Non-invasive systems and methods to detect cortical spreading depression for the detection and assessment of brain injury and concussion

Abstract

The present invention provides systems and methods for detection and diagnosis of concussion and/or acute neurologic injury comprising a portable headwear-based electrode array and computerized control system to automatically and accurately detect cortical spreading depression and acute neurological injury-based peri-infarct depolarization (CSD/PID). The portable headwear-based electrode system is applied to a patient or athlete, and is capable of performing an assessment automatically and with minimal user input. The user display indicates the presence of CSD/PID, gauges its severity and location, and stores the information for future use by medical professionals. The systems and methods of the invention use an instrumented DC-coupled electrode/amplifier array which performs real-time data analysis using unique algorithms to produce a voltage intensity-map revealing the temporally propagating wave depressed voltage across the scalp that originates from a CSD/PID on the brain surface.

Claims

1. A method of detecting concussion-based cortical spreading depression (CSD) non-invasively in a subject, the method comprising: using a portable, instrumented head-mountable detection unit comprising a plurality of scalp surface DC-electroencephalogram (DC-EEG) electrodes configured in a high density electrode array spaced between about 0.5 cm and about 1.5 cm apart from one another to detect a set of real-time scalp DC electrical potential signals non-invasively from a brain area of the subject and to transmit the real-time scalp DC electrical potential signals to an amplifier unit configured to amplify the detected electrical potential signals, said portable, instrumented head-mountable detection unit placed on a surface of a scalp area of the subject; using a computing device to detect the presence of the concussion-based CSD, said computing device comprised of a processing unit which includes one or more processors and a computer-readable memory containing programming instructions that, when executed, cause the processing unit to receive the amplified electrical potential signals to implement the programming instructions to determine that values of a first set of the electrical potential signals corresponding to a first portion of the brain area, representing a concussion-based CSD, are depressed as compared to values of a second set of the electrical potential signals corresponding to a second portion of the brain area, representing normal brain; and generating an output in response to the determining step, said output indicating that the subject is experiencing a concussion-based CSD.

2. The method of claim 1, wherein the plurality of scalp surface DC-EEG electrodes are spaced about 1.0 cm apart from one another.

3. The method of claim 1, further comprising: receiving a ground voltage from a ground electrode which is in contact with a non-brain area of the subject; using the received ground voltage to determine the primary DC voltage, V.sub.i, for each of the plurality of scalp electrodes; using the primary DC voltage, V.sub.i, to calculate a derived virtual ground voltage (V.sub.g) for the plurality of scalp electrodes; determining a derived electrode voltage (V.sub.ig) based on the mean of the derived virtual ground voltages (V.sub.g) for each of the scalp electrodes; determining whether the derived electrode voltages indicates a depression in a voltage level among a set of adjacent electrodes; and outputting a report indicating a level of the depression and the area to which the depression corresponds.

4. The method of claim 1, wherein the computing device determines severity, morphology, velocity of propagation and trajectory of the concussion-based CSD, said severity proportional to the magnitude of DC voltage depression and area over which the DC voltage depression occurs, said morphology exhibited as an expanding ring, and said trajectory comprising an initiation point, an extinguish point, and a branching pattern.

5. The method of claim 1, wherein a velocity of propagation between 1.0 mm/min and 9.0 mm/min is consistent with concussion-based CSD characteristics.

6. A system for detecting concussion-based cortical spreading depression n (CSD) non-invasively in a subject, the system, comprising: a portable, instrumented head-mountable detection unit comprising a plurality of scalp surface DC-EEG electrodes configured in a high density electrode array, said plurality of scalp surface DC-EEG electrodes spaced between about 0.5 cm and about 1.5 cm apart from one another and configured to detect a set of real-time scalp DC electrical potential signals non-invasively from a brain area of the subject and to transmit the real-time scalp DC electrical potential signals to an amplifier unit configured to amplify the detected electrical potential signals, said portable, instrumented head-mountable detection unit configured to be placed on a surface of a scalp area of the subject; and a computing device to detect the presence of the concussion-based CSD, said computing device comprised of a processing unit which includes one or more processors and a non-transitory computer-readable memory containing programming instructions that, when executed, causes the processing unit to: receive the amplified electrical potential signals and determine, for each received signal whether the signal corresponds to an electrode placed above a normal cortex area of the subject or above a concussion-based CSD cortex area of the subject; determine whether electrode voltages indicate a depression in a voltage level among a set of adjacent electrodes in one of the areas, and if so, determine whether the depression corresponds to electrodes above the normal cortex area or above the cortex area representing the concussion-based CSD cortex area of the subject; and output a report indicating a level of the depression and the area to which the depression corresponds.

7. The system of claim 6, wherein the portable, instrumented head-mountable detection unit further comprises: a ground electrode configured to detect a ground voltage when placed on a non-scalp area of the subject, and additional programming instructions that, when executed, cause the processing unit to: use the detected ground voltage to determine a mean derived normal area ground voltage (V.sub.g); determine a derived electrode voltage (V.sub.g) based on the mean derived normal area ground voltage (V.sub.g) for each of the received signals corresponding to the normal cortex area; and use the derived electrode voltages when determining whether the electrode voltages indicate a depression in a voltage level.

8. The system of claim 6, wherein the plurality of scalp surface DC-EEG electrodes are spaced about 1.0 cm apart from one another.

