Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 order of magnitude and make surgical cure of epilepsy widely available throughout the developed countries of the world. 2. Stroke Another important medical application is the possibility of assessing stroke damage during the acute phase when interventional therapy might be administered to prevent irreversible tissue damage. No noninvasive means exists today to evaluate the spatial extent of reversible brain damage, and therefore physicians are often reluctant to take risky therapeutic measures without reasonable assurance that they will benefit the patient. Again, a neuromagnetic brain imaging system offers the possibility to map out the three-dimensional regions of affected tissue by focusing on changes in spontaneous brain electrical activity that accompany an ischemic condition prior to tissue death. 3. Psychiatric Disorders There is much interest now in the potential use of MEG to assess psychiatric disorders. Some of . these disorders are known to be accompanied by abnormal spontaneous brain electrical activity, but the association is too tentative for useful diagnosis or therapeutic monitoring. Positron emission tomography has been shown to have diagnostic potential on the basis of abnormal patterns of metabolic activity that must have electrical counterparts. Because it relies on radiopharmaceuticals, PET scanning is an invasive procedure and is unsuitable for routine testing or therapeutic monitoring. The problem with current noninvasive tests based on EEG measurements to assess electrical activity abnormalities appears to be with their inadequate spatial selectivity. The 1000 channel neuromagnetometer should permit the spontaneous electrical activity of the brain structures known from PET and other means to be affected by the disorder to be measured directly, thus providing the necessary diagnostic specificity. 4, Head Trauma and Tumor Head trauma and brain tumor may be associated with regional damage to the brain or to its blood supply. The proposed whole head functional brain activity imaging system should be able to detect many signs of brain injury that may not show up on anatomic (MRI or CT) scans of the head. For example, an injured region may be visualized as a "hole" in the brain activity image. Also, regions of pathological brain activity such as abnormally slow ("focal slowing") or abnormally rapid activity, such as may be seen on the boundary of a damaged or compromised brain tissue. A neuromagnetic image, taken very early after head injury and throughout the recovery period, may provide immediate feedback on the effectiveness of a particular treatment, and could lead to improved management of head injuries. The brain imaging system may also be able to detect signs that indicate tumor or other inflamation of the brain before they show up in MRI or CT scans. Early detection of brain tumors would have a big impact on reducing mortality, morbidity, and medical costs. Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5
Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 5. Learnin g Disorders Learning disorders and dementias (Alzheimer's disease, and AIDs dementia, for example) have been studies primarily by behavioral (psychometric) testing and post mortem examination of the brain. More recently, tests have been developed to identify biochemical and genetic markers for some of these diseases. These categories are lumped together in this section for convenience and due to lack of quantitative evaluation of the roots of the observed behavioral symptoms. The proposed whole head brain imaging system can permit visualization of the actual brain activity of each individual while they perform cognitive or memory tasks. By studying and comparing the way the normal and the pathological brain operate, we may be able to improve pharmacological brain operate, we may be able to improve pharmacological treatment and rehabilitation programs. 6. Substance Abuse Substance abuse represents a serious problem throughout the world. The advanced neuromagnetometer may be able to detect fundamental differences in brain activity between those who are prone to substance abuse and those who are not. In addition, it is likely that such a brain imaging system could be used to noninvasively identify individuals currently using alcohol or other drugs, without the need for blood or urine tests. Such testing could be of value for screening personnel involved in hazardous or high-security jobs for which impaired judgement may have dire consequences. Lastly, our ability to quantitate brain activity may lead to improved management and treatment of substance abusers. 7. Pre-Operative Evaluation Functional localization of motor and sensory areas of the brain, including regions serving language can provide important information needed for planning neurosurgery. Pre-surgical knowledge of the physical/anatomical locations of brain functions will guide the neurosurgeon in the surgical approach so as to spare injury to critical regions. 8. Spinal Cord Injury Spinal cord injuries are often accompanied by motor deficits (paralysis) and loss of sensation for regions of the body connected below the injured spinal segment. The state of the medical art being limited, a permanently injured spinal cord cannot yet be regenerated, the connections between the brain’s motor cortex and the muscles are severed. Furthermore, the feedback to the brain for joint position and muscle tone may also be severed. The proposed neuromagnetic instrument will have the sensitivity and spatial selectivity to focus on, and extract in realtime, the signals from the motor cortex of the brain. It is therefore possible to use the brain activity - corresponding to intentional movement to control a prosthetic device to effect that movement. Although development of a fully portable system is still only conceptual, the principles could be tested using the 1000 sensor MEG based system. 9. Drug Evaluation Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5
Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 A final medical example is drawn from psychopharmaceutical treatment and new drug evaluation. Since it is generally impossible to noninvasively determine the effect of drugs on specifically targeted regions of the brain, their effectiveness is often judged solely on the basis of behavioral changes which are notoriously unreliable and may take days or even months to develop. At best, they are only consequences of the direct action of the drug on the brain. Moreover, measurements of drug concentrations in the blood stream frequently fail to indicate the drug concentrations at the brain cells where they are active. The best measurement is one that monitors the changes in brain activity directly, and preferably one that is noninvasive. There is a clear and large unmet need that appears to be a promising commercial opportunity for advanced MEG technology. B. Basic Neurological Science Problems 1. Cognitive Neuroscience Cognitive neuroscience has, in the past, relied heavily on localizing brain activity selected at a specific time latency relative to a signal averaged response. Signal averaging is, of course, useful for enhancing signal-to-noise ratio, but masks the trial to trial variations in the brain’s response. In addition, as we select longer latencies from the synchronizing stimulus, the brain’s response may have much weaker time-lock (vary in time delay), rendering signal averaging useless. The more important brain processes that distinguish humans from lower animals — language, imagination, and problem solving — are not readily locked to any external stimulus and will require more advanced types of signal processing to extract the desired signals from the background brain activity. 2. Lie Detection Present lie detectors are notoriously unreliable because they are unable to test the origin of the autonomic response resulting in measurable physiological phenomena. The location-specific recording of spontantaneous brain activity offered by the advance instrument should more clearly reveal the brain’s uncontrollable basic response to interrogation. 3. Man-Machine Interface Among the potential commercial military applications of an advance MEG system is the assessment of human mental performance under conditions of high work load. These measurements may lead to improved design of the man-machine interface by more effectively conveying essential information to the brain such that the mental work is reduced. A more speculative but somewhat related application is the possibility that an MEG array focused by advanced signal processing (adaptive beamforming) to a specific brain site could be used to control a machine by directed mental activity alone. This could lead to an entirely new interface between man and machine. Another commercial military application could be screening personnel for exceptionally demanding jobs. Some individuals are clearly better suited for some mentally stressful tasks, such as piloting a fighter aircraft in combat conditions, than others. A reliable early test could save significant money spent on candidates who are unable to complete Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5
Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 the final stages of their training due to latent inability to meet the demands of the job. Screening personnel for high security positions could also be an application of military importance. IV. System Requirements and Design Goals A. Sensor System Requirements The sensor array must have full head coverage. The sensors must be spaced closely to one another (approximately 10 mm center-to-center) so as to maximize spatial accuracy. The sensors, operating at 4 K should be spaced as close as possible to the head. Present commercial systems have a 15 to 20 mm spacing. Reducing this to 5 mm through good cryogenic design will improve signal-to-noise ratio by almost 20 dB. The SQUID sensors must have high linearity, wide dynamic range, and low noise. All these factors are key to reconstructing images of the brain’s electrical currents. The sensor array must also be able to discriminate against background ambient magnetic noise, and operate within a hospital environment. B. Computational Electromagnetics Model Requirements Imaging the continuous electrical currents of the brain requires high accuracy in computing the forward solution for magnetic fields and electrical potentials for any distribution of current in the head. This can be accomplished by creating a finite element model (FEM) from an anatomical scan (MRI or CT) of the head of each patient. The system must be capable of segmenting the anatomic image into regions of each tissue type (e.g., scalp, skull, dura, cortex, white matter, cerebrospinal fluid, etc.). By assigning a conductivity value to each of these regions, an accurate forward solution may be obtained. The image segmentation should be “turnkey” — that is, performed with little or no human intervention. The segmentation of an MRI or CT scan into a three-dimensional model, alone, would have significant medical value in the visualization of anatomic features. Segmentation of the brain’s cortical surface will further improve the computation of an image of the brain’s electrical activity. First, the cortical layer is the source of the dominant primary currents and activity (it is the layer of the brain containing the neurons and their dendritic input connection). No significant sources should lie outside this cortical layer. Next, the electrical current vector is known to flow at right angles to the cortical surface. By knowing the local normal vector to any part of the cortical surface, we can reduce the number of unknowns in the image to just one — the current amplitude. Without this normal vector, there are three unknowns for the X, Y, and Z current amplitudes. C. Supercomputer Requirements The typical volumetric MRI scan is composed of an array of 256 by 256 by 128 voxels (volume picture elements), each with a dimension of 1 by 1 by 1.5 mm. Segmenting these 8.4 million picture elements requires a computer with a large memory capacity and high speed. Once the image is segmented, a finite element model can be constructed. Assuming a model volume of about 3000 cm3, and a required localization accuracy of less than 0.5 cm, it is obvious that the FEM must contain at least 24,000 elements. Computation of the forward solution from this FEM Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5