An MRI-Based Atlas for Correlation of Imaging and Pathologic Findings in Alzheimer's Disease

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Abstract

BACKGROUND AND PURPOSE:

Pathologic diagnosis is the gold standard in evaluating imaging measures developed as biomarkers for pathologically defined disorders. A brain MRI atlas representing autopsy-sampled tissue can be used to directly compare imaging and pathology findings. Our objective was to develop a brain MRI atlas representing the cortical regions that are routinely sampled at autopsy for the diagnosis of Alzheimer's disease (AD).

METHODS:

Subjects (n= 22; ages at death = 70-95) with a range of pathologies and antemortem 3T MRI were included. Histology slides from 8 cortical regions sampled from the left hemisphere at autopsy guided the localization of the atlas regions of interest (ROIs) on each subject's antemortem 3D T1-weighted MRI. These ROIs were then registered to a common template and combined to form one ROI representing the volume of tissue that was sampled by the pathologists. A subset of the subjects (n= 4; ages at death = 79-95) had amyloid PET imaging. Density of β-amyloid immunostain was quantified from the autopsy-sampled regions in the 4 subjects using a custom-designed ImageScope algorithm. Median uptake values were calculated in each ROI on the amyloid-PET images.

RESULTS:

We found an association between β-amyloid plaque density in 8 ROIs of the 4 subjects (total ROIn= 32) and median PiB SUVR (r2 = .64;P< .0001).

CONCLUSIONS:

In an atlas developed for imaging and pathologic correlation studies, we demonstrated that antemortem amyloid burden measured in the atlas ROIs on amyloid PET is strongly correlated with β-amyloid density measured on histology. This atlas can be used in imaging and pathologic correlation studies.

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