Patent Application
20250073491
Light based therapies have been shown to be effective for a number of hyperproliferative medical conditions ranging from cancer to benign skin diseases such as psoriasis. Light based therapies, also known as phototherapeutics, have also been utilized to stimulate or control functions, exemplified for instance, by the use of light to control neurologic functions as known in the field of optogenetics. Light based therapies can require deep penetration of target tissues, on the order of centimeters or more, and thus may entail the utilization of high-power devices such as lasers, with potential safety issues including the risk of unwanted tissue damage. However, the need for high fluence rates due to severe and rapid light attenuation in tissues greatly limits the depth to which light-based treatments can typically be safely and effectively delivered, when light is delivered from an external skin surface. Thus, for some types of light-based treatments such as photodynamic therapy, an invasive procedure is required to insert an optical fiber or fibers, into or proximate to the treatment site, to enable delivery of enough light energy to produce the desired therapeutic effects. Invasive procedures have the risks and downsides of infection, bleeding, pain, accidental organ damage, need for some type of anesthetic or sedation, inconvenience, and off-target side effects. Various embodiments are disclosed herein that enable, directly and/or indirectly, greater therapeutic light energy or its net effects including generation of ultrasound pulses, to be delivered to deep tissues effectively and safely, in a non-invasive manner.
The photoacoustic phenomenon as is utilized in medical practice, is an effect whereby one or more non-ionizing pulsed light beams, which may be convergent at or proximate to the treatment site, are delivered, to create a distal zone of transient, heated tissue, inducing so-called thermoelastic expansion, which in turn generates an ultrasound pulse wave, which may be in the MHz range. The process of thermoelastic expansion occurs by optical absorption by endogenous or exogenously delivered chromophores or substances capable of absorbing light. This photoacoustic signal in the ultrasound range can be useful for in vivo tissue imaging, which comprises its typical medical applications and rather unexpectedly, serve as an activator of a class of compounds known in the art as photosensitizers. Photosensitizers can absorb light and produce singlet oxygen and other reactive oxygen species, and are used for treatment of tumors benign and malignant, against infections, and for treatment of other medical conditions. In addition to light activation, activation of photosensitive compounds or conjugates using ultrasound is also a known phenomenon known as sonodynamic therapy. One aspect of one or more of the various embodiments encompasses the use of tissue penetrating light, which induces beneficial biologic effects, in combination with generation of an acoustic pulse, typically within the ultrasound range, which also has a beneficial effect. The combination of effects can produce a variety of beneficial effects not readily realized by either modality alone, and with the advantage of requiring lower energy transmission through tissue to the target, which improves safety, since external intense light sources and external intense ultrasound sources are not required to enable deep tissue penetration. Another aspect of the one or more of the various embodiments is the delivery of light internally, from an external light source, utilizing water vapor or steam as a light transfer mechanism.
Light energy has been shown to increase adenosine triphosphate (ATP) production which is an absolute requirement for various important cellular functions, including cell repair, and can stimulate cell proliferation important for wound healing. Light therapy is also used to reduce pain, and inflammatory reactions, for example when used as a treatment for painful oral mucositis which can result from various cancer treatments.
Ultrasound energy has also been shown to stimulate tissue repair and healing effects, and can induce beneficial gene expression and protein production, amongst other therapeutic effects.
An additional feature for one or more of the various embodiments alluded to above is the use of water vapor or steam, which may or may not contain other medicaments located within or on the surface of the droplets, or aerosols, which may be passively or actively administered into an internal body cavity such as the mouth, nose, nasopharynx, the upper or lower respiratory tract, gastrointestinal (GI) tract, genitourinary (GU) tract, or by way of an artificially created stoma, or via a pathologic fistulous tract. Steam or liquid vapor can act as a series of photon reflectors or refractors, transmitting light in a confined volume, defined by the steam or liquid vapor stream or track, thus enabling non-invasive light delivery to superficial and deep tissue targets for phototherapeutic purposes. This effect can be seen for example, in commercially available “cold fireplace” apparatuses, whereby light generated and delivered to a water vapor column is confined to the vapor column and used to simulate a fireplace flame. These phototherapeutic purposes can be comprised of photo-biomodulation, photodynamic activation, photo-stimulation, and related known light induced effect. Steam or liquid vapor, which can be comprised of disinfected or purified water, can be aerosolized and inhaled or delivered through the mouth and/or nose, by way of an oral airway tube and/or a nasal cannula, which allows passive or active pressurized delivery of droplets or vapor, or actively inhaled delivery of droplets or vapor. A light source, consisting of one or more light emitting diodes (LEDs), laser diodes, lasers, or related light sources including but not exclusively semiconductor light devices, is used to provide the light to the vapor stream or track, introduced by way of a stoma, natural orifice, or artificial opening or fistula, into a hollow organ such as the oral cavity, the nasopharynx, the upper and lower respiratory tract, and/or the GU or GI tract by way of non-restricting example.
Contemplated light sources and devices in the one or more of the various embodiments can be lensed or configured in such a manner, to concentrate light from one or more external light sources into one or more organ lumen targets. Red light, green light, blue light, near infrared light, infrared light, and other wavebands and wavelengths of light are known to have phototherapeutic effects, due to light absorption by endogenous and/or exogenous chromophores and photosensitizers, and/or by absorption by various cellular components.
Contemplated photosensitizers include but are not limited to exogenous and endogenous substances such as known and contemplated porphyrins, chlorins, texaphyrins, methylene blue and derivatives, erythrosine and derivatives, riboflavin and derivatives, rose bengal and derivatives, protoporphyrin IX, aminolevulinic acid and derivatives, purpurins, curcuminoids, bergamot, psoralens, various photoactive citrus compounds, indocyanine green, and the many other known and contemplated photosensitizers and photocatalytic substances such as titanium dioxide and zinc oxide. Concentrations of at least one photosensitizer can range from 0.001 micromolar to 2.0 molar, or from 0.01% to 2.0% w/v or v/v. Also included in this disclosure is the use of known and contemplated cutaneous optical clearing agents such as mannitol or glycerol, as non-limiting examples, which aid in light and energy transmission through skin. Light and energy can also be transmitted through naturally occurring orifices achieving a photoacoustic effect, such as via the oral or nasal cavity, via the urethra or vagina, and/or the anus.
Also, one or more of the various embodiments may include known and contemplated ultrasonic imaging agents, which are injected intravenously. Ultrasonic contrast agents may be in the form of microbubbles, conjugates, and various types of particles which are echogenic. In addition to increasing the visibility of the signals received by an external ultrasound transducer, the ultrasonic contrast agents can increase the ischemic reperfusion effect, which is included in the one or more of the various embodiments by reacting with the delivered ultrasound energy at the target tissue or surface and increasing the transient closure of blood vessels, stopping or slowing blood flow. The ischemic reperfusion effect is known to induce apoptosis in tissues, and in the one or more of the various embodiments can be used to reduce unwanted tissues such as benign and malignant tumors and cancerous deposits.
Generally, disclosed herein are inventive elements and one or more of the various embodiments as follows:
Light wavelengths and wavebands can range from: the visible (approximately 400-800 nm) to near infrared and infrared spectrum (approximately 800-1350 nm), and even longer wavebands (1600-2500 nm), with red light and near infrared light and longer wavebands preferred for increased tissue penetration. Light pulsing can be accomplished using various light sources including various types of lasers, optical parametric oscillators, laser diodes, light emitting diodes, optionally comprising an array, positioned comfortably on the body, powered preferably by battery power to enhance portability and convenience. A light source array can be arranged such that light is directed in such a way so as to coalesce on a target volume or area of tissue, from different angles and directions, thus reducing the light energy required from any single point on the body, reducing risk of unwanted tissue heating. Light pulse duration ranges from several to hundreds of nanoseconds, and for some applications which include ultrasound imaging as an additional feature, tens of nanoseconds of light pulse duration are preferred, for example when working with a 10-MHz center frequency ultrasound array detector.
Light energy of 0.01 millijoules to hundreds of millijoules per pulse are preferred, delivered externally, though higher energies in the centijoule range per pulse may be useful, and which can be determined and optimized experimentally, using tissue phantoms known in the art, or be determined in vivo. Light energy in the 100-1000 microjoule range is also useful for treatment of very superficial tissue targets, for example on or within the skin surface, or on the internal surface of a hollow organ. The total length of time over which the treatment procedure takes place, number of sessions and duration of sessions within a particular treatment episode, frequency of sessions and related treatment parameters are determined through clinical trials. The treatments being non-invasive and essentially without risk, can be performed on an as needed basis as well, with individual patient experiences guiding the various treatment parameters, leading to personalized, precision treatments. Data from treatments and imaging results, clinical trials and tests, can be captured using smart watches and phones, tablets, laptops, computers, and the like, and uploaded to a central site for analysis, to optimize recommended treatment parameters for individual patients, groups of patients, and populations.
Light energy can be delivered from an array of individual light sources, for example from an LED array which employs an adjustable focusing feature, which enables light to be targeted to various depths, and volumes of tissues. Typical means of focusing light can employ known lenses, mirrors, and mechanical aiming mechanisms, and light intensity and pulsing can be varied using external known means of control and known electronic mechanisms as well.
Photoacoustic pulse waves can be used to ascertain changes in tissue characteristics, blood flow, tissue volume, and related effects, which reflect the efficacy of the photosensitizer activation by light and ultrasound treatment in real-time. Real-time imaging has major advantages in terms changing the treatment parameters on demand during particular treatment episodes, enabling effects to be modulated and increasing normal tissue protection.
