Systems and Methods for the Identification of Medical Conditions, and Determination of Appropriate Therapies, by Passively Detecting Acoustic Signals from Cerebral Vasculature
The present specification describes a system for diagnosing or screening one or more pathologies in a patient. The system includes a headset with at least one microphone or accelerometer to passively receive vibrations generated by the cerebral vasculature of the patient's brain, computing devices coupled with the headset for processing the received vibrations to obtain a unique signal, and a signal analyzer to analyze the signal in order to determine if the data includes patterns uniquely indicative of at least one of tension headaches, migraines, depression, dementia, Alzheimer's disease, epilepsy, Parkinson's disease, autism, cerebral vasospasm and meningitis.
The present application is a division application of U.S. patent application Ser. No. 16/380,841, entitled “Systems and Methods for the Identification of Medical Conditions, and Determination of Appropriate Therapies, by Passively Detecting Acoustic Signals from Cerebral Vasculature” and filed on Apr. 10, 2019, which relies on U.S. Patent Provisional Application No. 62/767,038, entitled “Systems and Methods for the Diagnosis of Medical Conditions Using a Detection of Signals Generated from Blood Flow in the Brain” and filed on Nov. 14, 2018, for priority, and U.S. Patent Provisional Application No. 62/655,752, entitled “Neurological Diagnostic and Therapeutic Device and Method” and filed on Apr. 10, 2018, for priority. All of the above referenced applications are hereby incorporated by reference in their entirety.
FIELDThe present specification relates generally to systems and method for non-invasively diagnosing and treating a plurality of medical conditions and/or pathologies. More specifically, the present specification relates to systems and methods for diagnosing and treating brain-related conditions, such as migraines and headaches, using a detection of signals generated from blood flow in the brain.
BACKGROUNDCurrently, there are approximately 39 million people suffering from migraines in the U.S. and about one billion worldwide. Migraine patients can have significant risks of strokes and other neurological impairments. They lose productivity and their work, personal and family lives are affected.
Some of the most common causes that lead to migraines in patients are underlying central nervous system disorders, irregularities in the brain's blood vessel system or vascular system, genetic predisposition, and abnormalities of brain chemicals and nerve pathways. It is also currently believed that vasodilation and vasoconstriction are a byproduct (or secondary effects) of migraines while neuronal dysfunction is the primary driver in the pathophysiology of the disorder. It has been observed that nerve fibers involved in the localization of pain ascend from the trigeminal to the thalamus and sensory cortex of the trigeminovascular system of a patient experiencing symptoms of migraine; and distribution of headache pain to the upper neck and head are from the trigeminal nerve. Also, a self-propagating wave of cellular depolarization (cortical spreading depression) that spreads slowly across the cerebral cortex and has been linked to migraine aura and headache, as it activates neurons in the trigeminal nerve leading to inflammatory changes and headaches. Further, the neurons of a patient suffering from migraines become increasingly responsive to nociceptive (i.e. pain) stimulation and many of the symptoms of migraine, including throbbing headache pain and exacerbation of headache by physical activity are linked to neuron sensitization.
A majority of migraine patients do not get a timely and appropriate diagnosis or prescriptions to address the migraines. Currently, when a new patient presents in a neurologist's office with a suspicion of migraines, the neurologist is required to have the patient fill out a questionnaire and subjectively perform a work up on the patient based on symptoms, family history, medical history, neurological history and exam, MRI/CT scan, and blood tests. Based on this subjective assessment, the neurologist prescribes drugs to treat. The neurologist then waits for the patient to return in weeks or months to perform another subjective workup and seek to understand the impact of the drugs on the migraine. This is a time-consuming process, which may frustrate the patient if the recommendations and therapy are not effective. Even worse, however, initial therapeutic prescriptions may not be appropriately tailored to the patient, leading to ineffective treatments, or more problematically, mini-strokes in the patient.
U.S. Pat. Nos. 6,887,199 and 6,491,647 disclose a head-mounted brain sensor which non-invasively senses acoustic signals generated from pulsing blood flow on or around a patient's head. The assessment monitor may be used to detect conditions such as head trauma, stroke and hemorrhage. However, the observed changes in signal characteristics from normal to pathological states has to do with changes in acoustic properties as a result of injury, not of chronic brain conditions such as migraines. Moreover, the indicated locations of where the brain sensor(s) should be mounted, such as the forehead, will likely result in the detection of peripheral blood flow around the patient's head, as opposed to the cerebral vasculature.
Similarly, U.S. Pat. Nos. 10,092,195 and 8,905,932 are directed toward a head sensing system which detecting a vascular condition non-invasively in the human body. The assessment system may be used to detect conditions such as stroke, aneurysms, and hemorrhage. Again, the observed changes in signal characteristics from normal to pathological states has to do with changes in acoustic properties as a result of acute injury, not of chronic brain conditions such as migraines, and the indicated locations of where the brain sensor(s) should be mounted will likely result in the detection of peripheral blood flow around the patient's head, as opposed to the cerebral vasculature.
Usually holistic approaches to treating migraine, such as but not limited to meditation, acupuncture, cold water on the scalp, Valsalva maneuver have either no effect or a placebo effect on migraine symptoms. Pain relieving medications such as aspirin, ibuprofen, acetaminophen, caffeine (NSAIDS) and other over the counter drugs usually only dull the migraine pain for 3-4 hours leading to rebound headaches and drug overuse and may cause ulcers and gastrointestinal bleeding. Some pain-relieving medications containing triptans may cause strokes, arrhythmia, rebound headache, nausea, dizziness, drowsiness and palpitations in migraine patients. Other pain-relieving medications containing ergots may cause vomiting, tingling of the extremities, Pruritis, weakness of the legs and worsening of nausea in migraine patients. Yet other pain-relieving medications containing opioids are habit-forming, addictive and may cause severe opioid induced constipation, respiratory depression with risk of death when combined with a sedative such as Ambien or Benzodiazepines such as Temazepam or Alprazolam in migraine patients. Other pain-relieving medications containing glucocorticoids may increase sugar level, diabetes, osteoporosis, ulcers, gastritis, elevate cholesterol, cause weight gain, hirsutism, acne, and severe osteoporosis in migraine patients.
