artery 3, internal carotid artery 90 and external carotid artery 91, and carotid bifurcation 2 using diagnostic ultrasound such as Doppler ultrasound. Such diagnostic ultrasound may provide an indication (e.g., visual images, acoustic, or electrical signals) of the vasculature by detecting blood velocity, direction of flow, pulsations of flow and turbulence while manipulating a catheter (e.g., rotational and translational manipulation) that comprises at least one ultrasound transducer.
In some embodiments translational aiming (in some instances being aligned with) may be achieved by detecting a carotid bifurcation saddle 2 and aiming an ultrasound treatment transducer (also referred to herein as an ultrasound ablation transducer or ultrasound ablation emitter) with a target site relative to the carotid bifurcation saddle. In some embodiments the ultrasound treatment transducer is aimed about 5 to about 15 mm cranial to the bifurcation, saddle in some embodiments about 10 to about 15 mm cranial to the bifurcation saddle, in some embodiments about 10 mm to about 12 mm cranial to the bifurcation saddle, and in some embodiments about 5 to about 10 mm cranial to the bifurcation saddle. A carotid bifurcation saddle can be detected from a position along the length of a jugular vein 12 as a location where one strong blood velocity signal representing a common carotid artery 3 separates abruptly into two arteries, the internal 90 and external 91 carotid arteries. An ultrasound ablation beam may be aimed at a location about 5 to about 15 mm above the level of the bifurcation saddle by advancing or retracting the catheter Aiming the beam at a location about 5 to about 15 mm caudal to the bifurcation saddle aims the beam into the carotid septum to facilitate ablating the carotid body.
In some embodiments a method of ablation includes detecting one or both of the internal and external carotid arteries. They can be detected by rotating a diagnostic transducer, which can occur with a catheter or balloon, or within the catheter or balloon. The treatment transducer can then be aimed at a target site relative to the internal and external carotid arteries. In some embodiments the external and internal carotid arteries are detected, and the treatment transducer is rotationally aimed approximately between the internal and external carotid arteries. In this orientation relative the two arteries, the ultrasound treatment transducer is aimed to ablate the septal tissue and thus the carotid body. In other embodiments aiming the beam is aided by other visualization techniques, such as MRI, CTA, or Fluoroscopy. An ultrasound transducer may optionally also be capable of delivering and receiving low power ultrasound that can be used for imaging of carotid arteries, Doppler imaging, or pulse Doppler imaging. Examples of transducers configured in this regard are described herein. Doppler signal feedback to an operator or computer controlling energy delivery need not be necessarily an image. It can be an indicator such as a curve, a number, an acoustic signal, an LED bar, or an indicator light color or intensity.
Alternatively or additionally, ultrasound imaging may be applied from an external transducer placed on skin of a patient's neck and used to guide therapy. Externally applied ultrasound imaging may incorporate biplane imaging and Doppler flow enhanced imaging. Alternatively, additional ultrasound emitters and receivers can be incorporated in the catheter design.
Alternatively or additionally, single or multiple ultrasound transducers may be positioned on the distal section of a trans-jugular catheter such that ultrasound reverberation between the exterior of the neck surface and ultrasound transducers is sensed in electrical impedance or by means of ultrasonic imaging thus allowing alignment of the catheter with respect to the lateral landmarks of the neck effectively pointing the therapeutic transducer in a medial direction toward the intercarotid septum. The lateral reflections provide acoustic guidance to the catheter ultrasound transducers with the effect maximized when catheter ultrasound imaging transducer becomes substantially coplanar with the exterior neck surface, which may coincide with a desired rotational position relative to the bifurcation of the carotid arteries. Alternatively, similar lateral guidance may be achieved by placing a substantially flat echogenic reflector or active low power ultrasound transducer on the surface of the neck.
In some embodiments herein the ablation catheter may be advanced into an internal jugular vein from the groin, from a subclavian, from a brachial vein, or by direct puncture using methods somewhat similar to ones used for biopsy or central access catheter placement. In some cases a facial vein, or other vein branching from an internal jugular vein, may provide a closer proximity to a carotid septum for placement of an energy delivery element of the catheter. The jugular vein as a venous position for the catheter is therefore merely illustrative.
As described in methods herein, a catheter may be advanced up and down the jugular vein until a bifurcation of a common carotid artery and carotid septum just above it are clearly detected. If external ultrasound is used, the catheter may be made visible with ultrasound by addition of an echogenic coating. This can be confirmed by a Doppler pulsatile velocity signal or ultrasonic imaging. A space, indicating a carotid septum, between two large vessels with high pulsatile blood flow should be easily detectable. Pulsed Doppler at the preselected depth of 3 to 10 mm (e.g., 3 to 5 mm) can be chosen to avoid interference from venous blood flow.
In some embodiments a catheter positioned in a jugular vein may be rotated around its axis until the ablation, or treatment, transducer aperture is facing the carotid septum pointing into the gap between internal and external arteries. Alternatively a transducer with a directional emitter can be rotated inside the catheter. If the Doppler emitter and receiver are located in the distal portion of the catheter placed in a jugular vein, certain advantages may be realized. A low energy Doppler beam can be facing the same direction as the high energy ablation beam. A Doppler signal can then be used for targeting and directing the ablation beam into the septum. The septum can be located as a valley of low velocity area between two peaks or high velocity areas. Alternatively, several Doppler transducers can be incorporated in the distal tip aiming beams silently at an angle to the direction of the face of the aperture of the high energy beam in order to detect both carotid arteries by their high velocity flow. A vein may be distended and a catheter tip maneuvered into position so that a high-energy emitter is aiming into the middle of the gap between two strong Doppler signals representing an internal and external carotid artery. A computer algorithm may assist or automate such aiming.
During ablation the ultrasonic energy emitter may get hot and may require cooling. The catheter may be configured to position the transducer in an internal jugular vein so it does not touch the wall of the jugular vein while delivering high energy for the purpose of ablation. For example, the catheter may comprise a protective membrane such as balloon 145, as shown in
A protective membrane may fully encompass the distal end of the catheter forming a balloon around ultrasound transducers or, as shown in
The ablation depth control may be achieved by placing a catheter in a jugular vein and manipulating the lens internal fluid pressure to expand the protective membrane in a predefined repeatable shape that produces an acoustic convergent or divergent lens effect to the ultrasound beam and preferentially targets the ultrasound beam into a specific target depth in the bifurcation of a carotid artery and a carotid septum. For example, as shown in
A distal end of an embodiment of a carotid body ablation catheter, shown in
In alternative embodiments, any of the catheters comprising an ultrasound ablation transducer and an expandable membrane, such as those in
An ablation catheter may comprise an ultrasound ablation transducer and an expandable membrane, such as membrane 250 shown in
The disclosure herein also includes methods, devices, and systems for ablating a target site by positioning an ablation needle within a lumen of a vein adjacent to the target site, inserting the needle through the vein and into perivascular space containing the target site, delivering an ablation agent into the perivascular space by using the needle, and withdrawing the needle from the perivascular space back into the vein. There may be potential benefits for positioning a device via a trans-venous approach for a carotid body ablation procedure compared to a trans-arterial approach. For example, jugular veins have thinner walls compared to carotid arteries which may be easier to pass an ablation needle through; jugular veins are distensible and flexible and a change in conformation may be achieved by applying force from inside or outside the vessel which may be advantageous for facilitating position of a catheter or accessing a target ablation site; jugular veins have no atherosclerotic or arteriosclerotic disease and blood flows away from the brain eliminating a risk of causing a brain embolism, which may be a concern with a procedure in carotid arteries; a trans-jugular approach may access an intercarotid septum from a lateral side; perforation with a needle or catheter through a wall of a vein (e.g., jugular, facial veins) has less risk of complications such as hematoma due to compressibility of the venous vessel compared to carotid arteries; possible reduction of blood flow in a jugular vein has less risk of flow limitation to the brain compared to reduction of flow in an internal carotid artery.
A representative exemplary anatomy with exemplary characteristic dimensions is shown in
Ultrasound Ablation Catheters with Imaging Transducers
In some embodiments an ultrasound carotid body ablation catheter comprises at least one diagnostic ultrasound transducer and an ultrasound treatment transducer, wherein the transducers are positioned on the catheter relative to one another such that when the diagnostic ultrasound transducers are aligned with vasculature landmarks, the treatment transducer is aligned with a target ablation site (e.g., carotid septum). Carotid vascular landmark as used herein includes an internal carotid artery, an external carotid artery, a carotid bifurcation, and a common carotid artery. This configuration allows an alignment of a diagnostic transducer and a landmark to indicate an alignment of a treatment transducer and target tissue. In some embodiments when the diagnostic transducer is aligned with the landmark, the treatment transducer will be in a proper position to be activated without additional movement to successfully ablate the target tissue. In
An endovascular catheter for carotid body ablation may be configured to both ablate target tissue using therapeutic ultrasound and image tissue for targeting purposes. A catheter may comprise an ultrasound ablation transducer (also referred to as a treatment transducer, or therapeutic transducer), be configured and adapted to accept an imaging catheter, be adapted to identify a direction of aim of the treatment transducer with respect to the image produced by the imaging catheter, and be adapted to direct energy from the treatment transducer to a target identified by the imaging transducer.
There are a number of ultrasound imaging catheters including intravascular ultrasound (IVUS) catheters and intracardiac echocardiography (ICE) catheters on the market that are used for imaging from within a patient's body. For example, Vision® PV 0.035 by Volcano is used for imaging diseased vessels from inside a vessel; UltraICE™ by Boston Scientific is used for imaging during endovascular cardiology procedures. An ICE catheter is used for imaging within a heart however may be functional in the applications described herein. Such imaging catheters may be configured to create an ultrasound-based video representing a cross sectional slice of tissue having a radius of about 50-60 mm around the imaging transducer on a distal region of the catheter. Ultrasound signals transmitted and received from the imaging catheter are controlled and processed by a console external to a patient and an image may be produced and displayed to help a user identify tissues or other objects in the field of view. Additional processing may help to identify features such as blood flow, presence of plaque, or tissue differentiation. Existing ultrasound imaging catheters may have a diameter of about 8 to 1° F. (e.g., 8.2F, 9F) for example. In some embodiments of ablation catheters an existing imaging catheter, or a custom made imaging catheter similar to those known in the art, may be inserted into a carotid body ultrasound ablation catheter to help identify a target ablation site (e.g., carotid body, carotid septum, carotid body nerves), and identify the position of the target ablation site relative to the treatment transducer or its direction of aim.
An embodiment of an ultrasound ablation catheter 305 that is adapted and configured for ultrasound imaging, as shown in
Alternatively, a similar configuration may comprise an imaging transducer or set of transducers that is manufactured as part of the ablation catheter instead of inserted as a separate device into an imaging catheter lumen of the ablation catheter.
In alternative embodiments a catheter may be configured to position imaging transducers of an imaging catheter proximal to the ablation transducer.
An Embodiment of an Ablation Catheter for Use with an Imaging Catheter
An ablation catheter configured to accept an ultrasound imaging catheter may have a distal assembly 510 as shown in
As shown in
The ablation transducer support component 512 is connected to the catheter shaft 511 and is configured to hold an ultrasound ablation transducer 513 in a position relative to an imaging transducer 533 and direct flow of coolant fluid that stops the ablation transducer from overheating. As the ablation transducer vibrates heat is produced. The coolant passes over the ablation transducer to remove heat and maintain a temperature below a predefined maximum (e.g., about 90 degrees C.). An ablation transducer temperature that gets too hot may result in damage to the transducer or other components of the catheter or uncontrolled conduction of heat to the blood, vessel or other tissues. The temperature sensor may monitor transducer temperature to ensure coolant is flowing properly. If the temperature rises above a predefined maximum the console may respond by giving an error message, stopping delivery of ablative energy or adjusting delivery of ablative energy.
As shown in
In an alternative embodiment a ablation transducer support component may be configured to create turbulent flow of coolant over and around an ablation transducer. For example, the ablation transducer support may have similar features to the ablation transducer support component 512 shown in
The echolucent shell shown in
In an alternative embodiment as shown in
In an alternative embodiment as shown in
In an alternative embodiment an echolucent chamber may contain an ultrasound ablation transducer but not an imaging transducer. An Imaging catheter lumen may be configured to place an ultrasound imaging transducer of an imaging catheter in proximity to the ablation transducer but in contact with the blood stream. A fiducial marker may be positioned in the field of view of the imaging transducer and may be for example a guidewire.
A fiducial marker 516 may be placed in a predefined position relative to the direction of aim 517 of the ablation energy such that an artifact is created on an ultrasound-based image or video indicating relative direction of aim of the ablation energy with respect to anatomical structures imaged. As shown in
At the proximal region of the ablation catheter the shaft may be connected to a proximal ablation transducer support, which may also function as a handle 544 as shown in
Optionally the ablation catheter may further be configured with a means for deflection or delivery over a guidewire as exemplified by embodiments disclosed herein.
Imaging Beam Aligned with Ablation Beam
An embodiment of a carotid body ultrasound ablation catheter may comprise a distal region that is delivered to a patient's vasculature and a proximal region that remains outside the body. The distal region is adapted to deliver ablative ultrasound energy from an ultrasound ablation transducer and ultrasound imaging signals from an ultrasound imaging catheter. The catheter is configured to provide an image of tissue proximate the distal region that is aligned and oriented with the direction of aim of the ablation transducer. The user may image tissue around the distal region to search for and identify a target ablation zone (e.g., an intercarotid septum), orient the catheter so the ablation transducer is aimed at the target ablation zone, and deliver ablative ultrasound energy to the target ablation zone. In
The carotid body ultrasound ablation catheter may comprise an elongate shaft 326, which may be made from an extruded polymer and may be a sufficient length (e.g., about 100 to 120 cm) to reach a patient's neck from a femoral vein when delivered through a vena cava to an internal jugular vein 12. Human internal jugular veins are typically about 8 to 20 mm in diameter. The shaft may be configured to fit in a jugular vein for example having a diameter of less than or equal to about 18 French (e.g., between about 9 and 11 French). The catheter may be delivered through a delivery sheath 327, a steerable delivery sheath, or over a guidewire 328. The shaft may comprise an Imaging catheter lumen 329 that slidably accepts an Imaging catheter 330. The lumen may extend from the proximal region of the catheter to the echolucent chamber at the distal region. The Imaging catheter may be inserted into the Imaging catheter lumen at the proximal region of the ablation catheter (e.g., in a handle) and advanced through the Imaging catheter lumen to the distal region. The Imaging catheter lumen may be oriented in the echolucent shell chamber such that the imaging transducer 331 of the imaging catheter is positioned along the direction of aim of the ablation transducer.