Photoacoustic pulse waves, can in of themselves result in vascular changes, including transient or permanent vessel closure, which can result in cellular apoptosis and tissue reduction. Indeed, vascular effects known in the art include vasospasm and thrombosis, which can lead to tissue ischemia. Reperfusion after transient reduced or cessation of vascular blood flow can compound tissue injury, and in one or more of the various embodiments, as a treatment against cancerous deposits, leading to downstaging of cancer and beneficial immune effects. Cellular apoptosis and other forms of cell death are induced by deliberate induction of tissue ischemia followed by reperfusion, which is known in the field to cause cellular apoptosis, and resultant reduction of tissue volume. Treatment of cancerous or benign tumors in deep or superficial anatomical locations in this manner has the significant advantage of being non-invasive, normal tissue sparing, painless, and lacking of inflammatory and other deleterious off target effects. In the case of cancer, apoptotic cell death induced by the ischemia reperfusion effect can lead to a secondary beneficial immune response, as noted in the cancer immunotherapy art. This important distinction of the one or more of the various embodiments teaches away from high intensity focused ultrasound (HIFU), which is a means of heating tissue to the point of necrosis, which causes pain, inflammation, and which can actually be tumor promoting due to induction of the stereotypic wound healing process involving growth factors and immune cell stimulation, which in this case, has been shown to have potential for enhancing growth of cancerous deposits not completely which are not completely treated.
Ultrasound is defined as sound waves with frequencies greater than 20 kHz.
The combination of light induced effects, with or without concomitant ultrasonic stimulation on specific tissue targets can also result in effects such as neural stimulation or suppression, cellular and tissue repair, due to accelerated adenosine triphosphate production, expression of genes leading to production of proteins and other biological substances, and various immune reactions leading to enhanced healing of damaged tissues.
Unlike ultrasound which is attenuated in air or gas filled containing organs and anatomical spaces, light is readily transmitted in a gaseous medium to, or through a solid or liquid tissue where a photoacoustic effect can then occur, proximate or within the target treatment site. Utilized in this manner, both deeply penetrating light, at and above wavelengths and wavebands 800 nm, and into the 2,500 nm range, can be combined with photoacoustic generated ultrasound for tissue stimulation, tissue healing, sonodynamic and photodynamic photosensitizer activation, and for ultrasound imaging.
The advantage of utilizing the ischemia reperfusion effect as an anticancer treatment is that lower energies are required since permanent vascular occlusion is not required, and indeed, ischemia reperfusion teaches away from permanent vascular occlusion required by other anticancer treatments such as high energy radiofrequency ablation, embolization, cryotherapy and the like, which have the downsides of pain, inflammation, and the potential for treatment failure due to downstream tumor promotion due to growth factor secretion and tumor promoting immune effects as secondary consequences of necrosis.
Water vapor, and suspended breathable droplets inhaled into the nasopharynx, upper and lower respiratory tract act as light reflectors, delivering light into hollow organs such as the lungs. Other anatomical routes of vapor or droplet administration utilizing natural orifices or artificially created orifices are also enabled, using pressurized modes of vapor or droplet delivery. Light delivered in this way to internal sites in the body avoids invasive disposition of light delivery devices such as optical fibers.
In one or more of the various embodiments, a photoacoustic device is comprised of one or more LEDs, or one or more laser diodes, which are tunable in the visible light spectrum, and controllable in terms of light intensity, light pulse frequency, and which are arrayed, so as to maximize light delivery to a tissue volume or surface area while minimizing light energy absorption by non-target tissue in the light path. This feature minimizes unwanted heating in non-target tissue. Targeting light in the near infrared range for example, enables tissue penetration from 1 mm to 10 cm as is known in the art. The generation of an acoustic pulse can affect injured tissues or abnormal tissues in various ways, ranging from reduction of inflammation, with promotion of tissue healing, to vascular injury leading to an ischemia reperfusion effect, which can be used to reduce the size and volume of cancerous deposits, while promoting antitumor immune stimulation due to tumor antigen release.
Also, in one or more of the various embodiments, a photosensitizer is administered locally or systemically, and the activated simultaneously by light absorption and by the sonodynamic effect, at a target site, in this case cancer, using both known anticancer treatments, which may act synergistically.
Additionally, in one or more of the various embodiments, the treatment effect is monitored in real-time by an incorporated or independent ultrasound transducer, which can image changes in echogenicity and changes in blood flow using power doppler or color flow doppler as an example. This feature permits real-time feedback as to the efficacy or treatment and permits adjustments of the light intensity and pulse train component of the photoacoustic treatment, to increase the acoustic pulse effect causing the ischemic reperfusion injury, as well as the photodynamic and sonodynamic therapy effect.
In yet one or more of the various embodiments, light is delivered using one or more optical fibers, inserted into the lumen of a hollow organ, by way of a naturally occurring orifice, or a fistula, or a stoma for treatment of the lungs, urethra, ureters, bladder, gastrointestinal tract, oral cavity, and nasopharynx, and auditory canal, as non-limiting examples.
In one or more of the various embodiments, an optical clearing agent such as mannitol, glycerol, polyethylene glycol (PEG), polypropylene glycol, dimethylsulfoxide (DMSO), optionally with hyaluronic acid is applied as a topical agent to skin, with other known clearing agents including glucose, dextrose, fructose, sucrose, sorbitol, xylitol, propylene glycol, butylene glycol, ethanol, oleic acid, sodium lauryl sulfate, azone, and thiazone. The formulations of optical clearing agents can range from 1 part agent to 0.0001-100 parts solvent, such as water, or a known skin penetration enhancer such as DMSO, ethanol, hyaluronic acid, and the like.
In one or more of the various embodiments, the use of an optical clearing agent topically applied the skin one hour or less prior to positioning of the light source(s) enhances light penetration intensity and depth in tissue, thus enhancing the phototherapeutic effect, the sonodynamic effect, and the photoacoustic effect as desired.
In one or more of the various embodiments, the photoacoustic device is used in the ultrasound only mode, and/or the light delivery mode only, and/or in the photoacoustic mode, to stimulate stem cell and/or progenitor cell proliferation and function, such as enhanced cell homing, where the stem cells may be naturally in situ, or deliberately harvested and proliferated and differentiated into specific tissues.
In one or more of the various embodiments, external light sources of different wavelengths or wavebands are used to generate photoacoustic pulses at varying depths, creating a “stacked” series of ultrasonic tissue pulses enabling deeper penetration of the photoacoustic pulses, for example, by combining 800 nm and 1064 nm light emitting diode focused arrays on a deep tissue target, whereby the photoacoustic pulses generated at the differing focal points, which vary according to tissue scattering and absorption characteristics, are able to penetrate well beyond the light focal points.
In one or more of the various embodiments the stacking of ultrasonic pulses is optimized by using tissue phantoms known in the art.
In one or more of the various embodiments, treatment related data, including ultrasound imaging data, user and patient or subject feedback is captured and recorded for analysis to improve patient or subject outcomes, for clinical and experimental purposes, and for cost benefit type of analysis.
In one or more of the various embodiments, the patients or subjects are human or animal, including companion animals, livestock, or animals used in preclinical studies.
In one or more of the various embodiments, light is delivered transcranially using near infrared light known to penetrate the skin, and skull bone to stimulate photoacoustic pulses intracranially, for purposes of improving neural function, reducing neuroinflammation, for photoactivation and sonodynamic treatment of brain tumors, malignant and benign, for treatment of vascular malformations, and other pathologic conditions.
In one or more of the various embodiments, a variety of body areas and tissue targets are stimulated such as the tibial area for treatment of overactive bladder, the vagal branches in the ear to treat dysautonomia, and other central nervous system disorders, and the stellate ganglion to treat cardiac arrhythmias. Further, in one or more of the various embodiments many other body areas and target tissues can be therapeutically stimulated.
In one or more of the various embodiments, light delivered that generates photoacoustic pulses reduces abnormal nerve function causing pathologic conditions such as neuropathic pain, or decreases action potentials in nerves to reduce pathologic muscle spasms.
In one or more of the various embodiments, nerves in any body location for example on the head, can be treated to reduce and relieve neuropathic pain, conditions such as trigeminal neuralgia, occipital neuralgia, migraine, cluster, and other types of headaches, and the like.
In one or more of the various embodiments, remote photoacoustic light delivery to the upper arm is used to relieve headache pain.
In one or more of the various embodiments, infrared and/or near infrared light/focused ultrasound can be aimed from the external occiput towards the occipital horn, imparting light and/or ultrasound energy into the hippocampal region of the brain, for therapeutic stimulation purposes. Another aiming direction point is the foramen magnum, directing therapeutic light and/or ultrasound towards the brainstem.
In one or more of the various embodiments, the photoacoustic device is positioned on the external skin surface proximate to segments of the spinal cord where an injury has occurred, from trauma, tumor compression and invasion, from an infection such as an abscess, or bleeding, such as from an epidural hematoma. Treatment by the photoacoustic device can enhance tissue healing from these pathologic conditions. In one or more of the various embodiments, the photoacoustic effect and/or phototherapy effect, and/or external ultrasound is used as a means of spinal cord stimulation.
In yet one or more of the various embodiments, the photoacoustic device, which delivers focused light from a light emitting diode array as an example, generating serial ultrasound pulses, which can be optionally supplemented or augmented by an incorporated ultrasound transducer. Additionally, the focused light itself adds synergistically or additively to the biological effect which may include wound/injury healing, tissue regeneration, neuromodulation, immunomodulation including upregulation or downregulation of the immune system by way of lymph organ stimulation, including lymph nodes, the thymus gland, and the spleen. In some of the one or more of the various embodiments, the incorporated ultrasound transducer array is used to identify the target tissues and organs, prior to photoacoustic/phototherapy/ultrasound treatment.