Currently available migraine preventive cardiovascular drugs such as beta blockers may have side effects such as arrhythmias, V-tach, worsened heart failure, depression, hallucinations, fatigue, marked impotence with males, bradycardia and hypotension in migraine patients. Sometimes anti-depressants may worsen or trigger migraine; and may cause sleepiness, dry mouth, constipation, weight gain, decreased cognition, anhedonia, lethargy, and increased suicide risk in migraine patients. Some anti-seizure drugs (Depacon AKA Valproic Acid, Depakote, Topamax) being used as migraine preventive drugs may cause nausea, tremors, weight gain, hair loss, dizziness, diarrhea, weight loss, memory difficulties, concentration problems, cognitive decline, tingling around the lips, hepatic issues, osteoporosis in migraine patients. Some patients are prescribed Botox (Chemodenervation with BOTOX A, Xeomin, Dysport, Myobloc) as preventive treatment for migraines. This is a costly, lengthy and painful process (involving sometimes up to 31 injections administered to the patient in three months) and may cause neck pain, headache, worsening of migraine, muscular weakness and eyelid ptosis in said patients.
Currently, there are no reliable, available diagnostic devices to provide a quick and efficient way of distinguishing between a migraine, tension headache and other non-traumatic injury brain-related conditions and deliver an objective, quantitative assessment of the patient's condition. Patients usually have to undergo elaborate examination procedures including CT scans, which are time consuming, tedious and expensive and are used to only rule out bleeding, not to diagnose migraines.
There is therefore a need for an objective means to determine the nature of a patient's condition and thereby help diagnose a spectrum of brain-related non-traumatic disease conditions and offer targeted therapies. There is also a need for a diagnostic system and method that would enable quick efficient and cost-effective diagnosis of several pathologies including migraines. There is also a need for a diagnostic system and method that would provide the requisite data needed to determine what therapy to diagnosis, what therapeutic protocol to adopt, and/or whether a particular drug or therapy is effective.
SUMMARYThe following embodiments and aspects thereof are described and illustrated in conjunction with systems, tools and methods, which are meant to be exemplary and illustrative, and not limiting in scope. The present application discloses numerous embodiments.
The present specification discloses a system for diagnosing one or more pathologies in a patient, wherein the system comprises: a headset comprising at least one microphone or accelerometer to passively receive vibrations generated by a cerebral vasculature of the patient's brain; at least one computing device coupled with the headset for processing the received vibrations to obtain a signal; and a signal analyzer coupled with the at least one computing device and configured to analyze the signal to identify a pattern indicative of one or more predefined pathologies, wherein the predefined pathologies comprise at least one of tension headaches, migraines, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm, or meningitis.
Optionally, the signal analyzer is configured to differentiate between each of the predefined pathologies and output an audio or visual indicator that specifically identifies one of the predefined pathologies while concurrently excluded a remainder of the predefined pathologies.
Optionally, the signal analyzer is not configured to identify a traumatic brain injury, stroke, aneurysm, or hemorrhage.
Optionally, the headset comprises two microphones, wherein each of the two microphones is provided within each ear covering of the headset.
Optionally, the at least one microphone captures and outputs bi-hemispheric data and has an output for detecting vibration in a range of 0-750 kHz.
Optionally, the headset is an electrostatic headset comprising a pre-amplifier, a frequency equalizer and a noise cancellation module.
Optionally, the headset comprises a signal quality indicator configured to indicate a quality of the vibrations being received, a light source configured to visually indicate that the headset is in an operational mode, and a light array configured to indicate a level of battery charge.
Optionally, the at least one computing device comprises at least one of an Internet of Things (IoT) device, mobile phone, tablet device, desktop computer or laptop computer.
Optionally, the at least one microphone or accelerometer is configured to be positioned within a predefined distance of at least one of the patient's basilar artery, anterior inferior cerebellar artery, anterior vestibular artery, internal auditory artery, common cochlear artery, internal carotid artery, or ophthalmic artery. Optionally, the predefined distance is 10 mm.
Optionally, the at least one microphone or accelerometer is configured to be positioned outside of a predefined distance from at least one of the patient's zygoma, external carotid artery, internal maxillary artery, facial artery, or occipital artery. Optionally, the predefined distance is 5 mm.
Optionally, the at least one microphone or accelerometer is configured to be positioned within a first predefined distance of at least one of the patient's basilar artery, anterior inferior cerebellar artery, anterior vestibular artery, internal auditory artery, common cochlear artery, internal carotid artery, or ophthalmic artery and outside of a second predefined distance from at least one of the patient's zygoma, external carotid artery, internal maxillary artery, facial artery, or occipital artery, wherein the first predefined distance is less than the second predefined distance. Optionally, the first predefined distance is within a range of 0 mm to 5mm and the second predefined distance is at least 5 mm.
Optionally, the signal analyzer is coupled with the at least one computer device via at least one of a wireless network connection, a wired connection or a Bluetooth connection.
Optionally, the system further comprises one or more databases coupled with the signal analyzer, wherein the one or more databases comprises pre-determined signal classifications comprising specific frequencies, frequency ranges, energies, energy ranges, periodicities or periodicity ranges unique to each of the predefined pathologies. Optionally, the signal analyzer comprises one or more algorithms configured to detect one or more of the predefined pathologies present in the signal by comparing the analyzed signal with the pre-determined signal classifications comprising specific frequencies unique to each of the predefined pathologies.
Optionally, the system further comprises a second computing device configured to receive the pattern, compare the pattern to a plurality of predefined patterns indicative of the one or more predefined pathologies, and categorize the pattern as being representative of the one or more predefined pathologies. Optionally, the plurality of predefined patterns are indicative of a plurality of different migraine types. Optionally, the plurality of different migraine types comprise aura, without aura, basilar, hemiplegic, ophthaloplegic, vestibular or chronic. Optionally, the plurality of predefined patterns is derived from signal measurements taken from individuals other than the patient.