As shown in
The ultrasound ablation catheter may further comprise a means to deliver coolant such as saline or sterile water to the echolucent chamber 322 of the distal region. For example, the shaft may comprise a coolant delivery lumen 332 and a coolant return lumen 333. The coolant delivery and return lumens may be connected to a coolant delivery 339 and coolant return 340 port at the proximal region of the ablation catheter. Coolant may be provided to the catheter by a coolant system comprising a coolant source such as a container of saline or sterile water, a conduit such as tubing, and pump such as a peristaltic pump. The coolant system may further comprise a flow pulsation damper or a flow meter. The coolant system may be controlled by the user or may be automatically controlled by a console 341 that coordinates delivery of coolant in coordination with delivery of ultrasound energy. For example, coolant may begin to circulate prior to delivery of ablation energy at a rate and time sufficient to ensure coolant is circulating in the echolucent chamber before ablation energy is delivered and continues at least until the ablation energy is stopped. Other signals may also be used in the control of coolant such as temperature of the ultrasound ablation transducer or echolucent chamber for example.
The ultrasound ablation catheter may further comprise electrical conductors connecting the ablation transducer to an electrical connector at the proximal region of the catheter (e.g., on the handle). The conductors may be held in a lumen in the shaft or a lumen in the hypotube (not shown). Other conductors may be present such as sensor conductors. A temperature sensor may be positioned in the echolucent chamber (e.g., on the echolucent shell surface, on the ablation transducer surface), which may measure temperature. Temperature measurements may be used to indicate sufficient power, excessive power, or overheating. The temperature signal may be used to control power delivery to the ablation transducer.
An alternative embodiment as shown in
Optionally, the ultrasound ablation catheter may comprise a means to be delivered over a guidewire 356. As shown in
An example of an image provided by an ultrasound imaging catheter deployed in an ultrasound ablation catheter is shown in
The ultrasound ablation catheter may further be adapted to articulate the distal region. Articulation may facilitate positioning of the ablation transducer in alignment with a target or expanding an ablation zone by creating multiple ablations associated with multiple positions of articulation. For example, the ablation catheter may comprise controllable deflection wherein a deflectable length 366 (e.g., about 1 to 3 cm) is bent from side to side up to a deflectable distance 367 (e.g., about 0.5 to 3 cm). Deflection may be in a plane that is coplanar with the ablation transducer as shown in
Deflection may be configured in a plane that is substantially orthogonal to the plane of the ablation transducer or in any other direction which may facilitate placement of the treatment transducer, creation of multiple ablations, creating a larger ablation, or maneuvering or deforming a vessel (e.g., vein, jugular vein, facial vein) that contains the catheter to place the ultrasound ablation transducer in a suitable position to deliver energy to a target or to place the ultrasound imaging transducer in a suitable position to identify the target or tissues in the area of the target.
An alternative embodiment of an ablation catheter 375 configured for ultrasound imaging and therapy, as shown in
In the embodiment shown the ablation catheter 375 comprises a shaft (e.g., having an outer diameter of about 11 F), made from extruded polymer with a soft durometer with a braided jacket layer for improved torque response. The shaft comprises an imaging catheter lumen 376 (e.g., about 9.5 F) used to receive an ultrasound imaging 377 catheter. This lumen may also be used for passage of coolant. The ablation catheter may also comprise a guide wire lumen 385 (e.g., having a lumen diameter to slidably contain a 0.018″ guidewire) for Over-The-Wire catheter delivery. The guidewire lumen may be a lumen in a tube (e.g., polyimide tube) passed through a lumen in the shaft and through the echolucent chamber to the distal end of the catheter. The ablation catheter may comprise a coolant delivery lumen, which may be a lumen in a coolant delivery tube that deposits coolant such as saline or sterile water in the echolucent chamber (e.g., distal to the ablation transducer). Coolant may flow within the echolucent chamber and out of a coolant exit lumen, which may be the imaging catheter delivery lumen. A temperature sensor (e.g., thermocouple, thermistor) may be placed within the echolucent chamber (e.g., on the ablation transducer, on the wall of the chamber) to monitor temperature and ensure sufficient coolant is delivered to avoid overheating. An aiming marker 386 may be positioned in the imaging plane next to the imaging catheter delivery lumen and opposite the direction of the delivery of ablation energy. The aiming marker may be made from a material that interacts with the imaging ultrasound waves to create a distinctive image on an ultrasound-based video. For example the aiming marker may be made from a material that absorbs ultrasound waves or that is a strong reflector of ultrasound waves. A distinctive image, or artifact, representing the aiming marker shown on an ultrasound-based video may be a shadow or highlight indicating that the ablation transducer is aimed in the opposite direction. Other configurations may be envisioned that create an unambiguous identification of the direction of aim.
An example of a method of use may comprise advancing a sheath 387 to a region proximate a target; advancing an ablation catheter 375 within a lumen of the sheath; advancing an imaging catheter in the lumen of the ablation catheter until the imaging transducer(s) is positioned in the echolucent chamber; deploying the ablation catheter containing the imaging catheter from the distal end of the sheath; while imaging with the imaging catheter using a combination of advancing and retracting the sheath together with the ablation catheter containing the imaging catheter and deflecting and torqueing the sheath to obtain a suitable position relative to the ablation target; torqueing the ablation catheter while imaging to aim the ablation transducer at the target. Optionally, a guide wire may be used. For example, a guidewire may be delivered first and the sheath and catheter may be delivered over the guidewire.
Angled Imaging Transducer
An alternative embodiment comprises an imaging transducer(s) 390 that is positioned at an angle to the ablation catheter shaft 391. A separate ablation transducer 392 may be parallel to the ablation catheter shaft or angled as shown in
Since the distance between a vein and a target area may vary the vein may be manipulated as described herein to achieve suitable position and distance. Alternatively, an ablation catheter may be configured to angle the ablation transducer to achieve an ablation at an appropriate distance. For example, multiple catheters may be provided that are configured for creating an ablation at varying distances and angles from the ablation catheter.
An embodiment of an ultrasound ablation catheter 400 configured to accept an imaging catheter 358 may have an ablation transducer 401 that may pivot to alter the angle 402 with the axis, as shown in
An ablation catheter may be configured to be used in conjunction with a separate imaging catheter, which can help a user identify tissue of and around a target ablation zone in order to deliver ablation energy safely and effectively to the ablation target. The separate imaging catheter may be for example an ultrasound imaging catheter such as an Intravascular Ultrasound (IVUS) catheter or Intracardiac Echocardiography (ICE) catheter. The imaging catheter may comprise enhancing technology such as photoacoustic or thermoacoustic imaging. Other medical imaging technology may be suitable.
A variety of IVUS and ICE catheters are available on the market. An ablation catheter configured to accept an ultrasound imaging catheter may be particularly configured to accept an imaging catheter available on the market, such as the Visions® PV 0.035 IVUS catheter by Volcano, or the UltraICE™ catheter by Boston Scientific Corporation.
A Visions PV 0.035 IVUS catheter has an imaging transducer on its distal region. The imaging plane is about 13.5 mm from the very distal end. The transducer is 8.2 FR in caliber and about 6.5 mm long. The distance from the proximal end of the transducer to the very distal end of the catheter is about 18.5 mm. The catheter shaft is 7.0 FR and the working length is about 90 cm. The imaging transducer is made of a 64-element cylindrical array. The catheter has a guide wire lumen running from its distal tip to proximal end. An ablation catheter configured to accept a Visions PV 0.035 IVUS catheter may comprise an Imaging catheter lumen having a minimal diameter about 8.5 FR and preferably with additional room for coolant return in the same lumen around the IVUS catheter. The space in the echolucent chamber may be long enough to contain the imaging transducer and portion of the catheter that is distal to the transducer. For example the distance from the distal edge of the ablation transducer support component to the end piece may be at least 18.5 mm (e.g., about 19 mm). The length of the ablation catheter may allow the imaging transducer to be positioned in the echolucent chamber while the Y-connector on the IVUS catheter's proximal end extends from the proximal end of the ablation catheter (e.g., from a handle on the proximal region). For example, the length of the ablation catheter from the distal end to the IVUS port on the proximal end may be no more than about 90 cm yet long enough to reach the target area (e.g., in a jugular vein near a carotid body) from an introduction site (e.g., femoral vein) while inserted through a deflectable delivery sheath. A valve such as a hemostasis valve on the IVUS port of the ablation catheter should be configured to allow passage of the 8.5 FR transducer while sealing around the 7 FR shaft to stop coolant from leaking for example up to a pressure of about 30 psi. The guidewire lumen of the IVUS catheter may be primed with coolant and sealed with a luer cap at the proximal end to stop coolant from leaking or air from entering.
An UltraICE™ catheter has a single 9 MHz imaging transducer mounted to a rotating drive shaft that passes through the catheter's shaft to the proximal region where it is connected to a motor to spin the transducer. The transducer is angled slightly toward the distal end. The imaging plane is about 5.5 mm from the very distal end. However, since the transducer is angled the image is a slightly distal looking cone rather than a transverse plane. The transducer is 9 FR in caliber and about 2 mm long. The distance from the proximal end of the transducer to the very distal end of the catheter is about 9.5 mm. The catheter shaft is 9 FR and the working length is about 110 cm. An ablation catheter configured to accept an UltraICE™ catheter may have an Imaging catheter lumen having a minimal inner diameter of about 9 FR and preferably with additional room for coolant return in the same lumen around the ICE catheter. The space in the echolucent chamber may be long enough to contain the imaging transducer and portion of the catheter that is distal to the transducer. For example the distance from the distal edge of the ablation transducer support component to the end piece may be at least 9.5 mm (e.g., about 10 mm). Consideration should be given to how the angle of the imaging transducer alters the position of the target relative to the image. The length of the ablation catheter may allow the imaging transducer to be positioned in the echolucent chamber while the connector on the ICE catheter's proximal end extends from the proximal end of the ablation catheter (e.g., from a handle on the proximal region). For example, the length of the ablation catheter from the distal end to the imaging catheter port on the proximal end may be no more than about 110 cm (e.g., about 104.5 cm+/−2 cm) yet long enough to reach the target area (e.g., in a jugular vein near a carotid body) from an introduction site (e.g., femoral vein) while inserted through a deflectable delivery sheath (e.g., having a useable length of about 93.5 cm+/−2 cm). A valve such as a hemostasis valve on the imaging catheter port of the ablation catheter should be configured to allow passage of the 9 FR shaft while sealing around it to stop coolant from leaking for example up to a pressure of about 30 psi. Since the imaging transducer rotates on a drive shaft caution should be taken to avoid pinching the drive shaft or impeding its rotation. For example the ablation catheter may be configured to have minimal bend radius or tortuosity. A component may be provided that contains the motor drive and proximal region of the ICE catheter relative to the proximal region of the ablation catheter to avoid kinking.
A system to support the ablation catheter may comprise an interconnect cable, a delivery sheath, a coolant tubing set, a coolant pump, and an ablation console. For embodiments configured to accept a separate imaging catheter the system may include an imaging catheter and imaging console or these may be provided separately. For embodiments configured with an integrated imaging transducer an imaging console may be integrated with the ablation console or a separate unit. Other components, such as coolant (e.g., sterile water or saline in an IV bag or bottle), introducers, site preparation supplies, and dressings, used in the procedure may be provided in a kit or procured from a procedure facility's supplies. A system may also comprise a brace to hold a patient's head and neck still relative to the torso. For embodiments configured for use with a guide wire a system may comprise a guidewire or a set of guidewires (e.g., guidewires having 0.018″ diameter or 0.035″ diameter, guidewires with preformed bends, deflectable guidewires).
The interconnect cable may be configured to connect the ablation catheter to the ablation console, for example with mating quick-connect connectors and suitable conductors. The interconnect cable may be a suitable length (e.g. about 8′) to separate the ablation console from the sterile field and not impede catheter maneuverability during the procedure.
The delivery sheath may deflectable in at least one direction. It may have a soft (e.g., about 35D durometer) atraumatic tip, a lumen with a diameter suitable to slidably fit the ablation catheter (e.g., about 0.174″), a corresponding outer diameter (e.g., about 0.210″), and a valve to allow passage of the ablation catheter (e.g., a Tuohy-Borst valve).
The coolant tubing set may be compatible with the coolant pump, for example having a section that feeds through and functions with a peristaltic pump. The coolant tubing set may comprise luer lock connections that are compatible with commercially available IV solution administration sets and extension sets. The tubing set may comprise a tube that delivers coolant from a pump tube section to the coolant delivery port of the ablation catheter's handle. This section of tube may further comprise a pressure relief valve to open in case of inadvertent high pressure for example caused by catheter occlusion. This section may further comprise a pulsation damper. The coolant tubing set also comprises a coolant return tube to be connected to the coolant return port of the ablation catheter handle. The coolant return tube may return coolant to the coolant storage vessel or discard it. In one embodiment the coolant storage vessel only contains enough coolant sufficient for a limited number of ablations and return coolant is discarded so in the case of a catheter leak only a limited amount of coolant is delivered to the patient's blood stream.
