Not Applicable.
The present disclosure relates to imaging and therapy methods, apparatuses, and devices, and more particularly to exemplary aspects of imaging and/or therapy methods and systems which can be suitable for use in visualizing and conducting therapy on a heart, valves, or blood vessels to obtain a diagnosis, acquire tissue, treat via the removal of pathology, or assist in the deployment of other devices.
Direct visualization of structures is often very useful for diagnosis and therapeutic interventions in medicine and surgery. However, physicians currently do not have a reliable means to directly visualize structures inside the beating heart and its chambers, or inside the major blood vessels. This is due to light being attenuated by blood.
Fluoroscopy and echocardiography are currently available modalities for real-time imaging of cardiovascular structures. While these techniques can be used to guide certain minimally invasive intracardiac procedures, but both are indirect and imprecise. This tends to make such procedures time and resource consuming. In addition to significantly prolonged procedural times, fluoroscopy is associated with risks. For example, fluoroscopy exposes patients and the clinical team to significant ionizing radiation. As another example, transesophageal echocardiography (TEE) is associated with a risk of esophageal injury. As yet another example, there is a risk of an inadvertent tissue injury or perforation by a device or a catheter that is guided by fluoroscopy or TEE during indirect visual navigation through the heart chambers or great vessels that is exacerbated by the relatively poor quality of the visualization.
Only a few methods have been attempted to directly visualize structures inside the heart, but none have found a widespread acceptance in clinical practice. For example, direct contact between an endoscope and cardiac tissue can provide a visualization, but such a visualization shows only an extremely small field. As another example, use of a transparent toroidal balloon chamber that displaces blood between the lens and the object could facilitate visualization, but does not allow any instrumentation through the balloon itself. As yet another example, displacement of blood with pressurized transparent fluid boluses is not capable of maintain imaging for sustained periods of time, and can cause hemodynamic instability. Finally, a complete replacement of intracardiac blood with a transparent nourishing perfusate can facilitate imaging, but also requires utilization of peripheral cardiopulmonary bypass and comes with substantial cost in addition to being a substantially more invasive procedure than fluoroscopy.
Therefore, the current unmet need lies in the absence of a method and apparatus for a direct imaging of the endocardial surface of the heart and blood vessels, also known herein as cardioscopy. In addition to diagnostic direct visualization, physicians also need a means for obtaining tissue, biopsy, and/or tissue removal of any pathology on a beating heart and blood vessels. Further therapeutic applications arise from a unique benefit of direct visualization of the intracardiac or intravascular structures in either energy delivery during ablative procedures or during delivery and deployment of various medical devices inside the heart or great vessels. All current diagnostic and therapeutic interventions on the heart and great vessels would potentially benefit from a radically new and direct imaging modality.
There are numerous examples of limitations of current imaging modalities in clinical practice. In case of massive or sub-massive pulmonary embolism (PE), currently available options (e.g., systemic thrombolysis, catheter-based direct thrombosis, and angiovac aspiration) have various drawings. For example, system thrombosis is very non-specific and frequently ineffective. As another example, catheter-based direct thrombolysis does not physically remove a large burden of the remaining clot. As yet another example, angiovac aspiration systems generally lack direct visualization of the thrombus, and procedures using such systems often rely instead on fluoroscopy, resulting in a very imprecise aspiration of the clot, in addition to requiring an invasive veno-venous bypass circuit. Ultimately, currently employed surgical embolectomy via sternotomy on a heart-lung machine is extremely invasive and requires substantial postoperative recovery. PE is very common and a massive or sub-massive PE is very morbid and frequently fatal. It is not surprising, therefore, that virtually all currently available therapeutic interventions targeted at PE are associated with substantial periprocedural morbidity and mortality either due to its significant ineffectiveness or a very radical invasiveness.
Further limitations include lack of direct visualization of the endocardial surface during ablative procedures for various arrhythmias, such as atrial fibrillation, supraventricular tachycardia, or ventricular tachycardia. Currently available options include employment of the catheter systems that deliver energy to create a tissue scar, thus interrupting micro or macro-reentrant circuits. The procedures tend to be long and frustrating because of lack of direct visualization of the catheter in relation to the endocardial surface and anatomical structures. Frequently fluoroscopy, transesophageal echocardiography, and/or intracardiac echocardiography are employed to get the task accomplished. However, despite all currently available indirect imaging modalities, most ablation procedures are frequently ineffective and require repeat interventions. The task would be much easier accomplished with a direct visualization of the catheter in the intracardiac chamber.