In yet one or more of the various embodiments, photoacoustic pulses are generated by a device worn on the fingertip similar to known fingertip pulse oximeters, wherein at least one high intensity light emitting (LED) diode array optionally emitting light at 800 nm or greater, or 1000 nm or greater is used to generate at least one photoacoustic pulse on one surface of a fingertip, which an optional second LED array positioned opposite the first LED array on the opposite side of the fingertip. The light and ultrasound pulses are interrogated and analyzed, optionally using known artificial intelligence (AI) techniques, for detection, characterization, and quantification in serial fashion of pathologic conditions in the blood circulating through nailbed capillaries. These abnormal conditions can include inflammatory cells, tumor/cancer cells, free DNA, free RNA, abnormally present cytokines, biomolecules, and the like. Blood glucose levels, hemoglobin A1c and the like can also be serially monitored in this fashion.
In one or more of the various embodiments, light delivered that generates photoacoustic pulses, in combination with the focused light itself, induces futile cycling in mitochondria, which generate adenosine triphosphate in excess, which ultimately results in caloric expenditure through glucose and free fatty acid utilization. This effect is used for weight loss, preferentially reducing adipose tissue while sparing muscle tissue. When focused on the liver, pathologic fatty liver conditions can be treated including nonalcoholic fatty liver disease, steatohepatitis, and the like.
In one or more of the various embodiments, an ultrasonic contrast agent solution is injected per known protocols, which increases the ability of the external ultrasound transducer array to image the target tissue area, which increases the accuracy of the focused light delivery to the target site. In the case of treatment of benign and malignant tissues, or to close pathologic blood vessels such as vascular malformations, the ultrasonic contrast agent also serves to increase speed of onset, duration, and intensity of the ischemic effect, by way of reaction of the contrast agents with the blood vessel walls and blood constituents.
In another embodiment, the external light source is utilized to reduce adipose tissue deep to the skin by way of increasing futile cycling in the mitochondria, in concert with induction of the ischemic reperfusion effect, which leads to apoptosis of adipose cells, further synergistically acting to reduce the size of the fat deposits, painlessly, avoiding detrimental necrosis, over a period of time.
In another embodiment the photoacoustic treatment parameters and the photoacoustic imaging parameters are different, with the photoacoustic device incorporating light sources such as lasers or light emitting diodes which are tunable or emitting at different fixed wavelengths or wavebands. In this embodiment, as a non-excluding example, the light emitted is in the range of 800-830 nm, which penetrates tissue deeply, enabling treatment of internal tissues with light alone, or which activates a photosensitizer absorbing in this spectral region, such as indocyanine green. After treatment, or sandwiched between or simultaneous to treatment, longer wavelength or waveband light in the range of 1500-2000 nm is used to induce ultrasound pulses/signals in the 1-10 MHz range, detectable by an incorporated or independent ultrasound transducer.
In yet another embodiment, photoacoustic pulses, and/or external ultrasound transducer(s), and/or external light delivery from a light device array may be used to stimulate gastrointestinal peristalsis for non-limiting conditions such as gastroparesis, constipation, post operative ileus, ureteral stones, and the like.
In another embodiment, the photoacoustic pulse generating external array may be comprised of multiple arrays, positioned at more than one bodily site, enabling a focused area or region which increases the intensity of photoacoustic pulse generation as well as the volume of tissue which can be stimulated. In yet another embodiment the ultrasound images, photoacoustic pulses, and light signature from tissue can be captured, recorded, and analyzed using artificial intelligence algorithms, and transmitted using telemetry as desired. Light absorbed within the treated or imaged tissue volume can be interrogated and analyzed using Raman spectroscopy techniques as an example. In another embodiment, images, and light analysis of tissue response is utilized in real-time to adjust treatment parameters as needed. For example blood flow in the treatment volume can be analyzed using colorflow doppler, and in the case of tumor treatment, therapeutic reduction and cessation of blood flow with or without reperfusion can be monitored in real-time and adjusted as desired.
In another embodiment known and contemplated acupuncture points and/or other vital points or meridians can be stimulated with focused light and/or ultrasound external or photoacoustically generated with or without optical skin clearing.
In one or more of the various embodiments, water vapor is generated by steam generators or humidifiers, or ultrasonic humidifiers, or various nebulizers, or vaporizers, which may be portable and battery powered. Generated water vapor or steam may be heated or cooled, and droplet size can range from 0.001 μm to 100 μm, and concentration can range from 0.001-1.0 mg/m3. Droplet or aerosol penetration deep into the lungs down to the alveolar level can occur in the ranges of 0.5-10 μm. In general, water vapor generated around 0.5 μm will penetrate deeper into the lungs, whereas 10 μm size droplets will tend to deposit in the mouth and nose. Thus, the general range of aerosol/droplet size is adjusted for the anatomical target. The water vapor may be transmitted to the nose and mouth by way of flexible tubing connected to a mask worn around the mouth and nose, whereby the mask incorporates the light source generating the desired wavebands or wavelength of light, which will typically be in the red range (approximately 620-780 nm), or in the near infrared range (approximately 780-2500 nm).
Droplet/aerosol/vapor size can be varied using different generation techniques known in the art such as, but not limited to: Nebulizers-ultrasonic wave devices which utilize electronic oscillators, vibrating mesh devices which utilize a mesh or membrane to create a mist, so-called “soft mist” inhalers which employ a spring mechanism and nozzles, and various types of jet nebulizers which use a compressed gas; and Humidifiers-Various devices utilize ultrasound to vibrate water into droplets, spray nozzles using compressed air/water, whereby the droplet/vapor size is varied depending on pressure and nozzle configuration, and steam generators using heat to boil water.
In another embodiment, various excipients or additives are included in the steam or vapor, such as menthol, various known bronchodilators, steroids, antibiotics and antivirals, salt solutions, nitric oxide, and the like.
In another embodiment, photoacoustic impulses optionally combined with external ultrasound transduction delivering ultrasound capable of compressing the dural sac, and/or compressing the venous system transiently exerts pressure to displace cerebrospinal fluid and reduce cerebral venous drainage. The temporary compression serves to prevent or reduce harmful brain movement and deformation within the cranium in the event of a collision, impact, or abnormal injurious head motion. The impending harmful collision, impact, or head movement is detected by a sensing device array which activates the compression device just prior to the harmful event, and therefore prevents or reduces brain injury caused by brain impact with the inner cranial structures.
Traumatic brain injury and concussion are very common adverse events, with millions of patients affected per year globally. Despite improvements in external head protection in the form of helmet design and function which mainly serves to protect the skin and skull, little has been done to prevent or reduce internal brain impact, harmful rotational motion, linear brain movement, and various types of uncontrolled brain stretch and deformation within the cranium resulting in brain cell, axonal injury, and vascular insults which contribute to traumatic brain injury, prevention of which is one of the intents of the one or more of the various embodiments. A large number of adverse events can occur after an impact to, or sudden acceleration or deceleration of the head with or without intracranial brain recoil including brain hemorrhage, coup and contra-coup contusions, compression from epidural and subdural hematoma, axonal injuries, and other brain cellular injury due to tensile, stretch, rotational, compressive, and shear forces, which may be prevented or reduced in severity by the one or more of the various embodiments. After initial injury, a large number of adverse, highly troublesome and difficult to treat secondary events have also been described including metabolic, neurotransmitter, and blood flow and vascular abnormalities, brain edema, hydrocephalus, pathologic brain shifts, increased intracranial pressure, and numerous other deleterious neurologic sequela and psychiatric disturbances, and increased dementia risk including the relatively recently recognized chronic traumatic encephalopathy condition.
The human brain is surrounded by cerebrospinal fluid contained within a dural sac, which provides support and cushioning for the brain within the cranium. A blow to the head, head collision, or a sudden head deceleration, acceleration, rotation, and the like can cause the brain to shift within the cranial vault, transiently displacing the surrounding cerebrospinal fluid which allows the brain to harmfully impact the inner dural surface which abuts the inner table of skull, as well as other fixed intracranial structures such as the falx or tentorium. The surface and the interior of the brain can suffer from contusions, hemorrhage, swelling and edema, and other forms of physical injury as well as a plethora of other microscopic and biochemical pathologic processes. Additionally, the soft brain tissue can internally deform, rotate, compress, and stretch at the same time, adding to the injury process, which includes shear and many other forms of damage to intracranial cell bodies, axons, and vascular structures.
The use of a neck collar (Myer 2016) has been described which applies pressure on a continuous basis during use, to the jugular venous system ostensibly to provide a measure of brain protection by stiffening the brain tissue and reducing compliance, but has the major potential drawbacks of: 1) Potentially compressing the carotid artery system in addition to the jugular vein system which would be very harmful to normal brain function, 2) Limiting neck mobility which greatly reduces practicality for users engaged in any sort of activity where head motion and change in visual field direction is required, 3) Discomfort from the constant neck compression required when wearing a tight, compressive neck collar, 4) Potential for neck collar dislodgement or rotation, leading to misplaced pressure on the neck surface which could lead to device malfunction and airway compromise if it applies pressure to the trachea for example, and 5) Continuous, sustained reduction of cerebral venous outflow during use which could induce brain vascular congestion causing headaches, visual problems, and a wide variety of other neurologic deficits and problems which could even include cerebral hemorrhage, if the collar is worn on a continuous basis, or if it fits too tightly around the neck.
Airbag devices worn by a user may have been described in the prior art that are positioned around the chest or head and are designed and intended to reduce injury to the user by acting as a cushion. Used in this manner, the airbag devices are in intended to reduce the impact force of a collision and reduce bodily deformation and compression, and reduce sudden head deceleration, which is an entirely different and opposite mechanism of action enabled by the one or more of the various embodiments, which teaches away from prior art, by inducing and enabling torso and pelvic compression, whose intent and purpose is to protect the brain internally by preventing or reducing brain motion relative to skull motion, and to simultaneously stiffen brain tissue, reduce brain tissue compliance, and therefore reduce brain compression, stretching, and deformation, actions not enabled by the cited patents. Some of the prior art describes an intracranial balloon apparatus which can compress the brain, which is in opposition to the one or more of the various embodiments, which teaches away from brain compression using an entirely external system. Also, compression devices for cardiopulmonary resuscitation (CPR) may have been described in the prior art but they differ from the one or more of the various embodiments, in that they are devices not suitable to be worn during activity, are specifically designed and intended to compress the heart repeatedly, and increase brain blood flow during chest compression and increase venous drainage from the brain during chest decompression.
