Neurovascular ultrasound analysis for allergy testing

Abstract

A computer-implemented method of neurovascular ultrasound analysis for determining the presence of an allergic reaction in a subject is disclosed. The method includes transmitting ultrasound waves to an area of ​​the subject at which an ultrasound probe is placed after exposure of the subject to a potential allergen, generating information representative of changes in the subject's circulatory system based on Doppler information received by the probe, and detecting a food allergy based on processing the information. Non-transitory computer readable media and devices for the disclosed methods are also disclosed.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 265,028, filed December 6, 2021, the contents of which are incorporated by reference in their entirety into this application.

[0002] The present disclosure relates to neurovascular ultrasound analysis, and in particular to methods, systems and devices for assessing allergies using neurovascular ultrasound analysis. [Background technology]

[0003] Allergies are immune system responses to foreign substances, also known as allergens, that occur after ingestion or exposure to such foreign substances. Allergens can be environmental substances such as pollen, dust, or pet dander that do not usually cause a reaction in most people. In some cases, allergens can be foods such as peanuts, sesame seeds, or dairy products. An allergic reaction to an allergen can be discomfort, mild inflammation, or a life-threatening emergency, depending on the severity of the immune system response. Trace amounts of allergens, especially ingested food allergens, can cause unpleasant and sometimes life-threatening signs and symptoms, including indigestion, hives, swelling of the airways, anaphylaxis, and / or shock (a drop in systemic blood pressure). Food allergies are estimated to affect 6-8% of children under the age of 3 and up to 3% of adults. There is no known cure, but some children may outgrow their food allergies. Additionally, food allergies are easily misdiagnosed as food intolerances, which do not involve an immune system response and are less severe symptoms than food allergies. Thus, accurate diagnosis of food allergy or elimination of allergy as the cause of a subject's symptoms is important to the health and well-being of a subject. Clinicians consider many factors before diagnosing a subject with an allergy, including food exposure history and symptoms, family history of allergies, physical examination, skin tests, blood IgE testing, elimination diet, and / or oral food challenge. However, currently available testing procedures cannot definitively confirm or disprove food allergy, particularly with relative ease. Thus, there is a need for methods and systems that effectively and reliably detect allergies to food or environmental allergens in a subject. Summary of the Invention

[0004] A computer-implemented method of neurovascular imaging and ultrasound (US) analysis for determining the presence of an allergic reaction is disclosed. A non-transitory computer-readable medium and apparatus for the disclosed method are also disclosed.

[0005] The present disclosure provides, in some aspects, a neurovascular US analysis system for determining the presence of an allergic reaction in a subject. The neurovascular US analysis system includes a US probe configured to transmit US waves to a region of the subject. The region includes an internal body structure. The neurovascular US analysis system includes a processor communicatively coupled to the US probe. The processor is configured to execute instructions for receiving, via the US probe, first information representative of a reflection of the US waves from the region, generating second information representative of the internal body structure or a characteristic thereof based on processing the first information, generating third information representative of changes in the circulatory system of the subject based on the third information, determining the presence of an allergic reaction to a potential allergen in the subject based on the third information, and outputting, via a user interface communicatively coupled to the processor, fourth information indicative of the presence of the allergic reaction.

[0006] In some embodiments, the third information includes one or more of: fifth information representative of changes in immune response associated with the circulatory system; sixth information representative of an amount of compensation to the circulatory system; and seventh information representative of changes in vascular circulation by the circulatory system. In some embodiments, the processor is configured to execute instructions for generating the second information by determining at least one of an antegrade pulsatility index, an antegrade volume flow rate, a retrograde pulsatility index, and a retrograde volume flow rate for a limb associated with the region, and determining a neurovascular index for the limb comprising at least one of the antegrade pulsatility index, the antegrade volume flow rate, the retrograde pulsatility index, and the retrograde volume flow rate. In some embodiments, the processor is configured to execute instructions for determining an arteriovenous (AV) shunt score for the limb based on the neurovascular index and a predetermined limb score. In some embodiments, the processor is configured to execute instructions for determining a cumulative anterograde volume flow score based on a sum of the anterograde volume flows of each of the limb and at least one further limb of the subject. In some embodiments, the processor is configured to execute instructions to generate third information by determining a decrease in the cumulative antegrade volumetric flow score and generating fifth information indicative of a change in immune response associated with the circulatory system based on the decrease in the cumulative antegrade volumetric flow score.

[0007] In some embodiments, the processor is configured to execute instructions for generating the third information by determining an increase in an amount of compensation for the circulatory system and generating sixth information representative of the amount of compensation for the circulatory system based on the increase in the amount of compensation for the circulatory system. In some embodiments, the processor is configured to execute instructions for generating the third information by determining a decrease in an amount of the body structure or a characteristic thereof circulating through the circulatory system and generating seventh information representative of a change in vascular circulation by the circulatory system based on the decrease in the amount of the body structure or a characteristic thereof circulating through the circulatory system.

[0008] In some embodiments, the processor is configured to output fourth information indicative of the presence of an allergic response after exposure of the subject to the potential allergen. In some embodiments, the processor is configured to output pre-exposure fourth information indicative of the presence of an allergic response before exposure of the subject to the potential allergen to establish a baseline measurement, and to output fourth information indicative of the presence of an allergic response after exposure of the subject to the potential allergen based on the baseline measurement and the post-exposure measurement.

[0009] In some embodiments, the region of the subject includes a first region of a plurality of test regions of the subject. The plurality of test regions can include a first region and a second region on a radial side of the arm, a first region and a second region on an ulnar side of the arm, a first region, a second region and a third region on a medial lower part of the leg, and a first region, a second region and a third region on a lateral lower part of the leg. In some embodiments, the body structure includes an artery associated with the region of the subject. In some embodiments, the region includes an upper limb of the subject or a lower limb of the subject. The upper limb can include one or more of a proximal radius, a proximal ulna, a distal radius and a distal ulna, and the lower limb can include one or more of a proximal tibia, a proximal fibula internal structure, a distal tibia and a distal fibula internal structure.

[0010] The present disclosure provides, in some aspects, a non-transitory computer-readable medium including instructions executable by a processor to perform operations for neurovascular ultrasound (US) analysis to determine the presence of an allergic reaction. The operations include directing, via the processor, a US probe communicatively coupled to the processor to transmit US waves to a region of the subject, the region including an internal structure. The operations include receiving, via the processor, first information representative of a reflection of the US waves from the region, generating, via the processor, second information representative of the internal structure or a characteristic thereof based on processing the first information, generating, via the processor, third information representative of changes in the circulatory system of the subject based on processing the second information, determining, via the processor, the presence of an allergic reaction to a potential allergen in the subject based on the third information, and directing, via the processor, a user interface communicatively coupled to the processor to output fourth information indicative of the presence of the allergic reaction.

[0011] In some embodiments, the third information includes one or more of a fifth information representative of a change in immune response associated with the circulatory system, a sixth information representative of an amount of compensation to the circulatory system, and a seventh information representative of a change in vascular circulation by the circulatory system. In some embodiments, determining the presence of an allergic response includes determining that one or more of the fifth information, the sixth information, and the seventh information are greater than one or more respective thresholds. In some embodiments, generating second information representative of an internal structure or a characteristic thereof includes determining an antegrade pulsatility index, an antegrade volumetric flow rate, a retrograde pulsatility index, a retrograde volumetric flow rate, or a combination thereof for one or more limbs of the subject, and determining a neurovascular index for the one or more limbs comprising an antegrade pulsatility index, an antegrade volumetric flow rate, a retrograde pulsatility index, a retrograde volumetric flow rate, or a combination thereof. In some embodiments, the one or more limbs include an upper limb or a lower limb. In some embodiments, generating the third information comprises determining a decrease in a cumulative forward volume flow score based on a sum of the forward volume flow of each of the one or more limbs, and generating fifth information indicative of a change in an immune response associated with the circulatory system based on the decrease in the cumulative forward volume flow score. In some embodiments, the third information comprises the fifth information.

[0012] In some embodiments, generating the third information includes determining an increase in an amount of compensation to the circulatory system and generating sixth information representative of the amount of compensation based on the increase in the amount of compensation to the circulatory system. In some embodiments, the third information includes the sixth information. In some embodiments, generating the third information includes determining a decrease in an amount of the body structure or a characteristic thereof circulating through the circulatory system and generating seventh information representative of a change in vascular circulation based on the decrease in the amount of the body structure or a characteristic thereof. In some embodiments, the third information includes the seventh information.

[0013] The present disclosure, in some aspects, provides a computer-implemented method of neurovascular ultrasound (US) analysis (NUA) for determining the presence of an allergic reaction in a subject. In some embodiments, the computer-implemented method includes directing, via a processor, a US probe communicatively coupled to the processor to transmit US waves to a region of the subject. The region includes an internal structure. The computer-implemented method includes receiving, via the processor, first information representative of a reflection of the US waves from the region, generating, via the processor, second information representative of the internal structure or a characteristic thereof based on processing the first information, and generating, via the processor, third information representative of a change in the circulatory system of the subject based on processing the second information. The third information includes one or more of information representative of a change in an immune response associated with the circulatory system, information representative of an amount of compensation for the circulatory system, and information representative of a change in vascular circulation. The computer-implemented method includes determining, via the processor, the presence of an allergic reaction to a potential allergen in the subject based on the third information, and directing, via the processor, a user interface communicatively coupled to the processor to output fourth information indicative of the presence of the allergic reaction.

[0014] In some embodiments, determining the presence of an allergic response includes determining that one or more of the information indicative of an altered immune response, the information indicative of an amount of compensation, and the information indicative of an altered vascular circulation are greater than one or more respective threshold values.

[0015] Other aspects and features of the present disclosure will become apparent to those skilled in the art after reading the detailed description and accompanying drawings herein.

[0016] The accompanying drawings, in which like references indicate like features, illustrate embodiments described herein by way of example, and not by way of limitation, and in which conventional details may be omitted so as not to obscure the inventive concepts described herein. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 illustrates a schematic example of a computer-implemented system for neurovascular ultrasound analysis for food allergy detection, according to an embodiment of the present disclosure.

[0018] [Diagram 2] FIG. 1 illustrates an example of a computer-implemented method of neurovascular ultrasound analysis for food allergy detection in a subject, according to an embodiment of the present disclosure.

[0019] [Figure 3A] FIG. 1 illustrates an example of a computer-implemented method for generating information related to neurovascular ultrasound analysis for food allergy detection according to an embodiment of the present disclosure, specifically, a method for generating second information representing an internal body structure or a characteristic thereof based on processing first information representing ultrasound reflections.

[0020] [Figure 3B] FIG. 1 illustrates an example of a computer-implemented method for generating information related to neurovascular ultrasound analysis for food allergy detection according to an embodiment of the present disclosure, specifically, another method for generating second information representing an internal body structure or a characteristic thereof based on processing first information representing ultrasound reflections.

[0021] [Figure 4A] FIG. 1 illustrates an example of a computer-implemented method for generating information regarding neurovascular ultrasound analysis for food allergy detection according to an embodiment of the present disclosure, specifically, a method for generating third information representative of changes in a subject's circulatory system based on processing second information.

[0022] [Figure 4B] FIG. 13 illustrates an example of a computer-implemented method for generating information related to neurovascular ultrasound analysis for food allergy detection according to an embodiment of the present disclosure, specifically, another method for generating third information representative of changes in a subject's circulatory system based on processing second information.