The present specification also discloses a method for determining if a patient is suffering from a condition, wherein the condition is at least one of tension headaches, migraines, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm or meningitis, the method comprising: positioning at least one microphone or accelerometer within a first predefined distance of at least one of the patient's basilar artery, anterior inferior cerebellar artery, anterior vestibular artery, internal auditory artery, common cochlear artery, internal carotid artery, or ophthalmic artery and outside of a second predefined distance from at least one of the patient's zygoma, external carotid artery, internal maxillary artery, facial artery, or occipital artery, wherein the first predefined distance is less than the second predefined distance; capturing a signal transduced through a medium, wherein the medium is at least one of air, tissue, bone, vasculature, or nerves, wherein the signal is generated by blood flow in a cerebral vasculature of the patient's brain and is not a function of a second signal originating external to the patient, and wherein the signal is captured using at least one of the accelerometer or the microphone; digitizing the captured signal using a first component in data communication with the accelerometer or microphone; transmitting the digitized captured signal to a signal analyzer using a second component in data communication with the first component; using the signal analyzer, acquiring the digitized captured signal and processing the acquired digitized captured signal to identify a signature, wherein the signature is a function of a non-zero amplitude, frequency and periodicity of the signal and wherein the signature is uniquely indicative of one of a tension headache, a migraine, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm or meningitis.
Optionally, the first predefined distance is within a range of 0 mm to 5mm and the second predefined distance is at least 5 mm.
Optionally, the method further comprises accessing one or more databases, wherein the one or more databases comprises pre-determined signal classifications comprising specific frequencies, frequency ranges, energies, energy ranges, periodicities or periodicity ranges unique to each of a plurality of predefined pathologies.
Optionally, the signal analyzer comprises one or more algorithms configured to detect one or more of a plurality of predefined pathologies present in the signal by comparing the signal with pre-determined signal classifications comprising specific frequencies unique to each of the plurality of predefined pathologies.
Optionally, the method further comprises, using a computing device, receiving the signature, compare the signature to a plurality of predefined patterns indicative of one or more predefined pathologies, and categorize the signature as being representative of the one or more predefined pathologies.
Optionally, the plurality of predefined patterns is indicative of a plurality of different migraine types. Optionally, the plurality of different migraine types comprise aura, without aura, basilar, hemiplegic, ophthaloplegic, vestibular or chronic. Optionally, the plurality of predefined patterns is derived from signal measurements taken from individuals other than the patient.
The present specification also discloses a diagnostic system for determining if a patient is suffering from a condition, wherein the condition is at least one of tension headaches, migraines, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm or meningitis, the diagnostic system comprising: at least one of an accelerometer or a microphone configured to capture a signal transduced through a medium, wherein the medium is at least one of air, tissue, bone, vasculature, or nerves, wherein the signal is generated by blood flow in the brain and is not a function of a second signal originating external to the patient, and wherein the accelerometer or the microphone is positioned no more than 1 foot from an ear of the patient; a digitizer in data communication with the accelerometer or microphone and configured to digitize the captured signal; a transmitter in data communication with the digitizer and configured to transmit the digitized captured signal; a signal analyzer configured to acquire the digitized captured signal and process the acquired digitized captured signal to identify a signature, wherein the signature is a function of a non-zero amplitude, frequency and periodicity of the signal and wherein the signature is uniquely indicative of one of a tension headache, a migraine, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm or meningitis.
The present specification also discloses a method for diagnosing one or more pathologies in a patient, the method comprising: receiving audio data comprising vibrations generated from cardiac cycles of the patient using a headset positioned on the patient's head; processing the audio data to obtain a spectrograph comprising a unique frequency pattern corresponding to the patient; comparing the obtained spectrograph with pre-recorded spectrographs comprising frequencies unique to a predefined type of pathology to obtain a diagnostic result; and conveying the diagnostic result to the patient.
Optionally, the pathology is a migraine. Optionally, the method further comprises collecting the patient's medical history relating to migraines by using a pre-treatment questionnaire before receiving the audio data from the patient.
Optionally, the processing of audio data comprises cancelling noise signals from the audio data by comparing the audio data with a plurality of pre-recorded identified environmental noises and filter the pre-recorded identified environmental noises from the audio data, wherein the noise signals comprise all signals not originating from the patient's ear canal. Optionally, the identified environmental noises comprise noises caused by at least one of air conditioning (AC), lighting, microphone, human movement, keyboard clicks, car traffic, low frequency noise, respiration, or speech.
Optionally, receiving audio data comprises capturing changes in pressure caused by a pulsation of blood through blood vessel walls of the patient in form of pressure-related audio waves and converting the captured pressure-related audio waves to electrical energy by using one or microphones placed within one or both ear coverings of the headset.
Optionally, the method further comprises differentiating between at least one of a non-migraine condition, an active migraine condition, an asymptomatic migraine condition and a post therapy migraine condition in the patient. Optionally, said differentiation between said migraine conditions is performed by determining unique frequency patterns within frequency analyses and/or spectrographs corresponding to each of the migraine conditions.
Optionally, conveying the diagnostic result to the patient comprises visually presenting the diagnostic result in a graphical user interface on a user device or a mobile phone.
Optionally, the method further comprises capturing facial expressions or speech patterns of the patient and using the captured facial expressions or speech patterns to enhance an accuracy of a diagnosis of the predefined type of pathology.
The present specification also discloses a method of diagnosing a migraine in a patient using a device having at least one of an accelerometer or a microphone, comprising: positioning the microphone or the accelerometer within a first predefined distance of at least one of the patient's basilar artery, anterior inferior cerebellar artery, anterior vestibular artery, internal auditory artery, common cochlear artery, internal carotid artery, or ophthalmic artery and outside of a second predefined distance from at least one of the patient's zygoma, external carotid artery, internal maxillary artery, facial artery, or occipital artery, wherein the first predefined distance is less than the second predefined distance; using the device, capturing an analog signal transmitted through a head of the patient, wherein the analog signal is generated by blood flow in the patient's brain and wherein the analog signal is not a function of a second signal originating external to the patient; using a digitizer in data communication with at least one of the accelerometer or the microphone, transforming the analog signal into a digital signal; using a transmitter in data communication with the digitizer, transmitting the digital signal to a digital signal processing module; using the digital signal processing module, acquiring the digital signal and processing the digital signal to identify a signature of the migraine, wherein the signature has a first signal peak having a non-zero amplitude and a frequency in a range of 20 Hz to 1000 Hz and a second signal peak having a non-zero amplitude and a frequency in a range of 20 Hz to 1000 Hz , wherein the first signal peak and second signal peak are separated by a time period of no more than 60 seconds; and, based on said processing of the digital signal, generating a visual or auditory output indicative of whether the patient has said migraine.