Another example is how heart transplant patients currently undergo multiple myocardial biopsies as part of their organ rejection surveillance regimen. Currently, a bioptome is advanced blindly under fluoroscopy guidance through the tricuspid valve. Not surprisingly, as the result of multiple biopsy sessions and blind passages across the tricuspid valve, the leaflets of the tricuspid valve are frequently injured and destroyed leading to a subsequent severe tricuspid regurgitation. Sometimes these very sick patients have to undergo either a heart re-transplant or a very high-risk tricuspid valve replacement via open heart surgery due to potentially avoidable injury of the tricuspid valve. Direct visualization of the bioptome passing across the tricuspid valve would ensure less injury to the tricuspid valve and make biopsy procedure more effective and less time consuming. The same can be said about guidance of the bioptome for biopsy of other intracardiac or intravascular pathologies.
However, perhaps most clinically relevant and time-pressing is the current suboptimal visualization modality in deployment of various currently available intracardiac or intravascular devices and related procedures, including, but not limited to, transcatheter aortic valve replacement, left atrial appendage occlusion, chronic total occlusion, transcatheter mitral valve repair, patent foramen ovale closure, transcatheter pulmonary valve replacement, paravalvular leak closure, and percutaneous transluminal coronary angioplasty. One example of percutaneous tricuspid or mitral annuloplasty devices, the currently available strategy employs both, fluoroscopy and echocardiography guidance to deploy and secure these devices around the valve hopefully well in the annular tissue. However, the platform is quite risky because of the neighboring coronary arteries, conduction system, and other anatomical structures. Due to the indirect imaging provided by fluoroscopy and echocardiography, the deployment is imprecise, time-consuming, and carries a high risk of injuring a neighboring anatomical structure, such as a coronary artery, conduction system, valve itself, or other anatomical structure. Further, the annulus of the valve, tricuspid or mitral, is a very thin structure and is best identified by its whitish colored line between atrial wall and actual valve leaflet tissue. The precision that is required to place an annuloplasty device into the annular tissue of the valve can be best achieved only by a direct visualization of the anatomical structure and not so much by a current guesswork-based on indirect and imprecise fluoroscopy and echocardiography. The current platform of indirect guidance by fluoroscopy or echocardiography is a far cry from what a proceduralist would prefer in terms of image quality to deploy a needed device.
Direct visualization and guidance in the delivery and deployment of various medical devices in the field of heart and vascular disease would provide a more successful, more durable, more precise, less time-consuming, and less complications-prone platform. It would literally revolutionize the way the numerous devices are placed in the heart and/or in the great vessels.
In an aspect, the present disclosure provides a probe. The probe includes a proximal portion and a distal portion. The probe includes a channel, an optical waveguide, and a ferrofluid attractor. The channel has a proximal port, a distal port, and an interior surface. The proximal port is positioned at the proximal end of the probe. The distal port is positioned at the distal portion of the probe. The interior surface is composed of a material that is chemically and magnetically inert to a ferrofluid. The channel, the proximal port, and the distal port have size dimensions that allow the ferrofluid to enter the channel via the proximal port, move along the channel, and exit the channel via the distal port when the ferrofluid is introduced at a predefined pressure. The optical waveguide has a proximal waveguide end and a distal waveguide end. The proximal waveguide end is positioned at the proximal portion of the probe. The distal waveguide end is positioned at the distal portion of the probe. The ferrofluid attractor is coupled to the distal end of the probe. The ferrofluid attractor has magnetic properties and positioning relative to the distal port to magnetically attract the ferrofluid when exiting the distal port.
In another aspect, the present disclosure provides a catheter. The catheter includes a probe as described herein and a sheath configured to receive the probe.
In a further aspect, the present disclosure provides an optical imaging system. The optical imaging system includes an optical imaging light source, an optical imaging detector, a probe as described herein, a circulator, and an optical imaging controller. The circulator is coupled to the optical imaging light source, the optical imaging detector, and the optical waveguide. The circulator is configured to direct light from the optical imaging light source to the optical waveguide and from the optical waveguide to the optical imaging detector. The optical imaging controller is coupled to the optical imaging detector and configured to provide an optical imaging signal output representative of an optical signal measured at the optical imaging detector.
In yet another aspect, the present disclosure provides an optical coherence tomography (OCT) system. The OCT system includes an OCT light source, an OCT detector, a probe as described herein, a circulator, and an OCT controller. The circulator is coupled to the OCT light source, the OCT detector, and the optical waveguide. The circulator is configured to direct light from the OCT light source to optical waveguide and from the optical waveguide to the OCT spectrometer. The OCT controller is coupled to the OCT spectrometer and configured to provide an OCT signal output representative of an OCT signal measured at the OCT spectrometer.
