Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 I. Executive Summary A. Proposed Work We propose the formation of a scientific center of excellence for the purpose of developing and evaluating superconducting instrumentation and high fidelity computational electromagnetic brain models for the high resolution study of human brain activity. The proposed center will utilize the strengths and expertise of scientists in New Mexico, including physicists, engineers, and medical neuroscientists. Working together, this team will translate their knowledge in diverse areas such as superconductivity, cryogenics, electronics, image processing, computational electromagnetics, advanced signal analysis, and neuroscience to develop hardware, software, analyses, and medical applications for a new generation of brain imaging systems. Such imaging systems would consist of a 1000 sensor biomagnetometer, parallel supercomputer, and graphic workstation operating seamlessly to translate the brain's magnetic and electrical signals into a three-dimensional moving image showing it's instantaneous intensity and distribution. This instrument, coupled with advanced signal processing techniques and a computational electromagnetic brain model, will be used to study the brain in health and disease states. The knowledge gained in medical and basic science about the brain could be used to: 1. Lower Health Care Costs: Health care costs for neurological disorders can be reduced through the development and use of more specific and sensitive diagnostics. 2. Minimize Surgical Risks: The risk to critical areas of the brain may be reduced by identifying those areas noninvasively, and sparing them during neurosurgery. 3. New and Improved Treatments: We can improve the treatment of neurological diseases by using tomographic images of the brain's activity to provide immediate quantitative feedback of how the brain responds to that treatment. 4. Psychiatric Disorders: The proposed noninvasive brain imaging system and computational model will expand our understanding and treatment of mental illnesses. 5. Basic Neuroscience: The proposed center, instrumentation, and computational model will further our knowledge of the higher functions of the brain--the essence of what it is to be human. The research instrumentation and computational electromagnetic brain model will be offered as a national resource center for the study of the brain. The technology developed for this biomagnetometer will be made available to U. S. industries, expanding our competitiveness in the international medical instrumentation marketplace. Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5
Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 B. Technical Benefits In order to develop an advanced neuromagnetometer, we will need to develop technology in the following areas: 1. Superconducting sensors: Thin-film SQUID (Superconducting Quantum Interference Device) magnetic sensors will be designed to improve upon the sensitivity and dynamic range of existing designs. An all digital sensor design will reduce parts count that will improve manufacturability and enable us to expand the number of sensors without increasing complexity. SQUID sensor development has extended application in many areas of remote sensing, where the highest attainable sensitivity is of importance. 2. Cryocoolers and Cryostats: Cryocoolers and low loss cryostats will be developed so as to reduce the size and portability, while increasing the flexibility of existing dewars. Instead of relying on a large reservoir of liquid helium for cooling, we propose developing low temperature, high efficiency, long-life refrigeration systems, thus reducing the 1000 sensor array to a “hair dryer" enclosure. The cryocooler technology we will develop will also benefit other types of low-noise sensors and portable quantum standards. 3. Image processing: We will develop computer algorithms for three dimensional segmentation of medical images from CT or MRI scans. Specifically, processes will be developed and tested to automatically recognize the different tissue types in the brain-- scalp, skull, dura, cortex, blood vessels, etc.--and create a model of each surface, layer by layer. This model will be used for electromagnetic calculations of the magnetic fields and electrical potentials resulting from brain activity. Automated image segmentation will also be valuable to radiologists, in that portions of the brain (as well as other organs) will be more readily visualized without the intervening tissue layers--ie., as they might appear during surgery. 4. Computational electromagnetics: The segmented model of the various tissues in the head, known as a finite element model (FEM), will be used to provide a high accuracy prediction of the magnetic fields and electrical potentials resulting from the brain's electrical activity. This is called the forward solution. A highly accurate forward solution is necessary in order to compute a high resolution unambiguous estimate of the brain's activity. Because of the complexity of these calculations, software will be developed for high speed parallel computer systems. 5. Signal processing: What does one do with 1000 channels of brain signal information? The classical EEG notion of displaying each individual channel on a chart recorder is both impractical and wasteful of the rich information of such a large array. Instead, we propose deriving signal processing techniques from the array processing used in phased array radar. This would enable the array of 1000 sensors to be instantaneously "steered" to any part of the brain, receiving the brain's signals with much higher sensitivity and selectivity than any single sensor. The array could then be "scanned" through the three-dimensional volume of the brain, generating a tomographic picture of its activity. This type of signal Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5
Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 processing would also improve the array's rejection of magnetic disturbances, such that an expensive and bulky magnetically shielded room will no longer be required for neuromagnetic measurements. C. Recommendations The proposed project utilizes scientific and engineering expertise that is unique to New Mexico. Success in any single portion of this project can boost our technological competitiveness in the world marketplace. The 90's have been dubbed, "The Decade of the Brain." This work will advance a noninvasive technology from a laboratory curiosity to commercially viable instrumentation, lending that phrase new meaning. In three years, New Mexico will host an international meeting on biomagnetism. The proposed center will demonstrate our creativity and know-how to the world scientific community. This project has low risk and a large potential benefit to medicine and neuroscience. We therefore strongly recommend its approval. D. Scientific and Engineering Research Partners The scientific and engineering research partners for this effort consists of components from each of the following areas: Government, National Laboratories, Industry, and Academia. Sandia National Laboratories brings experience in massively parallel supercomputer applications, cryogenic support systems, finite element modeling, and computational electromagnetics. Veterans Administration/Center for Magnetoencephalagraphy brings experience in neurological phemeneurology, medical imaging, and has experimentation facilities. The industrial partners would consist of IBM, TRW, and Conductus for SQUID design and fabrication alternatives. The Academic partners consists of University of New Mexico, University of Houston, and the University of Arizona who collectively bring expertise in signal/image processing, finite element modeling for biological applications, radiological imaging, and neurology. Il. Introduction In todays society brain disorders devastate the lives of 20% of the total population or approximately 50 million people. In monetary terms the per capita cost is $1690, which equates to approximately $400 billion per year or 7.3% of the Gross Domestic Product. This figure includes both direct costs such as medical treatement and services, and indirect costs such as lost wages and family caregiving expenses. In proportion the direct costs equal approximately one- fourth to one-half of the total ($104 billion in 1991) while the indirect costs make up the rest ($296 billion in 1991). Brain disorders include well over 650 disorders that can be divided into three general categories. Psychiatric disease ranging from schizophrenia to cognitive impairment account for of $136 Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5
Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5 billion in costs. Neurologic disorders - dementia, mental retardation, multiple sclerosis, head and spinal cord injuries, stroke, cerebral palsy, and epilepsy - cost $103 billion. Disorders of addiction such as alcohol and drug abuse cost $161 billion. Some disorders such as multiple scleroses are killers and as a category, brain disorders are a leading cause of death in the United States today. They are the most common and severe cause of social, economic, and psychological disabilities in this country. Empirical medicine has played a centrol role in understanding brain disorders. Much of the current medical knowledge relating to understanding brain function has relied heavily upon experiments conducted on surviving victims of unfortunate experiments of nature, such as stroke. In fact, most of what is currently known about the localization of normal language comes from the study of aphasia, a disorder of language that is found most often in patients who have suffered from a stroke or head trauma. Furthermore, almost everything we know about the anatomical organization of language and memory comes from clinical studies of patients with lesions of the brain. Today correlation of major mental illnesses to normal and abnormal brain activity is based primarily on postmortem studies, animal research, and the examination of peripheral metabolites in human beings. Ultimately one would like to somehow map the vast range of cognitive functions that become distorted or diminished, leading to brain disorders, by observing the structure and metabolic and neurochemical function of the brains of normal individuals. Serious brain disorders including anatomical and functional disorders typically possess characteristically abnormal electrical signatures that can be directly determined or inferred through current measurement techniques. The current technology used in diagnosing such disorders are categorized below with relevant examples of each technology. I. Active - Invasive: This category is characterized by requiring either direct access to the brain for stimulation or injection of radioactive sources that can be tracked by detectors. Position - emission tomography (PET) is a nonsurgical technique that falls within this category. It provides images of brain function and has revolutionized the study of human cognitive processes and psychiatric and neurological disease. This emission tomography technique requires one to substitute position - emitting isotopes (half-lives ranging from several minutes to several hours) for constituents of biologically important compounds such as oxygen, carbon, nitrogen, and hydrogen. The specific isotope is then injected or inhaled by the patient and subsequently accumulates in specific regions of the brain according to metabolic activity. In the process of position emission the isotope produces two gamma rays that can be detected and used for imaging concentrations of the isotope within the brain. Thereby localizing brain metabolic activity that must have electrical counterparts. Because PET scanning relies on radiopharmaceuticals, it is unsuitable for routine testing or therapeutic monitoring. II. Active - Noninvasive: This category is characterized by requiring either the use of energetic radiation or stimulated emission by constituent atomic nuclei. Approved For Release 2000/08/08 : CIA-RDP96-00789R003300190001-5