9. The system of claim 6, wherein the computing device determines severity, morphology, velocity of propagation and trajectory of the concussion-based CSD, said severity proportional to the magnitude of DC voltage depression and area over which the DC voltage depression occurs, said morphology exhibited as an expanding ring, and said trajectory comprising an initiation point, an extinguish point, and a branching pattern.

10. The system of claim 6, wherein the system is capable of determining a velocity of propagation across the high density electrode array of between 1.0 mm/min and 9.0 mm/min, which is consistent with concussion-based CSD characteristics.

11. A method of detecting an acute neurological injury-based cortical spreading depression and peri-infarct depolarization (CSD/PID) non-invasively in a subject, the method comprising: using a portable, instrumented head-mountable detection unit comprising a plurality of scalp surface DC-EEG electrodes configured in a high density electrode array spaced between about 0.5 cm and about 1.5 cm apart from one another to detect a set of real-time scalp DC electrical potential signals non-invasively from a brain area of the subject and to transmit the real-time scalp DC electrical potential signals to an amplifier unit configured to amplify the detected electrical potential signals, said portable, instrumented head-mountable detection unit placed on a surface of a scalp area of the subject; using a computing device to detect the presence of the acute neurological injury-based CSD/PID, said computing device comprised of a processing unit which includes one or more processors and a computer-readable memory containing programming instructions that, when executed, cause the processing unit to receive the amplified electrical potential signals to implement the programming instructions to determine that values of a first set of the electrical potential signals corresponding to a first portion of the brain area, representing an acute neurological injury-based CSD/PID, are depressed as compared to values of a second and third set of the electrical potential signals corresponding to a second portion of brain area, representing ischemic brain, and third portion, representing normal brain; and generating an output in response to the determining step, said output indicating that the subject is experiencing an acute neurological injury-based CSD/PID.

12. The method of claim 11, wherein the plurality of scalp surface DC-EEG electrodes are spaced about 1.0 cm apart from one another.

13. The method of claim 11, further comprising: receiving a ground voltage from a ground electrode that is in a contact region above a non-brain area of the subject; performing a data collection process for each of the electrodes above a brain area, said data collection process comprising: determining an initial voltage, V.sub.i, in reference to the ground voltage of the ground; sequentially dividing these voltages into two groups; determining mean values of each of these two groups; comparing, for each sequential determination of the two mean voltages, their difference; choosing among these two groups, the largest difference; choosing the electrode voltages of the group with the lowest mean voltage to be termed, V.sub.ig-ischemic; choosing the electrode voltages of the group with the highest mean voltage to be termed, V.sub.ig-normal; using this voltage, V.sub.ig-normal, to derive a virtual ground voltage for electrodes above the normal cortex area (V.sub.gm-normal); using the virtual ground voltage for electrodes above the normal cortex area (V.sub.gm-normal) and the voltage, V.sub.ig-normal, to derive a normal area virtual voltage for each electrode classed as being above a normal brain area (normal area V.sub.ig); using the voltage, V.sub.ig-ischemic, to derive a virtual ground voltage for electrodes above the ischemic cortex area (V.sub.gm-ischemic), using the virtual ground voltage for electrodes above the ischemic cortex area (V.sub.gm-ischemic) and the voltage, V.sub.ig-ischemic, to derive an ischemic area virtual voltage for each electrode originating above an ischemic area (ischemic area V.sub.ig); and combining the normal area V.sub.ig and the ischemic area V.sub.ig values to indicate a depression in a voltage level among a set of adjacent electrodes that corresponds to an acute neurological injury-based CSD/PID; repeating the data collection process for a plurality of epochs and using results of the data collection to determine whether a depression of voltage level travels at a velocity of propagation of between 1.0 mm/min and 9.0 mm/min, consistent with acute neurological injury-based CSD/PID characteristics; determining that the depression corresponds to electrodes within a region above an acute neurological injury-based CSD/PID when it is determined that the depression of voltage level travels at a velocity of propagation of between 1.0 mm/min and 9.0 mm/min, which is consistent with acute neurological injury-based CSD/PID characteristics; generating the output indicating that the subject is experiencing the acute neurological injury-based CSD/PID; and outputting a report indicating a level of the depression corresponding to the acute neurological injury-based CSD/PID and the area to which the depression corresponds.

14. The method of claim 11, wherein the computing device determines severity, morphology, velocity of propagation and trajectory of the acute neurological injury-based CSD/PID, said severity proportional to the magnitude of DC voltage depression and area over which the DC voltage depression occurs, said morphology exhibited as a globular region, and said trajectory comprising an initiation point, an extinguish point, and a branching pattern.

15. A system for detecting an acute neurological injury-based cortical spreading depression and peri-infarct depolarization (CSD/PID) non-invasively in a subject, the system comprising: a portable, instrumented head-mountable detection unit comprising a plurality of scalp surface DC-EEG electrodes configured in a high density electrode array, said plurality of scalp surface DC-EEG electrodes spaced between about 0.5 cm and about 1.5 cm apart from one another and configured to detect a set of real-time scalp DC electrical potential signals non-invasively from a brain area of the subject and to transmit the real-time scalp DC electrical potential signals to an amplifier unit configured to amplify the detected electrical potential signals, said portable, instrumented head-mountable detection unit configured to be placed on a surface of a scalp area of the subject; and a computing device to detect the presence of the acute neurological injury-based CSD/PID, said computing device comprised of a processing unit which includes one or more processors and a non-transitory computer-readable memory containing programming instructions that, when executed, causes the processing unit to: receive the amplified electrical potential signals and determine, for each received signal whether the signal corresponds to an electrode placed above a normal cortex area of the subject or above an ischemic cortex area of the subject or above an area of cortex that represents an acute neurological injury-based CSD/PID; determine whether electrode voltages indicate a depression in a voltage level among a set of adjacent electrodes above one of the areas, and if so, determine whether the depression corresponds to electrodes above the normal cortex area or above the ischemic cortex area or above the area of cortex that represents an acute neurological injury-based CSD/PID; and output a report indicating a level of the depression and the area to which the depression corresponds.