Other prior art references may have described an abdominal compression device intended to increase blood pressure for patients with orthostatic hypotension, using a pump to inflate a bladder, which is a slower filling process which would not enable brain protection due to compression delay, compared to the one or more of the various embodiments which utilizes much faster compressed gas and/or propellant to very rapidly fill a bag, balloon, or bladder just prior to a head impact or related brain injury event.
Also, in addition to incorrect compression activation timing and duration, the prior art does not make obvious or anticipate enabling testing and imaging to optimize compression area, volume, location, depth, speed, and duration, which would enable brain protection intended in the one or more of the various embodiments. Instead, the prior art that tends to treat hypotension due to hemodialysis and related critical care situations with the use of prolonged abdominal compression which may be manually performed, in combination with fluid infusion.
The one or more of the various embodiments detail apparatuses and methods of temporarily displacing cerebrospinal fluid and increasing the intracranial cerebrospinal fluid pressure which can prevent or reduce displacement and shifting of cerebrospinal fluid at a time point just prior to a cranial impact, blow or sudden acceleration, deceleration, or head rotation, thus stabilizing and maintaining the normal brain position within the skull, with concomitant transient stiffening of brain tissue just prior to the likely injurious event, thereby preventing or reducing brain tissue injury from abnormal and pathologic internal brain motion and deformation.
Another aspect of the one or more of the various embodiments is intended to mitigate against blast injury to the brain, which may occur in the combat/military setting. Research has demonstrated that an initial overpressure wave occurs with blasts, such as occurs with bomb detonations, and that the overpressure wave can induce a rapid rise in intracranial pressure. The one or more of the various embodiments enables transient reduction of intracranial pressure, which may mitigate or reduce brain injury from the overpressure wave induced intracranial pressure spike. Many individuals caught in blast situations can experience secondary impact events which are also addressed by the one or more of the various embodiments.
Many different embodiments are possible, and the various embodiments are capable of modification and alteration in many and various respects, all without departing from the scope of the claims. Accordingly, the embodiments, drawings. and descriptions herein are in no way meant to be regarded, or construed, as restrictive.
The one or more of the various embodiments prevent or reduce harmful brain movement and deformation from what would be an otherwise injurious head impact, collision, sudden acceleration, deceleration, or rotational brain movements. Protective devices and equipment have been described and developed that seek to protect the head, by utilizing cushioning external to the head which reduces deceleration. Unfortunately, these products mainly reduce scalp injuries and skull fractures, and the brain can still move abnormally, collide with the inner skull surface lining, and deform harmfully within intracranial space. Numerous studies have demonstrated the inability of helmets and external cushioning devices to prevent concussions and prevent traumatic brain injuries, and in fact, the more forceful the blow and impact to the head, the more likely that a concussion or traumatic brain injury will occur, despite the use of a helmet. For example, in the National Football League of the US, hundreds of new concussions are documented to occur each season, despite the use of state of the art helmets, and the cumulative brain injury effects have been shown to result in chronic traumatic encephalopathy, a devastating and severe type of dementia. The primary reason for the inability of helmets to prevent concussions is that helmets and related devices developed to date cannot prevent the internal brain movement that continues to occur relative to the inner skull, and within the accelerating or decelerating cranial vault, due to the fact that the brain remains in motion within the skull due to the separation of the brain from the skull by cerebrospinal fluid, such that even if the head is decelerating after an impact, blow, or whiplash, injurious brain movement occurs. The dyssynchronous movement of the brain relative to the skull causes uncontrolled brain tissue rotational motion, and forward and backward brain movement, with abnormal tissue shifting and compression, causing the brain and brain stem to rotate, stretch, and otherwise deform harmfully, as well as collide with the inner dural skull lining abutting the rigid inner skull surface and recoil, sometimes multiple times.
In contrast, the one or more of the various embodiments comprise apparatuses and methodologies which are capable of reducing and even preventing internal abnormal and harmful brain motion and deformation entirely. The one or more of the various embodiments and methodology enables brain protection by inducing rapid and transient intracranial cerebrospinal fluid displacement and pressure increase, just prior to the potentially injurious event, resulting in maintenance of cerebrospinal fluid volume, distribution, and compartment shape within the cranial vault, thus in essence cancelling out the effect of the differential brain-cerebrospinal fluid density which has been demonstrated to be approximately 1.046 for brain with cerebrospinal fluid density being approximately 1.00 (Babbs 2004). In other words, if the effective density of cerebrospinal fluid were to approximate that of the brain, there would essentially be no acceleration of the brain relative to the cerebrospinal fluid.
The one or more of the various embodiments may be designed to rapidly shift cerebrospinal fluid within the spinal dural sac in the lumbar and/or upper cervical and/or foramen magnum area/and or the cerebral venous drainage pathway anywhere from the intracranial compartment to the pelvic compartment or the spinal compartment toward the closed intracranial compartment which can result in a rapid, transient increase in intracranial cerebrospinal fluid pressure, which can in turn reduce brain motion due to head impact, sudden deceleration or acceleration, or rotation.
Further, the one or more of the various embodiments may induce a sudden rise in CSF pressure enabled by at least one external ultrasound generating device, which compresses for example, the lumbosacral thecal sac, which has been demonstrated to be a mechanism which can shunt cerebrospinal fluid from the spinal subarachnoid space toward the cranial cerebrospinal fluid compartment, increasing the intracranial fluid pressure which would tend to stabilize and fix the brain in its normal resting position relative to the inner table of the skull. Thus, the external cerebrospinal fluid cushion surrounding the brain and the internal intraventricular spaces which are also filled with cerebrospinal fluid are maintained by way of increased fluid pressure. This process reduces or precludes the movement of the brain towards the inner table of the skull that occurs when sudden head deceleration or acceleration occurs from collisions, crashes, and impacts, all of which are known to cause brain injuries, including coup and contracoup injuries and intracranial bleeding. Prevention or reduction of initial brain movement can also reduce or dampen secondary brain recoil, which is also injurious. Also, abnormal and harmful brain rotation and brainstem injury and other types of brain deformation may be prevented or lessened as well. The sudden shift of cerebrospinal fluid intracranially raises the intracranial pressure only transiently if the intra-abdominal CSF pressure increase is very transient as well, a process which is safe and well tolerated and enabled by the one or more of the various embodiments' design and function.
In addition to movement of cerebrospinal fluid towards the intracranial compartment, another key brain protection feature of the one or more of the various embodiments is that a sudden and transient increase in intra-abdominal pressure which is enabled, for example by ultrasound transmission affecting the venous compartment, which is normally very low, sub-atmospheric to less then 7 mmHg, with optional increased intra-pelvic pressure via the venous system in the pelvis, causes the diaphragm to be displaced upwards, which in turn increases intrathoracic pressure. This causes an increase in central venous pressure compressing the inferior vena cava resulting in reduced venous return to the heart via the jugular veins which in turn transiently reduces venous return from the brain. A temporary reduction of venous outflow in absence of decreased arterial inflow enabled by the one or more of the various embodiments and this process also transiently increases the internal stiffness of brain tissue, a phenomenon which can reduce the tendency for harmful brain deformation and movement to occur from blows to head, blast injuries, or sudden head deceleration, acceleration, and rotation. The brain is one of the softest solid organs, and prevention of internal and superficial brain deformation or sloshing can prevent direct brain cellular injury and damage, axonal stretching, shearing, and other similar adverse phenomena. Thus, the one or more of the various embodiments provides for brain protection from head trauma by way of at least two mechanisms, namely a rapid and transient increase in intracranial cerebrospinal fluid pressure which maintains normal brain position and reduces or precludes uncontrolled intracranial movement, and a transient reduction in venous outflow due to distal venous compression from the jugular venous system which temporarily stiffens the brain, reducing brain tissue compliance, a process which has been demonstrated to be a protective mechanism due to reduced harmful brain tissue rotation, shearing, stretching, compression, and the like.
The rapid, transient, and non-harmful increase in intra-abdominal pressure with an optional increase in pelvic pressure in the one or more of the various embodiments may also be enabled by the use of a specially designed abdominal binder, corset, or belt which encircles the abdomen at least partially, and may also be held in proper position by use of at least one optional shoulder strap. The binder, belt, or corset in one embodiment is entirely or partially rigid or entirely or partially flexible. In one embodiment the rigid segment of the belt, binder, or corset is fitted to the user's back, while the flexible segment conforms to the anterior abdominal wall. The flexible segment may be comprised of a polymeric substance such as nylon, or a metallic substance and construct such as a chain mail configuration, which allows for user torso movement, but is not stretchable, and thus is designed to permit a sudden, controlled, transient compressive force against the abdominal wall and optionally the pelvis, for example using an expanding balloon incorporated into the anterior or anterolateral aspect of the device, which temporarily compresses the abdominal and optionally the pelvic cavity, resulting in a transient, rapid shunting of lumbosacral spinal cerebrospinal fluid into the intracranial subarachnoid and intraventricular space. The polymeric balloon can be rapidly expanded using compressed gas contained in a small cylinder or similar container such as a CO2 cartridge, or the expanding gas within the balloon can be rapidly generated chemically as occurs in automobile crash protection airbags. The gas is rapidly vented through pre-existing holes in the balloon such as occurs after automobile airbag inflation.