The ablation console may be a computerized electrical signal generator that delivers high frequency (e.g., in a range of about 10 to 25 MHz, about 20 MHz) alternating current to an ultrasound ablation transducer. Parameters of the delivered energy may be selected by a user or may automatically be determined. For example, the console may read data from memory in a catheter and deliver energy accordingly or in combination with a desired parameter such a lesion depth. The console may also coordinate coolant pumping or imaging capabilities. The console may identify conditions that indicative of a malfunctioning catheter or undesired procedure and alert a user or adjust energy delivery to mitigate the problem. A console may be configured to deliver nerve stimulation signals to a catheter. For example, an ultrasound signal that mechanically or thermally stimulates a nerve may be delivered without ablating tissue to confirm effective or safe aim of an ablation transducer prior to delivery of ablation energy and following ablation to confirm successful ablation. Alternatively, a catheter may comprise one or more stimulation electrodes and the console may deliver an electrical nerve stimulation signal to assess proximity to a nerve.
Configuration of veins near a target site may vary from patient to patient or side to side within a patient. An ablation catheter 411 such as any of the embodiments of ultrasound ablation catheters disclosed herein may be delivered to a vein 12 that is near a target site 205 and in a suitable position for a carotid body ablation procedure. For example, conditions for a suitable position may comprise the distance 410 from an interior surface of a vein wall to a border of a target site such as an intercarotid septum to be within about 0 to 5 mm and alignment of the vein 12 with the target to allow delivery of ablative energy without obstruction or unsafe interference. Alternative conditions for a suitable position may depend on the configuration of the ablation catheter. In some patients there may not be a vein in a suitable position, however, an ablation catheter may be delivered to a vein that may be maneuvered to a suitable position. Maneuvering a vein, or a catheter within a vein, to a suitable position may comprise techniques such as palpating the neck, rotating the head, deflecting a deflectable ablation catheter, deploying a structure from an ablation catheter such as the deployable wire, deflecting a deflectable sheath, or a combination of these.
A deflectable sheath 412, as shown in
Alternatively, as shown in
A method of using a deflectable sheath with an ablation catheter may comprise delivering a sheath from an entry vein such as a femoral vein to a vein proximate to a target, e.g., in an internal jugular vein, a facial vein, or other vein connected to a jugular vein that is in proximity to a carotid body. A catheter such as the embodiments described herein of ablation catheters or ablation catheters configured to be used with imaging catheters may be delivered through the deflectable sheath. An imaging modality such as an ultrasound imaging catheter positioned in an ablation catheter, or imaging transducers integrated with an ablation catheter, or a transducer configured to both image and ablate may be used to image tissue around the ablation catheter and identify a relative position of a target. If the vein needs to be manipulated to achieve a suitable position for ablation of the target the following steps or combination of steps may conducted: the deflectable section of the sheath may be deflected by controlling an actuator; the sheath may be torqued at the proximal end or handle to torque the distal deflectable end; the ablation catheter may be advanced or retracted in the sheath to obtain a suitable distance from the sheath's deflectable section to the ablation transducer; the ablation catheter may be torqued at its proximal end or handle to rotate the direction of aim of ablation; and if the ablation catheter is configured to be deflectable it may be deflected. Imaging may continue while manipulating the vein or imaging may be intermittently performed until a satisfactory position is obtained. Adjustments to the position and direction of aim of ablation may be made during or after the vein has been satisfactorily manipulated. For example, the ablation catheter may be rotated, advanced, retracted or deflected to aim ablation energy toward the target while imaging.
An ultrasound ablation catheter may comprise a transducer assembly that is configured for both imaging and ablation. As shown in
For example embodiments of ultrasound ablation catheters with integrated imaging transducers such as those shown in
Alternatively, as shown in
The authors have conducted bench and animal studies to assess dosimetry of ultrasound ablation energy using transducers with the size of about 2 mm in width and 4 mm to 6 mm in length. A power between 3 to 8 acoustic watts, a frequency in a range of about 10 MHz to 25 MHz and a time range of between 5 s to 20 s may allow a reasonable controllable lesion depth between 2 mm and 9 mm and lateral dimensions determined by transducer width and length suitable for targeting a carotid septum from a jugular vein (e.g., tissue residing at about 2-9 mm from the inner wall of the jugular vein).
The ability to control ablation depth is critical for the efficacy and safety of clinical procedure. In light of significant anatomical variation in relative location of the carotid arteries, carotid body and jugular vein, ablation depth control is essential for effective ablation of target tissue (e.g., carotid septum) while safely containing an ablated region to avoid iatrogenic injury of important non-target nerves or tissues. From the lesion formation theory a region of thermal coagulation induced by ultrasound heating is defined as an integral of temperature exponent over time [Sapareto S. A., Dewey W. C. Thermal dose determination in cancer therapy Int. J. Radiat. Oncol. Biol. Phys. 1984. V. 10. No Bi P. 787-800]. A lesion produced by a flat rectangular element starts closest to transducer and propagates to deeper tissue that is more distant from the transducer along the ultrasound beam, depth over time. Using the thermal dose definition the theoretical lesion depth may be approximated by an integral over time:
Where d is depth of the lesion, T is tissue temperature, t is time. Based on finite element simulation the tissue temperature over time is roughly proportional to a product of applied acoustic power and ablation time:
T˜Pt
β (2)
Where β is a tissue and transducer dependent dimensionless coefficient less or equal to one. Combining equations (1) and (2) in a simplest case of β=1, applicable for active ultrasound power deposition with negligible volumetric thermal conduction, the lesion depth as a function of applied acoustic power and ablation time is given:
The more complex forms of lesion depth growth over time can be deduced assuming β deviates from unity, which corresponds to an ablation consisting of longer time and lower power in which thermal conduction effects cannot be neglected. Finite modeling of lesion formation provided theoretical data to evaluate different β coefficients and deduce the trend between applied acoustic energy and lesion depth. It was found that lesion depth and applied acoustic energy are best described by hyperbolic cosine function:
Where lesion growth parameter a is minimum acoustic energy required to initiate lesion nucleation and γ is a characteristic lesion inversed depth parameter dependent on the transducer geometry, frequency and surrounding tissue anatomy.
The authors have determined through anatomical studies that a range of target ablation depths between about 2 mm to 9 mm may be suitable for delivering ablation energy to a carotid septum from a catheter placed in a jugular vein. Based on above theory, bench and animal studies the authors have demonstrated that a catheter delivering ablative energy from an ultrasound ablation transducer with a resonant frequency of about 21+/−2 MHz approximately 1 mm in lesion depth is gained for every 10 acoustic Joules of energy in a first approximation consistent with equation (3). Energy is a product of acoustic power and duration thus various regimes of controlling energy delivery parameters may be used to control ablation depth. For example, energy delivery parameters may be chosen to optimize multiple variables such as: minimizing duration to reduce risk of patient movement; utilizing a duration-power range in which lesion width or height are fairly consistent; utilizing a duration that is not too fast for a user or console to react to an event requiring adjustment of energy delivery for safety reasons; using a power that is not too high to have increased incidence of overheating; using a power that results in a reasonable transducer temperature increase that can be managed by coolant flow; minimizing duration to minimize conductive heating of adjacent tissues; utilizing parameters that allow control of lesion depth to about 0.5 mm precision.
A user may determine a desired ablation depth for example by assessing images from the ultrasound-based video created by the imaging transducer(s) that may have reference dimensions, and select the desired ablation depth on the ablation console. Alternatively, a computerized algorithm may assess a desired ablation depth automatically, for example based on the ultrasound-based video data, and relay the desired ablation depth to an ablation control algorithm of the ablation console. Alternatively, a computerized algorithm may assess relative positions of anatomical features such as internal and external carotid arteries and jugular vein and the ablation transducer and suggest a desired ablation depth to a user who may confirm or adjust the desired ablation depth to be entered into an ablation control algorithm. The ablation control algorithm may deliver ablative energy using energy delivery parameters suitable for creating the desired ablation depth.
Using computer finite element modeling the authors have calculated dynamic temperature profiles for sets of ablation time (e.g., duration of energy delivery) and applied acoustic powers. Computed lesion parameters were consistent with experimental results and the theoretical trend expressed by equation (4). The results 571 of finite element modeling of lesion depth versus energy is shown in
The accumulative effect of temperature is a thermal dose derived from the amount of energy deposited, which correlates with lesion formation dynamics. Determined predominantly by transducer dimensions the lesion lateral dimensions (e.g., length and width) increased relatively quickly and plateaued while lesion depth increased more slowly. Lesion width and length may be considered substantially constant within a range (e.g., a range of about 5 s to 25 s) of ablation duration considered in the sets of power and time used to control lesion depth. The 2 mm deep lesion is considered to be the minimum controllable lesion depth of desired lateral dimensions consistent with the transducer lateral dimensions (e.g., 2 mm wide and 4-6 mm long). For each set of ablation time and power, lesion depth was modeled creating a plot and equation (4) representing the relationship between lesion depth and applied acoustic energy as shown in
The generic theoretical relationship between lesion depth and acoustic energy was confirmed using bench test studies using a polyacrylamide gel phantom that produced data points of lesion depth for power-time sets, which were used to create a relationship of lesion depth as a function of energy that closely resembled the theoretical relationship. In overall, the theoretical relationship expressed by equation (4) provided an accurate fit to both simulated (dotted line 573) and experimental (circles 574 and solid line 572) data. Computer simulations predicted nucleation energy α=3 J and characteristic inverse depth constant γ=0.5 mm−1, while experimental data yielded larger α=17 J and smaller γ=0.3 mm−1. The difference in deduced lesion growth parameters reflects difference in thermal dose assumed in simulation versus visually detectable lesion formation in polyacrylamide gel. Gel turns opaque at slightly higher 70° C. temperature and has zero perfusion compared to typical 42° C. onset of protein denaturation temperature in biological tissue with nonzero perfusion assumed in simulations. Each catheter may have a slightly different ablation transducer response to electrical power delivery and may be calibrated using acoustic measurements to identify its specific relationship of electrical power to total acoustic power. Based on the relationship of ablation depth to sets of acoustic power and time and the calibration of electrical power to acoustic power of each catheter, a dosimetry table unique to each catheter may be created that matches desired depth to a set of ablation time and electrical power.
An example of a dosimetry table-processing algorithm is shown in
F=√{square root over (αδP2+βδt2+γδd2)} (5)
Where δP and δt are acoustic power and time deviation from optimal trajectory, and δt is deviation from optimal depth, α=4, β=1, γ=1 are constants.
An example of a dosimetry table for a specific catheter is shown in
Ablation width is typically tied to ablation depth. Controllably creating a wider ablation may result in creating a deeper ablation. Ablation energy delivered from a catheter positioned in a vein (e.g., jugular vein) and aimed at a carotid septum may have a depth dimension that is oriented from a lateral to medial boundary of a carotid septum. The depth of an ablation may be optimized to cover the distance between these boundaries and it may be desired to avoid ablating beyond the medial boundary to reduce a risk of ablating an important non-target structure. With an optimized ablation depth the width may only cover a fraction of a carotid septum width depending on the anatomy of the patient. It may be desired to ablate a larger percentage of a carotid septum to increase efficacy. Ablation size (e.g., width or height) may be increased without increasing ablation depth by moving the ablation transducer and optionally the imaging transducer along with the ablation transducer. For example, motion of an ablation transducer may be accomplished by side-to-side deflection of the distal region of an ablation catheter, rotating the catheter or transducer within a catheter, or translational motion of a catheter or transducer along a length of a vessel. Motion may be performed to create multiple independent ablations or during energy delivery to spread a resulting ablation over a greater volume. Motion may be preformed while imaging wherein a user may identify boundaries of a desired target zone or an ablation may be computer controlled by detecting target zone boundaries and applying ablation energy only within the boundaries. Boundaries may include for example anatomical structures such as boundaries of a carotid septum. Motion of a transducer in a catheter may be accomplished manually by a user or automatically by a servomotor connected to a rotatable transducer mount that is computer controlled with a desired speed and distance and may comprise a feedback signal such as edge detection to identify a target zone. An alternative way to increase ablation size may be to direct ablation energy through a lens to diffuse or diffract energy. A lens may be inflatable with a liquid such as water or saline to adjust a desired diffusion or diffraction. Another alternative for creating wider ablations may include delivering ultrasound ablation energy from a transducer having a convex curved surface. A user may choose a catheter having a suitable curved transducer for a desired ablation width depending on a patient's anatomy. Alternatively, a catheter may have a convex curved transducer and a shield with an aperture that is adjustable to customize ablation width.
The embodiments described herein that contain an echolucent chamber with flowing coolant may be adapted to reduce or eliminate air bubbles in the coolant. Air bubbles can inadvertently become included in the supply of liquid coolant (e.g., saline or water). Through surface tension, air bubbles may stay trapped in an echolucent chamber or form during energy delivery near or on an ultrasound transducer. This may negatively affect ablation or imaging performance In the manufacture of a catheter a solution (e.g., isopropyl alcohol) carrying a surfactant may be circulated through the coolant delivery pathway and echolucent chamber, the solution may be drained and the catheter left to dry. The surfactant may be retained on the fluid-contact surfaces making all surfaces wettable, i.e., having a reduced surface tension that facilitates the removal of air bubbles.