16. The system of claim 15, wherein the portable, instrumented head-mountable detection unit further comprises a ground electrode configured to detect a ground voltage when placed on a non-scalp area of the subject, and the non-transitory computer-readable memory further comprises additional programming instructions that, when executed, cause the processing unit to: use the detected ground voltage to determine a mean derived normal area ground voltage (V.sub.g-normal) and a mean derived ischemic area ground voltage (V.sub.g-ischemic), determine a derived electrode voltage (normal area V.sub.ig) based on the mean derived normal area ground voltage (V.sub.gm-normal) for each of the received signals corresponding to the normal cortex area; determine a derived electrode voltage (ischemic area V.sub.ig) based on the mean derived ischemic area ground voltages (V.sub.gm-ischemic) for each of the received signals corresponding to the ischemic cortex area; and use the normal area V.sub.ig and the ischemic area V.sub.ig when determining whether the electrode voltages indicate a depression in a voltage level.

17. The system of claim 15, wherein the plurality of scalp surface DC-EEG electrodes are spaced about 1.0 cm apart from one another.

18. The system of claim 15, wherein the computing device determines severity, morphology, velocity of propagation and trajectory of the acute neurological injury-based CSD/PID, said severity proportional to the magnitude of DC voltage depression and area over which the DC voltage depression occurs, said morphology exhibited as a globular region, and said trajectory comprising an initiation point, an extinguish point, and a branching pattern.

19. The system of claim 15, wherein the system is capable of determining a velocity of propagation across the high density electrode array of between 1.0 mm/min and 9.0 mm/min, which is consistent with acute neurological injury-based CSD/PID characteristics.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) A fuller understanding of the invention can be gained from the following description when read in conjunction with the following drawings.

(2) FIG. 1 shows the results of an averaging scheme by displaying the scalp DC voltage after post-processing of a concussion- or acute neurological injury-induced CSD at two sequential times using a one-dimensional electrode array model, in accordance with an embodiment of the present invention. DC-potential measurements are plotted at each scalp electrode for the CSD detection scheme showing two sequential measurements separated by 20 s. The vertical axis displays the post-processed DC voltage, V.sub.ig, from the noise-reducing averaging scheme.

(3) FIG. 2 is a block diagram showing components of the system, in accordance with an embodiment of the present invention.

(4) FIG. 3 shows internal hardware used to contain or implement the various automated processing elements, in accordance with an embodiment of the present invention.

(5) FIG. 4 shows the results of a numerical simulation with the result that the electrode spacing of 1.0 cm allows accurate reconstruction of the CSD structure from scalp detection, in accordance with an embodiment of the present invention. FIG. 4A shows the estimated true scalp voltage intensity map at 10 min after CSD initiation; FIG. 4B shows the scalp voltage intensity accurately reconstructed from a 1.0 cm electrode array; and FIG. 4C shows the voltage intensity scale with black representing both 0 mV and ?2 mV.

(6) FIG. 5 are design drawings of the High Density Electrode Array with 1.0 cm electrode spacing used in conjunction with a DC-coupled amplifier to detect CSDs on the scalp, in accordance with an embodiment of the present invention.

(7) FIG. 6 is a diagrammatic representation of the Detection Algorithm System and the Display and Data Output module, in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

(8) As used in this document:

(9) The terms cortical spreading depression and peri-infarct depolarization are phenomena which are meant to be interchangeable. [K.sup.+].sub.ex=extracellular potassium concentration CSD=cortical spreading depression CT=computed tomography EEG=AC-coupled electroencephalography ECoG=electrocorticography DC-coupled-EEG=DC-coupled electroencephalography PET=positron emission tomography TBI=traumatic brain injury mTBI=mild traumatic brain injury PIDs=peri-infarct depolarizations MM=magnetic resonance imaging Vg=derived virtual ground voltage Vg-ischemic=derived virtual ground voltage of ischemic cortex Vg-normal=derived virtual ground voltage of normal cortex Vi=initial electrode DC voltage Vig=derived electrode voltage Vig-ischemic=derived electrode voltage for ischemic cortex electrodes Vig-normal=derived electrode voltage for normal cortex electrodes Vgm-ischemic=mean electrode voltage for ischemic cortex Vgm-normal=mean electrode voltage for normal cortex

(10) The need for concussion detection systems and methods that quickly, consistently, and reliably work is enormous, given the current publicity which currently surrounds concussion: newspaper articles, TV spots, and parental concern for young athletes. Sports-related concussion is an important and emerging health care issue, with enormous increasingly recognized impact on our children and adult athletes. Additionally, there is enormous need for a simple, reliable, and portable concussion detection systems and methods in many other situations, including law enforcement, military, construction, industry, and emergency care. Current methods for the testing of the effects of concussion are not effective, as they are slow, complicated, inaccurate, or inconsistent. Embodiments of the systems and methods of the present invention provide both the detection and the gauging of severity immediately following a concussion event, a potentially invaluable addition to current practices in the art. The systems and methods of the present invention help mitigate the economic impact of delayed treatment with the immediate knowledge of the severity and occurrence of a concussion.