In one or more of the various embodiments the structure surrounding the abdomen may be entirely rigid which also allows for all of the anterior compressive force to be transmitted against the abdominal wall. This construct also optionally incorporates a protective outer shell, which shields the device from direct impacts, which could damage or prematurely trigger the compressive device. In yet another embodiment a belt-like structure tightens rapidly and reversibly, which temporarily constricts the abdominal wall, raising the intra-abdominal pressure transiently. This belt movement which transiently constricts and compresses the abdomen can be accomplished using a high speed motor incorporated into a winding mechanism which tightens the belt transiently by rolling it into a cylindrical configuration, and allows for rapid active or passive release of the tightened belt construct as well, which decompresses the abdomen. In all device compression embodiments, the rapid but reversible abdominal and optional pelvic compression only occurs when imminent impact or blast is sensed using accelerometers, ultrasonic, electromagnetic, or infrared movement detectors, and/or pressure detectors, which may be all included in the one or more of the various embodiments. In other words, the compression device may be activated just prior to the impact, collision, or other harmful head movement event. The compressive force on the abdomen and optionally the pelvis occurs at an interval of several seconds or less before the harmful head injury event, allowing for enough time for lumbar cerebrospinal fluid shift towards the intracranial compartment and brain tissue stiffening from reduced jugular venous drainage to occur.
The lumbar cerebrospinal fluid volume and timing of shift toward the intracranial compartment and subsequent movement extracranially back into the lower spinal compartment can measured and ascertained using spinal MRI or myelography (Hogan 1996). These types of measurements can be used to optimize the speed, degree, and duration of abdominal and optional pelvic pressure needed to shift an adequate volume of cerebrospinal fluid which generates an adequate increase in cerebrospinal fluid pressure. Additionally, cerebrospinal fluid motion can be optionally assessed using the time-spatial inversion pulse (Time-SLIP) method which makes it possible to directly visualize the flow of cerebrospinal fluid using MRI (Yamada 2014).
The one or more of the various embodiments may contemplate that the variables and parameters of device induced abdominal compression can be optimized by direct measurements and visualization of cerebrospinal fluid movement from the thecal sac towards the intracranial space in clinical tests which may include imaging of motion and position of the brain, spinal cord, and cerebrospinal fluid. The variables and parameters that can be tested include abdominal venous and/or CSF compartment compression timing, speed, pressure, duration, and optimal location of the force applied to the abdomen. Likewise, the resolution parameters of compression can be similarly optimized. Injury to the abdomen is prevented due to limitation of the compressive force, degree of compression, and the transient nature of the compression, as well as the use of multiple focused ultrasound generation devices, which reduces the force imparted in one particular pathway. In addition, after determination of optimal compression parameters, the volume, shape, and surface area of the device component that accomplishes the bodily compression is determined, and the design and manufacture of the device component limits the expansion and degree of compression to further insure safety. In another embodiment, the compressive device incorporates a pressure sensor with automatically adjusts and regulates the abdominal compressive force to remain within a certain predetermined limit or to reach a certain predetermined degree of pressure.
The degree of brain stiffness induced by abdominal and optional pelvic compression which resists abnormal harmful brain rotation, whiplash movements, and deformation can be assessed using MRI elastography (Hiscox, 2016). The one or more of the various embodiments may contemplate that the intra-abdominal compression parameters sufficient to result in optimal brain protection can be ascertained by performing MRI elastography, by comparing brain stiffness with and without intra-abdominal compression, in an individual user, or in groups of users. In addition, diffusion tensor MRI and other techniques have been used as a surrogate measure of brain injury in before and after studies testing various venous cerebral drainage obstruction interventions (Myer et al 2016). Mathematical and computerized simulations of concussion and brain injuries, as well as phantoms and crash dummies, and other in vivo and in vitro models are also known in the art as means of testing brain protection interventions as well, and can also be optionally utilized to evaluate and optimize the design and compression parameters of the one or more of the various embodiments (Martin 2016, Holliday 2016, Wojnarowicz 2017, Ng 2017, Post 2017, Li 2015).
The abdominal binder, belt, or corset compression device is custom fitted to the user or is adjustable in diameter and tightness for example using a buckle, rachet, or clasp as is commonly employed in pants belt to insure maximal comfort and to minimize interference of normal lumbar and lower thoracic spinal movement. The tightness of the compression device can be optimized using an incorporated pressure sensor which communicates to the user the optimal degree of resting tightness. The binder, belt, or corset is optionally comprised of breathable material such as vapor permeable nylon or a perforated more rigid shield to reduce heat buildup and sweating on the abdominal surface, and may also utilize a flexible but inelastic material which deforms with abdominal movement but buttresses the expanding or abdominal pressure component of the device which leads to abdominal compression and a desired rise in intra-abdominal pressure. The mechanism that induces transient abdominal and optional pelvic compression can further be comprised of either a compressive polymeric bladder, balloon, or bag that is reversibly filled with air or a fluid using a high speed pump, compressor, a cylinder or container of compressed inert gas such as CO2·nitrogen, or argon gas, or a cinching belt-like mechanism whereby a band is rapidly tightened then loosened, and in yet another embodiment utilize at least one spring contacting a rigid, contoured plate in contact with the anterior abdominal wall which is maintained in compression then rapidly allowed to extend and retract to transiently compress the abdomen. In all cases the increase and decrease in intra-abdominal pressure is such that abdominal organ injury is avoided.
The range of transiently increased intra-abdominal pressure induced by the one or more of the various embodiments may be between the range of 1 mmHg to 50 mmHg, and is adjustable and customized for the user's size, weight, anatomy, and expected degree of required cerebrospinal fluid displacement. The intra-abdominal compression process is very rapid and occurs over a period of 1 millisecond (ms) to 1 second (sec) followed by immediate decompression occurring over a period of 1 ms to 1 sec. Optionally, the compression can be maintained for a period of 1 ms to 2 sec followed immediately by rapid decompression over 1 ms to 1 sec. Also, a pressure sensor is optionally incorporated into the abdominal compression device which senses and serves to regulate the desired compressive force, prior to, and during activation of the compressive device, and is optionally adjustable to accommodate differences in abdominal anatomy, size, shape, and volume. If desired, the abdominal compressive force is adjusted for the individual user in advance of activation, allowing for differences in abdominal anatomy, shape, size, volume, and desired degree of compression. For example, the degree, speed, and duration of abdominal compression required for brain protection in a soccer player who heads the ball, or a football player who may suffer a concussion, and may be different from a recreational bicyclist versus a user who rides a high speed motorcycle.
Correct and accurate activation of the abdominal compression and optional pelvic compression device and/or at least one ultrasound generating external device is enabled by use of a helmet, headband, or similar flexible or adjustable headgear, incorporating at least one or an array of pressure sensors, impending impact sensors, and/or motion sensors which may utilize ultrasound, infrared light from light emitting diodes, radar, lidar, or be electromagnetic, and/or at least one or an array of accelerometers and/or gyroscopes, and/or GPS or global positioning system locating devices, which detect impeding harmful head impacts, collisions, brain and head rotation, acceleration and deceleration events, with the events relayed to the compression device leading to activation of the brain protection mechanism just prior to the potentially harmful event. Pressure sensors, and/or accelerometers, and/or gyroscopes, and/or GPS, and/or ultrasonic, and/or infrared, and/or electromagnetic motion detectors collectively known as sensing devices may also be worn on the neck, torso, located in a mouthpiece, or on other body locations or even separate from the body on a cycle, vehicle, or other conveyance to detect impending or potential sudden head impact, body and head deceleration or acceleration.
Pressure sensors and/or accelerometers and/or gyroscopes and other collision and motion detector devices may also be incorporated into an object or conveyance utilized by the user, which may or may not be directly in physical contact with the user, with activation of the abdominal compression device accomplished by way of a directly wired or wireless connection, with data integration optionally occurring by way of a central processing unit or CPU which controls the activation of the compression device.
In a similar fashion, machine vision, imaging, and machine learning technologies and devices, radar, and the similar detection apparatuses such as those used in moving vehicles (Castano 2017, Navarro 2016, Muller 2017), can be used in a similar fashion to ultrasonic collision warning sensors or infrared or electromagnetically based collision or movement detection technologies and can be employed in the one or more of the various embodiments and are optional means of impending collision and impact sensing as well. Other collision detection systems that are optionally a part of the one or more of the various embodiments include radar or laser collision detection devices. In all embodiments where collision, impact, or abnormal head movement is detected, the sensing devices are powered by disposable or rechargeable batteries incorporated into the devices. One embodiment accomplishes rapid abdominal wall compression by way of at least one flexible, expandable bladder, balloon, or bag mounted on a rigid or flexible but not stretchable polymeric band which is connected to a compressed gas container or propellant container which rapidly produces expanding gas, or transfers compressed gas rapidly in 100 milliseconds or less to the bladder or balloon which compresses the abdomen. The compressed gas is preferably inert, non-toxic, and the propellant is preferably non-toxic, and is contained within at least one polymeric or metallic container incorporated into the device.
In another embodiment the propellant is contained within the expandable balloon, bladder, or bag. Just prior to the initiation of head contact, at least one pressure sensor and/or accelerometer or other detection device is activated and causes rapid release of the gas or generation of expanding gas into or within the bladder or balloon which causes rapid external abdominal wall compression, inducing a sudden rise in intra-abdominal pressure with resultant temporary shift of cerebrospinal fluid towards the intracranial subarachnoid and ventricular space, and transient reduction of cerebral venous return. These processes result in stabilization of the brain relative to the inner table of the skull by preventing or reducing cerebrospinal fluid shifts, and increase brain stiffness which reduces or prevents brain cell damage and axonal stretch injury and disruption by reducing or preventing brain deformation, rotation, and sloshing. The expanded gas is rapidly vented though openings in the bladder or balloon into the ambient air, as in a vehicular airbag, or by way of a gas release valve as is utilized in some airbag vests, which results in rapid return of the intra-abdominal pressure, intracranial pressure, cerebral blood flow, and cerebrospinal fluid dynamics back to normal range and location, as the impact force is dissipated or the harmful event passes.