Any of the methods of use herein may comprise ultrasound contrast enhanced imaging, which may improve the ability to image a carotid body. An ultrasound contrast, such as commercially available SonoVue, may contain microbubbles. Differential image analysis may be performed by taking an image of the target area using an ultrasound imaging transducer (e.g., on an imaging catheter or an external ultrasound transducer) before and after injecting ultrasound contrast and comparing the images to highlight contrast from the non-contrasted tissue. The contrast may be injected into the patient's vascular system by injecting through the sheath, which may have a gasket seal on the proximal end to seal around the ablation catheter, an injection port such as a luer lock with a stopcock valve through which contrast or other injectant may be injected into the sheath's lumen in the space around the ablation catheter to be deposited out the distal end of the sheath. Areas containing the contrast typically would be areas with blood flow, including a carotid body. If a precise location of a carotid body can be identified with imaging technology such as contrast enhanced ultrasound imaging, CT or MRI, then a target ablation area may be narrowed to the carotid body. If a precise location of a carotid body is not identified a target ablation area may include a larger zone such as an intercarotid septum.
An ablation catheter may comprise an ablation transducer acoustic insulator or backing component. An ablation transducer may transmit ultrasound waves in multiple directions. For example, a plate shaped transducer whether it is substantially flat or curved may transmit ultrasound energy from both faces of the transducer. The backing component may be used to shield transmission of ablation energy so ablation energy is only directed from one face of the ablation transducer and may further serve to reduce acoustic losses.
A backing may be acoustically absorptive or reflective. A backing element may be a component containing a thin layer of gas such as air or carbon dioxide having a thickness of at least about 1 mm. The acoustic insulator may be a dense material such as stainless steel, for example having a thickness of at least about 0.006″ (e.g., about 0.008″).
An embodiment of an acoustic insulator containing gas comprises microspheres of air that are embedded in a substrate such as epoxy. An acoustic insulator made from air-filled microspheres embedded in epoxy may have less of a mechanical coupling effect when a transducer is placed in contact with the acoustic insulator compared to an acoustic insulator made from brass or stainless steel. In other words the vibration of the transducer may be dampened significantly less when a transducer is placed in contact with a microsphere insulator than when it is placed in contact with a dense, rigid insulator such as stainless steel or brass. Thus an air-filled microsphere acoustic insulator may be more suitable in an embodiment where a transducer is positioned in contact with the acoustic insulator. Such a design may have benefits such as ease of manufacturing, less fragile transducer, smaller catheter diameter, or more space for coolant flow in front of the transducer. A combination of microspheres having a variety of diameters may increase volume of air in an insulator. For example smaller microspheres may occupy space between larger microspheres. An acoustic insulator may have a thickness in a range of about 200 to 300 microns (e.g., about 250 microns) and may contain a combination of microspheres having diameters in a range of about 15 to 25 microns (e.g., about 20 microns) and microspheres having diameters in a range of about 180 to 210 microns (e.g., about 200 microns), for example.
For embodiments described herein comprising one or more imaging transducers an fiducial marker may be positioned in the ablation catheter to interact with the imaging ultrasound waves to provide a distinguishable aiming artifact on the ultrasound-based video that identifies a relative position to the direction of delivery of ablation energy. This may be particularly useful for ablation catheters configured to accept a separate imaging catheter since the rotational positioning of the imaging catheter within the ablation catheter may be variable. A fiducial marker may have acoustic properties that are significantly different that the surrounding tissue for example so echoes are greater (hyperechoic) or less (hypoechoic) than the surrounding tissue. The material or surface of the fiducial marker may be highly reflective or highly absorptive of sound waves relative to surrounding tissue being imaged. A fiducial marker may have a more consistent echo compared to surrounding tissue being imaged. A fiducial marker may be positioned to indicate on an ultrasound-based video the opposite direction of delivery of ablation energy. In this configuration the image of the aiming artifact (e.g., a shadow) will not interfere with the image of the target region and surrounding tissues. The image of the aiming artifact on an ultrasound-based video may be a distinguishable shape such as a wedge or line that is black or white radiating from the center of the ultrasound-based video in one direction and a user may understand that the ablation energy is aimed in an opposite direction.
Other relative directions or arrangements of fiducial markers may be envisioned. For example, two fiducial markers may be positioned on either side of an ablation transducer to indicate that ablation energy is delivered between two resulting aiming artifacts. Alternatively, two thin fiducial markers may be positioned close to one another to create an image resembling two bright stripes bordering a narrow stripe, which may be a more precise and detectable aiming artifact. Alternatively a fiducial marker may be placed at other positions around a circumference of a catheter as long as its relative position to a direction of aim of ablative energy is understood.
A fiducial marker may comprise a material that interacts with imaging ultrasound waves to absorb or reflect ultrasound waves in a distinguishable manner compared to typical tissue in a target region. For example, the material may be a dense material such as stainless steel or an air-filled component that inhibits transmission of ultrasound. In some embodiments, an fiducial marker may be a component that also acts as a backing material for an ablation transducer that also inhibits transmission of ablation energy. In other embodiments a fiducial marker may be a separate component or may provide other functions such as structural support for a distal end component, a guide wire lumen, or an echolucent shell support.
An embodiment of a fiducial marker comprises a stainless steel hypotube with a lumen containing air or air-filled microspheres held in epoxy. The hypotube may be sealed at both ends with an adhesive to contain the air or microspheres. The hypotube may have an outer diameter of about 0.028″ to 0.038″ for example.
Another embodiment of fiducial marker comprises a wire such as a round wire (e.g., having a diameter of about 0.028″ to 0.038″), or a flat ribbon wire (e.g., having a profile of about 0.005″ by 0.030″). The wire may be stainless steel. Optionally, the wire may be surrounded by a component that further interacts with ultrasound imaging waves, for example a metal coil may be wrapped around the wire or the wire may be coated in an epoxy containing microspheres of air.
A fiducial marker may have increased echogenicity to increase its distinctive characteristics compared to surrounding tissue. For example, a fiducial marker may comprise a rough surface or a linear pattern of grooves or surface with a texture that enhances reflectivity of ultrasound waves. This may be particularly helpful when an imaging transducer is not parallel to the fiducial marker. Some ultrasound imaging catheters comprise transducers that are positioned at a slight angle to axis of the catheter. Although the angle may be small it may cause waves to reflect off of the fiducial marker at an angle of incidence that reduces the ability of the transducer to capture echoes.
A fiducial marker may comprise a piezoelectric element that vibrates when high frequency current is applied emitting an acoustic signal that may be detected by the imaging transducer to provide a robust image of the fiducial marker.
A system for imaging a target region and ablating tissue in the target region may provide a digital video, or ultrasound-based video, created from ultrasound signals transmitted from an ultrasound imaging transducer, reflected off of tissues, and received by the imaging transducer. An example of a frame of an ultrasound-based video created with an IVUS catheter placed in a jugular vein in proximity to a carotid bifurcation is shown in
An ultrasound-based video may be further augmented with visual aids, animations, or messages to provide information to a user that may assist understanding of the ultrasound-based video, planning or conducting a carotid body ablation procedure.
An embodiment of a system for imaging and ablation of a carotid body having image augmentation may comprise a catheter with an ultrasound imaging transducer and an ablation means, an ablation console, an ultrasound imaging console with a means for transmitting and receiving signals to and from the imaging transducer and a computer executed algorithm that creates an ultrasound-based video from signals received from the imaging transducer, an image augmentation unit that processes the ultrasound-based video with a computer algorithm that creates an augmented image, and a monitor to display the augmented image. A schematic diagram of a system is shown in
The catheter may be an embodiment described herein of an ablation catheter configured to accommodate an ultrasound imaging catheter or with an integrated imaging transducer(s) and may further comprise an aiming artifact to identify a direction of delivery of ablation energy on an ultrasound-based video. An ablation means may comprise an ultrasound ablation transducer or other ablation energy delivery device such as a needle that penetrates a vessel wall to deliver RF energy or a chemical agent to an ablation target tissue. The system may further comprise an ablation energy console suitable to the ablation means such as an ultrasound generator or RF generator.
The imaging transducer, or transducer, may be for example a piezoelectric or capacitive transducer positioned in or on a distal region of the ablation catheter near an ablation element (e.g., ultrasound ablation transducer, RF needle, needle for injecting a chemical agent, RF electrode, laser emitter). The imaging transducer may transmit acoustic waves to the space around the distal region of the catheter and receive acoustic waved echoed off of tissue in the space.
An ultrasound imaging console may generate an electrical signal and control delivery of the signal to the imaging transducer to be converted to ultrasound waves. Echoes received by the imaging transducer may be converted to an electrical signal, which is transmitted back to the imaging console. Some embodiments may use separate transmitter and receiver components or consoles. In some embodiments an imaging transducer may be positioned on an ultrasound imaging catheter (e.g., Visions® 0.035 catheter by Volcano Corporation, or UltraICE™ catheter by Boston Scientific) and an ultrasound imaging console maybe a system compatible with the imaging catheter. An imaging catheter and compatible imaging console may be provided separately from the system, which may be configured to accommodate the imaging catheter and imaging console. In another embodiment an imaging transducer may be integrated in an ablation catheter, an imaging console may be separate from an ablation energy console or may be integrated into a single unit, and both the imaging transducer and imaging console may be provided as part of the system.
The electrical signals generated by the echoes impacting the transducer and transmitted back to an imaging console may be used to create an image or video (i.e., ultrasound-based video) that may be displayed on a monitor. For example the signals may be processed by a computer-executed algorithm and output to a monitor or a video output port on the ultrasound imaging console.
Image grabber hardware, used to capture images or video, is known in the art and may consist of a hardware interface that captures single frames of video, converts the analogue values to digital and feeds the result into a computer. The image grabber may be connected to the video output port on the ultrasound imaging console, for example, and may send a digital interpretation of the video to an image augmentation computer, which may be incorporated into the ultrasound ablation console or be a separate unit.
The image augmentation computer may run an algorithm to augment the video. The algorithm may process each video frame in real time tracking the orientation of the ablation catheter using a fiducial marker or aiming artifact in the images. The algorithm may identify an aiming artifact by looking for any distinct marker that does not change shape when the orientation changes. Inputs to the algorithm may be provided by the ultrasound-based video, the ablation console (e.g., console status, energy delivery status, depth parameters), or a user interface (e.g., identification of anatomical features, settings, zoom, pan, contrast, features to display). Outputs may be to a monitor (e.g., an augmented image, an original ultrasound-based video, an augmented image overlaid on an ultrasound-based video), or to an ablation console (e.g., signal to control energy delivery, signal to control energy delivery parameters such as power and time).
In addition to the captured video, a user may control inputs to the algorithm. For example, a user may select a desired ablation depth or identify a part of the anatomy such as an internal carotid artery or external carotid artery. User inputs may be controlled by a user interface (e.g., knobs, dials, touchscreen, mouse, voice control) that may be on the unit containing the image augmentation computer (e.g., the ablation console). Before delivering ablation energy, a user may adjust ablation depth on the ablation console, for example if the overlaid image of an estimated ablation appears to be too long and extend beyond the borders of a carotid septum, or too short and not fill a carotid septum adequately, and the overlaid image of an estimated ablation may reflect the adjusted depth. In an embodiment wherein the ablation element is an ultrasound ablation transducer ablation depth may be controlled by automatically adjusting parameters such as power and time for a given frequency.
The image augmentation algorithm may output a signal to a monitor. For example, if the algorithm is on a computer physically contained in an ablation console the output may be to an output port (e.g., a VGA, SVIDEO, DVI, HDMI port) or cable connected to an external monitor or to a monitor on the ablation console. An external monitor may be supplied with the system or separately as part of a catheter lab's equipment. The monitor may display other information in addition to the ultrasound-based video with augmented image overlay such as fluoroscopy or X-ray, patient information, or physiological parameters.
Black and white versions of embodiments of augmented video frames are shown in
To confirm identification of the internal and external carotid arteries the user may be asked to slowly slide the catheter out and in by a few centimeters, which may create an video of the two carotid arteries converging to a common carotid artery as the catheter is pulled out and diverging to internal and external carotid arteries as the catheter is pushed in.
As shown in
After an ablation has been created an image of the ablation 453 with respect to the carotid arteries may be displayed, for example with distinct color such as white as shown in
The information computed by the image augmentation algorithm could be fed back to the energy delivery console. If there is inadvertent movement during delivery of ablation energy the augmented image algorithm may send a signal to the ablation console to pause or discontinue delivery of ablation energy and the augmented image may display a partially filled ablation outline in a color such as red to indicate a suitable time may not have been achieved to create a desired ablation depth and a user may choose to perform another ablation in the same location.
If the catheter is pushed forward or pulled back the image augmentation algorithm may calculate translational movement using the change in distance between the internal and external carotid arteries.
Information from other imaging sources such as fluoroscopy, MRI, CT, or a second ultrasound imaging transducer may be input into the image augmentation algorithm and may be used to create an image of location of a carotid body or nerves, to calculate bifurcation angle, to create a 3D image, or to calculate height of an ultrasound imaging plane above a carotid bifurcation.
Another fiducial may be used to identify distance from a carotid bifurcation (e.g. distance in a superior direction to a carotid bifurcation). For example a fiducial marker may be a wire that is slidable within a lumen of the catheter. The wire fiducial may have a distinguishable echogenic marking that may be aligned with a carotid bifurcation. The wire fiducial may be held in place as the catheter is advanced. The wire fiducial may have another distinguishing marking at a predetermined distance from the first marking (e.g., about 6 mm from the first marking). When the catheter is advanced until the second marking is seen it may be understood that the imaging plane is the predetermined distance (e.g., 6 mm) from the bifurcation. The wire fiducial may have multiple markings to indicate increments (e.g., every 2 mm). The wire fiducial may also have radiopaque markings that can be visualized on fluoroscopy.
The algorithm may control rotation of the image so the augmented image may be displayed for example, with the direction of aim always up.
