SYSTEMS AND METHODS FOR DETECTION OF CHANGES IN BLOOD FLOW INDICATIVE OF STROKE AND OTHER CONDITIONS

RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application Serial

No. 61/030,116, filed February 20, 2008, entitled "System and Method for Detection of Changes in Blood Flow Indicative of Stroke and Other Conditions," by Steinberg, et al. , incorporated herein by reference.

FIELD OF INVENTION The present invention relates to systems and methods for determining whether an injury has occurred to a subject, such as to a subject's head.

BACKGROUND

Approximately three-quarters of a million individuals suffer from stroke each year in the United States. Existing clinical systems used to assess anomalies (e.g. traumatic brain injury (TBI), stroke, tumors, aneurysm) in a subject's head include methods known to those of ordinary skills in the art such as computer tomography (CT) scans, magnetic resonance imaging (MRI) and the like. However, there is still a need for systems and methods which quickly and non-invasively diagnose trauma to the head or brain, and which may be portable. SUMMARY OF THE INVENTION

The present invention relates to systems and methods and devices for determining whether an injury has occurred to a subject, such as to a subject's head. The subject matter of the present invention involves, in some cases, interrelated products, alternative solutions to a particular problem, and/or a plurality of different uses of one or more systems and/or articles.

In one embodiment, a method of determining injury in a subject comprises determining a first acoustic signal of a first region of a head of a subject suspected of having an injury to the head, the first acoustic signal comprising one or more vibrations at frequencies of less than about 20 kHz, determining a second acoustic signal of a second region of the head, the second acoustic signal comprising one or more vibrations at frequencies of less than about 20 kHz, determining a difference between the first and second acoustic signals, thereby determining whether the subject has an injury to the head.

In another embodiment, a method of determining injury in a subject's head comprises determining an acoustic signal of a subject's head, the acoustic signal comprising one or more vibrations at frequencies of less than about 20 Hz, wherein the subject is suspected of having an injury to the head and determining injury in the subject's head based on the acoustic signal.

In another embodiment, a device for determining injury in a subject's head comprises an article comprising a plurality of sensors able to determine an acoustic signal of less than about 20 Hz, the article being configured and arranged to be immobilized with respect to a subject's head. In yet another embodiment, a method of analyzing a subject's head comprises directing light at a region of a subject's head, determining at least a portion of light reflected from the region of the subject's head, and determining an acoustic signal of the region of the subject's head based on the reflected light, wherein the acoustic signal comprises one or more vibrations at frequencies between about 0.1 Hz and about 20 kHz. Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and/or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference include conflicting and/or inconsistent disclosure with respect to each other, then the document having the later effective date shall control.

BRIEF DESCRIPTION OF DRAWINGS Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

Figures Ia-Ib depict regions of a subject's head in certain embodiments of the invention.

Figures 2a-2c depict examples of attaching a sensor to a subject's head. Figures 3 a and 3 b depict how a fiber optic may be employed to determine an acoustic signal in one embodiment of the invention.

Figures 4a and 4b show graphs of acoustic signals determined from a subject's wrist using a piezoelectric sensor, in some embodiments of the invention.

Figures 5a-5c show graphs of acoustic signals determined from light reflected off a region of a subject, in other embodiments of the invention.

DETAILED DESCRIPTION

The present invention relates to systems, articles, and methods for determining whether injury has occurred to a subject, such as to a subject's head. In one embodiment, acoustic signals from various regions of a subject's body (e.g., various regions of the head) are determined and compared. In some cases, the acoustic signals may be compared to determine whether an injury has occurred, for instance, a traumatic brain injury or stroke. The acoustic signals may comprise one or more vibrations, and in some cases, the vibrations that are determined occur at frequencies between about 20 Hz and about 20 kHz, and in certain cases, at frequencies less than 20 Hz. In some embodiments, a plurality of sensors which can determine acoustic signals are employed, for example, attached to a helmet, a strap, or the like. Additionally, in some embodiments, light is directed at a region of a subject (such as the head), and light reflected from the region is determined to determine the acoustic signals that occurs in the region.