In another embodiment, more than one gas expansion event is enabled in rapid succession by use of multiple contained gas or propellant devices, to address the need for more prolonged brain protection in the event of detection of multiple successive potentially injurious events, or where secondary brain recoil requires prevention.
In another embodiment, at least one of the bladder or balloon is filled with compressed ambient air contained in at least one cylindrical container, and at least one pump enabling refilling of at least one cylindrical container is part of the device system enabling prompt reuse. This embodiment could be used in activities or sports such as football, soccer, boxing, skiing, or any other sport, competition, or activity including martial arts or combat where brain injuries are known to occur, where the device could be reset between plays or events, as required or when convenient. The air pump can be employed manually, or in an automated mode after brain protective release of the gas into the bladder or balloon ensemble. A variant of this embodiment would utilize at least one compressed gas container which is single use, for instances when refilling is not practical, for example during a combat situation. Incorporating multiple compressed gas containers which may optionally be cylindrical in shape, into the compression device allows for multiple abdominal compression device activation sequences without the need to refill between use.
In another embodiment the abdominal compression mechanical or ultrasound device is incorporated into body armor, on the anterior inner surface of the armor which abuts the abdomen, thus shielding the device from projectile or blast damage and accidental inappropriate device activation. This embodiment is intended for use by individuals who may be more likely to be exposed to such hazards, such as military or law enforcement personnel. Further, in a related embodiment, the abdominal compression device is incorporated into an article of clothing abutting the abdominal area, with the compression device in contact with the anterior abdominal wall. Another variant of the abdominal compression device is protected on its external aspect by a rigid polymeric shell, or sufficient dense padding which precludes inadvertent device activation or damage to the device by a blow to the abdominal region, that may occur while playing football as an example.
In yet another embodiment the abdominal or ultrasound compression device is incorporated into a seatbelt or lap belt such as would be commonly found in a vehicle such as an automobile, truck, airplane, or related conveyance. The abdominal or ultrasound compression device is correctly positioned over the user's abdominal region when the seatbelt or lap belt is fastened, and reduces risk of brain injury from head impacts or whiplash due to vehicular collisions or sudden braking or stops. This embodiment can be utilized along with a standard vehicular airbag protection system, and the abdominal or ultrasound compression device can be optionally activated at the same time as the airbag. Further, in another related embodiment the expanding gas which inflates the airbag also inflates the abdominal compression construct or activates the ultrasound device which is incorporated into the seatbelt apparatus.
In another embodiment a high speed flat motor rapidly winds a strap mechanism which transiently squeezes the abdomen, rapidly increasing the intra-abdominal pressure, followed by immediate release of the mechanism which rapidly relieves the pressure. In yet another embodiment, a roller which conforms to, and exerts pressure on the anterior pelvis or lower abdomen, when activated moves rapidly by rotation around the long roller axis in a caudal to cephalad direction, essentially milking the cerebrospinal fluid in the lumbar dural sac in an upward direction, increasing the intracranial cerebrospinal fluid pressure and brain stiffness transiently.
In another embodiment, abdominal and optional pelvic compression can also occur from a combination of mechanical compression by pressure from an expanding bag, balloon, or bladder, together with a squeezing action on the abdomen caused by a transient tightening band or belt-like apparatus around the abdomen. In yet another embodiment, compression of the torso and pelvis can be accomplished by an expanding bag, balloon, or bladder which abuts a rigid or semi-rigid polymeric plate which conforms to, and in in contact with the anterior or anterolateral pelvis, abdomen or thorax, spreading the compression force over a broader area than would be encompassed by the bag, balloon, or bladder alone.
In another embodiment, a pressure sensor incorporated into the compression apparatus indicates to the user the optimal pre-activation degree of tightness and snugness of fit of the abdominal, pelvic, and thoracic compression devices. Furthermore, the pressure sensor can also be utilized to regulate and adjust the degree of abdominal, pelvic, and thoracic compression that occurs with device activation, to optimize cerebrospinal fluid displacement and brain stiffening, as well as to prevent injury to the abdomen, pelvis, or thorax by excessive compressive force.
Collision, impact, and injurious movement prediction algorithms based on motion detection of the user's head and/or body, or by object, projectile, or pressure detection in the surrounding environment, can optionally be a part of the one or more of the various embodiments as a means of enabling correct timing of device activation and degree of abdominal with optional pelvic compression that leads to effective cerebral protection. Collision, impact, and movement related data from the sensing devices can be collected and integrated by a CPU or central processing unit which is optionally a part of the one or more of the various embodiments, which enables correct timing of abdominal and optional pelvic compression just prior to the potentially injurious event. Another embodiment utilizes a lanyard or cable which connects the user to conveyance such as a bicycle, a motorcycle, or an animal such as a horse or donkey such that the compression device is triggered in the event of a sudden separation or fall of the user from the means of conveyance.
In yet another embodiment, a multifaceted warning system is enabled by multiple sensing device arrays which communicate wirelessly between a primary user defined as an individual about to experience a harmful brain injury event, a secondary user who may be a contributor to that event which can cause impending brain injury affecting the primary user, a moveable or moving object in the immediate environment of the primary user, and/or a fixed non-moveable location, in any combination or permutation. Examples include two users engaging in American football, where a primary user wearing a sensing device array carrying a football is about to be tackled by a secondary user also wearing a sensing device array, and where the sensing device arrays from each user relays data to the primary user's CPU that a harmful impact to the head and brain of the primary user is imminent. The primary user's CPU integrates the impending impact and collision data and determines that brain harm is imminent and activates the primary user's compression device. Further, in a related embodiment, the football field itself can also be equipped with a sensing device array which monitors impending collisions and contributes data regarding impending brain harming collision, impact, or abnormal uncontrolled head movement such as whiplash type movements. The stationary sensing device array serves to relay additional probable collision and impact data which contributes to brain injury prevention or reduction in a complex multi-user environment.
Also, in another somewhat similar sports environment, soccer players who may head the soccer ball may be equipped with sensing devices worn by each player. The soccer ball itself also incorporates a sensing array which communicates with the user sensing device enabling the CPU worn by the user to determine when the compression device should be activated to prevent or reduce harmful brain motion and deformation resulting from head impact with the soccer ball. In addition to events leading to concussions and traumatic brain injuries, impending subconcussive events which have been defined as events similar to those which give rise to an overt concussion but with less force and acceleration/deceleration (Slobounov 2017) capable of causing cumulative brain harm, can occur hundreds or thousands of times over a single competitive season, for example in American football, and can be detected and the compression device activated appropriately multiple times in yet another embodiment.
In another embodiment, thoracic compression may be 1 millisecond to 1 second after abdominal compression in a sequenced, predetermined, pre-programmed fashion, optionally regulated by an incorporated CPU. This embodiment maintains the brain protective cerebrospinal fluid shift from the lumbar compartment towards the intracranial compartment, as well as reducing venous return from the brain inferiorly, thus reducing brain compliance which is also brain protective. Thoracic compression is enabled by utilizing the same variety of apparatus and methods as described for abdominal compression. In one embodiment the thoracic compression is accomplished using a bag, balloon, or bladder which exerts transient compression against the sternum when inflated by compressed gas or a propellant substance. The sternal compression depth is between 1 to 8 cm. The range of transiently increased intra-thoracic pressure induced by the one or more of the various embodiments is between the range of 1 mmHg to 50 mmHg, and is adjustable and customized for the user's size, weight, anatomy, and expected degree of maintenance of required cerebrospinal fluid displacement. The intra-thoracic compression process is very rapid and occurs over a period of 1 millisecond (ms) to 1 second (sec) followed by immediate decompression occurring over a period of 1 ms to 1 sec, by way of a gas release valve or openings in the bag, balloon, or bladder. Optionally, the compression can be maintained for a period of 1 ms to 2 sec followed immediately by rapid decompression over 1 ms to 1 sec. Also, a pressure sensor is optionally incorporated into the thoracic compression device which senses and serves to regulate the desired compressive force, and is optionally adjustable to accommodate differences in thoracic anatomy, size, shape, and volume.
In one embodiment, the abdominal and optional pelvic and thoracic compression or ultrasound device is integrated into a vest, shirt, or protective garment such as body armor, which encompasses the thorax and abdomen. The garment can be flexible but not elastic, which allows for user movement such as torso flexion, extension, lateral bending, and rotation, along with effective abdominal and thoracic compression.
In another embodiment a high speed flat motor rapidly winds a strap mechanism which transiently squeezes the thorax, rapidly increasing the intra-thoracic pressure, followed by immediate release of the mechanism which rapidly relieves the pressure.
In yet another embodiment the thoracic compression or ultrasound device is incorporated into a shoulder belt or harness such as would be commonly found in a vehicle such as an automobile or a truck, or in a related conveyance. A combination of a seat belt and torso harness such as may be found in a baby or child car seat restraint system can also incorporate compression or ultrasound devices which are triggered in advance of a collision or a sudden stop to provide brain protection, especially useful in prevention or reduction of brain injury due to whiplash types of head motion.
In another embodiment the various embodiments is utilized in combination with other protective devices and equipment that are intended to act as a cushion during a collision, for example in combination with an airbag vest and/or an airbag helmet, or in combination with vehicular mounted airbags. The one or more of the various embodiments can also be used in combination with any head trauma protective gear, such as helmets, protective facemasks, neck collars and braces, protective garments, body armor, external cushion airbags, or any sort of protective gear which is intended to reduce harmful bodily impact forces and head deceleration.
