R01NS121761

A Toolkit for Analysis and Visualization of Preclinical Rodent Neuroimaging Experiments - Project Summary

Rodent models remain an important tool in preclinical studies of brain disease and disorders, as well as basic neuroscience investigations. Rodent imaging data, acquired through techniques including MRI and microscopy, play a critical role in many of these studies. However, much of the software tools developed for analyzing MRI of the brain have been focused largely on human data. As a result, investigators studying animal models of disease often have to adapt these tools for their research.

In this project, we aim to address this need by developing a dedicated suite of open-source software tools for processing, analyzing, and visualizing neuroimaging data acquired from rodent brains. These tools will operate on structural diffusion and functional MRI, as well as optical microscopy of optically cleared serially sectioned tissue samples. Our development of these tools will be built upon our decades of experience in developing software for analyzing human and mouse imaging data, our expertise in developing multimodal atlases of the mouse brain, and our active efforts in community engagement and dissemination while applying these resources in neuroscientific studies.

Where suitable, we will make use of deep learning methods to produce powerful segmentation and registration networks trained on manually annotated and delineated data. Additionally, we will develop easy-to-use interfaces that will facilitate data processing and provide advanced visualization capabilities for datasets with sizes on the order of one terapixel.

The project has five specific aims:

Aim 1: Develop MRI processing tools, including intrasubject co-registration of MRI modalities, extraction of brain tissue from whole head scans, tissue classification, and processing of diffusion and functional MRI data.

Aim 2: Develop tools for processing microscopy of cleared and sectioned tissue, with the major goal of aligning these data to a reference atlas generated from either optical microscopy or MRI. These tools will perform cell counting in automatically segmented regions, axon following, dendritic arborization, and dendritic spine counting.

Aim 3: Develop a statistical analysis toolbox that will perform statistical inference for neuroimaging measures from microscopy and MRI data analyzed using methods from Aims 1 and 2.

Aim 4: Integrate the components from Aims 1-3 into an informatics platform that will provide command line tools for easy scripting, interoperability with related imaging tools, and a graphical interface for visualizing data across different scales.

Aim 5: Perform evaluation of our software tools using two studies: imaging an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis and imaging a mouse model of normative aging. We will also collaborate with a network of small animal imaging experts external to the project who will use and evaluate the software. These driving projects will serve as testbeds to ensure the practical utility of the software in a research setting, providing direction for the development of our research platform.

We will distribute the software freely under an open-source license and provide user support through our website.

Los Angeles University Of California

(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 THE NEUROSCIENCE WORKFORCE, 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.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

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

Los Angeles, California 900950001 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 388% from $626,523 to $3,058,240.