Optionally, the signature has a first signal peak having a non-zero amplitude and a frequency in a range of 20 Hz to 800 Hz. Optionally, the signature has a second signal peak having a non-zero amplitude and a frequency in a range of 20 Hz to 800 Hz.
Optionally, the first signal peak and second signal peak are separated by a time period ranging from 1.7 seconds to 5 seconds.
Optionally, the first signal peak and second signal peak are separated by a time period that is 30 seconds or less.
Optionally, the first predefined distance is less than 10 mm and the second predefined distance is more than 5 mm.
The present specification also discloses a system for diagnosing one or more pathologies in a patient, the system comprising: a sensor positioned to passively detect vibrations generated by the vasculature of the patient's brain; at least one computing device coupled with the sensor for recording and processing the received vibrations to obtain a signal; and a signal analyzer coupled with the at least one computing device and configured to analyze the signal to identify a pattern indicative of one or more predefined pathologies, wherein the predefined pathologies comprise at least one of tension headaches, migraines, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm, or meningitis.
Optionally, the sensor is positioned to detect vibrations in at least one of basilar artery, anterior inferior cerebellar artery, anterior vestibular artery, internal auditory artery, common cochlear artery, or internal carotid artery of the patient.
Optionally, the sensor is positioned in an ear canal of the patient.
Optionally, the sensor is positioned to detect vibrations in an ophthalmic artery of the patient.
Optionally, the sensor is a stethoscope positioned over closed eyelids of the patient.
Optionally, the system further comprises a reference sensor for enabling removal of signals detected from peripheral arteries of the patient.
The aforementioned and other embodiments of the present specification shall be described in greater depth in the drawings and detailed description provided below.
These and other features and advantages of the present specification will be further appreciated, as they become better understood by reference to the detailed description when considered in connection with the accompanying drawings:
In an embodiment, the present specification provides a system and method for diagnosing and treating a plurality of medical conditions/pathologies such as, but not limited to, non-traumatic brain conditions, migraines, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's, autism spectrum, cerebral vasospasm, and meningitis pathologies. These chronic, non-traumatic brain conditions differ from traumatic brain injuries (TBI) which present acutely and involve brain swelling and bleeding with a gross insult on the brain. The neuro-chronic pathologies listed above present differently from an acoustic perspective, relative to acoustic characteristics seen with TBI, wherein each condition has a vascular component and a resultant frequency expression resulting in a unique signature different from the signature produced by TBI. Furthermore, detection of non-traumatic brain conditions requires a careful determination of what vasculature structures are being detected to avoid detecting blood flow signatures through a patient's peripheral head vasculature as opposed to blood flow signatures through the patient's brain.
The present specification is directed towards multiple embodiments. The following disclosure is provided in order to enable a person having ordinary skill in the art to practice the specification. Language used in this specification should not be interpreted as a general disavowal of any one specific embodiment or used to limit the claims beyond the meaning of the terms used therein. The general principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of the specification. Also, the terminology and phraseology used is for the purpose of describing exemplary embodiments and should not be considered limiting. Thus, the present specification is to be accorded the widest scope encompassing numerous alternatives, modifications and equivalents consistent with the principles and features disclosed. For purpose of clarity, details relating to technical material that is known in the technical fields related to the specification have not been described in detail so as not to unnecessarily obscure the present specification.
In the description and claims of the application, each of the words “comprise”, “include”, and “have”, and forms thereof, are not necessarily limited to members in a list with which the words may be associated. It should be noted herein that any feature or component described in association with a specific embodiment may be used and implemented with any other embodiment unless clearly indicated otherwise.
In the specification the term “module” represents any digital or software component ranging from a discrete chip to a software algorithm the processing of which is distributed across multiple servers.
In an embodiment, the present specification provides a headset designed to be placed on a patient's head with at least one sensor, such as an accelerometer or microphone, positioned proximate to the patient's ear canal, such as within an ear cover of a headset. The headset is configured to passively detect the vibration of a fluid or elastic solid generated from the cardiac cycle of the patient and, more specifically, from the pulsatile cerebral blood flow, as opposed to peripheral blood flow in the patient's head. In embodiments, the headset may be configured to passively detect acoustic frequencies. In various embodiments, the detected vibrations are compared with a predefined set of pre-recorded vibrations for determining whether the detected vibrations from the patient correspond to any of a plurality of medical conditions/pathologies such as, but not limited to, non-traumatic brain conditions, migraines, depression, dementia, Alzheimer's disease, epilepsy, Parkinson's, autism spectrum, cerebral vasospasm and meningitis.
In an embodiment, the one or more sensors passively receive the vibrations generated by the vasculature of the patient's brain. The vibrations (data) may be, in an embodiment, transmitted via Bluetooth from the headset to an Internet of Things (IOT) device that is configured to store algorithms configured to identify the pathology of interest, provide diagnostic data to the patient or transmit the diagnostic data to a cloud computing platform for analysis, and send the information back to the patient's smart device allowing the patient to obtain therapy for the pathology. In embodiments, data may be transmitted via any wired or wireless means. In embodiments, the headset may include a microchip or real-time operating system (RTOS).
In an embodiment, the vibrations generated by the pulsatile cerebral hemodynamics (cardiac cycle) of the patient is displayed as a heat spectrograph, which when compared with the heat spectrograph of a healthy person, demonstrates a shift in frequencies associated with one or more pathologies.
Referring to
In another, less preferred embodiment, the headset 102 is an electrostatic headset comprising a pre-amplifier, a frequency equalizer and a noise cancellation module. The headset comprises a signal generating apparatus configured to generate an acoustic or ultrasound signal into the brain. In preferred embodiments, the headset 102 is configured to passively receive the vibrations generated by the vasculature of the brain of a patient and does not include a signal generating apparatus, including any acoustic or ultrasound generating apparatus.
In various embodiments, the microphone 104 is accurate in the time and frequency domain and has a uniform polar response, a flat free-field frequency response, fast impulse response and is stable with respect to temperature changes. An exemplary microphone is the M30 microphone 103 provided by Earthworks, Inc.™, illustrated in
In an embodiment, the headset 102 comprises an accelerometer to detect movement from a patient's head, and not just from the patient's vasculature. In an embodiment, the patient is held still by using head gear or one or more harnesses and multiple accelerometers are used to capture signals indicative of movement by the patient. Those captures signals can then be used to cancel out noise generated from movement. In various embodiments, the site of the transducer is distant from muscles and skin that are activated and can move during the examination.