In yet another embodiment, a compact, self contained miniature sensing device array and CPU incorporates a small portable battery power supply and is comprised of at least one of a magnetic sensor device (Wu 2017), radar device (Moses 2011), inertial sensor (accelerometer, gyroscope), pressure sensor such as a piezoelectric sensing device, infrared and ultrasound detectors (Gabay 2016), and related technologies that are used along with a CPU which captures, integrates data, and activates at least one compression device. The self-contained system can be manufactured in quantity and adapted for multiple environments, uses, and incorporated into head gear, garments, belts, various objects such as sports equipment such as soccer balls, conveyances such as bicycles, safety equipment such as seatbelts, and the like.
In another embodiment, brain injury from blasts can be mitigated by a device induced drop in intracranial pressure and simultaneous increase in venous return from the brain towards the heart, which is transient. This process is enabled by abdominal and optional pelvic decompression, by way of a suction device affixed to the abdomen and optionally the pelvis. The relatively low profile suction device is optionally dome shaped, and a vacuum can be rapidly generated within its interior using at least one vacuum cylinder or container, or at least one ultra high speed pump. The suction device is affixed to the abdominal wall and optionally the pelvic wall anteriorly, and is triggered upon detection of a blast wave. Suction on the anterior body wall reduces the intra-abdominal pressure suddenly and transiently. This action mitigates the sudden increase in intracranial pressure caused by the action of the overpressure blast wave on the brain. Cerebral stiffness is also simultaneously and transiently decreased, which can add a measure of brain protection from the blast. This embodiment may also incorporate a compression device, which then raises the intracranial pressure and decreased brain tissue compliance transiently, which is protective against brain impact and/or deformation which also commonly occurs in blast situations, as a secondary phenomenon.
In one embodiment, an ultrasonic pressure wave is transiently generated by at least one external ultrasonic transducer/and or at least one external photoacoustic device, aimed at the venous drainage system in the pelvis/and or abdomen, and/or at the lumbosacral dural sac, leading to a transient compression of said structures. Compression of said structures over periods ranging from 1 to 100 milliseconds to 1000 milliseconds to 5000 milliseconds leads to stiffening of the CSF column which impedes or prevents brain motion from abnormal harmful movement. In yet another embodiment, the ultrasonic pressure wave is sequentially generated starting in the lumbosacral region and moving superiorly towards the abdomen and then optionally to the thorax, resulting in a more prolonged compression of the CSF column. Ultrasonic pulses can range from at least one or more cycles of less than 2 Hertz (Hz) to between 2 and 100 Hz, to 100 to 1000 Hz, from 1000 Hz to 500 kHz with high peak pressures ranging from 1 to 30 Megapascal (MPa), to 30 to 200 MPa, or more, with at least one pulse lasting from 1 microsecond to 500 microseconds, to one second. In various cases, experiments using known in vivo and in vitro brain movement and brain injury models and experiments may be used to optimize the parameters and internal body targets.
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Optimization of the one or more of the various embodiments by design, function, operation, other characteristics, and device compression parameters that enable brain protection against trauma is enabled by use of noninvasive MRI imaging and analysis of cerebrospinal fluid movement, brain movement, brain deformation, and MRI elastography determined brain stiffness caused by device induced compression of the pelvis, and/or abdomen, and/or thorax (Bayly 2005, Feng 2010, Hiscox 2016). Graded, controlled compression of the pelvis, abdomen, and thorax using various weights (Citerio 2001, Koral 2010), or other pressure applying mechanical apparatuses of various size and dimensions is used to cause and determine the optimal degree, rate, and volume of cerebrospinal fluid movement and the degree, and time course of brain stiffening which will provide optimal brain protection, when the head and body are in varying positions, anticipating various scenarios and situations.
In addition, the optimal anterolateral torso and pelvic location, direction, volume, and surface area of compression can be determined based on experimentally optimized cerebrospinal fluid movement and brain stiffening determinations. Also, the optimal sequence of compression, which may for example start in the pelvic region and progress in a cephalad direction can be determined. One or more of the various embodiments may also anticipate that different individual users with different anatomical characteristics and who are likely to experience different probable impact, collision, and head movement events will require different compression parameters to optimize brain protection. In general, the least amount and degree of compression that accomplishes the desired cerebrospinal fluid movement and reduction in brain compliance can be ascertained using MRI and other related or similar tests. In a similar fashion, controlled safe experimental head movement in human volunteers which simulates collision and impact scenarios with the head in flexion, /or extension, and/or rotation is evaluated with MRI imaging and elastography can be used to determine optimal compression parameters (Bayly 2005, Hiscox 2016, Ji 2004, Zhu 2003) to prevent or minimize abnormal, harmful brain movement and brain tissue deformation. Device compression parameters are optimized by including testing variables such as torso pressure onset timing, rate of compression increase and decrease, duration of peak pressure, and the torso volume, area, and location of compression that lead to and correlate with optimal protective timing, duration, and degree of cerebrospinal fluid displacement, along with optimal brain stiffening parameters. All of this data is used to determine the compression parameters that optimize brain protection, and to insure protection of the torso and pelvis against excessive compressive force which could cause inadvertent injury.
The belt, abdominal binder, corset, or thoracic located compressor can be adjusted to fit the user utilizing various buckles, a Velcro fastener, or lacing, or other types of fasteners and clasping mechanisms or be pre-fitted to the user. Adjustable shoulder straps and/or leg loops that help to secure the compression apparatus to the correct position on the torso are also an optional feature of the one or more of the various embodiments. The compression device can also be incorporated into clothing in contact with the abdominal, pelvic, and/or thoracic area, or as a component of body armor.
The impending injury sensing device array which is comprised of at least one pressure sensor, and/or accelerometer, and/or gyroscope, and/or ultrasound, infrared, electromagnetic, machine vision/imaging apparatus, radar, lidar, and the like are used to detect and assess the motion of the user's head and the likelihood of an impact, collision, blow, or other harmful head motion such as a whiplash type of movement. In addition, the sensing device array may sense an impending collision with a stationary or moving object in the environment around the user which poses a threat which is evaluated by the CPU, which in turn activates the compression device appropriately to negate or reduce brain injury. The sensing device array is worn by the user, and/or incorporated into a conveyance utilized by the user. The sensing device array enables the CPU to calculate time to impact, collision, and/or abnormal brain movement by sensing user head/body motion and/or movement of objects toward the user which can result in brain injuries. This warning capability optimizes the timing of the compression device activation. The compression device component is activated prior to the likely harmful event to reduce injurious brain movement and deformation.
In one embodiment at least one pressure sensor and regulator is incorporated into the compression device or is disposed separately from the compression device, which informs the user and allows the user to adjust the tightness, tension, snugness, and fit of the compression device over the abdomen, and optionally the pelvis and thorax. At least one of the same or a separate pressure sensor aids in regulation of the predetermined compression device parameters in terms of the speed, degree, and depth of compression, and optionally which part of the user's body is compressed and in what sequence, by a compression device segmented to allow for separate compression of the abdomen, pelvis, and thorax.
Head and brain injuries are an ever present threat to bicycle riders, skate board riders, those who engage in winter sports such as skiing and snowboard riding, ice skaters, roller skaters, and other individuals engaging in similar activities, where collisions with the ground can occur. Although a substantial number of these individuals may wear a helmet, it is widely acknowledged by those who study and research head and brain injuries that helmets may protect the scalp and skull from injury, and may increase the distance of deceleration, but cannot directly prevent harmful brain motion and deformation within the intracranial cavity. In one embodiment, a collision warning and impending impact sensor which uses lidar and ultrasound detectors are incorporated into a helmet worn by the user. Accelerometers and gyroscopic based fall detectors and algorithms are also incorporated into the helmet, and detect the falling event (Huynh 2015). The combination of data from these detectors is analyzed by the CPU which enables proper timing of deployment of the compression device. The compression device prevents or reduces abnormal and harmful brain motion upon impact, thus greatly augmenting the total head and brain protective capability afforded by the helmet alone, and preventing or reducing the degree of traumatic brain injury or concussion.
Elderly persons who may have an increased propensity towards falling can be at increased risk of brain injuries. For example, the elderly individual may be more prone to suffering acute and chronic subdural hematomas due to brain atrophy which can stretch the bridging cerebral veins rendering them more likely to rupture when the brain moves abnormally due to a fall. Prevention or reduction of abnormal brain movement by displacing cerebrospinal fluid towards the intracranial compartment and stiffening the brain by reducing compliance in users with brain atrophy represents an effective means to reduce this type of brain injury. For this type of user, a helmet may not be practical or acceptable and fall sensing devices worn on the torso or incorporated into a pants belt or a vest garment which detects falls can be an excellent solution.
Individuals who engage in boxing, martial arts, and related sport combat activities are at significant risk for head and brain injuries from impacts and abnormal, harmful internal brain rotation and deformation. The inflating bag component of the compression device that may be most suitable for users engaging in sports where blows to the torso are common can be constructed from a very thin elastomeric polymer utilizing nylon, which is a material commonly used for vehicular airbags. The deflated nylon sac can be collapsed into a waistband anteriorly and the compressed gas container can be positioned and padded for protection in the waistband posteriorly, where it is less likely to be damaged by a blow. The sensing array and CPU could be incorporated into a mouthguard which communicates wirelessly with the compressed gas container, since the blow to the head incurred during combat sports most likely would come from a forward facing position. A prolonged inflation duration is enabled by incorporation of a gas release valve which releases gas very slowly, over several minutes or less, which can afford increased brain protection in the event of a rapidly occurring series of blows.
Another of the various embodiments may utilize sensors that indicate position, movement, trajectory, and proximity that are worn by a secondary user or incorporated in an object not always associated with the primary user. The event leading to a blow, impact, or collision which can harm the primary user is detected by a sensing array worn by the secondary user, for example an opposing sports opponent, for example as in the game of American football, or incorporated in a separate object such as a soccer ball whose trajectory is to be changed by deliberate use of a soccer player's head, and is designed and programmed to activate the compression device worn by the primary user.