An image augmentation algorithm may use a known dimension such as diameter of the catheter or width of an aiming artifact as a scale and calculate distances between anatomical features for example, relative positions of an internal jugular vein, a carotid septum, an internal carotid artery, an external carotid artery, carotid septum boundaries, artery diameters, change in artery diameters, change in relative position of anatomical features, size and relative position of an estimated ablation or created ablation. Calculated distances may be displayed on an augmented image overlay, for example, as a list or with labels. The algorithm may provide user instructions or suggestions based on calculated distances, for example, how much to torque or deflect the catheter to manipulate the vessel (e.g., jugular vein) containing the catheter, how much and which direction to torque the catheter to adjust aim of the ablation element, adjustments to ablation depth or parameters affecting ablation depth, how to move the catheter in or out of the vessel to achieve a suitable position.
An image augmentation algorithm may input information to the ablation console. For example, measurements and relative positions calculated by the image augmentation algorithm may be used to automatically adjust parameters (e.g., power and time) to control ablation depth so the estimated ablation size is optimally within and filling space between medial and lateral borders of a carotid septum. The image augmentation algorithm may detect significant movement during ablation that may send a signal to the ablation console to pause or terminate delivery of ablation energy. Ablation may be performed in a sweeping mode where ablation energy is delivered while moving the aim, for example rotating an ultrasound ablation transducer to sweep across a carotid septum from one carotid artery to another. An image augmentation algorithm may indicate to a user when to move or how fast to move the aim and may signal the ablation console to pause energy delivery when a significant amount of energy is delivered to a position then continue to deliver energy when the image augmentation algorithm detects movement to a suitable position. Alternatively, motion of ablation aiming may be controlled by a mechanism such as a servomotor controlled by input from the image augmentation algorithm based on calculated measurements and relative positions.
Ablative energy, particularly ultrasound ablation energy, may be delivered for a duration of less than about 30 s (e.g. less than about 25 s, less than about 20 s, between about 7 to 23 s). While ablative energy is being delivered the direction of aim of ablative energy may move inadvertently from a desired target direction. This may cause a risk of creating an ineffective ablation in the desired target tissue, or injuring a non-target tissue. A number of methods of mitigating these risks are disclosed.
Movement of the directed ablation energy from the target tissue may be caused for example by patient movement (e.g., sudden or slow movement, caused by moving the head, coughing, sneezing, flinching), or movement of the catheter or a component external to the patient connected to the catheter.
Detection of potential movement of the directed ablation energy from the target tissue may comprise the following: monitoring movement of the patient's body or head manually by a user or automatically with image tracking or sensors such as an accelerometer; an imaging algorithm or image augmentation algorithm may be programmed to identify movement that is significant to increase risk; a sensor such as an accelerometer or multiply accelerometers may be positioned in an ablation catheter such as those disclosed herein; a 3D orientation and tracking system for example using a magnetic or electric field to detect a magnetic coil or electrode positioned in an ablation catheter may be used to track the device within a patient's body.
Mitigation of a risk of movement may involve the following methods: a user may manually disengage energy delivery if movement is detected; a user may be required to hold an actuator in an on position to deliver energy and may react quickly to movement by releasing the actuator; automatic patient movement detection may input to the energy delivery console to cease or adjust energy delivery; an imaging or image augmentation algorithm detecting significant movement may send a signal to the energy delivery console causing it to cease or adjust energy delivery.
Upon stopping or adjusting energy delivery, an energy delivery console may display a message to a user that the delivery of energy was cut short due to potential movement risk. The message may further display how much of the procedure was completed.
Many embodiments disclosed herein comprise high-energy ultrasound as an ablative energy. Alternative embodiments of an endovascular catheter with imaging capabilities may comprise other forms of ablative energy to ablate target tissue (e.g., tissue in a carotid septum) near a vessel (e.g., jugular vein). An ultrasound imaging guided needle ablation catheter may combine an endovascular ultrasound imaging transducer for detecting a target and directing an ablative needle toward the target. The ablative needle may deliver an ablative agent or other ablative energy such as radiofrequency or cooled radiofrequency. As shown in
As shown in
In embodiments wherein a chemical ablation agent is delivered to the target tissue the chemical agent may be delivered in a medium such as a gel with a low viscosity so it remains local to the target tissue.
Ablation Catheters with Integrated Imaging Transducer(s)
The embodiment shown in
An embodiment shown in
The embodiments shown in
An embodiment shown in
Alternative embodiments may have one or more imaging transducers positioned proximal to the ablation transducer, or both proximal to and distal to the ablation transducer, such as in
A distal end 700 of an embodiment of an ablation catheter comprising an integrated imaging transducer array 702 positioned proximal to the ablation transducer 703 is shown in
Methods of manufacturing imaging transducers or arrays are known in the art. For example, imaging transducer array 702 may be manufactured according to methods disclosed in U.S. Pat. No. 6,776,763 B2, assigned to Volcano Therapeutic Inc., and which is incorporated by reference herein.
As shown, in this embodiment the ablation catheter comprises a guidewire lumen 718, which is configured such that the catheter can be delivered over a guidewire 705. A guidewire may facilitate delivery of the catheter in particular to vessels that are small in diameter or across a tight bend, such as when delivering the catheter to a tributary of a jugular vein such as a facial vein. The catheter may also be delivered through a delivery sheath 706.
A tube 715 may be disposed and extend through the shaft's central lumen 708, through a central lumen in the imaging array, and into the proximal end of the ablation transducer support 710, as shown in
The embodiment of an exemplary ablation catheter shown in
In this embodiment the membrane 711 extends over an outer surface of the ablation transducer support at proximal and distal ends of the ablation transducer support, but in some embodiments it may extend over the support only at one end, or optionally not extend over an outer surface of the ablation transducer support. In this embodiment the membrane is arranged so that the echolucent chamber substantially conforms to an outer surface of the catheter proximal and distal to the echolucent chamber. In this embodiment membrane 711 has a configuration that generally follows the configuration of at least a portion of the outer surface of the catheter proximal and distal to the chamber. In this embodiment the membrane 711 is not adapted to expand outward as fluid is delivered into the chamber, but in other embodiments it may be adapted in such a way. By not being adapted to expand radially outward, the membrane 711 generally can be thought of having fixed configuration. In some embodiments the membrane 711 has a thickness between 0.0002″ and 0.009″.
The imaging array 702 may be configured to show an image artifact that identifies a relative direction of aim of the ablation beam, for example as described herein and shown in
The embodiment shown in
The distal region 700 of the ablation catheter may comprise a sheath alignment line 701 used to position the catheter in the sheath 722 to confirm that the sheath's marker 723 is the desired distance 725 from the imaging plane marker 720. The alignment line 701 may be printed or etched on the catheter shaft or applied as a heat shrink band or may be a visually distinguishable line applied to the catheter using methods known in the art of catheter manufacture. The thickness of the alignment line 701 may be in a range of 0.1 mm to 1 mm for example. A method of positioning the catheter in the sheath may comprise inserting the catheter into the sheath before inserting them into a patient's vasculature; visually aligning the distal end of the delivery sheath 722 with the sheath alignment line 701; positioning a movable depth gauge 739 such as a spring clip on a proximal end of the catheter shaft snug against the proximal port 741 of the delivery sheath as shown in
As shown in
Catheters Configured to be Used without a Delivery Sheath
A delivery sheath may provide several useful functions for a transvascular ablation catheter, in particular a catheter configured for carotid body ablation from a jugular vein. For example, a delivery sheath may provide a conduit to deliver multiple devices including an ablation catheter; it may protect the ablation catheter from physical damage during insertion; it may provide deflection or torque near its distal region to facilitate manipulation of the jugular vein to position the imaging or ablation catheter relative to a target ablation site (e.g., carotid septum, carotid body, carotid bifurcation, carotid arteries); it may allow the imaging or ablation catheter to be extended or retracted or rotated relative to the deflected region of the sheath to allow for a range of configurations suitable for manipulating a shape or alignment of the carrier vein (e.g., jugular vein) or achieving an ideal positioning of its imaging or ablation transducers or elements relative to a target ablation site. For example, an optimal position of an imaging transducer(s) during a carotid body ablation procedure may be within about 5 mm (e.g., within about 3 mm, within about 2 mm, within about 1 mm) distal or proximal to a carotid septum or a carotid bifurcation or anatomical landmarks such as carotid arteries. An optimal position of an imaging transducer(s) during a carotid body ablation procedure may alternatively or additionally be within a distance of anatomical landmarks and alignment with them such that a direction of aim of an ablation transducer relative to the ultrasound image obtained may be aimed at a target ablation site while avoiding passing through non-target tissues such as carotid arteries or other vessels or tissue that could interfere with delivery of ablation energy to the target site. For example, a direction of aim of an ablation transducer may be directed through a wall of a vein containing the catheter (e.g., jugular vein), through a limited amount of interstitial tissue (e.g., less than about 5 mm, less than about 4 mm, less than about 3 mm, less than about 2 mm, less than about 1 mm), and into a target tissue volume (e.g., a carotid septum).
In some embodiments a catheter for transvenous imaging and ablation may be configured to provide functions of a delivery sheath and may thus be used without a delivery sheath. For example, the catheter may be configured for delivery over a guide wire. The catheter may comprise a guidewire lumen along its full length or for a part of its length at a distal region. A guidewire may facilitate delivery of the catheter through tortuous portions of vasculature and may also be used to deliver other devices if needed.
In some embodiments, the catheter may have a deflectable section in its distal region, such as, for example, proximal to the imaging or ablation transducers or elements, to provide a function of distorting or manipulating the position or shape of the carrier vessel in which at least a portion of the catheter is positioned (e.g., a jugular vein). The catheter may be deflectable in multiple directions (e.g., 2, 3, or 4 directions). The catheter may have a plurality of deflectable sections that can deflect in different planes. For example, as shown in
As shown in
In some embodiments an ablation and imaging section of a catheter may be fixed relative to a deflectable section, or alternatively may have an adjustable relative position. As shown in
For example, the ablation and imaging section of the catheter may be telescopically adjustable relative to the deflectable section. For example, the distance between the imaging and ablation section and the deflectable section may be adjustable between about 0 mm to 50 mm (e.g., between 5 mm and 30 mm, between 5 mm and 20 mm, between 5 mm and 15 mm, between 5 mm and 10 mm). The imaging and ablation section of the catheter may be rotationally adjustable relative to the deflectable section. Rotational adjustability may be provided by a torque wire running from the proximal region of the catheter (e.g., in a handle), to the imaging and ablation section such that turning the torque wire at the proximal end rotates the imaging and ablation section. Alternatively, rotational adjustability may be provided by a torque coil, which may have a lumen running along its axis which may be a conduit for wires or coolant. Alternatively, as shown in
In an alternative embodiment of a catheter configured to be used without a separate delivery sheath, the catheter may be comprise an integrated sheath that is part of the catheter and not meant to be removed or used separately as shown in
A catheter configured for use without a delivery sheath may be configured to protect an imaging and ablation section of the catheter during delivery. In some embodiments a catheter may comprise a thin membrane defining an echolucent chamber or other components that are fragile and susceptible to damage during delivery. As shown in
Ablation Transducers Adapted and Configured to be Cooled with Saline Solution
An ablation catheter may comprise an ablation transducer particularly configured to be cooled with a sterile saline solution. Delivering sterile saline solution (e.g., normal saline) to the bloodstream may be safe because of the similar osmolarity of NaCl in blood as opposed to delivering water to the blood stream, which may have unwanted effects. Several embodiments described herein are configured with closed-loop coolant flow, in which coolant is intended to not enter the blood stream. However, if the coolant unintentionally leaks into a patient's blood stream the device or procedure may mitigate any risk of causing undue harm. For example, the catheter or system may be configured to monitor coolant flow rate or pressure and deliver a warning or cease coolant flow if a leak is detected. Another way to mitigate a risk of coolant entering the bloodstream is to use a coolant that is sterile and biocompatible. A small amount of water delivered to the bloodstream may be safe in some patients. However, using a sterile saline solution as a coolant could reduce a risk effect even further. Some embodiments described herein, such as the catheter shown in
Saline solution contains ions and is electrically conductive. An ablation transducer may comprise opposing poles of an electrical circuit connected to opposing faces of a piezoelectric plate. An ablation transducer configured to be cooled with saline solution may comprise provisions that resolve an effect of saline causing a short circuit between the two electrical poles.
An ablation transducer configured to be cooled with saline may comprise an electrical insulator that prevents saline from creating a short circuit between the two electrical poles. An electrical insulator may be applied to all electrically conductive surfaces of the transducer. Alternatively, as shown in
Examples of electrical insulation materials may include parylene, urethane, silicone, nylon, PEEK, polyamide, polyimide or other materials that have suitable electrically insulative properties in thin layers. The electrical insulation may be selected to prevent passage of electrical current as well as allow thermal conductance so heat may be removed from the transducer by the coolant, and allow the transducer to vibrate without significant dampening. A method of applying an insulation material may comprise masking a portion of an ablation transducer (e.g., a transmitting face), applying the insulation material (e.g., vapor deposition, thermosetting, adhesive or other coating method), and removing the mask to expose said portion.
An ablation transducer may be mounted or imbedded in a flex circuit or circuit board, which may facilitate manufacturability as well as provide electrical insulation to prevent saline coolant from short-circuiting the ablation transducer.
An ablation catheter may be configured to direct flow of saline coolant over an ablation transducer so that it is only in contact with one of the two electrical poles. For example, saline coolant may only contact a transmitting face of an ablation transducer and not the sides or back of the transducer. Coolant may be prevented from contacting the sides and back of the ablation transducer by positioning the transducer in a ablation transducer support component that prevents fluid flow from contacting the sides or back, for example, using a tight seal or glue.