[0023] [Figure 4C] FIG. 13 illustrates an example of a computer-implemented method for generating information related to neurovascular ultrasound analysis for food allergy detection according to an embodiment of the present disclosure, specifically, another method for generating third information representative of changes in a subject's circulatory system based on processing second information.

[0024] [Diagram 5] FIG. 1 illustrates an example of a network architecture used in a system for a computer-implemented method of neurovascular ultrasound analysis for food allergy detection, according to an embodiment of the present disclosure.

[0025] [Figure 6] FIG. 1 illustrates an example apparatus for providing a computer-implemented method of neurovascular ultrasound analysis for food allergy detection, according to an embodiment of the present disclosure.

[0026] [Figure 7] FIG. 1 illustrates an example of a network architecture used in a system for computer-assisted neurovascular ultrasound analysis of vascular changes, according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] While the present disclosure will be described in connection with certain specific embodiments, it will be understood that it is not intended to limit the disclosure to those embodiments, but rather the present disclosure is intended to cover all alternatives, modifications, and equivalents that may be included within the spirit and scope of the present disclosure as defined by the appended claims.

[0028] In the following description, various embodiments are described. For purposes of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the embodiments. However, it will be apparent to one skilled in the art that the embodiments may be practiced without these specific details. Furthermore, well-known features may be omitted or simplified so as not to obscure the described embodiments.

[0029] As mentioned above, it is particularly desirable to provide a method and system for effectively and reliably detecting allergies in subjects. Indeed, allergens can cause cumulative trauma to the neurovascular system, such as partial anaphylaxis. This trauma can lead to mastocytosis, which can cause immune hyperreactions to future perceived threats. Diffuse neurotrunk inflammation can also lead to migraines, fibromyalgia, peripheral neuropathy, and / or lack of response to conventional medical interventions for various diseases.

[0030] Traditional means of detecting food allergies rely on antibody testing, but measurements can vary depending on where blood is drawn for antibody testing. The gold standard for detecting food allergies is simply a food elimination diet, but this process is difficult, time-consuming, and subjective. Systems and methods according to various embodiments of the present disclosure can overcome one or more of the above and other deficiencies found in traditional approaches to detecting food allergies in human or other mammalian subjects. Additionally, while embodiments are described with reference to food allergies, embodiments of the present disclosure can also be utilized to diagnose environmental allergies. In some embodiments, the allergen can be a protein or carbohydrate, as a plant product or animal product. The allergen can be a pollen allergen, indoor allergen, mold allergen, insect allergen, food allergen, or any combination or derivative thereof. For example, the allergen can be derived from peanuts, tree nuts, eggs, shellfish, soy, milk, gluten, or any combination thereof.

[0031] For ease of understanding, some non-limiting definitions of terms are provided herein. The term "body structure" as used herein and variations thereof include at least one of tissue, organ, and organ system. Tissue refers to two or more cells organized to perform one or more functions. Types of tissue include nervous tissue, epithelial tissue, connective tissue, and muscle tissue. Examples of nervous tissue include brain tissue, spinal cord tissue, nerves, and the like. Examples of epithelial tissue include skin tissue, the GI tract lining, and the like. Examples of connective tissue include body fluids (such as blood, plasma, lymph, any combination thereof), cartilage, bone, ligaments, tendons, adipose tissue (adipose tissue, or fat tissue), and the like. Examples of muscle tissue include skeletal muscle, cardiac muscle, smooth muscle, and the like. An organ includes two or more types of tissue organized to perform one or more functions. Examples of organs include the heart, lungs, stomach, kidneys, skin, liver, and the like. An organ system includes (i) at least two organs that cooperate to perform one or more functions, or (ii) at least one organ and at least one tissue that cooperate to perform one or more functions. One example of an organ system is the vascular system, which can include blood vessels, bodily fluids, and at least one organ or tissue. Another example of an organ system is the cardiovascular system, which can include the heart, blood vessels, and bodily fluids. Other examples of organ systems include the lymphatic system, digestive system, endocrine system, internal organ system, muscular system, nervous system, reproductive system, respiratory system, skeletal system, urinary system, immune system, circulatory system, etc.

[0032] As used herein, the terms "circulatory system" and variations thereof refer to an organ system that includes a heart, at least one lung, at least one fluid, and at least one blood vessel (e.g., blood vessel, lymphatic vessel, etc.) that functions to transport at least one fluid between tissues and organs in the body. There are many types of circulation through the circulatory system. Examples include (i) pulmonary circulation, (ii) systemic circulation, and (iii) coronary circulation. Pulmonary circulation involves the transport of fluid between the heart and the lungs (e.g., from the heart to the lungs and back to the heart). Systemic circulation involves the transport of fluid between tissues and organs other than the heart and lungs. Coronary circulation involves the transport of fluid through the tissues of the heart.

[0033] As used herein, the terms "neurovascular," "NV," and variations thereof, refer to one or more internal structures associated with the nervous and vascular systems. Examples of such structures include blood vessels and nerves that are joined or connected to one another.

[0034] As used herein, the terms "arteriovenous," "AV," and variations thereof, refer to the relationship between arteries and veins. For example, AV abnormalities include connections or connections between arteries and veins that do not involve capillaries.

[0035] As used herein, the terms "arteriovenous shunting", "AV shunting", "shunting", and variations thereof refer to an abnormal circulatory process that involves repeating a first type of circulation instead of proceeding to a second type of circulation. For example, a normal circulatory process involves pulmonary circulation followed by systemic circulation. In this example, AV shunting occurs when pulmonary circulation is repeated instead of proceeding to systemic circulation. As a result, AV shunting creates an abnormal circulatory process. As used herein, the terms "arteriovenous shunt", "AV shunt", "shunting", and variations thereof refer to the passage of bodily structures, such as fluids, between arteries and veins without passing through capillaries.

[0036] As used herein, the term "sonogram" and variations thereof refer to an image (e.g., a sound image, etc.) generated using ultrasound (US). For example, generating a sonogram includes directing US at a body part, receiving one or more echoes reflected from an internal structure underlying the body part, and processing the echoes to generate a sonogram that represents the internal structure or a characteristic thereof. As used herein, the terms "ultrasound," "US," and variations thereof refer to one or more sound waves having a high frequency (e.g., a frequency of 20 kilohertz (KHz) or higher). US has a variety of applications. An exemplary application of US, referred to as diagnostic US or medical US, includes directing US at a body part to generate a sonogram that represents an internal structure or a characteristic thereof underlying the body part for diagnosis within a medical context (e.g., medical diagnosis, etc.). Examples of diagnostic US include, but are not limited to, Doppler US, duplex US, and any other US or combination of US capable of producing a sonogram representative of bodily fluids, characteristics of bodily fluids, bodily structures associated with bodily fluids, characteristics of bodily structures associated with bodily fluids, or any combination thereof.

[0037] As used herein, "neurovascular ultrasound analysis," "NV ultrasound analysis," "neurovascular US analysis," "NUA," and variations thereof refer to one or more embodiments of one or more techniques for processing NV information based on application of US to a subject to detect one or more abnormalities or conditions in the subject. One embodiment of NUA disclosed herein includes applying US to a body part of the subject after exposure of the subject to a potential allergen (e.g., food substance, environmental compound), receiving first information in response to applying US, generating second information representative of bodily fluids or characteristics thereof under the body part based on processing the first information generated by applying US to the body part, generating third information representative of changes in the circulatory system of the subject, and determining that the subject is allergic to the potential allergen based on processing the third information. One embodiment of NUA involves applying US to a body part of a subject following exposure of the subject to a potential allergen to determine (i) a change in the amount of antegrade circulation, (ii) the quality of circulation between one or more arteries and one or more nerves, (iii) a change in neurovascular circulation, or (iv) any combination thereof. Other embodiments will be apparent from the description provided herein and the accompanying figures.

[0038] As used herein, "subject" refers to animals such as mammals, including primates (such as humans and non-human primates such as monkeys) and non-primates (such as mice). In some aspects of the disclosure, the subject is a human. In some aspects, the subject is a pediatric subject, such as a neonate, infant, or child. In other aspects, the subject is an adult subject.

[0039] The phrase "at least one of A, B, or C" as used in this disclosure (e.g., in any or all of the detailed description, in one or more of the claims below, etc.) includes A only, B only, C only, a combination of A and B, a combination of B and C, a combination of A and C, and a combination of A, B, and C. That is, the phrase "at least one of A, B, or C" means A, B, C, or a combination thereof that includes one or more of the elements A, B, and C, and should not be construed as requiring at least one of each of the listed elements A, B, and C, regardless of whether A, B, and C are related categorically or otherwise. Furthermore, the use of "a" or "the" to introduce an element should not be construed as excluding a plurality of elements. Also, the phrase "A, B, and / or C" is equivalent to "at least one of A, B, or C." In this disclosure, the use of "a" means "one or more" or "at least one." For example, "a module" means "one or more modules" or "at least one module."

[0040] In some aspects, a computer-implemented method, system, and device for performing neurovascular ultrasound analysis (NUA) for allergy testing is provided. The NUA of the present disclosure includes an outcome-based tool that can assess a subject's response to an allergen and determine and present any changes in circulation as a result of exposure to the allergen. The NUA can include testing any suitable number of sites on the subject with ultrasound pulsed Doppler testing. In some embodiments, eight sites on the subject are tested to provide efficient and reliable allergy detection. Ultrasound measurements such as volumetric flow and pulsatility index of antegrade and retrograde circulation can be recorded both before and after the subject is exposed to a potential allergen. That is, a baseline can be established in each individual region by measuring and recording ultrasound measurements for each region. These ultrasound measurements are then evaluated by a controller that analyzes each portion of the relevant waveform and outputs an indication of an allergic response to the potential allergen. The present embodiment can also provide a neurovascular index (NVI), a tool designed to provide a quantifiable value to the quality of neurovascular circulation around the nerve. NVI also provides the user with the ability to zoom out (e.g., to expand the scope of evaluation) to assess circulation throughout the neurovasculature, or zoom in (e.g., to narrow the scope of evaluation) to examine circulation around specific cutaneous nerves, such as small nerve fibers. Additionally, NVI allows the user to compare circulation through the neurovasculature to make inferences regarding the cause of neurovascular challenge to specific nerves. In practice, NVI can distinguish and quantify the presence or absence of autonomic challenge to the neurovasculature, where the neurovascular challenge to the autonomic nerves exists, and / or the presence or absence of vascular deviation from one limb to another of the subject.

[0041] In one embodiment, the NUA method begins with placing an ultrasound device to assess a single region or site from which two measurements are collected. The measurements at this site include pulsatility index and volumetric flow rate. Both antegrade and retrograde versions of pulsatility index and volumetric flow rate are assessed. In general, ultrasound can function as a radar that examines the effect of structures on sound waves (rather than a precise image) to provide the results of the influence and control of the structure under examination. When the ultrasound device is examining an artery, four individual attributes can be determined in response to the pulsed Doppler waveform assessed via NVI, including (i) the level of capillary resistance below the transducer (e.g., probe) of the ultrasound device, (ii) the level of neural control of smooth muscle below the transducer, (iii) arterial control above the transducer, and (iv) capillary resistance above the transducer. These four measurements, assessed individually and / or in any suitable combination, indicate the quality of neurovascular circulation to the nerves directly below the transducer associated with the artery being examined.