(11) The need for a non-invasive CSD detection system for acute neurological injury is expressed repeatedly by those who currently use invasive electrocorticography method for its detection in the setting of the neurological intensive care unit. The systems and methods of the present invention for the non-invasive monitoring of brain-damaging CSDs/PIDs permit the investigation of brain-saving pharmaceutical and physiological stratagems in over twenty times the number of patients who are not candidates for medically mandated craniotomies, a procedure that is necessary for the placement of electrodes on the brain surface needed for ECoG recording procedures. The systems and methods of the present invention help mitigate the economic impact of further brain damage with the immediate knowledge of the severity and occurrence of CSDs.

(12) CSDs can be initiated experimentally by cortical pin-prick, electrical stimulation, cortical application of K.sup.+, or mechanical force to the cortex. The mechanical shock to the brain that precedes a concussion produces the same effect, a CSD. The present invention provides the surprising finding of a connection between concussion and CSDs which heretofore has been relatively unknown by those skilled in the art.

(13) In the prior art, propagating CSDs have been impossible to detect noninvasively from the surface of the scalp. Although propagating CSDs have been successfully detected on the brain surface, the system and method described in the embodiments of the present invention can detect CSDs on the scalp using DC-coupled-EEG combined with a post-processing averaging scheme to mitigate DC drift and noise.

(14) The present invention includes systems and methods that detect CSDs non-invasively from the surface of the scalp. Given the current understanding that CSDs are pathogenic and occur in virtually every form of acute neurological injury, the systems and methods of the present invention can be deployed non-invasively in a variety of situations, such as in the neuro-intensive care unit and at the emergency medical technician level. Embodiments of the systems and methods can be used, for example: 1) by sports medicine professionals, within any sport with concussion risk and at all levels of professional and amateur play; 2) in emergency medicine; and 3) in the neuro-intensive care unit. The systems and methods are fully portable and adaptable for ambulance, emergency room, and critical care use, as well as to sites where a concussion injury risk is present, such as construction and heavy industry.

(15) In various embodiments, the systems and methods of the present invention include a real-time scalp DC-potential data collection system which detects a CSD using electrode/amplifier/data transmission/post-processing/visual display technology. The systems and methods of the present invention are able to identify the presence of concussion and the pathological progression of acute neurological injury via the presentation of CSDscenters of low voltage which propagate across the brain as waves of depolarization in cerebral gray matterin real-time voltage intensity-map images of low-pass filtered scalp-potentials detected with DC-coupled-EEG.

(16) The systems and methods of the present invention include, without limitation, five or more components, described below and shown visually in the drawings. These five or more components include both a physical apparatus and software.

(17) The components of the systems and methods of the present invention include a high density electrode array incorporated into a head-net which fits inside a helmet, a stand-alone head-net, a head-band, a grid, or other electrode positioning unit which detects and transmits real-time scalp DC-potentials to a laptop/workstation or a computer which amplifies and evaluates the recordings to detect concussion and CSD/PID events and gauges their severity. The system includes a detection scheme that is based on the relationship between CSD and both concussion and acute neurological injury, and involves the detection of slowly moving (at 1 to 9 mm/min) ?10 to ?45 mV DC-potentials from the brain surface through the scalp using a 1.0 cm spaced active High Density Electrode Array and sensitive DC-coupled amplifiers.

(18) The components of the systems and methods of the present invention can gauge the severity of concussion and CSDs present in acute neurological injury by evaluating and recording a combination of the level of the depressed voltage that is a characteristic of CSD, the surface area on the scalp in which this depressed voltage resides, the velocity of the propagating CSD wave, the morphology and shape of the depressed voltage, and the propagation trajectory (e.g. initiation point, extinguish point, branching pattern) of the detected CSD wave.

(19) The rapid and reliable detection of CSD associated with concussion and following acute neurological injury is a critically important and potentially life-changing need in emergency health care, athletics, and the intensive care unit. The systems and methods of the present invention includes a portable headwear-based electrode array and computerized control system capable of automatically and accurately detecting CSD associated with acute neurological injury and concussion events following blows to the head. The systems and methods can be easily applied to the patient or athlete by minimally-trained medical technicians, and can perform a diagnosis automatically and with minimal user input and does not require a base-line, pre-concussion, or pre-injury test.

(20) The systems and methods of the present invention are a fully portable system which includes an array of scalp surface electrodes, the High Density Electrode Array, coupled with a computerized control unit with integrated signal amplifier. The High Density Electrode Array is incorporated into an elastic head-net or band or flexible grid for easy, rapid, and comfortable application and removal from a patient. Following application of the High Density Electrode Array to the patient, the control unit electrically assesses electrode placement and proper skin contact, and performs an automated diagnostic procedure by analyzing scalp electrical potentials to detect tell-tale signs of acute neurological injury or concussion. This portable system requires as little input from the medical technician as possible, and causes minimal discomfort to the injured patient. A user display indicates the presence of CSD as a positive indication of concussion and is used to detect CSD and PID presence, velocity, shape, trajectory, and location as evidence of severity, and the system stores the information in a non-transitory, computer-readable memory for future use by medical professionals.

