Novel Methods for Image Analysis to Evaluate Relationships Between Biomarkers in Alzheimer's Disease
Advisory Committee Chair
Jonathan E McConathy
Advisory Committee Members
Louis Justement
Jack Rogers
David Standaert
Kristina Visscher
Document Type
Dissertation
Date of Award
2020
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
Abstract
Neuroimaging biomarkers, including pathological amyloid and tau measured with positron emission tomography (PET) and neurodegeneration measured with magnetic res-onance (MR), are part of the research framework for Alzheimer’s disease (AD). Abnormal brain amyloid is currently the earliest established phenotypic marker of AD, and other imaging biomarkers such as tau-PET become abnormal later in the progression of AD pathophysiology. The ability to measure amyloid and predict both tau status and cogni-tion using a single amyloid-PET study through a method readily employed in both re-search and clinical settings would provide a valuable tool in assessing AD. The first goal of this dissertation was to validate a semi-automated, image processing methodology and design an accompanying image format converter for streamlined, efficient image pro-cessing of PET and MR data. We then hypothesized that early-frame amyloid-PET (efAP) would correlate with the presence of tau pathology on tau-PET and predict cogni-tive trajectory. The rationale is that regional brain concentrations of radioactivity during the first few minutes of dynamic amyloid-PET scans are primarily determined by blood flow, which in turn is decreased in the setting of tau pathology and related to cognition. In terms of the first objective, our methodology required only ~5 min plus segmentation time and strongly correlated with the reference standard across amyloid- and tau-PET standardized uptake value ratios with high inter-operator reproducibility. Our converter performed fully-automated reconstruction of research to clinical formats at a higher effi-ciency than the reference standard. We then showed how hippocampal efAP correlated significantly with tau-PET with superior stratification of tau-PET positivity compared to hippocampal volume. In relation to cognition, hippocampal efAP was significantly associ-ated with baseline memory and future cognitive decline at least 18 months post-imaging, providing additional value beyond amyloid burden and hippocampal volume. In conclu-sion, efAP, a biomarker acquired during the dynamic phase of amyloid-PET, can provide additional information beyond amyloid positivity determined during the standard de-layed phase, including estimation of the likelihood of tau positivity in amyloid-positive individuals and prediction of cognitive decline. The design utilizes an image processing workflow incorporating clinically-supported components for potential widespread uptake in both research and clinical settings.
Recommended Citation
Raman, Fabio, "Novel Methods for Image Analysis to Evaluate Relationships Between Biomarkers in Alzheimer's Disease" (2020). All ETDs from UAB. 897.
https://digitalcommons.library.uab.edu/etd-collection/897