[0042] When the capillary resistance below the transducer increases, the pulsatility and volumetric flow of the waveform of the examined artery changes in a unique way, and NVI evaluates the waveform and associates a specific number that is unique to this waveform. Similarly, if the sympathetic regulation of the neurovascular circulation of the arteriole below the ultrasound device is impaired by poor circulation, NVI quantifies the change in that specific waveform. The quantification of these Doppler waveform changes is based on observations before and after exposure to potential allergens and the development herein of a novel model of NVI (e.g., the NVI model) that provides an assessment based on the close synergistic relationship between the macrovasculature and the microvasculature. In fact, four forces that develop or affect the pulsed Doppler waveform are derived from the relationship between the microvascular circulation and the macrovasculature. When one force is prominent and another force is reduced, it is defined as a disorder that is likely to cause ischemia or reduced blood flow. This disorder with an imbalance between the macrovasculature and the microvasculature is revealed in the pulsed Doppler waveform and quantified in NVI using the NVI model. These types of imbalances can cause neurovascular congestion or ischemia. NVI and related NVI models have been developed to capture the number of disturbances to form a percent deficit that indicates an allergic reaction. Thus, the present embodiment quantifies the allergic reaction, which can be used to rigorously confirm or disprove a subject's specific allergy.

[0043] To date, over 50 body sites have been evaluated to implement the NVI model to develop the systems and methods disclosed herein. For example, these body sites include the cerebral blood vessels. The body sites also include the larger blood vessels in the body, such as the aorta, external iliac, and internal iliac. These larger blood vessels can be evaluated using a vascular or visceral probe of the ultrasound device, whereas the smaller blood vessels are measured using a musculoskeletal probe of the ultrasound device. In some embodiments, measurements are taken at the proximal and distal upper arms (proximal radius and proximal ulna, distal radius and distal ulna). Measurements can also be taken at both legs (proximal tibia and fibula regions, distal tibia and fibula regions), 8-10 different regions of the feet, 5 or more regions of the hands, upper arms, common and deep peroneal arteries, and popliteal arteries, etc. As described below, some embodiments of the present disclosure evaluate 10 body sites or regions to increase the accuracy and reliability of allergy diagnosis.

[0044] Based on the probe detecting the circulation of blood vessels, a pulse image is acquired and stored (e.g., "frozen") in a controller communicatively coupled to the probe. The user operating the probe can then measure the volumetric flow rate of blood vessels (both large and small) in both antegrade and retrograde directions, and can further measure the pulsatility index of blood vessels (both large and small) in both antegrade and retrograde directions. The measurements are stored in the controller as the subject's baseline. After the subject's exposure to a potential allergen, such as the subject's ingestion of a controlled amount of food or contact with a controlled amount of an environmental allergen, the measurements described above are taken again and compared to the subject's baseline. The deficits of each measurement are calculated and the total deficit is added up. In some embodiments, instead of constructing individual baselines, the deficits are calculated by comparing the post-allergen measurements to a fully functioning microvasculature around the nerve. The measurements are taken and compared to an ideal percentage of the individual measurements. These deficits are evaluated next to the deficits for other nerves, such as the left and right upper limb large fibers, the left and right lower limb large fibers, the left and right upper limb small fibers, and the left and right lower limb small fibers. The deficiency can also be divided into left and right visceral regions, NR and central aorta, left and right spinal track regions, etc.

[0045] In some aspects of the present disclosure, a NUA system for determining the presence of an allergic reaction in a subject is provided. The NUA system includes a US probe configured to transmit US waves to a region of the subject. The region includes an internal body structure. The NUA system includes a processor communicatively coupled to the US probe. The processor is configured to execute instructions for receiving, via the US probe, first information representative of a reflection of the US waves from the region, generating second information representative of the internal body structure or a characteristic thereof based on processing the first information, generating third information representative of changes in the circulatory system of the subject based on the third information, determining the presence of an allergic reaction to a potential allergen in the subject based on the third information, and outputting, via a user interface communicatively coupled to the processor, fourth information indicative of the presence of the allergic reaction.

[0046] In some embodiments, the third information includes one or more of: fifth information representative of changes in immune response associated with the circulatory system; sixth information representative of an amount of compensation to the circulatory system; and seventh information representative of changes in vascular circulation by the circulatory system. In some embodiments, the processor is configured to execute instructions for generating the second information by determining at least one of an antegrade pulsatility index, an antegrade volumetric flow rate, a retrograde pulsatility index, and a retrograde volumetric flow rate for a limb associated with the region, and determining a neurovascular index for the limb comprising at least one of the antegrade pulsatility index, the antegrade volumetric flow rate, the retrograde pulsatility index, and the retrograde volumetric flow rate. In some embodiments, the processor is configured to execute instructions for determining an arteriovenous (AV) shunt score for the limb based on the neurovascular index and the predetermined limb score. In some embodiments, the processor is configured to execute instructions for determining a cumulative antegrade volumetric flow rate score based on a sum of the antegrade volumetric flow rates of each of the limbs and at least one additional limb of the subject. In some embodiments, the processor is configured to execute instructions to generate third information by determining a decrease in the cumulative antegrade volumetric flow score and generating fifth information indicative of a change in immune response associated with the circulatory system based on the decrease in the cumulative antegrade volumetric flow score.

[0047] In some embodiments, the processor is configured to execute instructions for generating the third information by determining an increase in an amount of compensation to the circulatory system and generating sixth information representative of the amount of compensation to the circulatory system based on the increase in the amount of compensation to the circulatory system. In some embodiments, the processor is configured to execute instructions for generating the third information by determining a decrease in an amount of the body structure or characteristic thereof circulating through the circulatory system and generating seventh information representative of a change in vascular circulation by the circulatory system based on the decrease in the amount of the body structure or characteristic thereof circulating through the circulatory system. In some embodiments, the processor is configured to output fourth information indicative of the presence of an allergic response after exposure of the subject to a potential allergen. In some embodiments, the processor is configured to output pre-exposure fourth information indicative of the presence of an allergic response before exposure of the subject to the potential allergen to establish a baseline measurement, and after exposure of the subject to the potential allergen, output fourth information indicative of the presence of an allergic response based on the baseline measurement and the post-exposure measurement. In some embodiments, the baseline measurement is a measurement obtained or determined before exposure of the subject to the potential allergen and can reflect a normal state of the subject.

[0048] In some embodiments, NUA is based on immune activation in response to allergens and cardiac compensation following immune activation. The immune response includes histamine release and cardiac compensation, which result in waveform changes and increased volumetric flow (analyzed through NVI methods) in response to exposure to allergens. In some embodiments, the positive criteria for allergy detection relative to a baseline-generated control include determining: (1) a percent difference between the current value and the corresponding control value increases by more than 1.5 or decreases by less than 0.85; (2) an increase in UE of more than 1.25 and a decrease in LE of more than 0.8; (3) a change in AV shunt from UE-dominant to LE-dominant; (4) a change in total AV shunt of more than 0.15; or (5) any combination thereof.

[0049] In some embodiments for the detection of food allergies, the NUA of the present disclosure includes evaluating the macro / micro relationship after food introduction, evaluating the immune response, and evaluating cardiac compensation for the immune response. As should be understood with respect to the above and following descriptions, the methods, systems, and devices of the present disclosure can be used to test food allergies in a clinical setting and identify allergenic / non-allergenic foods in a subject. These methods, systems, and devices provide significant advantages over prior antibody detection or food elimination diets, including non-subjectivity, ease, and reduced invasiveness of allergy detection.

[0050] In an example, a computer-implemented system for neurovascular (NV) ultrasound (US) analysis (NUA) for allergy detection is disclosed. FIG. 1 illustrates an example of a computer-implemented NUA system 100 according to an aspect of the present disclosure. As can be appreciated, the NUA system 100 can detect allergies based on monitoring a series of controlled physical changes in at least one region 101 of at least one extremity of a subject. The extremity can be an upper or lower extremity, such as a hand, arm, leg, ankle, or foot, but in yet other examples, various other parts of the subject can be targeted, such as the neck or back. The region 101 of the subject includes an internal structure 103 disposed beneath a surface 105 (e.g., epidermis) and at least partially within the extremity of the subject. In some embodiments, the internal structure 103 includes an artery or blood vessel through which a fluid 107 flows. The internal structure 103 is associated with a circulatory system 111 that can directly or indirectly control the flow of the fluid 107 within the internal structure 103.

[0051] The NUA system 100 of this embodiment also includes a US device 120. The US device 120 includes a US probe 121 that is placed on or in the area 101 of the subject. As described above, the US probe 121 can be used to establish a baseline response of the subject, as well as to analyze an allergic reaction to a potential allergen after exposure of the subject to the allergen. The US probe 121 of this embodiment is communicatively coupled to one or more computers, hereinafter referred to as controller 125, via a cable 123. In other embodiments, the US probe 121 and the controller 125 are communicatively coupled wirelessly.

[0052] As shown, the US device 120 emits US waves into the region 101 via the US probe 107, such as based on instructions from the controller 125. The controller 125 of the NUA system 100 receives first information from the US probe 107, which is representative of the reflection of the US waves from the region 101. The NUA system 100 generates second information representative of the internal structure 103 or a characteristic thereof, such as based on processing the first information, such as via the controller 125. The controller 125 of the NUA system 100 generates third information representative of changes in the subject's circulatory system 111, such as based on processing the second information. Thus, the NUA system 100 can detect an allergy based on processing the third information and generate fourth information representative of the detection of an allergy for output to a user of the NUA system 100. Below, some examples of components and configurations of the NUA system 100 are presented, followed by further non-limiting examples of information generated, processed and used by the NUA system 100. As can be seen, the NVI presents and analyzes body inflammation information for allergy detection, and an increase in inflammation measurements after allergen exposure indicates an allergic reaction. Furthermore, if an allergic reaction is detected in a subject, an anti-allergy drug can be administered to the human subject to alleviate symptoms associated with the detected allergy. In some embodiments, the allergy drug can be an antihistamine, a corticosteroid, a bronchodilator, a mast cell stabilizer, a leukotriene inhibitor, a serine pulmonary protease inhibitor, or any combination or derivative thereof. In some embodiments, the antihistamine can be an H1-antihistamine, an H2-antihistamine, an H3-antihistamine, an H4-antihistamine, or any combination thereof.

[0053] FIG. 2 is a block diagram illustrating an exemplary computer-implemented method 200 for detecting food allergies in a subject via the NUA system disclosed herein. In some embodiments, the method 200 is executed by the processor of the US probe 107 and / or the controller 125 of FIG. 1. In FIG. 2, the method 200 begins at block 201 with transmitting US waves from the US probe into an area of ​​the subject. In some embodiments, the US probe transmits US waves in response to one or more commands from the controller. In each test area, a user or a healthcare provider may place a US probe on or into the area of ​​the subject. The healthcare provider may place the US probe after or immediately after ingestion of a food by the subject to analyze the allergen or food for an allergic response. In some embodiments, the allergic response to the allergen may be evaluated after a predetermined period of exposure of the subject to the allergen. In some embodiments, the allergic response may be evaluated after the subject has a visible or perceptible reaction to the allergen. Additionally, some NUA embodiments facilitate allergy diagnosis based on US measurements taken at 10 different body sites or areas. In some embodiments, the regions include four upper limb regions and six lower limb regions, such as two regions on the radial side of the arm, two regions on the ulnar side of the arm, three regions on the lower medial side of the leg (e.g., tibia), and three regions on the lower lateral side of the leg (e.g., fibula). In some embodiments, each of the ten regions can be measured via US before allergen exposure and again after allergen exposure.