(21) The system of the present invention implements a diagnostic procedure to detect DC-potential changes resulting from mechanical shock-induced CSD induced by concussion and from CSDs associated with acute neurological injury, using an instrumented DC-coupled electrode/amplifier array that performs real-time data analysis using novel and unique algorithms. These algorithms produce a voltage intensity-map image revealing the temporally propagating DC potential wave (which originates from the surface of the brain cortex) across the scalp surface. This voltage intensity map is displayed as an image on a computing device screen as a color-coded image of the propagating DC-potential propagating over a representation of the scalp. The system uses CSD as an important pathophysiological trait of acute neurological injury and concussion. CSD typically has been considered to be very difficult to detect on the scalp surface, as it manifests as a DC potential change well below the frequency range recorded using established EEG methodology, and whose spatial extend is not compatible with current clinical EEG configurations. The system of the present invention includes proven DC-coupled-EEG method to overcome this limitation through the use of high spatial density electrodes, a custom-configured amplification system, post-processing algorithms, and visual display units. Through this methodology, the systems and methods of the present invention can be deployed to detect CSDs associated with concussion, stroke, intracerebral hemorrhage, traumatic brain injury, intracerebral hemorrhage, and sub-arachnoid hemorrhage.

(22) Referring now to FIG. 1, the results of an averaging scheme are shown by displaying the scalp DC voltage after post-processing of a concussion- or acute neurological injury-induced CSD at two sequential times using a one-dimensional electrode array model for a clear description of the detection scheme. In this scheme, DC-noise and drift is mitigated by an averaging scheme that establishes a derived virtual ground. This derived virtual ground is then subtracted from each electrode voltage and further processed using temporal and spatial weighted averaging schemes to obtain post-processed DC voltage V.sub.ig for each electrode. The vertical axis displays V.sub.ig from this noise- and drift-reducing averaging scheme. This voltage is plotted at each scalp electrode for the CSD detection scheme showing two sequential measurements separated by 20 seconds.

(23) The systems and methods can include as many as five or more core elements. As shown in FIG. 2, a block diagram bringing together various components of an embodiment of the system includes: 1) the DC Electrode Assembly, a plurality of DC-EEG electrodes composed of a cylinder filled with cotton soaked with electrode gel or water, a sintered Ag/AgCl electrode, a preamplifier, an analog-to-digital converter, and multiplexer that is associated with each electrode (100); 2) the detection unit, which includes a High Density Electrode Array, a helmet/headband/grid-based DC-EEG High Density Electrode Array assembly composed of a plurality of closely-spaced DC-Electrode Assemblies (105); 3) a Signal Acquisition System that includes a de-multiplexer, amplifier, and a cable or wireless data transmission system (200) that provides a connection to a computing device (205); 4) a laptop- or tablet-based Detection Algorithm System that includes a Preprocessing Data Conditioning module, a CSD Detection system, a Concussion/CSD/PID Identification system, and a Location and Severity Estimation system (300); and 5) a display and data output/presentation system (400) that includes a Diagnostic Data Output module that displays textual diagnostic information and outputs to a computer-readable memory such as a USB thumb drive or a mobile electronic device such as a cell phone (405) and a Video Display screen (410) that shows a voltage intensity-map of the scalp surface over which the wave of negative DC potential passes from a propagating CSD on the brain surface.

(24) FIG. 3 shows internal hardware that is used to contain or implement the various automated processing elements of the present invention. An electrical bus 600 serves as an information highway interconnecting the other illustrated components of the hardware. CPU 605 is a central processing unit of the system, performing calculations and logic operations required to execute a program. CPU 605, alone or in conjunction with one or more of the other elements disclosed in FIG. 3, is a processing device, computing device or processor. Read only memory (ROM) 610 and random access memory (RAM) 615 are examples of memory devices employed in implementing the systems and methods of the present invention.

(25) A controller 620 interfaces with one or more optional memory devices 625 that serve as data storage facilities to the system bus 600. These memory devices 625 may include, for example and without limitation, an external DVD drive or CD ROM drive, a hard drive, flash memory, a USB drive or another type of device that serves as a data storage facility. As indicated previously, these various drives and controllers are optional devices. Additionally, the memory devices 625 can be configured to include individual files for storing any software modules or instructions, auxiliary data, incident data, common files for storing groups of contingency tables and/or regression models, or one or more databases for storing the information as discussed above.

(26) Program instructions, software or interactive modules for performing any of the functional steps associated with the processes as described above may be stored in the ROM 610 and/or the RAM 615. Optionally, the program instructions may be stored on a tangible computer readable medium such as a compact disk, a digital disk, flash memory, a memory card, a USB drive, an optical disc storage medium and/or other recording media.

(27) A display interface 630 permits information from the bus 600 to be displayed on the display 635 in audio, visual, graphic or alphanumeric format. Communication with external devices occurs using various communication ports 640. A communication port 640 is attached to a communications network, such as the Internet, a local area network or a cellular telephone data network.

(28) The hardware also includes an interface 645 which allows for receipt of data from input devices such as a keyboard 650 or other input device 655 such as a remote control, a pointing device, a video input device and/or an audio input device.