As shown in
As shown in
Imaging an Emission from an Ablation Transducer
Alternative or in addition to incorporating a fiducial marker to create an aiming artifact on an ultrasound-based video, an endovascular imaging and ablation system may be configured to generate an image of ultrasound echoes from a signal delivered from an ablation transducer to provide an accurate indication of a direction of aim of the ablation transducer. An ablation transducer may produce ultrasound signals that are synchronized with the imaging transducer and the imaging transducer can detect the signals. These ultrasound signals would not necessarily function to ablate tissue but primarily to communicate with the imaging transducer(s). The ultrasound signals would however emanate from the catheter ablation transducer and propagate in the same direction into a tissue that ultrasound ablation signals would during ablation. For example, as an ablation transducer may have a resonant frequency of about 20 MHz and an imaging transducer may have a resonant frequency of about 9 MHz. Imaging pulses (e.g., electrical current having a frequency of 9 MHz) may be delivered from a console to the imaging transducer(s), which vibrate sending ultrasound waves into the surrounding tissue. Echoes from the imaging waves bouncing off of tissue return to the imaging transducer(s) to be detected and converted by an imaging system in to an ultrasound-based video representing the surrounding tissue as shown in
A medical device or system such as the catheters and systems comprising a console disclosed herein may be configured to limit the use of a device that is intended to be disposable. A medical device may be engineered to be safe and effective and functional within limited parameters such as duration of time that energy is delivered or use in only one patient. In one embodiment a disposable medical device such as any of the catheters disclosed herein may be intended to be used in one patient only, and for one or multiple ablations in the patient. Furthermore, a user may be allowed to disconnect the device from the console or turn off the power to the console before attempting another ablation in the same patient. To stop a device from being used beyond its intended usage parameters the disposable medical device may be configured to provide information to the console allowing the console to determine if the disposable device has exceeded its intended usage allowance. For example, the information provided to the console may comprise an indication of whether or not the disposable device has ever been used before (e.g., if ablation energy has been delivered to it) and an indication of whether or not a predetermined duration of time has passed since the last use or initial use of the disposable device. Limiting use of a disposable device to a predetermined duration of time following its last or initial use may render it impractical to use the device on another patient yet provide sufficient time to use the device multiple times on the same patient. The predetermined duration of time may be for example 1, 2, 3, 4, 5, or 6 hours, or be less than an amount of time typically required between patients for example to sterilize a medical device.
In one embodiment as shown in
Included within the memory storage 802 are two general-purpose input/output (I/O) signals. A first I/O 806 is configured as an output and is connected to a direct current (DC) voltage regulator 810. When the timer initiation event (e.g., ablation energy is activated or the disposable medical device is activated) the voltage regulator 810 will enable its output to deliver a fixed voltage to a resistor/capacitor (RC) timing circuit 804. The DC voltage passes through a charge resistor 812 and charges the timing capacitor 814 up to full voltage within seconds. In this embodiment, setting the timer to full (e.g., filling the timing capacitor to full charge) occurs only with new disposable medical devices. The timing capacitor provides high capacitance, which allows for long duration timing options, and provides fast charge up times (e.g., seconds).
If a previously used disposable medical device is attached or reattached to the console 803 or another console, the memory device's output is not turned on and the DC regulator 810 will not supply any voltage to the RC timing circuit 804, thus not changing the charge present on the timing capacitor 814. When the console 803 is powered off or the disposable medical device 800 is disconnected from the console 803, all DC power is removed from the disposable medical device 800. The voltage across the timing capacitor 814 is now allowed to discharge through the discharge resistor 816. The value of the discharge resistor 816 determines the duration of time (e.g., number of minutes, hours, or days) that the disposable medical device 800 can be re-used within. In order to control any unwanted discharging of the timing capacitor 814, the use of an ultralow leakage diode 818 and high resistance isolation resistor 820 is used in the signal paths of the timing capacitor 814. These two items allow this circuit 804 to function accurately when no power is applied to the circuit.
When a disposable medical device is connected or re-connected to a console or when the console is powered back on, the console sends a command across the serial communications to the memory device 802 to check the second I/O signal 808, which is set as an input. This signal is connected to a voltage comparator 822, which will compare the voltage across the timing capacitor 814 to an accurate internal reference voltage level. If the timing capacitor voltage is above this reference voltage, the output of the comparator will be set to 1 indicating that time for allowed use remains. If the voltage is below this reference voltage, the comparator output will be set to 0 indicating that time for allowed use no longer remains. The memory device 802 communicates the status of the voltage comparator back to the console software 801.
As shown in a flowchart of
In another embodiment as shown in a flowchart of
Optionally, the console software 801 may set a second bit in the memory device 802 after the allowable usage time has expired. This second bit may be protected to prevent over-writing to prevent someone from gaining access to the circuit and applying a charge to the timing circuit to reset the timer of the disposable medical device.
Optionally, when the console 803 and disposable medical device 800 (i.e., system) are used in a medical procedure 836 of
Optionally, the system may be configured with a limited number of allowable uses, for example, following a use (e.g., delivering ablation energy) the console software 801 may increment a value stored in the EEPROM that may be under write once protection.
Any medical device that is adapted to receive a signal from a console can include the use limiter, such as any medical device that is adapted to be coupled to an energy delivery console.
An ablation energy source such as a high frequency current generator for therapeutic ultrasound may be located external to the patient. The generator may include computer controls to automatically or manually adjust frequency and strength of the energy applied to the catheter, timing and period during which energy is applied, and safety limits to the application of energy. It should be understood that embodiments of energy delivery electrodes described herein may be electrically connected to the generator even though the generator is not explicitly shown or described with each embodiment.
An endovascular ultrasonic ablation catheter configured to aim ultrasonic energy at a carotid septum may comprise ultrasound visualization capabilities. The ultrasound visualization may comprise Doppler to image blood flow. A catheter may be rotated within an external carotid artery using Doppler to identify when it is aimed through a carotid septum at an internal carotid artery. An ultrasound ablation may be aimed toward the direction of the internal carotid artery and be deposited in a targeted carotid septum.
An ablated tissue lesion at or near the carotid body may be created by the application of ablation energy from an ablation element in a vicinity of a distal end of the carotid body ablation device. The ablated tissue lesion may disable the carotid body or may suppress the activity of the carotid body or interrupt conduction of afferent nerve signals from a carotid body to sympathetic nervous system. The disabling or suppression of the carotid body reduces the responsiveness of the glomus cells to changes of blood gas composition and effectively reduces activity of afferent carotid body nerves or the chemoreflex gain of the patient.
A method in accordance with a particular embodiment includes ablating at least one of a patient's carotid bodies based at least in part on identifying the patient as having a sympathetically mediated disease such as cardiac, metabolic, or pulmonary disease such as hypertension, insulin resistance, diabetes, pulmonary hypertension, drug resistant hypertension (e.g., refractory hypertension), congestive heart failure (CHF), or dyspnea from heart failure or pulmonary disease causes.
A procedure may include diagnosis, selection based on diagnosis, further screening (e.g., baseline assessment of chemosensitivity), treating a patient based at least in part on diagnosis or further screening via a chemoreceptor (e.g., carotid body) ablation procedure such as one of the embodiments disclosed. Additionally, following ablation a method of therapy may involve conducting a post-ablation assessment to compare with the baseline assessment and making decisions based on the assessment (e.g., adjustment of drug therapy, re-treat in new position or with different parameters, or ablate a second chemoreceptor if only one was previously ablated).
A carotid body ablation procedure may comprise the following steps or a combination thereof: patient sedation, locating a target peripheral chemoreceptor, visualizing a target peripheral chemoreceptor (e.g., carotid body), confirming a target ablation site is or is proximate a peripheral chemoreceptor, confirming a target ablation site is safely distant from vital structures that are preferably protected (e.g., hypoglossal, sympathetic and vagus nerves), providing stimulation (e.g., electrical, mechanical, chemical) to a target site or target peripheral chemoreceptor prior to, during or following an ablation step, monitoring physiological responses to said stimulation, providing temporary nerve block to a target site prior to an ablation step, monitoring physiological responses to said temporary nerve block, anesthetizing a target site, protecting the brain from potential embolism, thermally protecting an arterial or venous wall (e.g., carotid artery, jugular vein) or a medial aspect of an intercarotid septum or vital nerve structures, ablating a target site or peripheral chemoreceptor, monitoring ablation parameters (e.g., temperature, pressure, duration, blood flow in a carotid artery), monitoring physiological responses during ablation and arresting ablation if unsafe or unwanted physiological responses occur before collateral nerve injury becomes permanent, confirming a reduction of chemoreceptor activity (e.g., chemosensitivity, HR, blood pressure, ventilation, sympathetic nerve activity) during or following an ablation step, removing a ablation device, conducting a post-ablation assessment, repeating any steps of the chemoreceptor ablation procedure on another peripheral chemoreceptor in the patient.
Patient screening, as well as post-ablation assessment may include physiological tests or gathering of information, for example, chemoreflex sensitivity, central sympathetic nerve activity, heart rate, heart rate variability, blood pressure, ventilation, production of hormones, peripheral vascular resistance, blood pH, blood PCO2, degree of hyperventilation, peak VO2, VE/VCO2 slope. Directly measured maximum oxygen uptake (more correctly pVO2 in heart failure patients) and index of respiratory efficiency VE/VCO2 slope has been shown to be a reproducible marker of exercise tolerance in heart failure and provide objective and additional information regarding a patient's clinical status and prognosis.
A method of therapy may include electrical stimulation of a target region, using a stimulation electrode, to confirm proximity to a carotid body. For example, a stimulation signal having a 1-10 milliamps (mA) pulse train at about 20 to 40 Hz with a pulse duration of 50 to 500 microseconds (μs) that produces a positive carotid body stimulation effect may indicate that the stimulation electrode is within sufficient proximity to the carotid body or nerves of the carotid body to effectively ablate it. A positive carotid body stimulation effect could be increased blood pressure, heart rate, or ventilation concomitant with application of the stimulation. These variables could be monitored, recorded, or displayed to help assess confirmation of proximity to a carotid body. A catheter-based technique, for example, may have a stimulation electrode proximal to the ablation element used for ablation. Alternatively, the ablation element itself may also be used as a stimulation electrode. Alternatively, an energy delivery element that delivers a form of ablative energy that is not electrical, such as a cryogenic ablation applicator, may be configured to also deliver an electrical stimulation signal as described earlier. Yet another alternative embodiment comprises a stimulation electrode that is distinct from an ablation element. For example, during a surgical procedure a stimulation probe can be touched to a suspected carotid body that is surgically exposed. A positive carotid body stimulation effect could confirm that the suspected structure is a carotid body and ablation can commence. Physiological monitors (e.g., heart rate monitor, blood pressure monitor, blood flow monitor, MSNA monitor) may communicate with a computerized stimulation generator, which may also be an ablation generator, to provide feedback information in response to stimulation. If a physiological response correlates to a given stimulation the computerized generator may provide an indication of a positive confirmation.
Alternatively or in addition a drug known to excite the chemo sensitive cells of the carotid body can be injected directly into the carotid artery or given systemically into a patient's vein or artery in order to elicit hemodynamic or respiratory response. Examples of drugs that may excite a chemoreceptor include nicotine, atropine, Doxapram, Almitrine, hyperkalemia, Theophylline, adenosine, sulfides, Lobeline, Acetylcholine, ammonium chloride, methylamine, potassium chloride, anabasine, coniine, cytosine, acetaldehyde, acetyl ester and the ethyl ether of i-methylcholine, Succinylcholine, Piperidine, monophenol ester of homo-iso-muscarine and acetylsalicylamides, alkaloids of veratrum, sodium citrate, adenosinetriphosphate, dinitrophenol, caffeine, theobromine, ethyl alcohol, ether, chloroform, phenyldiguanide, sparteine, coramine (nikethamide), metrazol (pentylenetetrazol), iodomethylate of dimethylaminomethylenedioxypropane, ethyltrimethylammoniumpropane, trimethylammonium, hydroxytryptamine, papaverine, neostigmine, acidity.
Described methods may include ultrasound activated drug delivery to carotid complex. Drugs can be incorporated into particles capable of ultrasound activation. Intravenous or direct intratumoral injection of such drug compositions comprising microbubbles, nanoparticles, liposomes and biologically active agents encapsulated in polymers undergo a physical change when subjected to ultrasound beam. The compositions include microemulsions which may create microbubbles as cavitation nuclei in the process of injection and enhance intracellular drug delivery in the carotid complex. The administration of the ultrasound beam to a carotid complex perfused with encapsulated drugs may stimulate a release of the therapeutic agent to a selected volume affected by the application of ultrasound. In addition to a release of a therapeutic agent the microbubbles generated in situ during an ultrasound irradiation procedure may produce additional guidance to ultrasound imaging.
A method of therapy may further comprise applying electrical or chemical stimulation to the target area or systemically following ablation to confirm a successful ablation. Heart rate, blood pressure or ventilation may be monitored for change or compared to the reaction to stimulation prior to ablation to assess if the targeted carotid body was ablated. Post-ablation stimulation may be done with the same apparatus used to conduct the pre-ablation stimulation. Physiological monitors (e.g., heart rate monitor, blood pressure monitor, blood flow monitor, MSNA monitor) may communicate with a computerized stimulation generator, which may also be an ablation generator, to provide feedback information in response to stimulation. If a physiological response correlated to a given stimulation is reduced following an ablation compared to a physiological response prior to the ablation, the computerized generator may provide an indication ablation efficacy or possible procedural suggestions such as repeating an ablation, adjusting ablation parameters, changing position, ablating another carotid body or chemosensor, or concluding the procedure.
The devices described herein may also be used to temporarily stun or block nerve conduction via electrical neural blockade. A temporary nerve block may be used to confirm position of an ablation element prior to ablation. For example, a temporary nerve block may block nerves associated with a carotid body, which may result in a physiological effect to confirm the position may be effective for ablation. Furthermore, a temporary nerve block may block vital nerves such as vagal, hypoglossal or sympathetic nerves that are preferably avoided, resulting in a physiological effect (e.g., physiological effects may be noted by observing the patient's eyes, tongue, throat or facial muscles or by monitoring patient's heart rate and respiration). This may alert a user that the position is not in a safe location. Likewise absence of a physiological effect indicating a temporary nerve block of such vital nerves in combination with a physiological effect indicating a temporary nerve block of carotid body nerves may indicate that the position is in a safe and effective location for carotid body ablation.