[0054] At block 203, first information representative of reflections of US waves from the region is received. For example, the processor may receive the first information from a US probe. In some embodiments, the first information includes a Doppler waveform associated with the region. At block 205, second information representative of the internal structure or a characteristic thereof is generated based on processing the first information. In some embodiments, the processor generates the second information by analyzing metrics of the Doppler waveform associated with the region. Some examples of generating the second information are described in more detail below with respect to methods 300, 350 of FIG. 3A, FIG. 3B. For example, the second information of some embodiments described in more detail below may include an antegrade pulsatility index (PI), an antegrade volumetric flow (VF), a retrograde PI, a retrograde VF, an AV shunt score, and / or a cumulative antegrade VF score.

[0055] At block 207, third information representative of changes in the subject's circulatory system is generated based on processing the second information. The processor of some embodiments generates the third information including (1) fifth information representative of changes in immune response associated with the circulatory system, (2) sixth information representative of an amount of compensation to the circulatory system, and / or (3) seventh information representative of changes in vascular circulation by the circulatory system. Some embodiments of generating the fifth, sixth, and / or seventh information for the third information embodiments are described below with respect to the method of FIGS. 4A-4C. At block 211, the presence of an allergic reaction or food allergy is determined (e.g., detected) based on processing the third information. For example, the processor of some embodiments may determine that the third information indicates the presence of an allergic reaction in response to comparing each value of the third information to either a corresponding individual reference value or a general reference value. In some embodiments, the processor may determine that the third information indicates the presence of an allergic reaction in response to (1) the fifth information indicative of a change in immune response greater than an immune response threshold, (2) the sixth information indicative of an amount of circulatory compensation greater than a compensation threshold, and / or (3) the seventh information indicative of a change in vascular circulation greater than a vascular circulation threshold. In block 213, a fourth information indicative of the presence of an allergic reaction is generated. In some embodiments, the processor may output the fourth information via any suitable visual and / or audible alert via a user interface communicatively coupled to the processor. In these embodiments, it may be desirable for the NUA system to present an allergy indication to the healthcare provider and / or the subject so that the subject may be isolated from the corresponding allergen based on the correct information.

[0056] As disclosed herein, the method for NUA facilitates the determination of the degree of allergic reaction to a tested allergen. For example, NUA can indicate that a subject has no reaction, low reaction, moderate reaction, or severe reaction to an allergen based on the quantification of inflammation detected in the subject's body. In practice, NVI presents and analyzes body inflammation information for allergy detection, and an increase in inflammation measurement after allergen exposure indicates an allergic reaction.

[0057] FIG. 3A is a block diagram illustrating an exemplary computer-implemented method 300 for generating second information representative of an internal structure or a characteristic thereof based on processing first information (as illustrated in block 205 of method 200). In some embodiments, all or part of method 300 may be executed by a processor or controller of a NUA system. Furthermore, method 300 may be repeated for each suitable limb of a subject, such as one or more of the left upper limb, the left lower limb, the right upper limb, and the right lower limb. In FIG. 3A, at block 301, an antegrade pulsatility index (PI) of a target limb of a subject is determined. As used herein, pulsatility index is defined as the difference between the peak systolic flow velocity and the minimum diastolic flow velocity divided by the average flow velocity recorded throughout the cardiac cycle. At block 303, an antegrade volumetric flow (VF) of the target limb is determined. At block 305, a retrograde PI of the target limb is determined. At block 307, a retrograde VF of the target limb is determined. As one of ordinary skill in the art will appreciate, antegrade measurements are assessed with respect to the forward flow direction and retrograde measurements are assessed with respect to the reverse flow direction.

[0058] At block 311, a cumulative neurovascular index (NVI) of the target limb is determined. The NVI includes one or more of antegrade PI, antegrade VF, retrograde PI, and retrograde VF. In some embodiments, a threshold number of antegrade PI, antegrade VF, retrograde PI, and retrograde VF may be evaluated to further increase the accuracy and reliability of the NUA system disclosed herein. For example, in some embodiments, the NUA system may specify that the threshold number is 2, 3, or 4. In embodiments where one or more of antegrade PI, antegrade VF, retrograde PI, and retrograde VF are not utilized in determining the cumulative NVI, the corresponding one or more of blocks 301-307 may be omitted. In some embodiments, the antegrade PI, antegrade VF, retrograde PI, and / or retrograde VF correspond to second information representative of an internal structure or a characteristic thereof.

[0059] In some embodiments, the NUA assessment evaluates any out-of-normal waveform variability changes in response to the tested allergen. In some of these embodiments, the normal range for NVI is 7-14. However, it should be understood that any suitable range for allergy detection based on variability changes can be established. In some embodiments, the NUA assessment evaluates any abnormal forward volumetric flow changes, such as increases or decreases outside of normal variation. Such volumetric flow changes include (1) an increase in forward volumetric flow of more than 1.5 times that of the control, indicative of cardiac changes (e.g., increases) in response to inflammation, (2) a decrease in forward volumetric flow indicative of histamine release in response to the tested allergen, and / or (3) a combination of upper extremity increases and lower extremity decreases, indicative of a pattern change related to the location of the tested area relative to the heart.

[0060] In block 313, the body's adaptation to the tested allergen is determined through examination of the standard deviation change in the cumulative NVI of each individual nerve. As described herein and shown in Example 2 below, a standard deviation analysis is performed to quantify a specific immune response. For example, an allergy diagnosis can be confirmed in response to a standard deviation analysis showing that the difference between the baseline measurement and the post-exposure measurement along the nerve is statistically significant. As disclosed herein, specific individual nerves that can be evaluated include the peroneal nerve, tibial nerve, dorsal nerve, and cervical nerve. In some embodiments, the standard deviation analysis or data thereof corresponds to second information representative of an internal structure or a characteristic thereof.

[0061] 3B is a block diagram illustrating an exemplary computer-implemented method 350 for generating second information representative of an internal structure or a characteristic thereof based on processing first information (as exemplified in block 205 of method 200). In some embodiments, all or part of method 350 may be performed by a processor or controller of the NUA system. Furthermore, method 350 may be repeated for each suitable limb of the subject, such as one or more of the left upper limb, the left lower limb, the right upper limb, and the right lower limb. In some embodiments, method 350 may be performed in combination with or in parallel with method 300. In other embodiments, only one of methods 300, 350 may be performed.

[0062] In Figure 3B, in block 351, an antegrade PI is determined for a target limb of a subject as described above in block 301 of Figure 3A. In block 353, an antegrade VF is determined for the target limb. In block 355, a retrograde PI is determined for the target limb. In block 357, a retrograde VF is determined for the target limb. In block 361, a cumulative neurovascular index (NVI) is determined for the target limb. The NVI is comprised of one or more of an antegrade PI, an antegrade VF, a retrograde PI, and a retrograde VF. In some embodiments, these steps of Figure 3B can correspond to the steps described above in Figure 3A.

[0063] At block 363, an arteriovenous (AV) shunt score is determined based on the cumulative NVI of the limb and a predefined target limb score. At block 365, a cumulative antegrade VF score is determined based on the sum of the antegrade VF of one or more target limbs. In some embodiments, the AV shunt score and / or the cumulative antegrade VF score also correspond to second information indicative of an internal structure or a characteristic thereof.

[0064] As described above, the third information representing the change in the circulatory system in some embodiments may include (1) information regarding the change in the immune response associated with the circulatory system (e.g., the fifth information), (2) information regarding the amount of compensation for the circulatory system (e.g., the sixth information), and / or (3) the change in vascular circulation by the circulatory system (e.g., the seventh information). In the following, for ease of understanding, each of these components will be described separately with reference to Figures 4A-4C. However, one or more of the methods in Figures 4A-4C may be performed simultaneously or sequentially in any suitable order. Furthermore, the methods in Figures 4A-4C may be performed by a processor or any other suitable component of the NUA system disclosed herein.

[0065] FIG. 4A is a block diagram illustrating an exemplary computer-implemented process 400 for generating third information representative of a change in the subject's circulatory system based on processing second information (as exemplified in block 207 of method 200). In FIG. 4A, a decrease in a cumulative antegrade VF score is determined in block 401. For example, the cumulative antegrade VF score may be determined to have a first value for a first time period and a lower second value for a second time period. In block 403, fifth information representative of a change in the immune response associated with the circulatory system is generated based on the decrease in the cumulative antegrade VF score. In some embodiments, the cumulative antegrade VF score and the corresponding determined decrease may be generated via block 365 of method 350. In such embodiments, the cumulative antegrade VF score corresponds to the second information and the decrease in the cumulative antegrade VF score corresponds to the third information and / or the fifth information.

[0066] Additionally or alternatively, FIG. 4B is a block diagram illustrating an exemplary computer-implemented method 430 for generating third information representative of a change in the subject's circulatory system based on processing second information (as exemplified in block 207 of method 200). In FIG. 4B, at block 431, an increase in the amount of compensation for the circulatory system is determined. As disclosed herein, immune activation can induce cardiac or circulatory compensation resulting in a change in the Doppler waveform. This waveform change can be detected and evaluated via the US probe and / or controller of the NUA system of the present disclosure. At block 433, sixth information representative of an amount of compensation for the circulatory system is generated based on the increase in the amount of compensation for the circulatory system. In such an embodiment, the change in the Doppler waveform corresponds to the second information, and the increase in the amount of compensation for the circulatory system based on the change in the Doppler waveform corresponds to the third information and / or the sixth information.

[0067] Additionally or alternatively, Figure 4C is a block diagram illustrating an exemplary computer-implemented method 460 for generating third information representative of a change in the circulatory system of a subject based on processing second information (as exemplified in block 207 of method 200). In Figure 4C, block 461 determines a decrease in the amount of the body structure or its characteristic circulating through the circulatory system. Block 463 generates seventh information representative of a change in vascular circulation by the circulatory system based on the decrease in the amount of the body structure or its characteristic circulating through the circulatory system. In such an embodiment, the amount of the body structure or its characteristic circulating through the circulatory system corresponds to the second information, and the change in vascular circulation corresponds to the third information and / or the seventh information.

[0068] FIG. 5 is a block diagram illustrating an exemplary data processing system 500 that can be used with one or more of the described embodiments. For example, system 500 can represent any data processing system (e.g., one or more of the systems described above performing any of the operations or methods described above in connection with FIGS. 1-4, etc.). System 500 can include many different components. These components can be implemented as integrated circuits (ICs), portions thereof, discrete electronic devices, or other modules that fit onto a circuit board such as a motherboard or add-in card of a computer system, or components otherwise integrated within a chassis of a computer system. Also, system 500 is intended to show an overhead view of many, but not all, components of a computer system. Nevertheless, it should be understood that in some implementations there may be additional components and that in other implementations the illustrated components may be further arranged differently. System 500 may represent a desktop computer system, a laptop computer system, a tablet computer system, a server computer system, a mobile phone, a media player, a personal digital assistant (PDA), a personal computer, a network router or hub, a wireless access point (AP) or repeater, a set-top box, or any combination thereof. Additionally, although only a single machine or system is depicted, the term "machine" or "system" should be interpreted to include machines or systems that individually or collectively execute instructions to perform any of the methodologies described herein.