In yet a further aspect, the present disclosure provides a ferrofluid for use in direct visualization medical imaging of an internal structure. The ferrofluid includes ferromagnetic particles and a biologically inert solvent. The ferromagnetic particles are present in an amount by weight of between 0.1 milligrams of iron per milliliter and 100 milligrams of iron per milliliter.
In another aspect, the present disclosure provides a method of acquiring a direct visualization medical image of an internal structure. The method includes: a) introducing a ferrofluid into an area near the internal structure, thereby displacing a biological fluid within the area, the ferrofluid retained in the area using a magnetic effect; and b) acquiring the direct visualization medical image of the internal structure through the ferrofluid.
The foregoing and other aspects and advantages of the invention will appear from the following description. In the description, reference is made to the accompanying drawings which form a part hereof, and in which there is shown by way of illustration a preferred embodiment of the invention. Such embodiment does not necessarily represent the full scope of the invention, however, and reference is made therefore to the claims and herein for interpreting the scope of the invention.
The invention will be better understood and features, aspects and advantages other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such detailed description makes reference to the following drawings.
FIGS. 10A1 to 10B3 are various schematics of probes, in accordance with aspects of the present disclosure.
Before the present invention is described in further detail, it is to be understood that the invention is not limited to the particular embodiments described. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. The scope of the present invention will be limited only by the claims. As used herein, the singular forms “a”, “an”, and “the” include plural embodiments unless the context clearly dictates otherwise.
It should be apparent to those skilled in the art that many additional modifications beside those already described are possible without departing from the inventive concepts. In interpreting this disclosure, all terms should be interpreted in the broadest possible manner consistent with the context. Variations of the term “comprising”, “including”, or “having” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, so the referenced elements, components, or steps may be combined with other elements, components, or steps that are not expressly referenced. Embodiments referenced as “comprising”, “including”, or “having” certain elements are also contemplated as “consisting essentially of” and “consisting of” those elements, unless the context clearly dictates otherwise. It should be appreciated that aspects of the disclosure that are described with respect to a system are applicable to the methods, and vice versa, unless the context explicitly dictates otherwise.
Numeric ranges disclosed herein are inclusive of their endpoints. For example, a numeric range of between 1 and 10 includes the values 1 and 10. When a series of numeric ranges are disclosed for a given value, the present disclosure expressly contemplates ranges including all combinations of the upper and lower bounds of those ranges. For example, a numeric range of between 1 and 10 or between 2 and 9 is intended to include the numeric ranges of between 1 and 9 and between 2 and 10.
Lengths and distances described herein are described in terms of optical path length lengths and distances, unless the context clearly dictates otherwise. Accordingly, light traveling along a coiled optical fiber travels a distance that is equal to the uncoiled length of the optical fiber, not the physical distance between the input and output of the optical fiber.
As used herein, the term “substantially-transparent” refers to the ability to successfully transmit light through a medium. “Substantially” referring to the fact that the medium is neither optically transparent nor completely absorbent. For example, a medium that is substantially transparent would allow visualization of a target image with a light based imaging device at a resolution that allows desired structures to be discernable. It is assumed that a substantially transparent medium will have an absorbance at minimum less than blood, allowing light transmittance at a depth and resolution necessary for the specific application. The present disclosure provides systems and methods that have a variety of advantages relative to those available in the art. The following description of these advantages is not intended to be limiting, nor is it intended to imply that the systems and methods can only be used to achieve these advantages.
For example, the present disclosure provides examples of probes, catheters, optical systems, OCT systems, ferrofluids, and processes as described herein. Features described in connection with one or more of aspects of these examples are generally applicable to the others. For example, features described in connection with probes are generally applicable to OCT systems, and features described in connection with ferrofluids are generally applicable to the processes.
In some aspects, mechanisms described herein can be used (e.g., by physicians) to directly image and conduct minimally-invasive therapy on cardiovascular structures in the presence of flowing blood. For example, a device for directly imaging cardiovascular structures can include a flexible cardioscope (e.g., an endoscope used in the cardiovascular system) that includes a magnetic tip. In such an example, a liquid that becomes magnetized when placed in the presence of a magnetic field (sometimes referred to herein as a ferrofluid), is injected through a working channel to the tip of the cardioscope. The magnetic field produced by the magnetic tip of the cardioscope in such an example can cause the ferrofluid to localize near the tip of the cardioscope scope, which can form a ferrofluid cloud that displaces blood. In such an example, light can more easily penetrate through the ferrofluid cloud than through blood, which can facilitate direct visualization of a target. Additionally, a minimally-invasive surgical procedure can be conducted through the ferrofluid cloud, while the target is continuously visualized. After such a procedure is over, suction through the working channel can be used to remove the ferrofluid from the tip of the cardioscope.