In an embodiment, the headset 102 comprises a signal quality indicator (SQI) to indicate the quality of a signal prior to a test being run, a light emitting diode (LED) to indicate that the headset is on and a light array to indicate a level of battery charge. In an embodiment, the headset 102 may be coupled with a plurality of user computing devices 106 such as, but not limited to Internet of Things (IoT) devices, mobile phones, tablets, and computers 106 via a wireless connection such as, but not limited, to a Wi-Fi network, cellular, or a Bluetooth connection. In embodiments, the user devices 106 enable display of data captured by the headset 102 and other notifications to the user using the headset. In embodiments, the user may be required to provide authentication information by using one of a plurality of authentication methods comprising custom authentication, or authentication methods provided by service providers 108 such as, but not limited to Google®, Facebook®, and Twitter®. In some embodiments, the headset 102, user devices 106, and service providers are grouped in an end user's tier 100.
In embodiments, a plurality of software applications 110 executing on the user devices 106 enable connection of the user devices 106 with the headset 102 as well as with a cloud solution computing platform (web and service tier) 112 via a wireless connection such as, but not limited, to a Wi-Fi network, cellular, or a Bluetooth connection. The applications 110 may comprise patient mobile applications 111, service provider mobile applications 113, service provider Windows® applications 115, and management applications 117, which also enable transfer and display of information captured/processed by the headset 102 and the cloud solution computing platform 112.
In various embodiments, the cloud solution computing platform (web and service tier) 112 comprises a management portal 122, a workflow module 121, and a set of service or storage modules, including, but not limited to, a translation service/localization module 123, a payment processing module 125, a blockchain module 127, and an analytics module 129. In embodiments, the management portal 122 comprises a patient portal, patient API services, patient BOT services, a provider portal, provider API service, and provider BOT services. The management portal 122 is in data communication with the workflow module 121, which controls IOT device application distribution, blockchain ledgers, a notification hub, mobile application distribution, API distribution, and BOT channel distribution. The management portal 122 is also in data communication with each of the translation service/localization module 123, payment processing module 125, blockchain module 127, and analytics module 129, providing patients and providers access to these modules via the patient portal and provider portal, for various services.
The vibrations detected by the microphones 104 are analyzed by a signal analyzer comprising at least one processor and a plurality of programmatic instructions stored in a memory, where the plurality of programmatic instructions include DSP, and machine learning, Artificial Intelligence, deep learning, neural networks (NN) and pattern recognition based algorithms, such as neural networks and artificial intelligence systems, in order to detect one or more of a set of pre-defined pathologies present in the detected vibrations of the patient. Preferably, pre-recorded acoustic patterns and specific frequencies unique to each kind of pathology are stored in one or more databases 114 coupled with the signal analyzer, which may be executed in a cloud solution computing platform 112.
Each pathology generates a unique acoustic pattern and specific frequency that enables identification of the pathology. For example, migraines generate (depicted by a spectrograph) a unique frequency pattern associated with the migraine. Using DSP, machine learning, and or AI pattern recognition based algorithms, the migraine severity levels may be identified. In an embodiment, data describing a pathology collected from each case is used to expand the database, which further enhances the quality/accuracy of the AI algorithms. In an embodiment, each patient's data is also sent to a secure website which provides patients an encrypted/password protected access to their data and history.
In an embodiment, the cloud solution computing platform 112 is coupled with one or more user devices 106 via a wireless connection such as, but not limited, to a Wi-Fi network, or a Bluetooth connection. In various embodiments, the user devices 106 comprise a graphical user interface (GUI) for displaying at least a diagnosis of the patient's condition. In an embodiment, the GUI displays one or more pathologies determined by the AI algorithms. In an embodiment, the user devices 106 also receive packets of diagnostic information from the cloud solution computing platform 112, to provide information on the severity of the pathology and display the information as a quantitative value.
At step 304, the captured audio data is digitized and transmitted to a cloud processing platform. In an embodiment, the audio data is stored in a mobile application, which in turn uploads the data to the cloud processing platform. Next the data is pre-processed at step 306. In an embodiment, the audio data is cleaned by applying noise reduction techniques to obtain clean audio patient data. In an alternate embodiment, the audio data is processed at a local device and then uploaded to a cloud platform.
In an embodiment, audio data may be processed via a beamforming technique. In this technique, two microphones would be employed in each ear, forming a beam of interest. In an embodiment, beamforming can be used to remove noise by attenuating all noises in the environment and focusing on the narrow beam pointing towards the ear canal to extract the signal of interest. In this embodiment, noise is not removed from the signal, rather any signal that falls outside of the beam of interest, and therefore any signal that is not coming directly from the ear canal, would be cancelled.
The cleaned or scrubbed audio data is then processed to obtain spectrograph images. At step 308 the pre-processed data is analyzed using AI and deep learning-based algorithms to determine if the patient is suffering from one or more predefined pathologies. At step 310 the results are transmitted to an application running on a predefined computing device which may be the user's mobile phone.
The method of determining and displaying pathologies corresponding to a patient's acoustic data is further described with reference to
At step 404 the data received from each microphone is processed. In an embodiment, the received data is separated into individual data packets and decomposed into constituent frequencies using any known data transformation algorithm such as but not limited to Fourier transform, wherein the frequencies and the amplitude of the received vibrations are examined as a function of time. In various embodiments the data received from each microphone may be used to generate unique patterns and features that may indicate an exclusive signature for different pathologies. The vibrations obtained from the cardiac cycle (diastole & systole) range from a normal baseline of approximately 15-20 Hz and shift further down the spectrum to approximately 30 to 80 Hz, depending on the pathology being assessed.
At step 406 the processed data is used to obtain a spectrograph comprising a unique pattern and indicating an exclusive signature for a pathology. In an embodiment, the processed data comprises predefined frames of audio signals having frequencies ranging from approximately 150 Hz to 1000 Hz. In an embodiment, a sum of all energies within said range is computed with respect to each frame to obtain a spectrograph of the captured data.