In some embodiments, an article of the present invention may be portable and can be employed at or near the location where an injury to a subject has occurred. For example, the article may be such that it may be transported in and/or stored at a specific location. Non-limiting examples of locations the article may be transported in and/or stored at include an ambulance, a medical kit, an emergency box in a building, and the like. The portable aspect of the article may be useful in determining the severity of the subject's injury at the location of the injury. Determination of the injury at the location of the injury may be advantageous as it may influence the location (e.g. hospital) the subject is transported to for treatment. In addition, determination of the injury at the location of the injury may also allow for quicker diagnosis and/or quicker administration of the required treatment. For example, the article may be able to determine the type

- A - and/or severity of stroke a subject has had at the location of the stroke. Determination of the type and/or severity of stroke may allow for the subject to be transported to the hospital which would be best able to provide treatment for the subject. In addition, treatment of the stroke may begin upon diagnosis of the severity and/or type of stroke and thus, may reduce the damage caused by the stroke.

In some embodiments, the present invention provides methods to determine acoustic signals in a subject. The signals may be determined qualitatively and/or quantitatively. It should be understood, however, that while the discussion herein primarily focuses on the subject's head, this is by way of example only, and other regions of the subject's body may be used in place of or in conjunction with the subject's head, in other embodiments. Examples of suitable subjects include humans, animals (e.g., mammals), or the like. Non-limiting examples of animals include pigs, monkeys, goats, sheep, and dogs. Thus, as can be readily appreciated by one of ordinary skill in the art, the methods of the present invention are suited for use with any animal. As used herein, an "acoustic signal" comprises one or more vibrations each having a specific frequency or frequency range. A "vibration" is a transmission of mechanical energy that propagates through matter as a wave, for example, sound. It should be noted, however, that in certain embodiments of the invention, the "acoustic" signal (or at least some of the vibrations that form the acoustic signal) may not necessarily be audible to the human ear. For instance, the vibrations of the acoustic signal may occur at frequencies that are above or below human hearing (e.g., ultrasound or infrasound), and/or the frequencies may have intensities that are not detectable by the human ear (i.e., the frequencies are below the sound threshold of human detection). Thus, an "acoustic signal" is not to be limited in the instant application in the sense of relating only to sounds that can be physically perceived (heard) by humans.

In some embodiments, the vibrations of the acoustic signals that are determined have frequencies of less than 20 kHz, or less than about 20 Hz in some cases. For instance, the frequencies may be between about 0.1 Hz and about 20 kHz, between about 20 Hz and 20 kHz, between about 1 kHz and about 10 kHz, between about 2 kHz and about 5 kHz, between about 0.1 Hz and about 20 Hz, between about 1 Hz and about 10 Hz, or the like. In a particular embodiment, the frequencies may be between about 0.1 Hz to 10 Hz. In one embodiment, the frequencies are not ultrasound.

As an example, in some aspects of the present invention, one or more acoustic signals are determined in a subject and the acoustic signals may be compared to determine whether an injury has occurred in a subject. For example, the acoustic signals may be determined from two (or more) regions of a subject. The two regions (or more) may each be in a subject's head, and/or other areas of the subject's body. The acoustic signals from the two regions can be compared, and differences between the acoustic signals can be correlated to differences in blood flow between the regions. For instance, the two regions may be located on opposite sides of a subject's body (e.g., on the left and on the right), and differences in acoustic signals between the two regions may be indicitive of an injury in the subject, as the injury may cause differences in blood flow of the two regions, resulting in differences in the acoustic signals.

One aspect of the present invention is generally directed to comparing a first acoustic signal from a first region of a subject's head with a second acoustic signal from a second region of the subject's head. For instance, if the regions are located on opposite sides of the subject's head (e.g., left and right), the regions may be compared, and differences in the first and second acoustic signals may indicate differences in blood flow, for example, that are caused by injuries such as strokes, etc., as noted above. Without wishing to be bound by any theory, it is believed that in a normal head, the blood flow on the left and right sides of a subject are substantially similar, and differences in blood flow that are detected using acoustic signals can be used to determine whether injuries have occurred in the subject.

Thus, in one embodiment, a first and second acoustic signal of the first and second regions of a subject's head are compared to determine whether an injury has occurred to the subject's head (or other portion of the body). Any asymmetry and/or abnormality between the first and second acoustic signal may be an indication of an injury. In certain cases, as mentioned above, a difference in the acoustic signals may correlate to a difference in blood flow within the head. The magnitude of the difference may be used to determine the severity of the injury, in some embodiments. For instance, a larger difference between the first and second acoustic signals determined from the first and the second regions of the subject's head may indicate a severe stroke has occurred, while a smaller difference may indicate a minor stroke has occurred.