[0069] In one embodiment, system 500 includes processor(s) 501, memory 503, network interface device(s) 505, input / output (I / O) device(s) 506, further I / O device(s) 507, storage device(s) 508, and standalone system / device 511 via bus or interconnect 710. System 500 also includes network 512. Processor(s) 501 may represent a single processor or multiple processors including a single processor core or multiple processor cores. Processor(s) 501 may represent one or more general purpose processors such as a microprocessor, a central processing unit (CPU), or a graphic processing unit (GPU). In particular, processor(s) 501 may be a complex instruction set computer (CISC), reduced instruction set computer (RISC), or very long instruction word (VLIW) computer architecture processor, or a processor implementing a combination of instruction sets. The processor(s) 501 can be one or more application specific processors, such as an application specific integrated circuit (ASIC), an application specific instruction set processor (ASIP), a cellular or baseband processor, a field programmable gate array (FPGA), a digital signal processor (DSP), a physical processing unit (PPU), an image processor, an audio processor, a network processor, a graphics processor, a graphics processing unit (GPU), a network processor, a communications processor, a cryptographic processor, a co-processor, an embedded processor, a floating point unit (FPU), or any logic capable of processing instructions;

[0070] The processor(s) 501, which may be a low-power multi-core processor socket such as an ultra-low voltage processor, may act as a main processing unit and a central hub for communicating with various components of the system. Such processor(s) may be implemented as one or more system-on-chip (SoC) integrated circuits (ICs). Within the processor(s) 501, a neurovascular ultrasound (NUA) logic / module 528A may reside, completely or at least partially. In one embodiment, the NUA logic / module enables the processor(s) 501 to perform some or all of the operations or methods described above in connection with FIGS. 1-4. Additionally or alternatively, the processor(s) 501 may be configured to execute instructions for implementing or executing the subject matter (e.g., operations, methodologies, etc.) described herein.

[0071] The system 500 may further include a graphics interface that communicates with any graphics subsystem, which may include a display controller, a graphics processing unit (GPU), and / or a display device. The processor(s) 501 may communicate with a memory 503, which in one embodiment may be implemented through multiple memory devices to provide a given amount of system memory. The memory 503 may include one or more volatile storage (or memory) devices, such as random access memory (RAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), static RAM (SRAM), or other types of storage devices. The memory 503 may store information, including a sequence of instructions to be executed by the processor(s) 501 or any other device. For example, executable code and / or data from various operating systems, device drivers, firmware (e.g., input / output basic system or BIOS), and / or applications may be loaded into the memory 503 and executed by the processor(s) 501. The operating system may be any type of operating system. The NUA logic / module 528B may also reside completely or at least partially within the memory 503.

[0072] In one embodiment, memory 503 includes the NUA logic / modules as executable instructions. In another embodiment, the instructions represented by the DAM logic / modules, when executed by processor(s) 501, cause processor(s) 501 to perform any, in whole or in part, of the operations or methods described above in connection with FIGS. 1-4.

[0073] System 500 may further include I / O devices such as device 506, including network interface device(s) 505, any input device(s) and any other I / O device(s) 507. Network interface device 505 may include a wired or wireless transceiver and / or a network interface card (NIC). The wireless transceiver may be a WiFi transceiver, an infrared transceiver, a Bluetooth transceiver, a WiMax transceiver, a wireless cellular telephony transceiver, a satellite transceiver (e.g., a Global Positioning System (GPS) transceiver), or other radio frequency (RF) transceiver, or a combination thereof. The NIC may be an Ethernet card.

[0074] The input device(s) may include a mouse, a touchpad, a touch-sensitive screen (which may be integrated with a display device), a pointer device such as a stylus, and / or a keyboard (e.g., a physical keyboard or a virtual keyboard displayed as part of a touch-sensitive screen). For example, the input device may include a touch screen controller coupled to a touch screen. The touch screen and touch screen controller may detect contact and movement or interruption thereof using one or more touch sensitivity technologies, including, for example, but not limited to, capacitive, resistive, infrared, and surface acoustic wave technologies, as well as other proximity sensor arrays or other elements to determine one or more contacts with the touch screen.

[0075] The I / O devices 506 may include audio devices. The audio devices may include speakers and / or microphones to facilitate voice-enabled functions such as voice recognition, voice duplication, digital recording, and / or telephone functions. Other I / O devices 507 may include universal serial bus (USB) port(s), parallel port(s), serial port(s), printers, network interfaces, bus bridges (e.g., PCI-PCI bridges), sensors (e.g., motion sensors such as accelerometers, gyroscopes, geomagnetic sensors, light sensors, compasses, proximity sensors, etc.), or combinations thereof. The device(s) may further include an image processing subsystem (e.g., a camera) that may include an optical sensor, such as a charge-coupled device (CCD) or a complementary metal-oxide semiconductor (CMOS) optical sensor, utilized to facilitate camera functions such as recording pictures or video clips. Depending on the particular configuration or design of system 500, some sensors may be coupled to interconnect 710 via a sensor hub (not shown), while other devices, such as a keyboard or thermal sensor, may be controlled by an embedded controller (not shown).

[0076] One or more mass storage devices (not shown) may also be coupled to the processor(s) 501 for persistent storage of information such as data, applications, and one or more operating systems. In various embodiments, this mass storage may be implemented via a solid state device (SSD) to allow for thinner and lighter system designs and to increase system responsiveness. However, in other embodiments, mass storage may be implemented primarily using a hard disk drive (HDD) with a small amount of SSD storage acting as an SSD cache to allow non-volatile storage of context state and other such information during power-down events for faster power-up upon restart of system activity. A flash device may also be coupled to the processor(s) 501 via, for example, any serial peripheral interface (SPI). This flash device may provide non-volatile storage of system software, including basic input / output software (BIOS) and other firmware.

[0077] The NUA logic / module 528C may be part of a specialized stand-alone computer system / apparatus 511 formed from hardware, software, or a combination thereof. In one embodiment, the NUA logic / module 528C performs any, in whole or in part, of the operations or methods described above in connection with FIGS. 1-4.

[0078] The storage device 508 may include a computer-accessible storage medium 509 (also known as a machine-readable storage medium or computer-readable medium) that stores one or more instruction sets or software, such as NUA logic / module 528D.

[0079] In one embodiment, the instruction(s) or software stored on storage medium 508 embody one or more of the methodologies or functions described above in connection with Figures 1-4. In another embodiment, storage device 508 includes NUA logic / modules as executable instructions. The instructions represented by the NUA logic / modules, when executed by processor(s) 501, cause system 500 to perform any, in whole or in part, of the operations or methods described above in connection with Figures 1-4.

[0080] The computer-readable storage medium 509 can persistently store some or all of the software functions of the NUA logic / modules described above. Although the exemplary embodiment shows the computer-readable storage medium 509 as a single medium, the term "computer-readable storage medium" should be interpreted to include a single medium or multiple media (e.g., centralized or distributed databases and / or associated caches and servers) that store one or more sets of instructions. The term "computer-readable storage medium" should also be interpreted to include any medium that can store or encode a set of instructions executed by the system 500 and cause the system 500 to perform any one or more of the disclosed methodologies. Thus, the term "computer-readable storage medium" should be interpreted to include, but is not limited to, solid-state memory, optical and magnetic media, or any other non-transitory machine-readable medium.

[0081] It should be noted that while system 500 is shown with various components of a data processing system, it is not intended to represent any particular architecture or manner of interconnecting the components, and thus the details are not relevant to the embodiments described herein, and it will be understood that network computers, handheld computers, mobile phones, servers, and / or other data processing systems having fewer or possibly more components may also be used with the embodiments described herein.

[0082] The present disclosure provides, in some aspects, a NUA system for determining the presence of an allergic reaction in a subject. The neurovascular US analysis system includes a US probe configured to transmit US waves to a region of the subject. The region includes an internal structure. The neurovascular US analysis system includes a processor communicatively coupled to the US probe. The processor is configured to execute instructions for receiving, via the US probe, first information representative of a reflection of the US waves from the region, generating second information representative of the internal structure or a characteristic thereof based on processing the first information, generating third information representative of a change in the circulatory system of the subject based on processing the second information, determining the presence of an allergic reaction to a potential allergen in the subject based on the third information, and outputting, via a user interface communicatively coupled to the processor, fourth information indicative of the presence of the allergic reaction. In some embodiments, the third information includes one or more of fifth information representative of a change in an immune response associated with the circulatory system, sixth information representative of an amount of compensation for the circulatory system, and seventh information representative of a change in vascular circulation by the circulatory system.

[0083] FIG. 6 illustrates an exemplary device 600 for providing a computer-implemented method for neurovascular ultrasound analysis (NUA) in a system according to aspects of the present disclosure. Specifically, a series of example components 602-618 are provided in the device 600. Thus, according to an embodiment, the device 600 can be the computer device in the example of FIG. 1. In an example, the device 600 can be an ultrasound device having advanced capabilities according to the present disclosure. For example, the ultrasound device can identify and process discriminant features from each of the first, second, third and fourth signals mentioned in the previous examples with the advanced capabilities. Thus, the ultrasound diagnostic device 600 includes instructions in the memory 604 for the microprocessor 602, the classifier 610 and the signal modification element 612 to generate or provide discriminant features from each of the first, second and third signals. The discriminant features in each of the first, second and third signals can include velocity values ​​that are clustered in a two-dimensional plane to aid in determining that a neuropathic problem is identified and managed.

[0084] The illustrated example device 600 includes at least one main microprocessor 602 that executes instructions stored in physical memory 604 on a device such as dynamic random access memory (DRAM) or flash memory, among other options. As will be apparent to one skilled in the art, the device 600 can include many types of memory, data storage, or computer readable media, such as a hard drive or solid state memory that serves as data storage or memory 604 for the device. Application instructions executed by the at least one microprocessor 602 can be stored in an additional data storage device (separate from memory 604) and loaded into memory 604 as needed for operation of the device 600. The microprocessor 602 can also have internal memory that is used to temporarily store data and instructions for processing in some embodiments. The device 600 can also support removable memory (either as part of memory 604 or separate from memory 604) that is useful for sharing information with other devices. The device can also include one or more power components 616 that provide power to the device. As one of ordinary skill in the art would readily appreciate, the power components may include a battery compartment for powering the device using a rechargeable battery, an internal power source, or a port for receiving external power, among other options.

[0085] The computing device may include or communicate with at least one type of display element 606, such as a touch screen, organic light emitting diode (OLED) or liquid crystal display (LCD). Some devices may include multiple display elements and may also include LEDs, projectors, and the like. The device may include at least one communication or networking component 614, allowing for sending and receiving various types of data or other electronic communications. The communication may be via any suitable type of network, such as the Internet, an intranet, a local area network (LAN), a 5G or other cellular network, or a Wi-Fi network, or may utilize transmission protocols such as BLUETOOTH or NFC, among others. The device may include at least an input element 618 that may receive input from a user or other source. The input device may include, for example, a button, a dial, a slider, a touchpad, a wheel, a joystick, a keyboard, a mouse, a trackball, a camera, a microphone, a keypad, or other such device or component. In some embodiments, the various devices may be connected by wireless links or other such links. In some embodiments, the device can be controlled via a combination of visual and audio commands or gestures so that the user can control the device without having to touch the device or a physical input mechanism. The device 600 can also include a probe transmit / receive element 608 that provides and receives signals, such as Doppler audio signals. In one operational example, the Doppler signal can also be converted into an audio signal, with higher blood flow velocities resulting in higher pitched sounds and lower velocities resulting in lower pitched sounds. The classifier 610 can be a neural network classifier that classifies discriminant features of the audio signal or directly from the Doppler audio sound. The discriminant features can be the Fourier transformed audio signal or the untransformed velocity values ​​presented from the audio signal.