As described above, one solution for direct cardioscopy entails a substantially transparent ferrofluid that displaces blood while staying around a magnetized tip of a flexible probe or cardioscope (see, e.g.,
The systems and methods described herein can be utilized in multiple clinical applications in cardiology, and can facilitate expansion of the field of minimally-invasive cardiovascular surgery. For example, the mechanisms described herein can be used in connection with diagnosis and/or treatment of atrial fibrillation, pulmonary embolism, heart valve disease, heart failure, coronary artery disease, conduction disorders, vascular disease, etc. As another example, the mechanisms described herein can facilitate direct imaging of the heart and endovascular structures, which can be used by a healthcare provider (e.g., a physician) during various procedures. For example, the physician can use the mechanisms described herein to perform directly visualized biopsy and tissue removal procedures. As another example, the physician can use the mechanisms described herein to more effectively extract and/or aspirate clots. As yet another example, the physician can use the mechanisms described herein to more efficiently perform ablation procedures. As still another example, the physician can use the mechanisms described herein to provide visual guidance during deployment of various intracardiac and endovascular devices. As a further example, the physician can use the mechanisms described herein to directly identify perivalvular leaks. As another further example, the physician can use the mechanisms described herein to perform numerous directly visualized intracardiac procedures such as atrial septectomy, stitch placement, and others. The mechanisms described herein can be used by various types of healthcare providers in a variety of settings. For example, the mechanisms described herein can be used by interventional cardiologists and cardiac surgeons performing procedures in hybrid operating rooms or cardiac catheterization labs.
In a more particular example, applications of this disclosure can include aspiration of blood clots from the pulmonary arteries in cases of pulmonary embolism. With the direct cardioscopy of this disclosure, the clot is identified in the pulmonary artery and then directly aspirated via a main lumen. This would allow a much more elegant, less expensive, less invasive, more expedited, and more thorough treatment of pulmonary embolism. Another application of the cardioscopy would include direct visualization of the endocardial surface during catheter ablation of either atrial fibrillation or ventricular tachycardia. Direct visualization would reduce risk of spontaneous and potentially very hazardous perforations that still occur during current fluoroscopic and echocardiographic guidance. It would also potentially improve the actual effectiveness of the ablation procedure due to a better and more precise localization of the catheter on the endocardial surface. Another application would include cardioscopic ferrofluid-guidance during placement of the miniaturized leadless pacemaker, which is currently placed under fluoroscopic guidance. Ferrofluid-guided cardioscopy would assist in a more precise and a less traumatic placement of the pacemaker device and potentially would reduce its future dislodgement or interaction with intracardiac structures such as valve or chordal tissue.
Other potential applications lie in the directly visualized endomyocardial biopsy of the right ventricle in the heart transplant patients. Having the means of directly visualized biopsies via this disclosure would obviate tricuspid valve injury.
Further applications include directly visualized biopsy capabilities of the entire spectrum of the right sided and left sided cardiac lesions—whether those are endocarditis vegetations or cardiac tumors. Also, ferrofluid cardioscopy would allow one to assist an interventionalist in deployment of numerous intracardiac devices, such as an Amplatzer device for ASD closure, Watchman device for the left atrial appendage occlusion, annuloplasty device on the tricuspid valve, MitraClip deployment on the mitral leaflets or Neochord placement on a flail mitral leaflet, as well as stent graft placement in the aorta, and so on. A robust ferrofluid cardioscopy device would enable numerous further developments of intracardiac interventions on a beating heart and blood vessels. The field of ferrofluid cardioscopy, in and of itself, is a completely unchartered territory with a practically unlimited spectrum of clinical applications.
In case of MitraClip deployment, one would have a much easier and quicker way to perform the transseptal puncture and to position the clip on the mitral leaflets. With the help of spherical fluid around the tip of the catheter providing direct visualization one would identify foramen ovale anatomy much more precise and quicker. One would assess the anatomy of anterior and posterior leaflets directly, one would identify the ruptured chords or other pathology, and one would much better identify the best location for the most successful placement of the MitraClip. This would obviate the need for a lengthy and frustrating guidance by the TEE and fluoroscopy and would significantly shorten procedural time while allowing a much easier and more satisfying placement of the device on the leaflets resulting in a much more durable and effective treatment.