As a specific example, differences between acoustic signals in different regions of the head may indicate that an injury has occurred to the head. Non-limiting examples of injuries that may be determined in a subject's head include traumatic brain injury, stroke, tumors, aneurysms, or the like. In one aspect, a difference in acoustic signals between regions in a subject's head may indicate that the injury is a stroke, which may cause differences in blood flow between the regions. The type of stroke may also be determined in some cases, based on the differences in acoustic signal, for example, whether the stroke is an ischemic stroke or a hemorrhagic stroke. In an ischemic stroke, blood supply to part of the brain is decreased, usually due to an occlusion, which may lead to dysfunction and necrosis of the brain tissue in that area. Hemorrhagic stroke involves bleeding within the brain, which can damage nearby brain tissue. In specific cases, a particular type of ischemic stroke, a proximal cerebral artery occlusionstroke may be determined.

However, it should be understood that the regions are not necessarily the left and right hemispheres of the head, but may be any region on the subject's head (and/or other areas of the body) where acoustic signals are determined. In some cases, one region may or may not overlap with another region. As shown in Figure Ia, when acoustics signals are determined from two different regions of the subject's head, the first region 8 may be on the left side 4 of the subject's head 2 and the second region 10 may be on the right side 6 of the subject's head. As shown in Figure Ib, the first region 12 and second region 14 may also be on the same side 4 of the subject's head 2. As another specific example, a first region may be selected to determine an acoustic signal arising from the left hemisphere of the brain, while a second region may be selected to determine an acoustic signal arising from the right hemisphere of the brain. Non-limiting examples of parameters of acoustic signals that may be compared include frequency, amplitude, intensity, and the like. The acoustic signals may be compared, directly or indirectly. For instance, the acoustic signals may be converted into electrical signals or mathematical constructs (e.g., a matrix), which can then be compared. As a specific example, the intensity of the acoustic signals may be converted into electrical signals, which can then be compared to each other. Techniques for converting an acoustic signal into a response are discussed in more detail below.

In some embodiments, acoustic signals from more than two regions of the head (or other portion of the body) may be determined, for example, using an array of sensors (e.g., immobilized on a helmet) as discussed below. For example, at least three regions, at least four regions, at least five regions, at least eight regions, at least fifteen regions, at least twenty-five regions, at least fifty regions of the head, at least one regions, at least 500 regions, or at least 1000 regions may be determined using an array of sensors.

The determination of acoustic signals in multiple regions may allow for determination of the spatial location of an injury in some cases. For example, triangulation may be employed to determine the location of an injury. The severity of the injury may also be determined in certain embodiments. For example, when the injury is a stroke, the location of the stroke may be determined, as well as determining the type of stroke, e.g., whether the stroke is an ischemic stroke (and/or a proximal cerebral artery occlusionstroke) or a hemorrhagic stoke, etc.

In some embodiments, at least some of the vibrations forming an acoustic signal may have intensities that are not detectable by the human ear, e.g., the vibrations may be below the threshold of human hearing. The threshold of hearing is the minimum sound level that an average human ear with normal hearing can hear in a noiseless environment and is generally reported as the RMS sound pressure. In some cases, the RMS sound pressure of the vibrations that are determined are less than about 50 uPa, less than about 40 uPa, less than about 30 uPa, less than about 20 uPa, less about than 10 uPa, or the like. Typically, the threshold of hearing is defined to be 0 decibels, and more intense (louder) sounds are defined logarithmically, using 0 decibels as the reference intensity.

The acoustic signals may be determined directly or indirectly using a sensor. The sensor may be any suitible type which is able to sense an acoustic signal. The sensors may, in some embodiments, convert the acoustic signal into other signals, e.g., electrical signals. In some cases, the sensors may be able to determine vibrations of an acoustic signal which have RMS sound pressures less than about 50 uPa, about 40 uPa, about 30 uPa, about 20 uPa, or about 10 uPa, etc. Non-limiting examples of sensors that may be used include piezoelectric, micro electomechanical, piezoelectric polymer, magnetic film, magnetostrictive, strain gauge, moving coil type, air coupled electronic stethoscope, microphone, geophone, optical fiber, pulsation, or the like, as discussed below.

In some embodiments, an acoustic signal may be indirectly determined, for example, by attaching one or more transmitters to the subject's head (or other portion of the body), where the transmitters may be connected to sensors. The transmitter may transmit the acoustic signal (or another signal indicative of the acoustic signal) to the sensor.

In some aspects, a sensor may comprise using light to determine an acoustic signal. For instance, vibrations of an acoustic signal may be determined by directing light at region of a subject, such as a subject's head. At least a portion of the light may be reflected off a region of the subject, and the vibrations may be determined based on the reflected light, which may be sensed directly or indirectly, e.g., using an optical fiber as a transmitter that optically couples the region of the subject to the sensor.

