HIGH-THROUGHPUT OPTICAL INVESTIGATION INTO INTACT LARGE-SCALE NERVOUS SYSTEMS FOR ALZHEIMERS DISEASE - PROJ…

Assistance award details

Assistance award identifier

ASST_NON_R00AG059946_075

FAIN

R00AG059946

Recipient

THE GENERAL HOSPITAL CORPORATION

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$857,221

Period

Jul 15, 2019 – Mar 31, 2026

Fiscal year

2023

Place of performance state

MA

Source file

FY2023_All_Assistance_Full_20261006.zip

Description

HIGH-THROUGHPUT OPTICAL INVESTIGATION INTO INTACT LARGE-SCALE NERVOUS SYSTEMS FOR ALZHEIMERS DISEASE - PROJECT SUMMARY ALZHEIMER’S DISEASE (AD) IS AN IRREVERSIBLE NEURODEGENERATIVE DISEASE WITH ITS UNDERLYING CAUSE POORLY UNDER- STOOD. ALTHOUGH MANY RESEARCH HAVE BEEN CONDUCTED TO UNDERSTAND ITS PATHOLOGICAL ORIGIN USING ADVANCED IMAGING TECHNOLOGIES, CURRENT DISCOVERIES HAVE MAINLY STEMMED FROM STUDIES ON MICROSCOPIC SYSTEMS WITH LIM- ITED NUMBER OF CELLS. WHILE INCREASINGLY MANY EVIDENCES HAVE INDICATED THAT THE INTERACTION AMONG VARIOUS GROUPS OF CELLS ACROSS THE ENTIRE NERVOUS SYSTEM HOLDS THE KEY TO THOSE UNANSWERED QUESTIONS IN AD, LARGE- SCALE VOLUMETRIC INVESTIGATION ARE LIMITED BY CURRENT IMAGING TECHNOLOGIES. FIRST, MICROSCALE METHODS USED IN CONVENTIONAL HISTOPATHOLOGY, SUCH AS ELECTRON OR LIGHT MICROSCOPY, REQUIRE EXTENSIVE TISSUE SECTIONING FOR THICK SAMPLES, LEADING TO PROLONGED IMAGING TIME AND THE DICULTY OF 3D RECONSTRUCTION FROM 2D IMAGES DUE TO TISSUE DEFORMATION. ON THE OTHER END, INSUCIENT SPATIAL RESOLUTION AND LIMITED MOLECULAR SPECICITY OF MACROSCALE APPROACHES, SUCH AS MR/PET/CT, HAVE MADE THEM LESS ATTRACTIVE FOR PATHOLOGICAL STUDIES. THUS, THE GOAL OF THIS PROJECT IS TO DEVELOP AN OPTICAL IMAGING METHOD THAT NOT ONLY PROVIDES HIGH RESOLUTION AND MOLECULAR CONTRAST SUITABLE FOR THE PATHOLOGY OF THE NERVOUS SYSTEMS IN AD MOUSE MODELS, BUT ALSO OERS EN- ABLING HIGH-THROUGHPUT FOR THOSE LARGE-SCALE INVESTIGATIONS DEMANDED BY MANY OF TODAY’S AD RESEARCH. THIS PROPOSAL PLANS TO ADDRESS THE ABOVE IMAGING NEEDS BY CREATING COHERENT OPTICAL IMAGING APPARATUS TO PRO- VIDE THE ENABLING HIGH-THROUGHPUT AND HIGH RESOLUTION, BY DEVELOPING NEW TISSUE PROCESSING METHODS TO OER THE MOLECULAR CONTRAST IN INTACT TISSUES, BY BUILDING COMPUTATIONAL TOOLS TO ASSIST THE BIOLOGICAL INTERPRETATION OF IMAGING RESULTS. THE OUTCOME OF THE PROPOSED RESEARCH IS EXPECTED TO BE A SET OF NEW RESEARCH TOOLS THAT FACILITATE LARGE-COHORT STUDIES ON AD MOUSE MODELS WITH B