(29) FIG. 4 shows the results of a numerical simulation with the result that the electrode spacing of 1.0 cm allows accurate reconstruction of CSD structure from scalp detection. FIG. 4A shows the estimated true scalp voltage intensity map at 10 min after CSD initiation in a 10 cm?10 cm simulation domain. The symbol X marks the focal point of the CSD on the underlying brain surface. FIG. 4B shows the scalp voltage intensity reconstructed from a 1.0 cm-spaced electrode array. FIG. 4C shows the voltage intensity scale with black representing both 0 mV and ?2 mV. Zero mV values are apparent at both the focal point of the CSD and completely outside the ring. Minus 2 mV values and other values are present within the ring structure. These scalp voltages represent about 8% of the voltage on the brain surface used in this simulation. This modeling and simulation approach is utilized to determine the optimum number and spatial distribution of sensors required to detect a CSD-based concussion and an acute neurological injury-based PID, while minimizing noise. The model can use previous data, such as data of PIDs detected from a model of ischemic stroke from both laser speckle flowmetry and fast apparent diffusion coefficient magnetic resonance imaging.

(30) FIG. 5 shows the High Density Electrode Array that is used in conjunction with a DC-coupled amplifier to detect CSD on the scalp of the individual. FIG. 5A shows orthogonal views (edge, top, and side) of the High Density Electrode Array. FIG. 5B shows the configuration of the High Density Electrode Array. The detection of CSDs from a concussion and from acute neurological injury is based on the mathematical simulation of the scalp detection of a CSD using the High Density Electrode Array with 1.0 cm spacing described above, and the averaging scheme for eliminating noise and drift. All electrodes are placed 1.0 cm apart: center-to-center, with each electrode having a 2.0 mm diameter.

(31) FIG. 6 is a diagrammatic representation of the computing device 700 combining the Detection Algorithm System 300 and the Display and Date Output 400 shown in FIG. 2 which includes components to detect the presence of the CSD, the severity of the CSD, morphology of the particular CSD (e.g. globular, expanding ring), velocity of CSD propagation, and trajectory of CSD propagation (e.g. initiation point, extinguish point, branching pattern) in the individual: 1) screen for informational text including diagnostic data output 750; control buttons 775; video display 750 which shows a diagrammatic representation of the individual's scalp 775; the voltage intensity map of depressed voltage that identifies the CSD 800; the High Density Electrode Array 105; and Signal Acquisition System 200 shown in FIG. 2.

(32) Detection of CSDs and PIDs (CSD/PID)

(33) Two schemes are used for the detection of CSDs, one scheme for the detection of concussion, and the other scheme for the detection of CSDs/PIDs in acute neurological injury.

(34) Detection of CSDs from Concussion

(35) A scheme for the detection of CSDs from concussion is based on post-processing with a different reference scheme and increased electrode array spacing compared to standard EEG practice. This detection scheme is based on DC potentials detected from a finely spaced multi-electrode array. The DC potential of each electrode in the array is obtained repetitively every 10 to 30 seconds, or at other suitable intervals. The DC potential of a single electrode is referenced to a derived virtual ground voltage obtained by summation of all the other DC potentials and further processed with weighed-averaging schemes. A CSD is detected if this processed signal shows a negative value that moves with the appropriate velocity consistent with known CSD properties across the electrode array. Depending on the electrode spacing, several electrodes within or near an area of about 4 mm diameter, the area of a depolarization wave, should show a similar negative signal.

(36) A one-dimensional array of electrodes composed of electrodes E.sub.1, . . . , E.sub.i, . . . , E.sub.n placed on the scalp, is used to describe this detection scheme. Every 10 to 30 seconds, or at other suitable intervals, the DC voltage from each of these electrodes is determined as V.sub.i in reference to an Ag/AgCl ground electrode placed on the skin of the neck. A derived virtual ground voltage, Vg, is calculated as:

(37) $\mathrm{Vg}=\frac{\underset{i=1}{\overset{n}{.Math.}}{V}_i}{n}$
and a derived electrode voltage, V.sub.ig, is calculated as:
V.sub.ig=V.sub.i?V.sub.g.

(38) A plot of these V.sub.ig's is shown in FIG. 1. The depression between V.sub.i and V.sub.i+7 shows the position of a CSD. A new calculation of V.sub.ig is performed every 10 to 30 seconds, or at other suitable intervals.

(39) In another embodiment of the present invention for detecting CSDs from concussion, these derived virtual ground averaging schemes can also use weighted averaging over: 1) a limited number of 10 to 30 second (or other suitable) collection epochs; and 2) a limited number of electrodes rather than a greater number of electrodes.

(40) The Detection of CSDs from Acute Neurological Injury

(41) A scheme for the detection of CSDs from acute neurological injury including ischemic stroke, traumatic brain injury and sub-arachnoid hemorrhage, is based on post-processing with a different reference scheme and increased electrode array spacing compared to standard EEG practice. This detection scheme is based on DC potentials detected from a finely spaced multi-electrode array. The DC potential of each electrode in the array is obtained repetitively every 10 to 30 seconds, or at other suitable intervals. The DC potential of a single electrode is referenced to a derived virtual ground voltage obtained by summation of all the other DC potentials and further processed with weighed-averaging schemes. A CSD is detected if this processed signal shows a negative value that moves with the appropriate velocity across the electrode array. Depending on the electrode spacing, several electrodes within or near an area of about 4 mm diameter, the area of a depolarization wave, should show a similar negative signal.

(42) A one-dimensional array of electrodes composed of electrodes E.sub.1, . . . , E.sub.i, . . . , E.sub.n placed on the scalp, is used to describe this detection scheme (FIG. 1). Every 10 to 30 seconds, or at other suitable intervals, the DC voltage from each of these electrodes is determined as V, in reference to an Ag/AgCl ground electrode placed on the skin of the neck of a patient. A derived virtual ground voltage is calculated as described below.

(43) This CSD/PID detection scheme for acute neurological injury includes the effect that the V.sub.I differ according to whether they originate from normal or ischemic cortex. This situation is implemented by a computation scheme that sequentially separates all the electrodes into two groups, chosen from all the possible divisions of contiguous electrodes (n?1 divisions in the one-dimensional model and n.sup.2?1 for the electrode grid). Separate mean V.sub.g's, V.sub.g-ischemic and V.sub.g-normal, are calculated for each grouping. The final grouping used for the calculation of the new derived virtual ground voltages, one for ischemic cortex and one for normal cortex, is chosen based on the widest difference between the V.sub.g-ischemic and V.sub.g-normal. The voltages at the electrodes in these two groups are termed V.sub.g-ischemic and V.sub.ig-normal. The mean derived virtual ground voltages for the ischemic and normal cortex electrode groups, V.sub.gm-ischemic and V.sub.gm-normal, are calculated from the averages using the number of electrodes in each V.sub.gm-ischemic and V.sub.gm-normal groups as the divisor,

(44) $V_{\mathrm{gm}.Math.\mathrm{ischemic}}=\frac{\underset{i=1}{\overset{n_{\mathrm{ischemic}}}{.Math.}}{V}_{\mathrm{ig}}-\mathrm{ischemic}}{n_{\mathrm{ischemic}}}{V}_{\mathrm{gm}-\mathrm{normal}}=\frac{\underset{i=1}{\overset{n_{\mathrm{normal}}}{.Math.}}{V}_{\mathrm{ig}-\mathrm{normal}}}{n_{\mathrm{normal}}}$
The derived electrode voltages, V.sub.ig, are calculated as:
V.sub.ig=V.sub.ig-ischemic?V.sub.gm-ischemic or V.sub.ig=V.sub.ig-normal?V.sub.gm-normal.

(45) A plot of these V.sub.ig's is shown in FIG. 1. The depression between V.sub.ig and V.sub.(i+7)g shows the position of a CSD, as shown by the plot of V.sub.ig at t+20 s. A new calculation of V.sub.ig is performed every 10 to 30 seconds, or at other suitable intervals.

(46) In another embodiment of the present invention for detecting CSDs from acute neurological injury, these derived virtual ground averaging schemes can also use weighted averaging over: 1) a limited number of 10 to 30 second (or other suitable) collection epochs; and 2) a limited number of electrodes rather than a greater number of electrodes.

(47) Detection Algorithm

(48) The size/area, velocity, shape, and location (center of mass) of the CSD is determined using processed DC voltages from each electrode. Averaging over time also is exploited with boundaries at approximately 20 data acquisition epochs of 10 to 30 seconds before and after a suspected CSD. This average is subtracted from all epochs, so that the CSD will be apparent. This is followed by threshold segmentation. Finally, cluster tracking for automatic identification of contiguous and moving values of diminished DC voltage is implemented. This approach identifies regions of diminished DC voltage with the crucial criteria that the velocity of the identified object must travel with known CSD velocities of 1-9 mm/min. As described above, the algorithm uses filters and temporo-spatial averaging for background subtraction based on the weighted least-square method, taking advantage of the array density. The weights are calculated combining the method of Kriging and objective interpolation. The reference potential, against which the active electrode voltages are compared, is obtained by averaging across all signals for each sample point. The algorithm explores the spatial derivatives as a tool of accentuating the leading edge of the CSD wave using the spatial LaPlacian. Machine learning methods are used to train a machine learning classifier for CSD detection parameters of optimal electrode offset and critical voltage initially using numerical simulation-based disease-specific models for a range of simulated CSD motion paths and then updated with training based on acquired CSD data.

(49) The embodiments of the systems and methods of the present invention eliminate the complex and seemingly inaccurate process of concussion diagnosis based on symptomatology that presently is the state of the art in amateur and professional athletics and provides increased diagnostic capabilities for acute neurological injury. There is no similar technology that involves the recognition that CSDs are a property of concussion and acute neurological injury that can be detected from processed DC-potentials from a finely spaced scalp electrode grid.

EXAMPLES

(50) The present invention is more particularly described in the following non-limiting examples, which are intended to be illustrative only, as numerous modifications and variations therein will be apparent to those skilled in the art.

(51) Four prophetic examples of the embodiments of the present invention are: 1) an instrumented electrode cap fitted under a helmet that transmits data to a sideline laptop or other computing device for data analysis; 2) an electrode head-net or head-band at the sidelines associated with a laptop or other computing device for analysis; 3) an electrode head-net, head-band, or grid in a neuro-intensive care unit for traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage associated with a laptop for analysis; and 4) an electrode head-net or head-band in an emergency medical transport unit for traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage associated with a laptop or other computing device for analysis.