A direct cardioscopy platform such as the one described herein would allow a much more precise placement of the annuloplasty ring and would ensure a higher success, shorter procedure time, and less injury of the neighboring structures. Overall, the benefit of a direct visualization during deployment of the intracardiac or intravascular devices is multifaceted and difficult to quantify.
With the present disclosure, the patient benefit lies in the less invasive approach, since open heart surgery is very invasive and carries significant associated morbidity and mortality. If there is a way to remove a clot from the pulmonary artery without opening the sternum and being placed on the heart lung machine, every patient would sign up for it. The clinician benefit lies in a more expedited, less invasive aspiration of the clot. Potentially, with the established technology, the ferrofluid cardioscopy procedure could be performed at the bedside, just like bronchoscopy or some other endoscopic procedure. The payer benefit of this disclosure lies in the less expensive treatment (both surgery and catheter-based thrombolysis or Vortex procedure need to be done in either an operating room or in an angio suite) and shorter hospital stay. With the direct ferrofluid cardioscopic aspiration of the clot, the procedure could potentially be done at the bedside and would involve only a percutaneous access via the femoral vein. Overall, percutaneous embolectomy by means of ferrofluid cardioscopy would be a significantly more elegant solution than currently existing alternatives.
Referring to
The channel 110 can have a proximal port (not illustrated) positioned at a proximal portion of the probe. The channel 110, the proximal port, and the distal port 130 can have size dimensions that allow the ferrofluid to enter the channel via the proximal port, move along the channel 110, and exit the channel 110 via the distal port 130 when the ferrofluid is introduced at a predefined pressure. The size dimensions also allow the opposite motion when suction is introduced to the proximal port at a predefined negative pressure. The channel 110 has an interior surface that can be a material that is chemically and magnetically inert to the ferrofluid.
The ferrofluid attractor 120 can attract the ferrofluid based on magnetic properties of the ferrofluidic attractor 120 and the ferrofluid, and can be implemented using various different materials that have various different magnetic properties. For example, the ferrofluid attractor 120 can include a permanent magnet component. In a more particular example, the ferrofluid attractor 120 can be a neodymium iron boron permanent magnet, a samarium cobalt permanent magnet, an alnico permanent magnet, a ceramic permanent magnet, and/or a ferrite permanent magnet. The ferrofluid attractor 120 can be a printed 3D magnet that is printed by a magnet 3D printer to more precisely control the position of the dipoles. As another example, the ferrofluid attractor 120 can include an electromagnet component. As yet another example, the ferrofluid attractor 120 can include a ferromagnetic (which may be generally unmagnetized), that has a magnetic susceptibility sufficient to magnetically attract a ferrofluid having a persisting ferromagnetism. A variety of different coatings can be used in connection with the ferrofluidic attractor 120, such as nickel, gold, chrome, copper, epoxy resin, zinc, Teflon, silver, etc., to prevent undesirable chemical interactions between the ferrofluidic attractor 120 and biological fluid 180 (or other components of the probe 100). The ferrofluid attractor 120 can be a single component (e.g., a single permanent magnet, a single electromagnet, a single ferromagnetic (but unmagnetized) component, etc.). In such an example, the ferrofluid attractor 120 can be monolithic. Alternatively, the ferrofluid attractor 120 can include multiple attractor components. For example, the ferrofluid attractor 120 can include a permanent magnet, and an electromagnet. As another example, the ferrofluid attractor 120 can include multiple permanent magnets that are arranged to provide a particular magnetic field strength and/or shape.