Important nerves may be located in proximity of the target site and may be inadvertently and unintentionally injured. Neural stimulation or blockade can help identify that these nerves are in the ablation zone before the irreversible ablation occurs. These nerves may include the following:
Vagus Nerve Bundle—The vagus is a bundle of nerves that carry separate functions, for example a) branchial motor neurons (efferent special visceral) which are responsible for swallowing and phonation and are distributed to pharyngeal branches, superior and inferior laryngeal nerves; b) visceral motor (efferent general visceral) which are responsible for involuntary muscle and gland control and are distributed to cardiac, pulmonary, esophageal, gastric, celiac plexuses, and muscles, and glands of the digestive tract; c) visceral sensory (afferent general visceral) which are responsible for visceral sensibility and are distributed to cervical, thoracic, abdominal fibers, and carotid and aortic bodies; d) visceral sensory (afferent special visceral) which are responsible for taste and are distributed to epiglottis and taste buds; e) general sensory (afferent general somatic) which are responsible for cutaneous sensibility and are distributed to auricular branch to external ear, meatus, and tympanic membrane. Dysfunction of the vagus may be detected by a) vocal changes caused by nerve damage (damage to the vagus nerve can result in trouble with moving the tongue while speaking, or hoarseness of the voice if the branch leading to the larynx is damaged); b) dysphagia due to nerve damage (the vagus nerve controls many muscles in the palate and tongue which, if damaged, can cause difficulty with swallowing); c) changes in gag reflex (the gag reflex is controlled by the vagus nerve and damage may cause this reflex to be lost, which can increase the risk of choking on saliva or food); d) hearing loss due to nerve damage (hearing loss may result from damage to the branch of the vagus nerve that innervates the concha of the ear): e) cardiovascular problems due to nerve damage (damage to the vagus nerve can cause cardiovascular side effects including irregular heartbeat and arrhythmia); or f) digestive problems due to nerve damage (damage to the vagus nerve may cause problems with contractions of the stomach and intestines, which can lead to constipation).
Superior Laryngeal Nerve—the superior laryngeal nerve is a branch of the vagus nerve bundle. Functionally, the superior laryngeal nerve function can be divided into sensory and motor components. The sensory function provides a variety of afferent signals from the supraglottic larynx. Motor function involves motor supply to the ipsilateral cricothyroid muscle. Contraction of the cricothyroid muscle tilts the cricoid lamina backward at the cricothyroid joint causing lengthening, tensing and adduction of vocal folds causing an increase in the pitch of the voice generated. Dysfunction of the superior laryngeal nerve may change the pitch of the voice and causes an inability to make explosive sounds. A bilateral palsy presents as a tiring and hoarse voice.
Cervical Sympathetic Nerve—The cervical sympathetic nerve provides efferent fibers to the internal carotid nerve, external carotid nerve, and superior cervical cardiac nerve. It provides sympathetic innervation of the head, neck and heart. Organs that are innervated by the sympathetic nerves include eyes, lacrimal gland and salivary glands. Dysfunction of the cervical sympathetic nerve includes Homer's syndrome, which is very identifiable and may include the following reactions: a) partial ptosis (drooping of the upper eyelid from loss of sympathetic innervation to the superior tarsal muscle, also known as Müller's muscle); b) upside-down ptosis (slight elevation of the lower lid); c) anhidrosis (decreased sweating on the affected side of the face); d) miosis (small pupils, for example small relative to what would be expected by the amount of light the pupil receives or constriction of the pupil to a diameter of less than two millimeters, or asymmetric, one-sided constriction of pupils); e) enophthalmos (an impression that an eye is sunken in); f) loss of ciliospinal reflex (the ciliospinal reflex, or pupillary-skin reflex, consists of dilation of the ipsilateral pupil in response to pain applied to the neck, face, and upper trunk. If the right side of the neck is subjected to a painful stimulus, the right pupil dilates about 1-2 mm from baseline. This reflex is absent in Horner's syndrome and lesions involving the cervical sympathetic fibers.) Overview:
Ablation of a target ablation site (e.g., peripheral chemoreceptor, carotid body) via directed energy in patients having sympathetically mediated disease and augmented chemoreflex (e.g., high afferent nerve signaling from a carotid body to the central nervous system as in some cases indicated by high peripheral chemosensitivity) has been conceived to reduce peripheral chemosensitivity and reduce afferent signaling from peripheral chemoreceptors to the central nervous system. Additionally, ablation of a target ablation site (e.g., peripheral chemoreceptor, carotid body) via a transvenous endovascular approach in patients having sympathetically mediated disease and augmented chemoreflex (e.g., high afferent nerve signaling from a carotid body to the central nervous system as in some cases indicated by high peripheral chemosensitivity) has been conceived to reduce peripheral chemosensitivity and reduce afferent signaling from peripheral chemoreceptors to the central nervous system. The expected reduction of chemoreflex activity and sensitivity to hypoxia and other stimuli such as blood flow, blood CO2, glucose concentration or blood pH can directly reduce afferent signals from chemoreceptors and produce at least one beneficial effect such as the reduction of central sympathetic activation, reduction of the sensation of breathlessness (dyspnea), vasodilation, increase of exercise capacity, reduction of blood pressure, reduction of sodium and water retention, redistribution of blood volume to skeletal muscle, reduction of insulin resistance, reduction of hyperventilation, reduction of tachypnea, reduction of hypocapnia, increase of baroreflex and barosensitivity of baroreceptors, increase of vagal tone, or improve symptoms of a sympathetically mediated disease and may ultimately slow down the disease progression and extend life. It is understood that a sympathetically mediated disease that may be treated with carotid body ablation may comprise elevated sympathetic tone, an elevated sympathetic/parasympathetic activity ratio, autonomic imbalance primarily attributable to central sympathetic tone being abnormally or undesirably high, or heightened sympathetic tone at least partially attributable to afferent excitation traceable to hypersensitivity or hyperactivity of a peripheral chemoreceptor (e.g., carotid body). In some important clinical cases where baseline hypocapnia or tachypnea is present, reduction of hyperventilation and breathing rate may be expected. It is understood that hyperventilation in the context herein means respiration in excess of metabolic needs on the individual that generally leads to slight but significant hypocapnea (blood CO2 partial pressure below normal of approximately 40 mmHg, for example in the range of 33 to 38 mmHg).
Patients having CHF or hypertension concurrent with heightened peripheral chemoreflex activity and sensitivity often react as if their system was hypercapnic even if it is not. The reaction is often to hyperventilate, a maladaptive attempt to rid the system of CO2, thus overcompensating and creating a hypocapnic and alkalotic system. Some researchers attribute this hypersensitivity/hyperactivity of the carotid body to the direct effect of catecholamines, hormones circulating in excessive quantities in the blood stream of CHF patients. The procedure may be particularly useful to treat such patients who are hypocapnic and possibly alkalotic resulting from high tonic output from carotid bodies. Such patients are particularly predisposed to periodic breathing and central apnea hypopnea type events that cause arousal, disrupt sleep, cause intermittent hypoxia and are by themselves detrimental and difficult to treat.
It is appreciated that periodic breathing of Cheyne Stokes pattern occurs in patients during sleep, exercise and even at rest as a combination of central hypersensitivity to CO2, peripheral chemosensitivity to O2 and CO2 and prolonged circulatory delay. All these parameters are often present in CHF patients that are at high risk of death. Thus, patients with hypocapnea, CHF, high chemosensitivity and prolonged circulatory delay, and specifically ones that exhibit periodic breathing at rest or during exercise or induced by hypoxia are likely beneficiaries of the proposed therapy.
Hyperventilation is defined as breathing in excess of a person's metabolic need at a given time and level of activity. Hyperventilation is more specifically defined as minute ventilation in excess of that needed to remove CO2 from blood in order to maintain blood CO2 in the normal range (e.g., around 40 mmHg partial pressure). For example, patients with arterial blood PCO2 in the range of 32-37 mmHg can be considered hypocapnic and in hyperventilation.
For the purpose of this disclosure hyperventilation is equivalent to abnormally low levels of carbon dioxide in the blood (e.g., hypocapnia, hypocapnea, or hypocarbia) caused by overbreathing. Hyperventilation is the opposite of hypoventilation (e.g., underventilation) that often occurs in patients with lung disease and results in high levels of carbon dioxide in the blood (e.g., hypercapnia or hypercarbia).
A low partial pressure of carbon dioxide in the blood causes alkalosis, because CO2 is acidic in solution and reduced CO2 makes blood pH more basic, leading to lowered plasma calcium ions and nerve and muscle excitability. This condition is undesirable in cardiac patients since it can increase probability of cardiac arrhythmias.
Alkalemia may be defined as abnormal alkalinity, or increased pH of the blood. Respiratory alkalosis is a state due to excess loss of carbon dioxide from the body, usually as a result of hyperventilation. Compensated alkalosis is a form in which compensatory mechanisms have returned the pH toward normal. For example, compensation can be achieved by increased excretion of bicarbonate by the kidneys.
Compensated alkalosis at rest can become uncompensated during exercise or as a result of other changes of metabolic balance. Thus the invented method is applicable to treatment of both uncompensated and compensated respiratory alkalosis.
Tachypnea means rapid breathing. For the purpose of this disclosure a breathing rate of about 6 to 16 breaths per minute at rest is considered normal but there is a known benefit to lower rate of breathing in cardiac patients. Reduction of tachypnea can be expected to reduce respiratory dead space, increase breathing efficiency, and increase parasympathetic tone.
Chronic elevation in sympathetic nerve activity (SNA) is associated with the development and progression of certain types of hypertension and contributes to the progression of congestive heart failure (CHF). It is also known that sympathetic excitatory cardiac, somatic, and central/peripheral chemoreceptor reflexes are abnormally enhanced in CHF and hypertension (Ponikowski, 2011 and Giannoni, 2008 and 2009).
Arterial chemoreceptors serve an important regulatory role in the control of alveolar ventilation. They also exert a powerful influence on cardiovascular function.
Delivery of Oxygen (O2) and removal of Carbon Dioxide (CO2) in the human body is regulated by two control systems, behavioral control and metabolic control. The metabolic ventilatory control system drives our breathing at rest and ensures optimal cellular homeostasis with respect to pH, partial pressure of carbon dioxide (PCO2), and partial pressure of oxygen (PO2). Metabolic control uses two sets of chemoreceptors that provide a fine-tuning function: the central chemoreceptors located in the ventral medulla of the brain and the peripheral chemoreceptors such as the aortic chemoreceptors and the carotid body chemoreceptors. The carotid body, a small, ovoid-shaped (often described as a grain of rice), and highly vascularized organ is situated in or near the carotid bifurcation, where the common carotid artery branches in to an internal carotid artery (IC) and external carotid artery (EC). The central chemoreceptors are sensitive to hypercapnia (high PCO2), and the peripheral chemoreceptors are sensitive to hypercapnia and hypoxia (low blood PO2). Under normal conditions activation of the sensors by their respective stimuli results in quick ventilatory responses aimed at the restoration of cellular homeostasis.
As early as 1868, Pflüger recognized that hypoxia stimulated ventilation, which spurred a search for the location of oxygen-sensitive receptors both within the brain and at various sites in the peripheral circulation. When Corneille Heymans and his colleagues observed that ventilation increased when the oxygen content of the blood flowing through the bifurcation of the common carotid artery was reduced (winning him the Nobel Prize in 1938), the search for the oxygen chemosensor responsible for the ventilatory response to hypoxia was largely considered accomplished.
The persistence of stimulatory effects of hypoxia in the absence (after surgical removal) of the carotid chemoreceptors (e.g., the carotid bodies) led other investigators, among them Julius Comroe, to ascribe hypoxic chemosensitivity to other sites, including both peripheral sites (e.g., aortic bodies) and central brain sites (e.g., hypothalamus, pons and rostral ventrolateral medulla). The aortic chemoreceptor, located in the aortic body, may also be an important chemoreceptor in humans with significant influence on vascular tone and cardiac function.
The carotid body is a small cluster of chemoreceptors (also known as glomus cells) and supporting cells located near, and in most cases directly at, the medial side of the bifurcation (fork) of the carotid artery, which runs along both sides of the throat.
These organs act as sensors detecting different chemical stimuli from arterial blood and triggering an action potential in the afferent fibers that communicate this information to the Central Nervous System (CNS). In response, the CNS activates reflexes that control heart rate (HR), renal function and peripheral blood circulation to maintain the desired homeostasis of blood gases, O2 and CO2, and blood pH. This closed loop control function that involves blood gas chemoreceptors is known as the carotid body chemoreflex (CBC). The carotid body chemoreflex is integrated in the CNS with the carotid sinus baroreflex (CSB) that maintains arterial blood pressure. In a healthy organism these two reflexes maintain blood pressure and blood gases within a narrow physiologic range. Chemosensors and barosensors in the aortic arch contribute redundancy and fine-tuning function to the closed loop chemoreflex and baroreflex. In addition to sensing blood gasses, the carotid body is now understood to be sensitive to blood flow and velocity, blood pH and glucose concentration. Thus it is understood that in conditions such as hypertension, CHF, insulin resistance, diabetes and other metabolic derangements afferent signaling of carotid body nerves may be elevated. Carotid body hyperactivity may be present even in the absence of detectable hypersensitivity to hypoxia and hypercapnia that are traditionally used to index carotid body function. The purpose of the proposed therapy is therefore to remove or reduce afferent neural signals from a carotid body and reduce carotid body contribution to central sympathetic tone.