[0086] Most of the functionality utilized with various embodiments can operate in a computing environment that can be operated by or for a healthcare provider or entity. Additionally or alternatively, there can be one or more dedicated computing resources allocated as part of the cloud environment. FIG. 7 illustrates an exemplary network architecture or environment 700 used in a system for a computer-implemented method for neurovascular ultrasound analysis (NUA) to detect food allergies according to aspects of the present disclosure. The exemplary network architecture or environment 700 can also be used for sharing or remote control of the NUA detection process. The resources can utilize any of a number of operating systems and applications and can include any number of workstations or servers 702, 704. Various embodiments can utilize at least one cloud or Internet-based network 706 that supports communication using any of a variety of commercial protocols such as TCP / IP or FTP, among others. Other example networks 706 include, for example, local area networks, wide area networks, virtual private networks, the Internet, intranets, and various combinations thereof. A server 712 can be used to host offerings such as parts of the classifier 610. This allows the classifier to be retrained to provide test or training neural networks to improve the accuracy of the system. In one example, once a waveform of a subject with a detected allergy is identified, the values ​​or points of the waveform are stored to train the network. Once NUA detection is made, improvements are made to the waveform in the form of new values ​​or points that can be used to train a second network. For future human subjects, the human subject is then tested against the two networks to determine where to classify the waveform obtained from each future human subject. If the classification indicates a normal blood flow pattern, the subject's condition is determined to be non-allergic.Further, if the classification indicates an allergic reaction in the subject, an anti-allergy medication can be administered to the human subject to alleviate symptoms associated with the detected allergy. In some embodiments, the allergy medication can be an antihistamine, a corticosteroid, a bronchodilator, a mast cell stabilizer, a leukotriene inhibitor, a serine pulmonary protease inhibitor, or any combination or derivative thereof. In some embodiments, the antihistamine can be an H1-antihistamine, an H2-antihistamine, an H3-antihistamine, an H4-antihistamine, or any combination thereof.

[0087] Since the neural network process is a complex data-intensive process, the classifier or a portion of the classifier 718 may be run from the server 712. Data for each session of NUA detection may be encrypted and stored in data storage 714 with anonymity except for an indication of the severity of the condition. The session information 716 is useful for ongoing NUA detection, and after the session is completed, the data may be moved from the session information 716 to the data storage 714. The data may then be moved to the classifier 718 to improve it. In some examples, apart from the neural network, a support vector machine (SVM) or k-nearest neighbor algorithm may also be used. As with the neural network, pitch or other features may be extracted from the audio version of the signal received from the probe, including Fourier transform and linear prediction coefficients. These features are used to train or classify the data into clusters.

[0088] The functions performed by the servers 708, 710, 712 may be effected by instructions configured to execute a program or script in response to a request from the user device 702, 704. Such a process may include executing one or more applications that may be implemented as one or more scripts or programs written in any suitable programming language. The servers 708, 710, 712 may also include one or more database servers that perform other such operations in response to data requests. The environment 700 may also include any of a variety of data stores and other memory and storage media as described above. Where the system includes computerized devices, each such device may include hardware elements that may be electrically coupled via a bus or other such mechanism. As one skilled in the art will readily appreciate, example elements include at least one central processing unit (CPU), as described above, and one or more storage devices, such as disk drives, optical storage devices, solid-state storage devices such as random access memory (RAM) or read-only memory (ROM), removable media devices, memory cards, flash cards, and the like. Such an apparatus may also include or utilize one or more computer-readable storage media that store instructions executable by at least one processor of the apparatus. An example apparatus may also include a number of software applications, modules, services, or other elements disposed in memory, including an operating system and various application programs. It should be understood that alternative embodiments may have numerous variations from those described above.

[0089] Various types of non-transitory computer-readable storage media can be used for various purposes as described and suggested herein. For example, these purposes include storing instructions or code executable by at least one processor to cause the system to perform various operations. The media can correspond to any of various types of media, including volatile and non-volatile memory, which in some implementations can be removable. The media can store various computer-readable instructions, data structures, program modules, and other data or content. Types of media include, for example, RAM, DRAM, ROM, EEPROM, flash memory, solid-state memory, and other memory technologies. Other types of storage media can also be used, including optical (e.g., Blu-ray or digital versatile disc (DVD)) storage devices or magnetic storage devices (e.g., hard drives or magnetic tapes), etc. Based on the disclosure and teachings provided herein, one of ordinary skill in the art will recognize other ways and / or methods of implementing various embodiments.

[0090] The present disclosure provides, in some aspects, a non-transitory computer-readable medium including instructions executable by one or more processors to perform operations of the NUA detecting an allergic reaction. The operations include directing, via the processor, a US probe communicatively coupled to the processor to transmit US waves to a region of the subject. The region includes an internal structure. The operations include receiving, via the processor, first information representative of a reflection of the US waves from the region; generating, via the processor, second information representative of the internal structure or a characteristic thereof based on processing the first information; generating, via the processor, third information representative of a change in the circulatory system of the subject based on processing the second information; determining, via the processor, the presence of an allergic reaction to a potential allergen in the subject based on the third information; and directing, via the processor, a user interface communicatively coupled to the processor to output, via the processor, fourth information indicative of the presence of the allergic reaction. In some embodiments, the third information includes one or more of fifth information representative of a change in an immune response associated with the circulatory system, sixth information representative of an amount of compensation for the circulatory system, and seventh information representative of a change in vascular circulation by the circulatory system. In some embodiments, determining the presence of an allergic response includes determining that one or more of the fifth information, the sixth information, and the seventh information are greater than one or more respective thresholds. In some embodiments, generating second information representative of an internal structure or a characteristic thereof includes determining an antegrade pulsatility index, an antegrade volumetric flow rate, a retrograde pulsatility index, a retrograde volumetric flow rate, or a combination thereof for one or more limbs of the subject, and determining a neurovascular index for the one or more limbs comprising an antegrade pulsatility index, an antegrade volumetric flow rate, a retrograde pulsatility index, a retrograde volumetric flow rate, or a combination thereof. In some embodiments, the one or more limbs include an upper limb or a lower limb. In some embodiments, generating third information includes determining a decrease in a cumulative antegrade volumetric flow rate score based on a sum of the antegrade volumetric flow rates for each of the one or more limbs, and generating fifth information representative of a change in an immune response associated with the circulatory system based on the decrease in the cumulative antegrade volumetric flow rate score.In some embodiments, the third information comprises fifth information. In some embodiments, generating the third information comprises determining an increase in an amount of compensation to the circulatory system and generating sixth information representative of the amount of compensation based on the increase in the amount of compensation to the circulatory system. In some embodiments, the third information comprises sixth information. In some embodiments, generating the third information comprises determining a decrease in an amount of the body structure or a characteristic thereof circulating through the circulatory system and generating seventh information representative of a change in vascular circulation based on the decrease in the amount of the body structure or a characteristic thereof. In some embodiments, the third information comprises seventh information.

[0091] In one embodiment, the environment of Figure 7 can be a distributed computing environment utilizing multiple computer systems and components interconnected through communications links using one or more computer networks or direct connections. However, one of ordinary skill in the art will appreciate that such a system may operate similarly in systems having fewer or more components than those depicted. Thus, the depictions of various systems and services herein should be considered exemplary in nature and not limiting of the scope of the disclosure.

[0092] Various aspects may be implemented as part of at least one service or web service, such as part of a service-oriented architecture. Services, such as web services, may communicate using any suitable type of messaging, such as messages in Extensible Markup Language (XML) format, exchanged using a suitable protocol, such as SOAP (derived from "Simple Object Access Protocol"). Processes provided or performed by such services may be written in a suitable language, such as Web Services Description Language (WSDL). Use of a language such as WSDL may enable features such as automatic generation of client-side code in various SOAP frameworks.

[0093] In embodiments utilizing a server, the server may run any of a variety of server or mid-tier applications including an HTTP server, an FTP server, a CGI server, a data server, a Java server, and a business application server. The server(s) may also execute programs or scripts in response to requests from user devices, such as by executing one or more web applications, which may be implemented as one or more scripts or programs written in any programming language, such as Java, C, C#, or C++, or any scripting language, such as Perl, Python, Tool Command Language (TCL), and combinations thereof. The server may also include database servers, including, but not limited to, those commercially available from Oracle, Microsoft, Sybase, and IBM.

[0094] The environment may include various data stores and other memory and storage media as described above. These may reside in a variety of locations, such as on storage media local to (and / or resident on) one or more computers, or across a network, remote from some or all of the computers. In a particular set of embodiments, information may reside in a storage area network ("SAN"), as known to those skilled in the art. Similarly, any files necessary to perform functions by a computer, server, or other network device may be stored locally and / or remotely, as appropriate. Where a system includes computerized devices, each such device may include hardware elements that may be electrically coupled via a bus, including, for example, at least one central processing unit (CPU), at least one input device (e.g., a mouse, keyboard, controller, touch screen, or keypad), and at least one output device (e.g., a display device, printer, or speaker). Such a system may also include one or more storage devices, such as disk drives, optical storage devices, solid-state storage devices such as random access memory ("RAM") or read-only memory ("ROM"), removable media devices, memory cards, and flash cards.

[0095] Such devices may include computer-readable storage media readers, communication devices (e.g., modems, network cards (wireless or wired), infrared communication devices, etc.), and working memories as described above. The computer-readable storage media readers may be connected to or configured to receive computer-readable storage media representing remote, local, fixed and / or removable storage devices, as well as storage media that temporarily and / or more permanently contain, store, transmit, and retrieve computer-readable information. The systems and various devices may also include a number of software applications, modules, services, or other elements located within at least one working memory device, including an operating system and application programs such as client applications or web browsers. It should be understood that alternative embodiments may have numerous variations from those described above. For example, customized hardware may be used and / or certain elements may be implemented in hardware, software (including portable software such as applets), or both. Additionally, connections to other computing devices, such as network input / output devices, may be employed.

[0096] The vascular restrictions imposed on a single neuron are complex and involve multiple systems involved distally and proximally in regulating and promoting neurovascular circulation. These systems may have distal or local damaged vasculature that can affect circulation proximally and distally through proximal and distal hypo- or hyper-function of regulatory systems.

[0097] In the above description, numerous specific details are provided, such as specific configurations, dimensions, and processes, to allow a thorough understanding of the embodiments. In other instances, well-known processes and ultrasonic techniques are not described in detail so as not to unnecessarily obscure the embodiments. References throughout this specification to "one embodiment," "an embodiment," "another embodiment," "other embodiments," "some embodiments," and variations thereof mean that a particular feature, structure, configuration, or characteristic described in connection with an embodiment is included in at least one embodiment. Thus, the appearance of "in one embodiment," "in an embodiment," "in another embodiment," "in other embodiments," "some embodiments," or variations thereof in various places throughout this specification are not necessarily referring to the same embodiment. Furthermore, particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more embodiments.

[0098] In the following description and claims, the terms "coupled" and "connected," along with their derivatives, may be used. It should be understood that these terms are not intended as synonyms for each other. "Coupled" is used to indicate that two or more elements or components that may or may not be in direct physical or electrical contact with each other co-operate or interact with each other. "Connected" is used to indicate the establishment of communication between two or more elements or components that are coupled with each other.

