U24NS133945

Federated Digital Pathology Platform for AD/ADRD Research and Diagnostics - Project Summary/Abstract

We will connect multiple Alzheimer's Disease and Related Dementias (AD/ADRD) research centers for optimized and standardized whole slide image (WSI) advanced analytics. We propose these specific aims:

Specific Aim 1: Generate a federated platform for data sharing and analysis of human digital neuropathological (DNP) slides.

Specific Aim 1A: Develop an open-source platform to aggregate data distributed across multiple repositories into a central registry portal. This subaim will follow federated data curation, harmonization, annotation, and standardization employing FAIR (Findable, Accessible, Interoperable, and Reusable) principles.

Specific Aim 1B: Develop a federated data curation and management system. This subaim provides methods to curate physical data, such as digital images, across federated sites. WSI data and metadata will be shared with private repositories and high-performance clusters.

Specific Aim 2: Develop and demonstrate a platform for federated machine learning/artificial intelligence (ML/AI), result evaluation, and central project information, constituting a management hub for AD/ADRD studies.

Specific Aim 2A: Develop a federated data annotation and automated AI/ML processing system. This subaim provides methods for users to prepare AI-ready multimodal (WSIs, metadata, demographics, etc.) datasets from distributed sources and conduct multi-site data transfer and federated training. Services and tools developed in Aim 1 will be used to programmatically generate and populate user-defined AI/ML pipelines.

Specific Aim 2B: Develop an open-source platform for the generation and review of datasets and associated models. This subaim will provide a project evaluation portal integrating cohort, dataset, and model training results in a unified interface. A public-facing model hub will provide project, data, specifications, and model data to support data sharing and analysis requirements.

To optimize and demonstrate the strengths of the novel federated network, five integrated projects are proposed. These will span a diverse sampling of human populations and diseases to leverage the unique strengths of DNP. The following sites will contribute resources, expertise, experimental study design, data, and analyses: University of Kentucky (PIs Nelson and Bumgardner, Co-Is Cheung and Fardo). Generate standardized SOPs useful for DNP diagnoses and research along with ML/AI expertise for a federated network. Northwestern/NUN Study and UTSA Universities (PI Flanagan). A focus on TDP-43 proteinopathy in community-based cohorts and ethno-racially diverse populations. University of São Paulo and UCSF (Co-Is Suemoto and OSC Grinberg). Evaluate ADNC from the brains of individuals with African and non-African ancestries. University of Toronto (Co-I Kovacs): Use ML to study white matter tau pathologic changes for novel insights into multiple tauopathies. University of Washington (Co-I Keene): Study tau pathologies across ages and environmental exposures with a focus on traumatic brain injuries.

University Of Kentucky Research Foundation

(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.

93.866 - Aging Research

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

National Institute on Aging (NIA) [HHS - NIH]

Lexington, Kentucky 40526 United States

Single Zip Code

Connecting Machine Readable Digital Human AD/ADRD Neuropathological Library Platforms for Advanced Analytics (U24 Clinical Trial Not Allowed) (RFA-NS-22-062)

Amendment Since initial award the End Date has been extended from 08/31/25 to 08/31/28 and the total obligations have increased 173% from $1,778,991 to $4,861,895.