Another of the various embodiments may pertain to mitigation of brain injury from blasts, such as can occur in the military and combat setting. Blasts from bomb explosions can produce a high pressure wave, followed by a zone of low pressure. Research has shown that intracranial pressure can be elevated initially, and possibly followed by a cavitation process in brain tissue. Some evidence suggests that the types of brain injuries due to blasts may have different neuropathological characteristics compared to impact injuries, such as astroglial scarring and evidence of tissue and cell injuries at brain tissue interfaces. Sensing of a blast wave such as by a pressure sensing device mounted on a vehicle containing the user, or mounted on a object remote from the user, can allow for wireless signaling and triggering of protection just prior to arrival of the blast wave. In this case, activation of the protective device can transiently reduce the intracranial pressure of the user, by decompressing the abdomen/pelvis, rapidly followed by a device induced increase in intracranial pressure, to protect the brain from the low pressure zone and/or secondary head and brain impact which commonly occurs from blast injuries, due to impacts from flying objects or from the user impacting objects, or impacting the inside of a vehicle, which commonly occurs in improvised explosive device events affecting occupants of military vehicles.
The need for and benefits of intracranial pressure reduction, and optimization of timing, degree, and duration of pressure reduction in the event of blast events is determined by in vitro, in vivo, preclinical, clinical testing, as well as using simulations, and models of blast events, and imaging of brain motion and deformation, and cerebrospinal fluid motion and movement. Testing that aids in device optimization can also include intracranial pressure measurements in vivo, and various types of simulations known in the art. Likewise, the combination of, and optimal timing, duration, and degree of intracranial pressure reduction and increase in venous return, followed by transient intracranial pressure increase and venous return reduction is modeled, simulated, and tested, to optimize device design and function. In a similar manner, the surface area of the abdomen and optionally the pelvis that the suction device interfaces with, and the shape, dimensions, configuration, and height of the suction device dome, as well as the construction materials of the suction device are optimized by way of in vitro, in vivo testing, simulations and modeling, and preclinical, clinical testing, and imaging.
Various embodiments have been described herein for exemplary illustration. Modifications of the various embodiments described herein could be made by those skilled in the art. All such modifications, which are within the scope of the claims, are intended to be inclusive within the scope and spirit of the one or more of the various embodiments.
At least one external ultrasound transducer and/or at least one photoacoustic device is positioned such that at least one ultrasound beam or beamlet can converge on a known target within the CSF axis, or onto a venous compartment capable of creating a very rapid, transient protective rise in intracranial CSF pressure, just prior to anticipated harmful head motion and brain impact or deformation.
The user is defined as an individual who is human or animal, who utilizes the brain protection apparatus.
The term sensing devices and sensing device array encompasses at least one of, and any combination of a pressure sensor, and/or accelerometer, and/or gyroscope, and/or ultrasound, infrared, electromagnetic, laser, machine vision/imaging apparatus, radar, lidar, and related devices.
The term compression device encompasses at least one apparatus capable of exerting force against the abdomen, and/or pelvis, and/or thorax, in an anterior location or an anterolateral location.
The term brain and brain tissue includes neurons, axons, astrocytes, other brain cells, blood vessels and vascular structures within the brain, and the brain stem.
The term cerebrospinal fluid refers to the fluid surrounding the brain and within the brain parenchyma, including the cerebral ventricular system.
The term body wall can refer to the thorax, abdomen, pelvis, individually, or in any combination.
Photoacoustic energy is applied in a discrete zone and depth to the vagal nerve stimulation points in the ear, in particular to the auricular branch of the vagus nerve, and/or to the cervical (neck) branch of the vagus nerve, and/or along the length of the vagus nerve.
A variety of disorders have been investigated and may be treated using noninvasive vagal nerve stimulation, including headaches, tinnitus, depression, epilepsy, various pain disorders, disturbances involving cardiac regulation, mental disorders including schizophrenia. Post-infectious adverse sequelae can be treated by the combination of light directed at the target tissue site, augmented in an additive or synergistic fashion by the combined effect of light and ultrasound at the treatment site.
The external, noninvasive device utilizes both focused light and focused ultrasound, enabling a large number of vagal nerve stimulation parameters to be easily, safely, and conveniently set, altered as needed, and monitored. The use of ultrasound imaging incorporated to the function of the device enables precise aiming of the device energy, comprising light and ultrasound, at the target, due to the imaging capability, as well.
Vagal nerve stimulation parameters to be optimized experimentally include polarity, stimulation frequency, duration, pulse width, intensity, waveform, and duty cycle.
Preferred targets in the ear include vagal nerve branches within the cavum conchae, the cymbae conchae, the tragus, and the antihelix. The preferred targets in the neck include the lesser occipital nerve, the great auricular nerve, the accessory nerves, the supraclavicular nerves, and transverse cervical nerves. It is understood that any combination of nerves, or individual nerves, unilaterally, or bilaterally (one or both ears, one or both sides of the neck) can be stimulated.
Any number of known acupuncture points can be stimulated, in a discrete zone, and depth by the device, which utilizes the combination of localized ultrasound pulses and targeted light, which may be pulsed, to stimulate the desired acupuncture point(s). In addition, neural tissues may be directly stimulated in a targeted manner, to increase or decrease neural activity, which can reduce pain, stimulate muscle contraction, increase or decrease neuronal function, as examples, which in no manner preclude other uses.
A series of experiments are performed utilizing a tubular, hollow polymeric phantom which is intended to simulate the oral cavity, the nasopharynx, and the upper and lower respiratory tract. Water vapor is generated using a steam generator capable of expressing water droplets of varying sizes to ascertain the droplet size ranges which afford the furthest red light penetration into the depths of the phantom.
Water vapor is inhaled through a circular or oblong mouthpiece tube, similar to that incorporated into inhaler devices used for asthma treatment, or similar to that used for nebulized mist treatments. A light source, preferably comprised of one or more red LEDs, is incorporated into the mouthpiece tube, with light directed into the water vapor droplet stream, enabling light to be delivered into the oral cavity, the nasopharynx, and the upper and lower respiratory tract. The red light reduces tissue inflammation, promotes tissue healing, and can also activate red light absorbing photosensitizers administered locally or systemically. Alternatively, the tube transmitting water vapor is connected to a facemask, fitting comfortably over the mouth and nose, which enables light from a light source incorporated into the mask to be aimed and launched into the upper and lower respiratory tract.
The photoacoustic effect enable ultrasound mediated imaging, which aids in real-time visualization of photodynamic therapy, which is of great value in the treatment of cancerous deposits, since the photoacoustic parameters can be adjusted to maximize the desired effect. For example, the use of a photoacoustic technique to induce the ischemia reperfusion can be monitored in real-time during the therapy session, to ascertain adequate cessation of blood flow with subsequent reflow. By not requiring complete and permanent vascular closure, the need for high energy delivery is avoided, safety is increased, and deleterious and painful inflammation is avoided, which can be tumor promoting conditions.
The photoacoustic effect is utilized to provide combined light therapy and ultrasound to the left and/or right stellate ganglion, in the cervical area, which has been shown to reduce autonomic dysfunction leading to cardiac arrhythmias. The intensity of light therapy . . .
The photoacoustic effect is used to treat a cancerous deposit, by aiming and directing the light source, which may be emitted from one or more photoacoustic devices, after administration of one or more photosensitizers, systemically or by way of local application. The antitumor effect induced by the acoustic pulse and by the directed light is monitored in real-time by an incorporated ultrasound transducer, which is used to alter the therapy to increase efficacy if required. For example, after a fixed amount of one or more photosensitizers is administered, the ultrasound transducer is used to image the cancerous deposit to ascertain change in image signal and reduction in blood flow, indicative of a beneficial anticancer effect. If no changes occur, the light intensity is increased, to improve the photodynamic and sonodynamic effect.
A variety of light delivery intensity and pulse parameters and modes, wavelengths, and wavebands, photoacoustic stimulation parameters, treatment time lengths, treatment schedules, and the like can be assessed and analyzed using ascending dose intensity study designs, and appropriate statistical analysis to ascertain effective treatment parameters, which also informs optimized light device design and engineering.
A patient suffering from post-infectious sequelae of viral and microbial infection, which can include difficulty with memory, concentration, and mental executive function, cardiac and pulmonary problems, autonomic instability, pain, headaches, reduced exercise tolerance, fevers, flu-like symptoms and fatigue, autoimmune phenomenon and the like, is treated using the photoacoustic device which stimulates the vagus nerve, and which can be directed to other tissues to stimulate or decrease function. The general treatment parameters are determined by way of preclinical research and clinical trials, using well known research methods. Treatments may be individualized by adjusting the intensity and duration of the photoacoustic effect, in real-time, for in sequence, after determination of general treatment parameters.
Effects can be measured by capturing data relating to inflammatory blood markers, physiologic parameters such as heart rate variability, quality of life measurements, pain scales, disability scores and the like, which can be analyzed and used to optimize the therapy sessions.
A hollow organ such as the lung is illuminated externally by a light source array, such as a focused LED array aiming light from a location on the surface of the thorax, which generates a photoacoustic ultrasonic pulse wave within the lung tissue. This technique enables delivery of an ultrasonic pulses, which are therapeutic as a single modality, or which may be used to sonodynamically activate one or more photosensitizers, in a manner not feasible using external ultrasound which does not transmit well through air filled organs and spaces.
Additionally, in one or more of the various embodiments or examples, artificial intelligence (AI) feedback and/or heart rate variability (HRV) feedback may be provided before, during, after, wireless communication to external devices.
This application is a Utility Patent application based on previously filed U.S. Provisional Patent Application No. 63/434,885, filed on Dec. 22, 2022, the benefit of the filing date of which is hereby claimed under 35 U.S.C. § 119 (e) and the contents of which is herein incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63434885 | Dec 2022 | US |