The carotid sinus baroreflex is accomplished by negative feedback systems incorporating pressure sensors (e.g., baroreceptors) that sense the arterial pressure. Baroreceptors also exist in other places, such as the aorta and coronary arteries. Important arterial baroreceptors are located in the carotid sinus, a slight dilatation of the internal carotid artery 201 at its origin from the common carotid. The carotid sinus baroreceptors are close to but anatomically separate from the carotid body. Baroreceptors respond to stretching of the arterial wall and communicate blood pressure information to CNS. Baroreceptors are distributed in the arterial walls of the carotid sinus while the chemoreceptors (glomus cells) are clustered inside the carotid body. This makes the selective reduction of chemoreflex described in this application possible while substantially sparing the baroreflex.
The carotid body exhibits great sensitivity to hypoxia (low threshold and high gain). In chronic Congestive Heart Failure (CHF), the sympathetic nervous system activation that is directed to attenuate systemic hypoperfusion at the initial phases of CHF may ultimately exacerbate the progression of cardiac dysfunction that subsequently increases the extra-cardiac abnormalities, a positive feedback cycle of progressive deterioration, a vicious cycle with ominous consequences. It was thought that much of the increase in the sympathetic nerve activity (SNA) in CHF was based on an increase of sympathetic flow at a level of the CNS and on the depression of arterial baroreflex function. In the past several years, it has been demonstrated that an increase in the activity and sensitivity of peripheral chemoreceptors (heightened chemoreflex function) also plays an important role in the enhanced SNA that occurs in CHF.
Role of Altered Chemoreflex in CHF:
As often happens in chronic disease states, chemoreflexes that are dedicated under normal conditions to maintaining homeostasis and correcting hypoxia contribute to increase the sympathetic tone in patients with CHF, even under normoxic conditions. The understanding of how abnormally enhanced sensitivity of the peripheral chemosensors, particularly the carotid body, contributes to the tonic elevation in SNA in patients with CHF has come from several studies in animals. According to one theory, the local angiotensin receptor system plays a fundamental role in the enhanced carotid body chemoreceptor sensitivity in CHF. In addition, evidence in both CHF patients and animal models of CHF has clearly established that the carotid body chemoreflex is often hypersensitive in CHF patients and contributes to the tonic elevation in sympathetic function. This derangement derives from altered function at the level of both the afferent and central pathways of the reflex arc. The mechanisms responsible for elevated afferent activity from the carotid body in CHF are not yet fully understood.
Regardless of the exact mechanism behind the carotid body hypersensitivity, the chronic sympathetic activation driven from the carotid body and other autonomic pathways leads to further deterioration of cardiac function in a positive feedback cycle. As CHF ensues, the increasing severity of cardiac dysfunction leads to progressive escalation of these alterations in carotid body chemoreflex function to further elevate sympathetic activity and cardiac deterioration. The trigger or causative factors that occur in the development of CHF that sets this cascade of events in motion and the time course over which they occur remain obscure. Ultimately, however, causative factors are tied to the cardiac pump failure and reduced cardiac output. According to one theory, within the carotid body, a progressive and chronic reduction in blood flow may be the key to initiating the maladaptive changes that occur in carotid body chemoreflex function in CHF.
There is sufficient evidence that there is increased peripheral and central chemoreflex sensitivity in heart failure, which is likely to be correlated with the severity of the disease. There is also some evidence that the central chemoreflex is modulated by the peripheral chemoreflex. According to current theories, the carotid body is the predominant contributor to the peripheral chemoreflex in humans; the aortic body having a minor contribution.
Although the mechanisms responsible for altered central chemoreflex sensitivity remain obscure, the enhanced peripheral chemoreflex sensitivity can be linked to a depression of nitric oxide production in the carotid body affecting afferent sensitivity, and an elevation of central angiotensin II affecting central integration of chemoreceptor input. The enhanced chemoreflex may be responsible, in part, for the enhanced ventilatory response to exercise, dyspnea, Cheyne-Stokes breathing, and sympathetic activation observed in chronic heart failure patients. The enhanced chemoreflex may be also responsible for hyperventilation and tachypnea (e.g., fast breathing) at rest and exercise, periodic breathing during exercise, rest and sleep, hypocapnia, vasoconstriction, reduced peripheral organ perfusion and hypertension.
Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity. It is a symptom of a variety of different diseases or disorders and may be either acute or chronic. Dyspnea is the most common complaint of patients with cardiopulmonary diseases.
Dyspnea is believed to result from complex interactions between neural signaling, the mechanics of breathing, and the related response of the central nervous system. A specific area has been identified in the mid-brain that may influence the perception of breathing difficulties.
The experience of dyspnea depends on its severity and underlying causes. The feeling itself results from a combination of impulses relayed to the brain from nerve endings in the lungs, rib cage, chest muscles, or diaphragm, combined with the perception and interpretation of the sensation by the patient. In some cases, the patient's sensation of breathlessness is intensified by anxiety about its cause. Patients describe dyspnea variously as unpleasant shortness of breath, a feeling of increased effort or tiredness in moving the chest muscles, a panicky feeling of being smothered, or a sense of tightness or cramping in the chest wall.
The four generally accepted categories of dyspnea are based on its causes: cardiac, pulmonary, mixed cardiac or pulmonary, and non-cardiac or non-pulmonary. The most common heart and lung diseases that produce dyspnea are asthma, pneumonia, COPD, and myocardial ischemia or heart attack (myocardial infarction). Foreign body inhalation, toxic damage to the airway, pulmonary embolism, congestive heart failure (CHF), anxiety with hyperventilation (panic disorder), anemia, and physical deconditioning because of sedentary lifestyle or obesity can produce dyspnea. In most cases, dyspnea occurs with exacerbation of the underlying disease. Dyspnea also can result from weakness or injury to the chest wall or chest muscles, decreased lung elasticity, obstruction of the airway, increased oxygen demand, or poor pumping action of the heart that results in increased pressure and fluid in the lungs, such as in CHF.
Acute dyspnea with sudden onset is a frequent cause of emergency room visits. Most cases of acute dyspnea involve pulmonary (lung and breathing) disorders, cardiovascular disease, or chest trauma. Sudden onset of dyspnea (acute dyspnea) is most typically associated with narrowing of the airways or airflow obstruction (bronchospasm), blockage of one of the arteries of the lung (pulmonary embolism), acute heart failure or myocardial infarction, pneumonia, or panic disorder.
Chronic dyspnea is different. Long-standing dyspnea (chronic dyspnea) is most often a manifestation of chronic or progressive diseases of the lung or heart, such as COPD, which includes chronic bronchitis and emphysema. The treatment of chronic dyspnea depends on the underlying disorder. Asthma can often be managed with a combination of medications to reduce airway spasms and removal of allergens from the patient's environment. COPD requires medication, lifestyle changes, and long-term physical rehabilitation. Anxiety disorders are usually treated with a combination of medication and psychotherapy.
Although the exact mechanism of dyspnea in different disease states is debated, there is no doubt that the CBC plays some role in most manifestations of this symptom. Dyspnea seems to occur most commonly when afferent input from peripheral receptors is enhanced or when cortical perception of respiratory work is excessive.
A surgical treatment for asthma, removal of the carotid body or glomus (glomectomy), was described by Japanese surgeon Komei Nakayama in 1940s. According to Nakayama in his study of 4,000 patients with asthma, approximately 80% were cured or improved six months after surgery and 58% allegedly maintained good results after five years. Komei Nakayama performed most of his surgeries while at the Chiba University during World War II. Later in the 1950's, a U.S. surgeon, Dr. Overholt, performed the Nakayama operation on 160 U.S. patients. He felt it necessary to remove both carotid bodies in only three cases. He reported that some patients feel relief the instant when the carotid body is removed, or even earlier, when it is inactivated by an injection of procaine (Novocain).
Overholt, in his paper Glomectomy for Asthma published in Chest in 1961, described surgical glomectomy the following way: “A two-inch incision is placed in a crease line in the neck, one-third of the distance between the angle of the mandible and clavicle. The platysma muscle is divided and the sternocleidomastoid retracted laterally. The dissection is carried down to the carotid sheath exposing the bifurcation. The superior thyroid artery is ligated and divided near its take-off in order to facilitate rotation of the carotid bulb and expose the medial aspect of the bifurcation. The carotid body is about the size of a grain of rice and is hidden within the adventitia of the vessel and is of the same color. The perivascular adventitia is removed from one centimeter above to one centimeter below the bifurcation. This severs connections of the nerve plexus, which surrounds the carotid body. The dissection of the adventitia is necessary in order to locate and identify the body. It is usually located exactly at the point of bifurcation on its medial aspect. Rarely, it may be found either in the center of the crotch or on the lateral wall. The small artery entering the carotid body is clamped, divided, and ligated. The upper stalk of tissue above the carotid body is then clamped, divided, and ligated.”
In January 1965, the New England Journal of Medicine published a report of 15 cases in which there had been unilateral removal of the cervical glomus (carotid body) for the treatment of bronchial asthma, with no objective beneficial effect. This effectively stopped the practice of glomectomy to treat asthma in the U.S.
Winter developed a technique for separating nerves that contribute to the carotid sinus nerves into two bundles, carotid sinus (baroreflex) and carotid body (chemoreflex), and selectively cutting out the latter. The Winter technique is based on his discovery that carotid sinus (baroreflex) nerves are predominantly on the lateral side of the carotid bifurcation and carotid body (chemoreflex) nerves are predominantly on the medial side.
Hlavka in U.S. Patent Application Publication 2010/0070004 filed Aug. 7, 2009, describes implanting an electrical stimulator to apply electrical signals, which block or inhibit chemoreceptor signals in a patient suffering dyspnea. Hlavka teaches that “some patients may benefit from the ability to reactivate or modulate chemoreceptor functioning.” Hlavka focuses on neuromodulation of the chemoreflex by selectively blocking conduction of nerves that connect the carotid body to the CNS. Hlavka describes a traditional approach of neuromodulation with an implantable electric pulse generator that does not modify or alter tissue of the carotid body or chemoreceptors.
The central chemoreceptors are located in the brain and are difficult to access. The peripheral chemoreflex is modulated primarily by carotid bodies that are more accessible. Previous clinical practice had very limited clinical success with the surgical removal of carotid bodies to treat asthma in 1940s and 1960s. Renal Denervation:
The embodiments of systems or devices disclosed herein may be used to ablate target tissue near a body lumen (e.g., an artery, vein, blood vessel, respiratory lumen, esophagus, bronchioles, a digestive lumen) by placing the ablation catheter either having integrated imaging elements or configured to be used with a separate imaging catheter (e.g., ultrasound imaging) in the lumen, using the imaging element to provide an image of tissue (e.g., an anatomical landmark or target tissue) to facilitate directing ablation energy toward target tissue, and delivering ablation energy (e.g., ultrasound ablation energy, chemical agent, radiofrequency electrical current) to the target tissue. The target tissue may be within a range from 0 mm to 2 cm (e.g., 0 to 1 cm, 0 to 1.5 cm, 0 to 0.5 cm) from the wall of the lumen. Renal denervation may be an alternative procedure to carotid body ablation for which the disclosed device or system may be used. A renal denervation procedure incorporating the disclosed devices and systems may comprise delivering an ablation catheter to a renal vein and directing ablation energy from the catheter to renal nerves. The target renal nerves may be in or proximate to renal artery adventitia, in tissue between a renal artery bifurcation, in tissue around a renal artery proximate a renal artery ostium from an aorta. Other renal denervation procedures often involve delivering radiopaque contrast agent to a renal artery for radiographic imaging. However, some patients' kidneys cannot tolerate contrast agent. The proposed procedure may be performed without delivering contrast or a device to a renal artery. Imaging may be used to identify a renal artery bifurcation and ablation energy may be delivered to the tissue between the bifurcating arteries. This volume of tissue may be referred to as a renal artery bifurcation septum and contains a high concentration of renal nerves. In addition or alternatively, imaging may be used to identify location of small blood vessels in target zones that could impede effective ablation by acting as a heat sink removing thermal energy. Ablation energy may be delivered to regions in the target zones that do not comprise small vessel heat sinks.
This application is a continuation of U.S. application Ser. No. 15/263,174, filed Sep. 12, 2016, which is a continuation-in-part of U.S. application Ser. No. 15/069,531, filed Mar. 14, 2016, now abandoned, which claims priority to U.S. Provisional Application No. 62/132,459, filed Mar. 12, 2015, the disclosures of which are all incorporated by reference herein. U.S. application Ser. No. 15/069,531 is a continuation-in-part of U.S. application Ser. No. 14/656,635, filed Mar. 12, 2015, now U.S. Pat. No. 9,955,946, which claims priority to the following U.S. Provisional Applications: App. No. 61/952,015, filed Mar. 12, 2014; App. No. 62/017,148, filed Jun. 25, 2014; and App. No. 62/049,980, filed Sep. 12, 2014. The disclosures of the aforementioned applications are all incorporated by reference herein. This application also claims the benefit of the following U.S. Provisional Applications, the disclosures of which are both incorporated by reference herein: App. No. 62/217,570, filed Sep. 11, 2015, and App. No. 62/219,595, filed Sep. 16, 2015. The following applications are also incorporated herein by reference: U.S. Pat. No. 9,283,033, issued Mar. 15, 2016; and U.S. Publication 2014/0350401, which published on Nov. 27, 2014. All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
| Number | Date | Country | |
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| 62132459 | Mar 2015 | US | |
| 61952015 | Mar 2014 | US | |
| 62017148 | Jun 2014 | US | |
| 62049980 | Sep 2014 | US | |
| 62217570 | Sep 2015 | US | |
| 62219595 | Sep 2015 | US |
| Number | Date | Country | |
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| Parent | 15263174 | Sep 2016 | US |
| Child | 16683071 | US |
| Number | Date | Country | |
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| Parent | 15069531 | Mar 2016 | US |
| Child | 15263174 | US | |
| Parent | 14656635 | Mar 2015 | US |
| Child | 15069531 | US |