[0099] Some portions of the detailed description are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory. These algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. An algorithm is generally conceived herein as a self-consistent sequence of operations leading to a desired result. These operations require physical manipulations of physical quantities. It should be noted, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels given to these quantities. As is apparent from the above description, unless otherwise stated, throughout the description, descriptions utilizing such terms as set forth in the following claims should be understood to refer to the operations and processing of a computer system or similar electronic computer system that manipulates data represented as physical (electronic) quantities in the registers and memories of the computer system, and transforms it into other data similarly represented as physical quantities in the memory, registers, or other such information storage, transmission or display device of the computer system.

[0100] The embodiments described herein may include or relate to an apparatus that executes a computer program (e.g., the operations described herein). Such a computer program is stored on at least one non-transitory computer-readable medium. A machine-readable medium includes any mechanism for storing information in a form readable by a machine (e.g., a computer). For example, a machine-readable (e.g., computer-readable) medium includes a machine (e.g., computer) readable storage medium (e.g., read-only memory ("ROM"), random access memory ("RAM"), magnetic disk storage media, optical storage media, flash memory devices).

[0101] Although one or more embodiments of at least two of the above-mentioned operations or methods are described in a sequential order, it is to be understood that any two or more of these operations or methods may be performed in a different order. Furthermore, at least two or more of these operations or methods may be performed in parallel rather than sequentially. The embodiments described herein have not been described with reference to any particular programming language. It will be understood that various embodiments of the disclosed subject matter may be implemented using a variety of programming languages. It is to be understood that at least one of the embodiments described herein may be combined, modified, or varied in utilizing various aspects of the embodiments described herein to manage at least one of the components of a processing system to enhance the power and performance of the components. Thus, various modifications may be made to these embodiments without departing from the broad spirit and scope of at least one of the concepts of the present disclosure as set forth in the following claims. Accordingly, the specification and drawings are to be regarded in an illustrative and not restrictive sense.

[0102] In developing any implementation of one or more of the disclosed concepts (e.g., software and / or hardware development projects), numerous decisions must be made to achieve the developer's particular goals (e.g., adhering to system-related and / or business-related constraints). These goals may vary from implementation to implementation, which may affect the actual implementation of one or more of the disclosed concepts as illustrated in the embodiments described herein. While such a development effort may be complex and time-consuming, it may be a routine undertaking for one of ordinary skill in the art in designing and / or implementing one or more of the inventive concepts as illustrated in the embodiments described herein.

[0103] Ultrasound imaging with the NUA systems, methods and devices disclosed herein is particularly useful for identifying which systems of a subject, including either proximally located systems or distally located systems, may be impaired by the tested allergen. Ultrasound imaging can also be used to identify which nerves surrounding the ultrasound probe may be affected. Thus, ultrasound imaging identifies which systems are affecting neural circulation and any level of ischemia occurring in neurovascular structures proximate to the ultrasound probe. This identification facilitates quantitative and efficient detection of an allergic response in a subject.

[0104] More specifically, the monitored allergic reaction generated according to the present embodiment may generate neurovascular inflammation at some point on a particular nerve, reducing nerve conduction from that point. In general, nerve conduction drives its own endoneurial circulation, and reduced nerve firing slows down the endoneurial circulation, further reducing nerve firing. In essence, neurovascular inflammation creates a positive feedback loop. This can result in immune intervention of a positive feedback loop involving nerve ischemia, where fluid leaks from the perforated capillaries, thus closing off circulation from the epineurial capillaries, resulting in perineural occlusion of the transperineural communicating capillaries. The neurovascular index (NVI) of the NUA embodiments disclosed herein facilitates detection of areas that generate this downstream inflammation.

[0105] Neuropathy is a combination of decreased electrical / endoneurial ischemia occurring upstream or distally, where local resistance increases with decreased lateral / medial hydraulic pressure. This decreased hydraulic pressure often occurs distal to the subject's limb. The user can evaluate the NVI-related measurements described above to assess the larger macrovascular picture or condition of the system and / or the small vessels or details of the system. When electrical breakdown is present, such as in the insular cortex, precentral or postcentral cortex, or distal nerves, a dissociation will occur between the proximal and distal nerve measurements. The most common dissociation is a decrease in the proximal measurements and an increase in the distal measurements. In general, distal measurements do not benefit from the strong endoneurial blood flow driven by anterograde or anterograde nerve firing. Circulation is driven solely by local arterial to small vessel push. When this occurs, a separation occurs between the two measurements because the hydraulic push closest to the heart overcomes the greater neurocapillary resistance provided by the deeper circulation, but this circulation becomes turbulent and backflow occurs back into the arteries, resulting in a lossy waveform on the more proximal Doppler ultrasound image.

[0106] In contrast, distal regions of the subject experience less waveform defect due to the reduced strength of hydraulic push away from the heart. This relationship indicates that in the absence of a strong endoneurial circulatory system, the epineural circulation is more superficial and clean while offering less resistance. However, along with the epineural circulation, some AV shunting can occur along with deeper capillary ischemia. This degree of discrepancy in NVI measurements between the proximal and distal nerves can provide the user of the NUA system with an understanding of the degree of congestion of the endoneurial capillaries. The greater the discrepancy, the greater the congestion and vice versa.

[0107] In some embodiments, examination of upper extremity (UE) and lower extremity (LE) NVI measurements provides a systems level view of the circulation within a subject. A user equipped with an embodiment of the NUA disclosed herein can compare small fiber UE NVI measurements to small fiber LE NVI measurements, compare small fiber NVI measurements to large fiber NVI measurements, and / or refocus the examination to the individual nerves of choice. Visceral inflammation can also be assessed with NVI measurements, as it can affect adjacent sympathetic nerves that serve the ipsilateral LE by creating ischemia in the paravertebral ganglion. The user can also assess the nerve root circulation. Some examples of major systems and problems that can be identified with regard to the nerve root circulation include autonomic neuropathy that alters the input into the microvascular circulation, small fiber degeneration and its degree, large fiber degeneration and its degree, individual nerves affected by ischemia, and general inflammation and its degree throughout the system. The NUA technique also facilitates examination of local hydraulic (macrovascular to microvascular) versus systemic / local electrical (endoneurial) causes of neuropathy.

[0108] Thus, the NVI-based embodiment of the NUA system for allergy detection can provide an objective and quantifiable estimate of the degree of inflammation a person is experiencing overall. The sum of the h (epineurial) and e (endoneural) circulations allows a medical professional to assess the severity of inflammation in a particular subject and identify ischemic bias, such as whether ischemia is primarily outside or inside the fascia of the nerve. Adding both factors also provides a total ischemic factor that a medical professional can use to estimate the degree to which a subject is allergic to a particular allergen tested. The non-limiting examples below illustrate the use of some of these factors for allergy detection by the NUA method disclosed herein.

[0109] In fact, as mentioned above, food allergy has traditionally been difficult to diagnose. However, the changes recorded in NVI measurements show the improvement or deterioration of the relationship between the microvasculature and the macrovasculature after exposure to certain types of food. As can be understood by those skilled in the art, the NUA method and system disclosed herein can assist in the study of food or medicine and how they affect the microvascular circulation of certain affected subjects.

[0110] Embodiments of the present disclosure can be further understood with reference to the following examples. EXAMPLES

[0111] This embodiment of neurovascular ultrasound analysis (NUA) facilitates non-subjective and non-invasive evaluation of a subject for allergic response to an allergen. In an embodiment of the present disclosure, a US probe is placed on or in an area of ​​a subject's limb. In this example, several areas of the left upper extremity (LUE) and left lower extremity (LLE) are evaluated before exposing the subject to a specific allergen to determine personalized baseline NVI measurements of the subject's area. The subject was also evaluated after exposure to a controlled specific allergen to determine post-exposure NVI measurements. During baseline and post-exposure testing, the US probe emits US waves in the area and NUA evaluation is performed according to an embodiment of the present disclosure.

[0112] As disclosed herein, the method for NUA facilitates the determination of the degree of allergic reaction to the tested allergen. For example, NUA can indicate that a subject has no reaction, a low reaction, a moderate reaction, or a severe reaction to an allergen based on the quantification of inflammation detected in the subject's body. In this embodiment described below, the severity of the subject's allergic reaction to an allergen is evaluated in terms of the neurovascular index (NVI), which evaluates the above-mentioned h factor (epineurial) and e factor (endoneural), in order to identify ischemic bias. In fact, the NVI presents and analyzes body inflammation information for allergy detection, and an increase in the inflammation measurement after allergen exposure indicates an allergic reaction.

[0113] In some embodiments, the NUA assessment evaluates any out-of-normal range waveform variability changes in response to the tested allergen. In some of these embodiments, the normal range for NVI is 7-14, and the test region includes the subject's cervical, dorsal, tibial and / or peroneal nerves. In some embodiments, the NUA assessment also evaluates any abnormal antegrade volumetric flow changes, such as increases or decreases outside of normal variation. Such volumetric flow changes include (1) an increase in antegrade volumetric flow of more than 1.5-fold over control, indicative of cardiac changes (e.g., increases) in response to inflammation, (2) a decrease in antegrade volumetric flow indicative of histamine release in response to the tested allergen, and / or (3) a combination of upper extremity (UI) increases and lower extremity (LE) decreases, indicative of pattern changes related to the location of the test region relative to the heart.

[0114] As shown below, some complete or full spectrum NUA embodiments provide robust allergy detection based on US measurements taken at 10 different body sites. In some embodiments, these sites include 4 UE regions and 6 LE regions, such as 2 on the radial side of the arm, 2 on the ulnar side of the arm, 3 on the inferior medial side of the leg (e.g., tibia), and 3 on the inferior lateral side of the leg (e.g., fibula). All 10 US measurements are collected before allergen exposure and again after allergen exposure.

[0115] Example 1 of Neurovascular Ultrasound Analysis for Allergy Detection The initial measurements of the first allergen tested and the corresponding results are shown in Tables 1-4 below. Table 1 shows the baseline NVI measurements of the subjects' LUE and LLE. Table 2 shows the post-exposure NVI measurements of the subjects' LUE and LLE. Table 3 shows the results for individual nerves of the large fiber nerve. Table 4 shows the results of NUA for allergy detection within subjects. The results of Tables 3 and 4 are described below. Table 1: Baseline NVI measurements for the left upper and lower extremities JPEG2024546473000002.jpg93135 Table 2: Post-exposure NVI measurements of the left upper and lower limbs JPEG2024546473000003.jpg99142 Table 3: Individual nerve results for large fiber nerves JPEG2024546473000004.jpg130153 Table 4: NUA results for allergy detection JPEG2024546473000005.jpg73142

[0116] In some embodiments, positive criteria for allergy detection relative to an individually generated baseline include determining: (1) a rate of change between the post-exposure total NVI measurement and the corresponding baseline total NVI measurement increases by greater than 1.5 or decreases by less than 0.85; (2) a rate of change after exposure in the UE NVI measurement increases by greater than 1.25 and in the LE NVI measurement decreases by greater than 0.8; (3) an AV shunt changes from UE dominant to LE dominant; (4) a rate of change in total AV shunt of greater than 0.15; or (5) any combination thereof.

[0117] The NUA system determines that the subject has a definite allergic reaction to the tested allergen according to Table 4 above. For example, the AV shunt changes by -0.538÷-0.229=2.349 between the control and post-exposure measurements, which is greater than the threshold of 0.15. Also, the rate of change between the post-exposure total NVI measurement and the corresponding baseline total NVI measurement is 101.560÷124.620=0.815, which is less than the threshold of 0.85. It should be understood that an allergic reaction can be confirmed by reaching a positive criterion. Furthermore, the positive criterion can be adjusted as part of the training of the classifier or neural network described above in Figures 6-7, respectively, as more tests are performed and more data is accumulated.