At step 408 the spectrograph is compared with a spectrograph obtained by using pre-recorded vibrations of a healthy human having no pathologies. In various embodiments, the patient's spectrograph may be compared with a plurality of pre-recorded spectrographs for determining if any of a set of pre-defined pathologies are present in the patient's acoustic data. In an embodiment, the time, frequency and amplitude of vibrations generated by the vasculature of the brain of the patient are compared with those of a healthy human or of humans with specific pathologies, such as tension headaches, migraines, depression, dementia, Alzheimer's disease, epilepsy, Parkinson's disease, autism, cerebral vasospasm and meningitis.
In various embodiments the comparison of the patient's spectrograph with other spectrographs to obtain if the patient suffers from any of a plurality of pre-defined pathologies is achieved in the signal analyzer by using artificial intelligence (AI), machine learning or pattern recognition based algorithms. In an embodiment, distinctive acoustic patterns and frequencies generated from a pathology, if present in a patient's spectrograph, are identified by using AI, machine learning and pattern recognition-based algorithms. In an exemplary embodiment, the spectrograph of a patient suffering from migraine is analyzed with respect to a spectrograph of a person not suffering from migraines. In various embodiments, specific types of migraines (with Aura, without Aura, Basilar, Hemiplegic, Ophthaloplegic, Vestibular or Chronic) can be detected by analyzing vibration spectrographs by using the signal analyzer.
Accordingly, referring to
At step 410 one or more pathologies detected in the patient's spectrograph are displayed to the user via a GUI running on a computing device. In an embodiment, the signal analyzer detects the features of the waveform and provides a qualitative and quantitative diagnostic output to assess if the patient has the pathology or not. In an embodiment, the qualitative output is a simple stop light where green is no pathology present, yellow is pathology below a threshold level present and red is pathology above a threshold present. In other embodiments, a quantitative number, on a scale of 1 to 10 is displayed to describe the severity of the detected pathology.
In various embodiments, cerebral vasculature response (vasodilation and vasoconstriction), byproducts of the underlying migraine condition, can be measured and identified. Since the human heart pumps blood bilaterally to the brain through the carotid arteries, pumping of the heart, along with asymmetric blood flow, pulses the blood through the cerebral blood vessels.
Referring to
In contrast, it is preferred to avoid placing sensors in locations that would result in the detection of peripheral blood flow, which is not indicative of the actual cerebral vasculature. Such locations may include above the zygoma which is the bony arch of the cheek formed by connection of the zygomatic and temporal bones of the person, the external carotid artery, the internal maxillary artery, the facial artery, the occipital artery or the branches of any of the aforementioned arteries (“Non-Target Peripheral Vasculature”). In particular, it is preferable to place a sensor outside of a predefined distance from a wall of one or more of the Non-Target Peripheral Vasculature. In one embodiment, the predefined distance is outside of 20 mm, preferably outside of 10 mm, more preferably outside of 5 mm, even more preferably outside of 2 mm, or any increments therein.
Therefore, it is important to position the sensors in a location and configuration where the primary signals being received by the sensors are indicative of the acoustic properties of blood flow through the Target Vasculature and not indicative of the acoustic properties of blood flow through the Non-Target Vasculature. In one embodiment, one, more than one, or all of the sensors are physically positioned closer to at least one of the Target Cerebral Vasculature relative to each of the Non-Target Peripheral Vasculature. In one embodiment, one, more than one, or all of the sensors are physically positioned within 5 mm of a wall of at least one of the Target Cerebral Vasculature and further than 5 mm from each of the Non-Target Peripheral Vasculature. In one embodiment, one, more than one, or all of the sensors are physically positioned within 10 mm of at least one of the Target Cerebral Vasculature and further than 10 mm from each of the Non-Target Peripheral Vasculature. In one embodiment, one, more than one, or all of the sensors are physically positioned within 0 mm to 5 mm of at least one of the Target Cerebral Vasculature and further than 5 mm from each of the Non-Target Peripheral Vasculature.
In an embodiment, the pulsation of blood through artery walls is picked up by sensitive microphones placed near the ear canal.
In embodiments, where cerebral vasculature response is measured via the ophthalmic artery 434, a sensor may be placed over closed eyelids of the person. It is to be noted that in various embodiments, the cerebral vasculature response is measured via internal arteries within the head of a person and not via peripheral arteries which can be felt pulsating via the forehead of the person. Prior art discloses acquiring signals from superficial arteries from the patient's forehead and comparing the signal to a reference signal indicative of peripheral vasculature (radial artery), which is a completely different method than that disclosed in the present specification. It is not possible to passively capture a signal indicative of cerebral vasculature from a person's forehead. Hence, the present specification discloses alternate locations (such as, but not limited to those disclosed above) for placement of sensors for collecting the cerebral vasculature response. It should be appreciated, therefore, that the microphone in the present invention is positioned to acquire signals that are more indicative of the cerebral vasculature of the patient's brain than of the peripheral vasculature of the patient's brain. In one embodiment, it is preferred to position the microphone, sensor, and/or accelerometer away from peripheral vessel structures such as, but not limited to, the superficial temporal artery and proximal branches (terminal branches of the internal carotid artery, supratrochlear artery, supraorbital artery).
In an embodiment a reference sensor is employed to enable removal of signals from non-cerebral sources, such as but not limited to peripheral arteries. In other embodiments, no reference sensor is employed, no reference signal is used to generate the signatures described herein, or no reference signal indicative of a patient's arterial or radial blood flow is used to generate the signatures described herein.
In an embodiment, cerebral vasculature response may be measured via the ophthalmic artery of a person by using retinal sensing methods. In an embodiment, ophthalmic artery response is measured by using a stethoscope over closed eyelids of a person. Ocular auscultation is a physical exam maneuver that consists of listening to the vascular sounds of the head and neck by placing the stethoscope on the surface of the eyelids and surrounding structures.
In an embodiment, electronic stethoscopes may be used for ocular auscultation. A conventional problem with acoustic stethoscope is that the sound level captured may be very low. A low sound level may be overcome by using digital stethoscopes which amplify the low sounds or ‘bruits’ captured from the eye. An electronic stethoscope converts the acoustic sound waves obtained through the ‘chest piece’ of the stethoscope into electronic signals which are then transmitted from specially designed circuits and processed for best hearing and also allow the energy to be amplified and optimized for listening at various different frequencies. The circuitry also allows the sound energy to be digitized, encoded and decoded, to have the ambient noise reduced or eliminated, and sent through speakers or headphones or transmitted for further processing.