One or more magnetic properties of the ferrofluid attractor 120 can be tuned to be control how strongly the ferrofluid is magnetically attracted to the ferrofluid attractor 120. For example, the magnetism can be tuned to be strong enough to retain the ferrofluidic cloud 140 in a stable orientation despite the movement of surrounding fluid, such as the pumping of blood through a blood vessel. In a more particular example, the ferrofluid attractor 120 can be configured to transition between a state of relatively high magnetism and a state of low relatively low (or no) magnetism. For example, a magnet of the ferrofluid attractor 120 can be coupled to an actuator that is configured to move the magnet closer to, and farther from, the distal port(s) 130 and/or a surface of the probe 100, altering the magnetic field strength outside of probe 100. As another example, a magnetic component of the ferrofluid attractor 120 can be configured to have an adjustable magnetic field strength. In a more particular example, when a component of the ferrofluid attractor 120 is implemented as an electromagnet, a magnetic field strength can be controlled based on the amount of current passed through the electromagnet, based on a position of a core material (e.g., a ferromagnetic core) within a coil of the electromagnet, etc. Additionally or alternatively,
The ferrofluid attractor 120 can be modified to alter a shape of the magnetic field. For example, in the case of a toroidal-shaped magnet, the corners of the top of the magnet (i.e., the portion of the magnet closest to the distal port 130 can be covered by a material that reduces the magnetic attraction in that region, forcing the ferrofluid cloud toward the center axis of the probe 100 in a region of relatively less dense magnetic field lines. This is merely an example, and a similar technique can be utilized with differently shaped and sized magnets to alter the shape of the magnetic field of the ferrofluid attractor 120 and influencing the shape of the ferrofluidic cloud 140. Additionally, cohesion of the ferrofluidic cloud 140 with the surrounding biological fluid 180 can be used to collect the ferrofluid cloud 140 more densely at the center axis of the probe 100. The ferrofluid attractor 120 can extend beyond the probe 100 circumferentially to stabilize and concentrate the ferrofluidic cloud 140, while leaving an opening that still maintains the ability to direct light forward and/or to the side and utilize tools or suction. The ferrofluid attractor 120 can have an oscillating magnetic field direction, which can control a net movement of the ferrofluid in a manner that resists dissipation into flowing of the biological fluid 180 (e.g., blood and/or other solutions around the ferrofluid cloud 140). For example, a permanent magnet can be physically rotated to cause net movement of the ferrofluid cloud 140 which can be controlled based on the rotation of the permanent magnet. As another example, oscillation of the current through an electromagnet can cause net movement of the ferrofluid cloud 140 which can be controlled based on the frequency, amplitude, and/or magnitude of the current signal.
The target 150 can be an intracardiac structure, a blood vessel wall, cardiovascular tissue, skin, gastrointestinal tissue, lung tissue, brain tissue, urologic tissue, gynecologic tissue, a thrombus, cardiac vegetation, a certain pathology of interest, a foreign body, a medical device, or the like.
The working channel 170 can be configured to receive a medical instrument or other device for delivery to the distal portion of the probe 100. The medical instrument or other device can be a suction catheter, biopsy forceps, a clip, a stent, a blood clot retrieval basket, a tissue ablator, a hook, an ablation catheter, a retrieval basket, a brush, a fixation device (e.g., a screw), an annuloplasty device or the like, a small leadless catheter, or a combination thereof.
The present disclosure also provides catheters. The catheter can include a probe (e.g., the probe 100) as described herein and a sheath configured to receive the probe. The catheter can be of various diameters for different applications. The catheter can be an angioscope, cardioscope, endoscope, cardioscopic catheter, nasogastric tube, any laparoscopic imaging device, etc.
The present disclosure also provides optical imaging systems. The optical imaging systems can include an optical imaging light source, an optical imaging detector, a probe (e.g., the probe 100) as described herein, an optical circulator, and an optical imaging controller. The optical circulator is coupled to the optical imaging light source, the optical imaging detector, and an optical waveguide (e.g., the optical waveguide 160). The optical circulator can be configured to direct light from the optical imaging light source to the optical waveguide and from the optical waveguide to the optical imaging detector. The optical imaging controller can be coupled to the optical imaging detector and configured to provide an optical imaging signal output representative of an optical signal measured at the optical imaging detector. The optical imaging system can be a fluorescence, autofluorescence, Raman, OCT, SECM, or other spectroscopic imaging system. The optical light source and optical detector can be chosen for the appropriate type of spectroscopic imaging.
The present disclosure also provides OCT systems. The OCT systems includes an OCT light source, an OCT detector, a probe (e.g., the probe 100) as described herein, an optical circulator, and an OCT controller. The circulator is coupled to the OCT light source, the OCT detector, and an optical waveguide (e.g., the optical waveguide 160). The optical circulator can be configured to direct light from the OCT light source to the optical waveguide and from the optical waveguide to the OCT detector. The OCT controller can be coupled to the OCT detector and configured to provide an OCT signal output representative of an optical signal measured at the OCT detector. The OCT light source can be a broadband light source.
