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Statistical methods to improve reproducibility and reduce technical variability in heterogeneous multimodal neuroimaging studies of Alzheimer?s Disease

Award Number: R01AG063752
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract: Alzheimer's disease (AD) is a public health crisis with a burden of epic proportion on the American society given its estimated cost of $277 billion in 2018 alone. Brain imaging combined with new morphometric analytic methods has fundamentally changed our understanding of AD progression. However, progress has been slowed because the AD brain exhibits substantial atrophy, white matter pathology, and large deformations, which make it difficult for the most commonly used software package to carry out the tissue segmentation on which longitudinal studies of AD patients depend heavily. We propose to develop novel, generalizable and reproducible statistical neuroimaging pre-processing methods tailored specifically for highly heterogeneous AD MRI/PET image populations and to subsequently assess these methods relative to standard approaches. Specifically, we will focus on tissue class segmentation, which is often used directly for statistical analyses or as an intermediary step for spatial or multimodal registration, as we evaluate the performance of standard software for tissue class segmentation in a heterogeneous AD and elderly control study population. The primary goal of this project is to produce improved, reproducible, and open source statistical methods for tissue class segmentation for AD patients and elderly controls. To achieve this goal we propose three main hypotheses: 1) develop new tissue class segmentation methods for heterogeneous cross-sectional and longitudinal studies of healthy controls, AD subjects and healthy elderly controls; 2) extend the methods to account for different studies and experimental conditions (e.g., MRI scanner) and evaluate their reproducibility for structural MRI and PET in young healthy controls and AD subjects and 3) develop online, freely accessible, reproducible software tools for the assessment, validation, and reproducibility of published analytic pipelines. The completion of this research will provide powerful tools for the analysis of neuroimaging clinical studies from subjects with AD. This work will aid in validation, reproducibility and experimental design by improving existing analysis techniques to accurately quantify biomarkers and treatment impact on brain pathology in AD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $634,388 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	5	4/24/2023	NON-COMPETING CONTINUATION	$634,388
														Subtotal = $634,388

Issue Date FY: 2022 ( Subtotal = $592,972 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	4	4/7/2022	NON-COMPETING CONTINUATION	$592,972
														Subtotal = $592,972

Issue Date FY: 2021 ( Subtotal = $583,383 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	3	4/9/2021	NON-COMPETING CONTINUATION	$583,383
														Subtotal = $583,383

Issue Date FY: 2020 ( Subtotal = $584,985 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Aging Research	000	2	3/24/2020	NON-COMPETING CONTINUATION	$584,985
														Subtotal = $584,985

Issue Date FY: 2019 ( Subtotal = $619,772 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Aging Research	000	1	8/14/2019	NEW	$619,772
														Subtotal = $619,772

Grand Total All Awards = $3,015,500

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Statistical methods to improve reproducibility and reduce technical variability in heterogeneous multimodal neuroimaging studies of Alzheimer?s Disease

Award Number: R01AG063752

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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