[0118] Example 2 of Neurovascular Ultrasound Analysis for Allergy Detection Example 2 shows a further implementation of the NUA disclosed herein for analyzing a subject's response to a tested potential allergen. That is, Example 2 generally follows the same procedure as Example 1, but provides allergen-specific data quantifying any associated inflammation in the subject's body. In this embodiment, the tested allergen is bread. In such an embodiment, a positive diagnostic indication of bread allergy can be indicative of Celiac disease. Table 5 shows the baseline NVI measurements of LUE and LLE of the subject before ingesting bread. Table 6 shows the post-exposure NVI measurements of LUE and LLE of the subject after ingesting bread. Table 7 shows the results of NUA for allergy detection in the subject. The results of Table 7 are described below. Table 5: Baseline NVI measurements for left upper and lower extremities JPEG2024546473000006.jpg99142 Table 6: Post-exposure NVI measurements of the left upper and lower extremities JPEG2024546473000007.jpg93135 Table 7: NUA results for allergy detection JPEG2024546473000008.jpg73142

[0119] The NUA system can determine in this NUA step that the subject does not have a significant allergic reaction to the tested allergen according to Table 7 above. As an example, the AV shunt changes by 0.014÷0.103=0.136 between the control and post-exposure measurements, which is below the threshold of 0.15. Also, the positivity criteria can be adjusted as part of training the classifiers or neural networks described above in Figures 6-7, respectively, as further testing is performed and more data is accumulated.

[0120] Furthermore, Table 8 shows the standard deviation of the left NVI score. In this example, the analyzed nerves of the upper limb include the proximal radial nerve, the proximal ulnar nerve, the distal radial nerve, and the distal ulnar nerve. The analyzed nerves of the lower limb include the proximal peroneal nerve, the proximal PTA nerve, the distal peroneal nerve, and the distal PTA nerve. Furthermore, Table 9 shows the three-point analysis of specific nerves. The standard deviation of the NVI score is also shown. As shown, a statistically significant change is detected via NUA after the subject is exposed to the tested allergen. Therefore, it can be reliably diagnosed that the subject is allergic to the tested allergen. Table 8: Standard deviation of left NVI scores JPEG2024546473000009.jpg21138 Table 9: Three-point neurospecific analysis JPEG2024546473000010.jpg62141

[0121] Example 3 of Efficacy Statistics of Neurovascular Ultrasound Analysis Table 10 shows efficacy statistics for certain Intraneural Facilitation Treatment (INF(TF)) evaluations performed with and without the NVI analysis techniques disclosed herein. As shown, the statistical significance of various factors of the Pain Quality Assessment Scale (PQAS) is expressed via P-values. The P-values ​​are generally lower for evaluations involving NVI analysis, indicating higher statistical significance for the corresponding observed factors based on the NUA techniques of the present disclosure. Table 10: Efficacy statistics for NUA without vs. with NVI analysis JPEG2024546473000011.jpg41147

[0122] Prior to the present disclosure, there was no method to estimate or quantify microvascular circulation. More advantageously, the NUA method and system of the present disclosure can assess the entire circulatory system and individual nerves, including both large and small nerves. These devices or devices can further assess certain autonomic nervous dysregulations found in neuropathy patients. The NUA method and system disclosed herein addresses these needs while actively assessing and providing an image of the microvasculature. Indeed, the method, system and device disclosed herein provide several notable advantages over prior allergy assessment methods, such as non-subjectivity, increased ease and reduced invasiveness to the subject.

[0123] Thus, the present disclosure described herein is well adapted to carry out the objects and attain the ends and advantages mentioned and inherent therein. While a number of specific embodiments have been shown and described for purposes of this disclosure, numerous changes in the details of the method and system exist and can be made to achieve the desired results. These and other similar modifications will be readily apparent to those skilled in the art, and are intended to be included within the spirit of the disclosure as set forth herein and the scope of the appended claims.

Claims

1. 1. A neurovascular ultrasound (US) analysis system for determining the presence of an allergic reaction in a subject, comprising: an US probe configured to transmit US waves to a region including an internal structure of the subject; a processor communicatively coupled to the US probe; wherein the processor: receiving, via the US probe, first information representative of reflections of the US waves from the region; generating second information representative of the internal structure or a characteristic thereof based on processing the first information; generating third information representative of changes in the subject's circulatory system based on processing the second information; determining the presence of the allergic reaction to the potential allergen in the subject based on the third information; outputting, via a user interface communicatively coupled to the processor, fourth information indicative of the presence of the allergic reaction. A neurovascular US analysis system configured to execute instructions for:

2. The third information is Fifth information representative of changes in immune responses associated with the circulatory system; sixth information representative of a compensation amount for the circulatory system; and Seventh information representative of changes in vascular circulation by the circulatory system; The neurovascular US analysis system of claim 1 , comprising one or more of:

3. The processor, determining at least one of an antegrade pulsatility index, an antegrade volumetric flow, a retrograde pulsatility index, and a retrograde volumetric flow for a limb associated with the region; determining a neurovascular index for the limb comprising at least one of the antegrade pulsatility index, the antegrade volume flow, the retrograde pulsatility index, and the retrograde volume flow; The neurovascular US analysis system of claim 1 , configured to execute instructions for generating the second information by:

4. The neurovascular US analysis system of claim 3 , wherein the processor is configured to execute instructions for determining an arteriovenous (AV) shunt score for the limb based on the neurovascular index and a predetermined limb score.

5. The neurovascular US analysis system of claim 3, wherein the processor is configured to execute instructions for determining a cumulative antegrade volumetric flow score based on a sum of the antegrade volumetric flow rates of each of the limbs and at least one further limb of the subject.

6. The processor, determining a reduction in the cumulative forward volume flow score; generating fifth information representative of a change in an immune response associated with the circulatory system based on the decrease in the cumulative forward volume flow score; The neurovascular US analysis system of claim 5 , configured to execute instructions for generating the third information by:

7. The processor, determining an increase in compensation to the circulatory system; generating sixth information representing an amount of compensation for the circulatory system based on an increase in the amount of compensation for the circulatory system; The neurovascular US analysis system of claim 1 , configured to execute instructions for generating the third information by:

8. The processor, determining a reduction in the amount of the body structure or characteristic thereof circulating through the circulatory system; generating seventh information representative of a change in vascular circulation by the circulatory system based on a decrease in the amount of the body structure or characteristic thereof circulating through the circulatory system; The neurovascular US analysis system of claim 1 , configured to execute instructions for generating the third information by:

9. The neurovascular US analysis system of claim 1 , wherein the processor is configured to output the fourth information indicative of the presence of the allergic reaction following exposure of the subject to the potential allergen.

10. The processor, outputting a pre-exposure fourth information indicative of the presence of the allergic response prior to exposure of the subject to the potential allergen to establish a baseline measurement; outputting the fourth information indicative of the presence of the allergic reaction based on the baseline measurements and the post-exposure measurements after exposure of the subject to the potential allergen. The neurovascular US analysis system according to claim 1 , configured to:

11. The region of the subject includes a first region of a plurality of test regions of the subject, the plurality of test regions comprising: a first region and a second region on the radial side of the arm; a first region and a second region on an ulnar side of the arm; a first region, a second region, and a third region on a lower medial side of the leg; a first region, a second region, and a third region on a lower lateral side of the leg; The neurovascular US analysis system of claim 1 , comprising:

12. 2. The neurovascular US analysis system of claim 1, wherein the region comprises an upper or lower limb of a subject, the upper limb comprising one or more of a proximal radius, a proximal ulna, a distal radius, and a distal ulna, and the lower limb comprising one or more of a proximal tibia, a proximal fibula internal structure, a distal tibia, and a distal fibula internal structure.

13. 1. A non-transitory computer readable medium comprising instructions executable by a processor to perform operations for neurovascular ultrasound (US) analysis to determine the presence of an allergic reaction, the operations comprising: commanding, via the processor, an US probe communicatively coupled to the processor to transmit US waves to a region including an internal structure of the subject; receiving, via the processor, first information representative of reflections of the US waves from the region; generating, via the processor, second information representative of the internal structure or a characteristic thereof based on processing the first information; generating, via the processor, third information representative of changes in the subject's circulatory system based on processing the second information; and determining, via the processor, the presence of an allergic reaction in the subject to the potential allergen based on the third information; and instructing, via the processor, a user interface communicatively coupled to the processor to output fourth information indicative of a presence of the allergic reaction; A non-transitory computer readable medium comprising:

14. The third information is Fifth information representative of changes in immune responses associated with the circulatory system; sixth information representative of a compensation amount for the circulatory system; and Seventh information representative of changes in vascular circulation by the circulatory system; One or more of the following:

14. The non-transitory computer-readable medium of claim 13, wherein determining the presence of an allergic reaction comprises determining that one or more of the fifth information, the sixth information, and the seventh information are greater than one or more respective threshold values.

15. Generating the second information indicative of the internal structure or a characteristic thereof includes: determining an antegrade pulsatility index, an antegrade volume flow, a retrograde pulsatility index, a retrograde volume flow, or a combination thereof, for one or more extremities, including an upper extremity or a lower extremity, of the subject; determining a neurovascular index for the one or more limbs comprising the antegrade pulsatility index, the antegrade volume flow, the retrograde pulsatility index, the retrograde volume flow, or a combination thereof; 14. The non-transitory computer readable medium of claim 13, comprising:

16. Generating the third information includes: determining a reduction in a cumulative antegrade volume flow score based on a sum of the antegrade volume flow of each of the one or more limbs; generating fifth information representative of a change in an immune response associated with the circulatory system based on the decrease in the cumulative forward volume flow score; and the third information comprises the fifth information.

17. Generating the third information includes: determining an increase in compensation for the circulatory system; generating sixth information representative of an amount of compensation based on an increase in the amount of compensation for the circulatory system; and the third information comprises the sixth information.

18. Generating the third information includes: determining a decrease in the amount of the body structure or characteristic thereof circulating through the circulatory system; generating seventh information indicative of a change in vascular circulation based on the decrease in the amount of the body structure or the characteristic thereof; and the third information comprises the seventh information.

19. 1. A computer-implemented method of neurovascular ultrasound (US) analysis (NUA) for determining the presence of an allergic reaction in a subject, comprising: commanding, via a processor, an US probe communicatively coupled to the processor to transmit US waves to a region including an internal structure of the subject; receiving, via the processor, first information representative of reflections of the US waves from the region; generating, via the processor, second information representative of the internal structure or a characteristic thereof based on processing the first information; generating, via the processor, third information representative of changes in the subject's circulatory system based on processing the second information; and The third information includes information representative of changes in immune responses associated with the circulatory system; information representative of the amount of compensation for the circulatory system; and Information showing changes in vascular circulation, and wherein the computer-implemented method includes one or more of: determining, via the processor, the presence of an allergic reaction in the subject to the potential allergen based on the third information; and instructing, via the processor, a user interface communicatively coupled to the processor to output fourth information indicative of a presence of the allergic reaction; The computer-implemented method further comprising:

20. 20. The computer-implemented method of claim 19, wherein determining the presence of an allergic reaction comprises determining that one or more of the information indicative of a change in the immune response, the information indicative of the amount of compensation, and the information indicative of a change in vascular circulation are greater than one or more respective threshold values.

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