Referring back to migraines, a migraine may be caused by a neurogenic disorder causing a secondary change in cerebral profusion associated with neurogenic inflammation. These changes in cerebral profusion produce identifiable vibration that are analyzed by the signal analyzer, classified, and the results provided to the clinician
In an embodiment, the questionnaire comprises questions, such as but not limited to:
In various embodiments, the patient's response to the questionnaire is automatically analyzed using the signal analyzer to provide predictive analytics as an additional feature to the diagnostic system of the present specification, further enhancing the accuracy, sensitivity, or specificity of a migraine diagnosis. Moreover, the data captured on a single patient can be compared to that of recorded responses of other patients to obtain a goal-directed therapy for the patient. In an exemplary scenario, a pre-treatment questionnaire may be used to query similar patient profiles and help detect patterns around food allergies. For example, it is documented that migraine can be caused by food allergies. By providing similar cases, the signal analyzer may direct a physician to instruct a patient to avoid the determined foods causing allergies.
At step 510 data is received from a headset placed on a patient's head with at least one accelerometer or one microphone positioned within at least one of the headset ear covers to passively detect and record vibrations generated from cardiac cycles of the patient. In an embodiment, the microphone or accelerometer passively receives vibrations generated by the vasculature of the brain. In an embodiment, the headset converts any changes in pressure caused by the pulsation of the blood through the vessel walls to electrical energy using the microphone or accelerometer placed near the ear canal of the patient. In an embodiment, due to the sensitivity required to measure the changes in pressure, the patient is placed in an environment with noise contributing equipment turned off and lighting minimized for detecting and recording the vibrations.
At step 512 the data received from each microphone of the headset is processed by audio processing APIs (Application Processing Interface), which are responsible for digitizing the audio data. At step 514 the processed data is uploaded to a cloud processing platform. In an embodiment, the data generated from each microphone of the headset is stored in a mobile application, where it is processed by using the audio processing APIs, and is then uploaded to the cloud processing platform at step 514. Because there are two microphones on different channels, the data may be captured and processed separately or the data is separated into unique channels and processed separately. At step 516, the data from each microphone is processed by using a channel separator. At step 518, noise is removed from the processed data by using a noise reduction module comprising a database of classified and identified noises that may be present in the environment when a patient's recording is made, such as, but not limited to noises caused by air conditioning (AC), electric lights, overhead lights, microphone, floor creaking, keyboard clicks, respiration, or speech.
Referring back to
Referring back to
In various embodiments, each patient data collected via headphones generates unique patterns and features. These unique features are used to create an exclusive signature for each pathology. In an embodiment of the present specification, a unique signature of the data collected with respect to persons suffering from migraine as well as key attributes to characterize the active migraine signature have been identified and are used for diagnosing a patient suffering from migraines. Patients that present with a headache and are diagnosed and treated by using the methods described in the present specification may be classified into the following categories:
-
- Non-Migraine: patient does not experience migraine and does not have any identified underlying condition(s);
- Migraine Asymptomatic: patient is not currently afflicted with a migraine or patient who have complained of migraine previously but does not have any identified underlying condition(s);
- Migraine Active: patient from Migraine Asymptomatic classification afflicted with an active migraine at the time of the recording;
- Migraine Active after Treatment (Rx): patient from Migraine Active who has taken medicine known to alleviate the migraine and waited 30 to 60 minutes prior to the acoustic recording.
At step 552, if the patient's spectrogram is indicating migraine, it is determined if it is required to give the patient prescription drugs. At step 554 if prescription drugs are not required, the patient is kept under observation for a predefined time. Next, treatment by way of anti-migraine prescription medicine, anti-CGRP (calcitonin gene-related peptide) migraine medication at step 556, or anti-SHT1D (human serotonin 1D receptor variant) migraine medication at step 558, is provided to the patient and the patient is observed for a predefined period of time. These medications are of low risk to the patient. At step 560, after providing treatment and keeping the patient under observation, the patient is screened again by using the methods of the present specification. At step 562 if there is improvement in the patient's headache/condition, the treatment is considered a success and the patient obtains relief at step 564. At step 566, if the patient's condition has not improved, the patient is either observed for predefined time; or sent for CT scan or Mill testing; or sent to Neurologist for examination and further analysis of headache.
At step 568 it is determined if the patient is suffering from a chronic headache. At step 570, if the patient is suffering from a chronic headache, the patient is screened by using the methods of the present specification. At step 572, the results of screening of the chronic headache are analyzed and it is determined if the patient is an active migrainer. If the results of the analysis are inconclusive at step 574, step 570 is repeated. In an embodiment, the analyzes involve obtaining an acoustic spectrogram of the patient as explained with respect to
In an embodiment, the present specification provides unique signatures obtained from recorded vibrations generated from cardiac cycles of patients suffering from migraines, by using the signal analyzer employing AI and deep learning based algorithms.
In an embodiment, the present specification provides AI based methods of detection and analysis of human emotion/speech by detecting changes in tone, volume, speed and voice quality; and using said detected speech attributes to determine emotions like anger, joy, pain and laughter. In embodiments, such audio files obtained by detecting and analysis speech of a plurality of persons are recorded in a database and are compared against a patient's audio data to determine if the patient is suffering from one or more predefined pathologies such as migraine by using specialized computing algorithms, as described in the context of the present specification. For example, even if a patient is saying that he is experiencing symptoms of migraine, his speech may be detected and analyzed by using the method of the present specification, and if a emotions of joy and laughter are detected, then it is determined that the patient is not suffering from migraine symptoms.
In an embodiment, the diagnostic system of the present specification comprises a facial (emotion) recognition Biometric Artificial Intelligence (BAI) technology for determining and recording a patient's facial expressions which are indicative of the patient's emotions. In an embodiment, the recorded facial expressions are evaluated in conjunction with the patient's response to pre-treatment questionnaire to diagnose the patient's pathological condition. BAI can identify a patient's unique facial patterns based on facial textures and shapes. The facial images recorded by BAI enable the AI based diagnostic algorithm of the present specification to compare selected facial emotional features to those pre-recorded in a database, to enhance the accuracy of the algorithm. In embodiments, BAI based facial expression recognition enables detection of patterns in the recorded facial images that are representative of an active migraine (pain expression) versus an asymptomatic migraine. Hence, the present specification provides an A.I. driven platform for diagnosing migraines, that incorporates EMR/pre-treatment questionnaire, integrated with facial and speech emotional recognition to enhance the algorithm to provide greater accuracy and productiveness.
