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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.
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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-i.e., 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
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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.
II. 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
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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.
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