Example 1Instrumented Electrode Helmet Transmitting Data to a Sideline Laptop for Analysis

(52) In this example, a football player wearing a helmet instrumented with an electrode array cap that includes a High Density Electrode Array that transmits DC-coupled-EEG data to the sidelines is hit by another player on the right upper temporal aspect of the player's head. The player falls to the ground and is unable to get up. Data transmitted from the helmet cap to the sideline analysis system composed of the portable processing unit with visual display then is assessed. The system begins the analysis and identification procedure, while at the same time a doctor logs the standard concussion assessment questions and patient history into system. The system continues its performance for about thirty minutes, at which time the system provides information that the player has suffered a concussion by displaying a region of depressed voltage of about 200 ?V on a diagrammatic representation of the player's head in the form of an expanding ring with a width of about 3.0 mm that originates at the right temporal aspect of the player's head and expands at a velocity of about 3 mm/min, which is characteristic of a CSD. Thus, within a period of approximately 30 minutes after a suspected concussion, and when either on or being removed from the field, an electrode head unit, which includes a High Density Electrode Array, contained in the player's helmet, allows for the recording and processing of DC-coupled-EEG data of the player. At the sidelines, data is received by a data processing system comprised of a computing device. The data is transformed to a voltage intensity-map showing the location and propagation of a wave of CSD as a visually distinct ring-shaped region traveling across a representation of the scalp surface of the player.

Example 2Electrode Cap at the Sidelines Associated with a Laptop for Analysis

(53) In this example, a football player is hit by another player on the right upper temporal aspect of the player's head. The player falls to the ground and is unable to get up. The player is assisted off the field and placed on the sidelines. A portable headband/electrode net and processing unit with visual display is fastened onto the player's head and a button is clicked to start the software for the analysis and identification procedure of the condition of the player. At the same time, a doctor logs the standard concussion assessment questions and patient history into system. The system continues its performance for about thirty minutes, at which time the system provides information that the player has suffered a concussion by displaying a region of depressed voltage of about 200 ?V on a diagrammatic representation of the player's head in the form of an expanding ring with a width of about 3.0 mm that originates at the right temporal aspect of the player's head and expands at a velocity of about 3 mm/min, which is characteristic of a CSD. Thus, within a period of approximately 30 minutes after a suspected concussion, an electrode head unit, which includes a High Density Electrode Array, is placed on the player at the sidelines after an injury, allows for the recording and processing of DC-coupled-EEG data of the player. Data is received by a data processing system comprised of a computing device. The data is transformed to a voltage intensity-map showing the location and propagation of a wave of CSD as a visually distinct ring-shaped region traveling across a representation of the scalp surface of the player.

Example 3Electrode Cap in a Neuro-Intensive Care Unit for Traumatic Brain Injury, Acute Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage Associated with a Laptop for Analysis

(54) In this example, a patient in the neuro-intensive care unit is monitored with an electrode head unit which includes a High Density Electrode Array for the presence of CSDs and PIDs using DC-coupled-EEG data and the processing scheme as described above in Examples 1 and 2. A health care practitioner places the electrode head unit on the patient's head over the border between normal undamaged brain and the suspected region of brain damage as deduced from imaging or a neurological exam. The electrode unit is connected to the processing and display unit via wireless or wired connections. Over a period of up to seven days, the system collects data consisting of globular regions of about 3.0 mm diameter of depressed voltage of about 200 ?V which travel along the border of the suspected region of damaged brain and propagate at a velocity of approximately 3.0 mm/min in various trajectories including branching into two globular regions, disappearing into a sulcus and not reappearing, disappearing into a sulcus and then reappearing on the adjacent gyms, propagating into regions of normal or damaged brain and extinguishing themselves, all of which are characteristic of a CSD/PID. These CSD/PID events are stored in memory and reviewed by the medical personnel as indications of an ongoing process which causes more brain damage. In addition, therapies are investigated to mitigate and diminish the frequency and occurrence of the observed CSDs/PIDs.

Example 4Electrode Cap in an Emergency Medical Transport Unit for Traumatic Brain Injury, Acute Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage Associated with a Laptop for Analysis

(55) In this example, a patient in an emergency medical transport unit is monitored with an electrode head unit which includes a High Density Electrode Array for the presence of CSDs and PIDs using DC-coupled-EEG data and the processing scheme as described above in Examples 1 and 2. Emergency medical personnel place the electrode head unit on the patient's head. The electrode unit is connected to the processing and display unit via wireless or wired connections. During the journey to the medical facility, the system collects data consisting of globular regions of about 3.0 mm width or diameter of depressed voltage of about 200 ?V which travel along the border of the suspected region of damaged brain and propagate at a velocity of approximately 3 mm/min in various trajectories including branching into two globular regions, disappearing into a sulcus and not reappearing, disappearing into a sulcus and then reappearing on the adjacent gyms, propagating into regions of normal or damaged brain and extinguishing themselves, all of which are characteristic of a CSD/PID. These CSD/PID events are stored in memory and reviewed by the medical personnel as indications of an ongoing process that causes more brain damage. In addition, therapies are investigated to mitigate and diminish the frequency and occurrence of the observed CSDs/PIDs.

(56) While the invention has been particularly shown and described with reference to embodiments described above, it will be understood by those skilled in the art that various alterations in form and detail may be made therein without departing from the spirit and scope of the invention, as defined by the appended claims.