U01NS142013

FAST-ET: FAST AUTOMATED SERIAL TAPE-ENABLED ELECTRON TOMOGRAPHY - PROJECT SUMMARY THIS PROJECT AIMS TO DEVELOP A SOLUTION FOR HIGH-THROUGHPUT BRAIN CONNECTOMICS BY INTEGRATING GRIDTAPE-BASED AUTOMATED SECTION COLLECTION AND HANDLING WITH ADVANCED SERIAL ELECTRON TOMOGRAPHY (ET). ET IS AN INDISPENSABLE TOOL FOR ULTRA-HIGH RESOLUTION IMAGING, TYPICALLY USED TO STUDY VERY SMALL REGIONS IN DETAIL BY COMPUTATIONALLY RECONSTRUCTING 3D VOLUMES FROM 2D PROJECTIONS. USING INTERMEDIATE VOLTAGE TRANSMISSION ELECTRON MICROSCOPY (IVEM), ET GENERATES VOLUMETRIC INFORMATION THROUGH THICK SECTIONS (UP TO 2 ΜM). BY COMBINING ET OF THICK SECTIONS WITH AUTOMATED SECTION COLLECTION AND HANDLING, WE AIM TO SIGNIFICANTLY ADVANCE WHOLE MOUSE BRAIN CONNECTOMIC IMAGING IN TERMS OF ROBUSTNESS AND PRACTICALITY, IMPROVING UPON CAPABILITIES FOR HIGH- AND MULTI-RESOLUTION IMAGING FOR MAMMALIAN BRAINS, AND MORE EFFICIENTLY ELUCIDATING THE ORGANIZATIONAL PRINCIPLES OF BRAIN CIRCUITS. OUR APPROACH WILL FURTHER FACILITATE SAMPLE-PRESERVING IMAGING, ALLOWING FOR MULTI-SCALE INTERROGATIONS WITHOUT SAMPLE DESTRUCTION, THEREBY SIGNIFICANTLY REDUCING THE RISKS ASSOCIATED WITH DATA ACQUISITION AND AMPLIFYING THE VALUE OF PREPARED SAMPLES. THE EFFICACY OF THIS SOLUTION WILL BE VALIDATED USING THE MOUSE CEREBELLUM, PROVIDING INSIGHTS INTO CELL-TO-CELL COMMUNICATION WITHIN THIS BRAIN REGION CRUCIAL FOR MOTOR CONTROL. THE PROJECT WILL BE DRIVEN BY THREE COMPLEMENTARY AIMS STRUCTURED TO: 1) EVALUATE ET SCALABILITY BY ASSESSING IMAGING CONDITIONS, LOSSLESS SECTIONING, AND GRIDTAPE CHARACTERISTICS, 2) DEVELOP TAPE-ENABLED SERIAL ET THROUGH THE DESIGN AND TESTING OF A REEL-TO-REEL TAPE SYSTEM, A TAPE TILTING SYSTEM, AND RELATED SOFTWARE, AND 3) AUGMENT TAPE-ENABLED ET WITH ADVANCED MACHINE LEARNING ALGORITHMS, ENERGY-FILTERED TEM STRATEGIES (E.G., AUTOMATED MOST-PROBABLE LOSS TOMOGRAPHY (MPL)), CONTINUOUS IMAGING, AND MODIFICATIONS FOR LARGE SECTION TOMOGRAPHY. DELIVERABLES FROM THIS WORK WILL INCLUDE THE DEVELOPMENT, TESTING, AND TROUBLESHOOTING OF PROTOTYPE FAST-ET PLATFORM, CRITICAL REFERENCE DATASETS FOR THE NEUROSCIENCE COMMUNITY, AND SCALABLE METRICS FOR MAMMALIAN WHOLE-BRAIN CONNECTOMICS. OUR GOAL IS TO SIGNIFICANTLY ADVANCE UNDERSTANDING OF BRAIN FUNCTION AND DYSFUNCTION WITH BROAD IMPLICATIONS FOR NEUROSCIENCE, ENGINEERING, AND ARTIFICIAL INTELLIGENCE.

Children's Hospital Corporation

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.372 - 21st Century Cures Act - Brain Research through Advancing Innovative Neurotechnologies

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Boston, Massachusetts 021155724 United States

Single Zip Code

BRAIN Initiative Connectivity across Scales (BRAIN CONNECTS): Specialized Projects for Scalable Technologies (U01 Clinical Trial Not Allowed) (RFA-NS-22-049)