The present disclosure also provides ferrofluids for use in connection with the probes and systems described herein. The ferrofluids can be used for direct visualization medical imaging of an internal structure. The ferrofluids can include ferromagnetic particles (e.g., iron particles) and a biologically inert carrier fluid. Ferromagnetic particles present in an amount of 0.1 mg Fe/ml or less to as high as 100 mg Fe/ml is conceivable. Also, dosages ranging from less than 0.2 mg Fe/kg to as high as a single dose of 1000 mg Fe is conceivable. Specific dosage and concentration may vary based on the desired application and imaging device. Also, the ferromagnetic particle content (e.g., iron content) may be able to be higher, as limited by toxicity of the specific ferrofluid in the human body.
The ferromagnetic particles can include a coating. There are a wide range of conceivable coatings, and the specific coating may vary based on the specific application and imaging device. Possible carbohydrate coatings include dextran, galactose, mannose, glucose, ethylene glycol, citrate, fucose, carboxymaltose, carboxydextran, polyethylene glycol, carboxy-methyldextran, arabinogalactan, and poly-styrene, and the like. Other coatings include hydroxyphosphonate, folate, sodium ferric gluconate, silica, carboxylates, polyamidoamine, lipid bilayers, curcumin, hydrophilic polymers, hydrophobic polymers, polymers that are neither hydrophobic nor hydrophilic, amphiphilic ligands, and additional bound proteins that can be single amino acids or chains of amino acids, etc. Coatings with a range in weight from 1 kilodalton (kD) to 2000 kD are conceivable. Dextran, which is often used as a ferromagnetic nanoparticle coating, ranges from 3 to 2000 kD.
The ferromagnetic particles can be of a size that substantially reduces the amount of light that is scattered by the ferromagnetic particles. The ideal ferromagnetic particle size will differ on the application and the light based imaging device. For example, depending on the resolution or wavelength utilized in the light-based imaging device, different particles sizes will scatter more or less light. Particle coatings ranging from 6 to 100,000 nm is conceivable. Further, the use of superparamagnetic iron oxide particles (SPIO) which range from 100 to 200 nm, ultrasmall superparamagnetic iron oxide particles (USPIO) which are less than 50 nm, and micron sized particles of iron oxide (MPIO) which are greater than 1000 nm, are all conceivable.
The ferrofluid can include a viscosity enhancing agent. The viscosity enhancing agent can be present in as little as 1% or less of the solution, or as much as the saturation point of the solution. For example, for dextran the saturation point occurs roughly when the ratio of dextran to water is 2:1. Besides dextran, other viscosity enhancing agents can include any agent that is both water-soluble and non-toxic. Examples of which can include other polysaccharides or oligosaccharides, such as starch, glycogen, callose, chyrsolaminarin, xylan, arabinoxylan, mannan, fucoidan, hydroxyethyl cellulose, and galactomannan. In addition, biocompatible oils can be used as a viscosity enhancing agent for some clinical applications.
Ferrofluid with a viscosity between 0.089 centipoise (cP) to 10,000 cP is conceivable. In certain applications, the viscosity can be between 3 to 10 cP, which is near the viscosity of blood.
The ferrofluid can be substantially transparent. The ferrofluid can have an average optical absorbance greater than water and less than blood for at least one wavelength between 400 and 1400 nm. The specific wavelength and transparency can vary based on the clinical application and imaging device, and can be related to the concentration and type of ferrofluid used.
The biologically inert carrier fluid can be water, which can act as a solvent for the ferromagnetic particles and/or viscosity enhancing agent. Alternatively, the biologically inert carrier fluid can be a buffer solution, such as a phosphate buffered saline (PBS) buffer, which can act as a solvent for the ferromagnetic particles and/or viscosity enhancing agent.
The present disclosure also provides a method of acquiring a direct visualization medical image of an internal structure. The method includes: a) introducing a ferrofluid into an area near the internal structure, thereby displacing a biological fluid within the area; b) acquiring the direct visualization medical image of the internal structure through the ferrofluid. The method can also include, prior to the acquiring of step b), contacting the internal structure with the ferrofluid. The internal structure can be any of the targets 150 described above. The introducing of step a) can be done via the channel 110 of the probe 100. The acquiring of step b) can be done via the optical waveguide 160 of the probe 100 and/or using the optical imaging system or OCT imaging system described herein. The contacting the internal structure with the ferrofluid can be achieved by moving the ferrofluid attractor 120 or by moving a distal tip or distal portion of the probe 100.
The systems, probes 100, and methods described herein can be used for any processes utilizing catheters, including flexible catheters. Such processes include in vivo imaging, such as in vivo cardiology or gastrointestinal tract imaging.
Referring to
The optical waveguide 160 can be an optical fiber, for example coupled to a laser emitting diode or other light source. The optical fiber can be a single-mode fiber. The optical fiber can be a double clad optical fiber. The optical waveguide 160 can serve as a sample arm for an OCT system.