In some embodiments, an acoustic signal may be directly determined, for example, by immoblizing one or more sensors with respect to one or more regions of the subject's head (or other portion of the body). The sensors may each be the same, or there may be more than one type of sensor used. One or more of the sensors may be, for example, a piezoelectric sensor. A piezoelectric sensor is a device that uses the piezoelectric effect to measure pressure, acceleration, strain and/or force through conversion to an electrical signal. As another example, one or more sensors may be a microphone, which is an acoustic-to-electric transducer or sensor that can convert vibration of an acoustic signal into an electrical signal. As yet another example, one or more sensors may be a geophone, which converts movements (displacement or vibration) into voltage. Microphones, geophones and piezoelectric sensors are known to those of ordinary skill in the art.

One or more sensors and/or transmitters may be directed at a region of a subject (e.g., the subject's head) by any suitable technique such that the sensors and/or transmitters can determine the acoustic signal of the region. The sensors and/or transmitters may be contained in an article that is rigid, or flexible in some cases. Examples of such articles include, but are not limited to, a strap, a headband, a helmet, a cap, or the like. In some cases, the article also comprises an analyzer (discussed below) to record and/or compare the acoustic signals collected from the sensors. In some cases, the article is small enough such that it is portable and can be employed at or near the location where an injury to a subject has taken place. For instance, the device may have

a weight of less than about 8 kg, less than about 7 kg, less than about 6 kg, less than about 5 kg, less than about 4 kg, less than about 3 kg, less than about 2 kg, less than about 1 kg, etc. and/or have a largest dimension that is no more than 50 cm, less than about 40 cm, less than about 30 cm, less than about 20 cm, less than about 10 cm, etc. As an example, as shown in Figure 2a, a sensor 30 may be directly attached to the subject 2 (e.g., the head), for example, by using tape 32. The sensors and/or transmitters may also be arranged on an article (e.g. a headband, a strap, a helmet, etc.) that at least partially conforms to the subject's head (or other region). For example, as shown in Figure 2b, sensors 34 are attached to a headband 36 that can be placed on a subject 2. As another example, as shown in Figure 2c, sensors 38 may be attached to a helmet- shaped object 40 which can be placed on a subject 2. The article may comprise mechanismsto securely fasten the article to the subject in some cases, for example, spring mechanisms, straps, or the like.

Sensors and/or transmitters may be directed at any area of the subject, e.g., the head. For instance, non-limiting areas of the head that the sensors and/or transmitters may be directed at include the forehead, the area covering the sinus cavity, and/or the top area of the head (often covered by hair). In some embodiments, sensors and/or transmitters that are directed to areas of the head that may be covered by hair can be placed such that the sensor and/or transmitters comes in direct contact with the skull between the hair folicles. For example, an optical fiber may be small enough to be positioned between hair folicles. The sensors and/or transmitters may be placed in direct contact with the skin of the subject in some cases, or a material (e.g., a gel, a pad, or the like ) may be placed between the skin and the sensors and/or transmitters.

As described above, is some embodiments, light is used to determine acoustic signals in a region of a subject. Acoustic signals created by blood flow within the region may alter the light that is reflected from that region, which can be determined and used to determine the acoustic signal of that region. In some cases, the light directed at the subject may be coherent light (e.g., laser light). In other cases, the light may not be coherent light. As a particular non-limiting example, light may be directed at a region of a subject's head (or other portion of the body) using an optical fiber, where one end of the optical fiber is directed to a region of the subject's head. At least a portion of the

reflected light can be collected, in some instances, by the same (or a different) optical fiber. The reflected light may then be determined by a sensor, e.g., situated at the other end of the optical fiber, and used to determine acoustic signals in the region of the subject's head. In some cases, multiple optical fibers may be used, e.g., to determine a region (or multiple regions) on the subject. For instance, at least one optical fiber, at least 2 optical fibers, at least 3 optical fiber, at least 4 optical fiber, at least 5 optical fibers, at least 8 optical fibers, at least 15 optical fibers, at least 25 optical fibers, at least 50 optical fibers, at least 100 optical fibers, at least 500 optical fibers, at least 1000 optical fibers may be used. An example of such a sensor is depicted in Figure 3. As shown in Figure 3a, an optical fiber 48 is directed at a region 50 of a subject's head 2. A light source 52 directs light 54 through the optical fiber. As shown in Figure 3b, some of the light may then be reflected off the subject 2 (e.g., the head), and a portion of the reflected light 56 can be directed to towards a sensor 58 through the optical fiber 48. As shown in Figure 3, sensor 58 and light source 52 are housed in the same device, although they need not be.