The diagnostic system and method of the present specification provides numerous benefits and advantages over known migraine assessment approaches. In embodiments, the specification utilizes a passive microphone approach that analyzes signals by an algorithm and classifies them, which allows an objective detection of migraines, non-invasively. Moreover, the low cost non-invasive, acoustic based approach removes the subjective diagnosis of migraines, therefore, enhancing the screening, diagnosis and prescription of drug appropriate forms of therapy. Furthermore, the diagnostic system and method of the present specification can detect a normal condition (not suffering from migraine) from an asymptomatic migraine; an asymptomatic migraine from an active migraine and an active migraine from an active migraine after having received therapy.
The above examples are merely illustrative of the many applications of the system and method of present specification. Although only a few embodiments of the present specification have been described herein, it should be understood that the present specification might be embodied in many other specific forms without departing from the spirit or scope of the specification. Therefore, the present examples and embodiments are to be considered as illustrative and not restrictive, and the specification may be modified within the scope of the appended claims.
Claims
1. A method of diagnosing a migraine in a patient using a device having at least one of an acoustic sensor, accelerometer or a microphone, comprising:
- positioning the acoustic sensor, microphone or the accelerometer within a first predefined distance of at least one of the patient's basilar artery, anterior inferior cerebellar artery, anterior vestibular artery, internal auditory artery, common cochlear artery, internal carotid artery, or ophthalmic artery and outside of a second predefined distance from at least one of the patient's zygoma, external carotid artery, internal maxillary artery, facial artery, or occipital artery, wherein the first predefined distance is less than the second predefined distance;
- using the device, capturing an analog signal transmitted through a head of the patient, wherein the analog signal is generated by blood flow in the patient's brain and wherein the analog signal is not a function of a second signal originating external to the patient;
- using a digitizer in data communication with at least one of the acoustic sensor, the accelerometer or the microphone, transforming the analog signal into a digital signal;
- using a transmitter in data communication with the digitizer, transmitting the digital signal to a digital signal processing module;
- using the digital signal processing module, acquiring the digital signal and processing the digital signal to identify a signature of the migraine:, determining if the patient has the migraine based on the processing of the digital signal; and
- based on said processing of the digital signal, generating a visual or auditory output indicative of whether the patient has said migraine.
2. The method of claim 7, wherein the frequency of the first signal peak is in a range of 20 Hz to 800 Hz.
3. The method of claim 2, wherein the frequency of the second signal peak in a range of 20 Hz to 800 Hz.
4. The method of claim 7, wherein the first signal peak and second signal peak are separated by a time period ranging from 1.7 seconds to 5 seconds.
5. The method of claim 7, wherein the first signal peak and second signal peak are separated by a time period that is 30 seconds or less.
6. The method of claim 1 wherein the first predefined distance is less than 10 mm and wherein the second predefined distance is more than 5 mm.
7. The method of claim 1, wherein the signature has a first signal peak having a non-zero amplitude and a frequency in a range of 20 Hz to 1000 Hz and a second signal peak having a non-zero amplitude and a frequency in a range of 20 Hz to 1000 Hz.
8. The method of claim 7, wherein the first signal peak and second signal peak are separated by a time period of no more than 60 seconds.
9. The method of claim 1, further comprising, based on the processing of the digital signal, generating a visual or auditory output indicative of a type of the migraine.
10. The method of claim 9, wherein the type of the migraine is at least one of an aura migraine, a migraine without an aura, a basilar migraine, a hemiplegic migraine, an ophthaloplegic migraine, a vestibular migraine or a chronic migraine.
11. The method of claim 10, further comprising recommending a medication specific to one of the types of the migraines.
12. The method of claim 1, further comprising, if the patient is determined to have the migraine based on the processing of the digital signal, recommending at least one of an anti-calcitonin gene-related peptide medication or a human serotonin 1D receptor variant medication.
13. The method of claim 1, wherein the digital signal processing module is configured to analyze the digital signal to identify a pattern indicative of one or more predefined pathologies, wherein the one or more predefined pathologies comprise at least one of tension headaches, migraines, depression, vascular dementia, Alzheimer's disease, epilepsy, vascular Parkinson's disease, autism, cerebral vasospasm, or meningitis.
14. The method of claim 13, wherein the digital signal processing module is configured to differentiate between each of the one or more predefined pathologies and output an audio or visual indicator that specifically identifies one of the one or more predefined pathologies while concurrently excluding a remainder of the predefined pathologies.
15. The method of claim 14, wherein the digital signal processing module comprises one or more algorithms configured to detect one or more of the predefined pathologies present in the digital signal by comparing the analyzed digital signal the pre-determined signal classifications comprising specific frequencies unique to each of the one or more predefined pathologies.
16. The method of claim 14, wherein the digital signal processing module is configured to receive the digital signal, compare the digital signal to a plurality of predefined digital signals indicative of the one or more predefined pathologies, and categorize the digital signal as being representative of the one or more predefined pathologies, wherein the plurality of predefined digital signals comprises acoustic signal data indicative of a plurality of different migraine types.
17. The method of claim 16, wherein the plurality of different migraine types include at least two of an aura migraine, a migraine without an aura, a basilar migraine, a hemiplegic migraine, an ophthaloplegic migraine, a vestibular migraine or a chronic migraine.
18. The method of claim 1, wherein the at least one of an acoustic sensor, accelerometer or a microphone is integrated into a headset.
19. The method of claim 18, wherein the headset further comprises a pre-amplifier, a frequency equalizer and a noise cancellation module.
20. The method of claim 18, wherein the headset further comprises a signal quality indicator configured to indicate a quality of the analog signal being received.
Type: Application
Filed: Jun 14, 2021
Publication Date: Dec 2, 2021
Inventors: Benjamin William Bobo (Irvine, CA), David Robbins Asbury (Wildomar, CA), Devendra Goyal (Yorba Linda, CA), Mohsin Shah (Tustin, CA), John Chen (Tustin, CA), Sahar Bou-Ghazale Toukmaji (Irvine, CA)
Application Number: 17/346,306