The imaging optic 175 can be a lens, a reflector, other optics known to those having ordinary skill in the art to be useful for coupling light for the purposes of imaging, or combinations thereof. In some cases, the lens can be a ball lens, a spherical lens, an aspherical lens, a graded index (GRIN) fiber lens, an axicon, a diffractive lens, a meta lens, lensing with phase manipulation, or the like.
The driveshaft 195 can be coupled to the optical waveguide 160, the imaging optic 175, including a lens and/or a reflector, or a combination thereof.
The probe 100 can include a pump (not illustrated) for providing positive pressure to the ferrofluid when introducing the ferrofluid to the target and/or for providing negative pressure to remove the ferrofluid from the target.
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Referring to FIGS. 10A1 to 10B3, various schematics of probes are shown. FIG. 10A1 shows a catheter 1000 with an uninflated balloon 1010 at a distal end and forward-facing imaging tip 1020. FIG. 10A2 shows the balloon 110 inflated with iron particles 1030 in order to create a magnetic field at the tip of the catheter. For example, iron particles 1030 can be included in a ferrofluid, which can be the same ferrofluid that is used to produce a ferrofluid cloud, or a ferrofluid having different properties (e.g., a different concentration of particles, a different solvent, etc.). FIG. 10A3 shows a ferrofluid cloud 1040 that is injected outside of the catheter 1000 so that the particles concentrate around the magnetized balloon 1010. The ferrofluid cloud 1040 displaces surrounding biological fluid (e.g., blood) allowing light 1050 to be transmitted more easily toward a sample. FIG. 10B1 shows another catheter 1001 which includes two uninflated balloons 1060 on either side of a side viewing imaging tip 1070. FIG. 10B2 shows the balloons 1060 inflated with iron particles 1080 to create and/or augment a magnetic field at the tip of the catheter. FIG. 10B3 shows a ferrofluid cloud 1090 surrounding the magnetized balloons 1060. The ferrofluid cloud 1090 displaces surrounding biological fluid (e.g., blood) allowing light 1091 to be transmitted more easily toward a sample. The probe of FIGS. 10B1 to 10B3 can, for example, be used in connection with transcatheter procedures that involve navigation of the catheter through smaller vessels to reach a desired region in the heart.
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The following examples set forth, in detail, ways in which the optical systems and/or the probes (e.g., the probe 100, the probes depicted in
An exemplary ferrofluid for cardioscopy was prepared by mixing dextran-coated ferromagnetic particles having a mean diameter of 9 nm into PBS to provide a suspension. The average molecular weight of the dextran coating on the ferromagnetic particles was 40 kD.
The ferrofluid of Example 1 was introduced via an optical probe having features described elsewhere herein into a PBS solution. Referring to
A ferrofluid having 40 kD dextran coated ferromagnetic nanoparticles in an amount of 0.4% (w/w) suspended in a 5% aqueous dextran solution was prepared and introduced into a blood sample via an optical probe having features described elsewhere herein. Referring to
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Thus, while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto. Indeed, the arrangements, systems, and methods according to the exemplary embodiments of the present disclosure can be used with and/or implemented any OCT system, OFDI system, SD-OCT system or other imaging systems capable of imaging in vivo or fresh tissues, and for example with those described in International Patent Application PCT/US2004/029148, filed Sep. 8, 2004 which published as International Patent Publication No. WO 2005/047813 on May 26, 2005, U.S. patent application Ser. No. 11/266,779, filed Nov. 2, 2005 which published as U.S. Patent Publication No. 2006/0093276 on May 4, 2006, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9, 2004 which published as U.S. Patent Publication No. 2005/0018201 on Jan. 27, 2005, U.S. Patent Publication No. 2002/0122246, published on May 9, 2002, U.S. Patent Application 61/649,546, U.S. patent application Ser. No. 11/625,135, and U.S. Patent Application 61/589,083, the disclosures of which are incorporated by reference herein in their entireties. The entire disclosure of each patent and publication cited herein is incorporated by reference, as if each such patent or publication were individually incorporated by reference herein.
This application is based on, claims the benefit of, and claims priority to U.S. Provisional Application No. 62/577,042, filed Oct. 25, 2017, which is hereby incorporated herein by reference in its entirety for all purposes.
Filing Document | Filing Date | Country | Kind |
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PCT/US2018/057584 | 10/25/2018 | WO | 00 |
Number | Date | Country | |
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62577042 | Oct 2017 | US |