Signals from the sensors (whether acoustic, electric, or otherwise) may be recorded and compared using an analyzer, such as a computer or a dedicated device. The analyzer may compare the signals from one or more regions of the subject's head and the comparison may be used to indicate whether an injury has occurred. As discussed above, for example, a large difference between a first and second acoustic signal determined from a first and second regions of a subject's head may indicate a severe stroke has occurred, while a small difference may indicate a minor stroke has occurred. In some cases, the signals may be independently processed using any suitable signal processing technique, depending on the application; for instance, a signal may be filtered, amplified, subject to Fourier transforms, decomposed using wavelet decomposition, or the like. Two or more signals may be compared using any suitable technique, for example, by addition, subtraction, multiplication, division, distance between peaks and/or troughs, shape of the signal, and/or the like, depending on the application. In some embodiments, acoustic signals arising from regions of a subject may be analyzed, in some cases, to detect frequency bandwidths of the vibrations of the acoustic signals. As discussed above, the acoustic signals may arise, at least in part, from blood

flow moving through blood vessels within the subject. The presence of particular frequencies may be matched to blood vessel size, as vessels with different diameters can produce different frequencies of vibrations. As a specific example, a drop or deviation within a particular frequency range may be used to determine the diameter of the vessel that is injured, arid therefore, the type of vessel that is injured. Multiple acoustic signals may provide a baseline for the subject that is being assessed in some cases, as each subject may have a "fingerprint" baseline acoustic signals. In some embodiments, however, an injury may be determined without necessarily determining baseline acoustic signals; for instance, the acoustic signals on opposite sides of the subject's head (e.g., left and right), the regions may be compared, and any differences in acoustic signals that are determined may be used to determine that an injury occurred in the subject, without necessarily determining which side of the head the injury occurred on.

U.S. Provisional Patent Application Serial No. 61/030,116, filed February 20, 2008, entitled "System and Method for Detection of Changes in Blood Flow Indicative of Stroke and Other Conditions," by Steinberg, et al, is incorporated herein by reference.

The following examples are intended to illustrate certain embodiments of the present invention, but do not exemplify the full scope of the invention.

EXAMPLES Figures 4a-4b show the acoustic signal of a subject that was determined acquired when employing a piezoelectric sensor. In this example, a piezoelectric sensor was placed on the one wrist of a subject. As shown in Figure 4a, the regular signal pattern was determined from the sensor. The regular pattern correlated with the subject's pulse.

Figure 4b shows the same subject with the sensor still attached to the subject's wrist. However, in this example, the subject's wrist was bent back. The difference in amplitude of the two signals that were observed in Figure 4a and Figure 4b may arise from the vessels being closer to the sensor in Figure 4b. For example, the vessels may be closer to the skin's surface when the wrist was bent back, hence, causing the vessels to be closer to the sensor. Therefore, the pulse of the heartbeat through the vessels may be more readily determined when the wrist is bent back in this example. Figures 5a-5c are examples of a similar experiment. However, in these examples, the acoustic signals were determined by determining the light reflected off a region of the subject (in this case, the wrists and head). A light was directed at a region of the subject,

and the reflected light was collected. The reflected light collected was then analyzed to determine the acoustic signals of the region of the subject that the light was directed at. In this case, a laser was directed at the subject's left wrist (Figure 5a), right wrist (Figure 5b), and left temple of the head (Figure 5c). Light that was reflected off the subject was collected and analyzed. As shown in Figures 5a-5c, a regular acoustic signal was observed. This regular signal correlated with the subject's pulse. Thus, as this example shows, by determining such acoustic signals, differences in blood flow within a subject can be determined, for instance, that are caused by various injuries.

While several embodiments of the invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and/or claimed. The present invention is directed to each individual feature, system, material and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials and/or methods, if such features, systems, articles, materials and/or methods are not mutually inconsistent, is included within the scope of the present invention.

All definitions as used herein are solely for the purposes of this disclosure. These definitions should not necessarily be imputed to other commonly-owned patents and/or patent applications, whether related or unrelated to this disclosure. The definitions, as used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one act, the order of the acts of the method is not necessarily limited to the order in which the acts of the method are recited.

In the claims, as well as in the specification above, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases "consisting of and "consisting essentially of shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedure, Section 2111.03. What is claimed is: