Tensor-based morphometry as a neuroimaging biomarker for Alzheimer’s Disease: An MRI study of 676 AD, MCI, and normal subjects
Source: NeuroImage
2008 Nov;43(3):458-469.
Author: Hua X, Leow AD, Parikshak N, Lee S, Chiang MC, Toga AW, Jack Jr. CR, Weiner MW, Thompson PM PubMed ID: 18691658
Abstract:
In one of the largest brain MRI studies to date, we used tensor-based morphometry (TBM) to create 3D maps
of structural atrophy in 676 subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI), and
healthy elderly controls, scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using
inverse-consistent 3D non-linear elastic image registration, we warped 676 individual brain MRI volumes to
a population mean geometric template. Jacobian determinant maps were created, revealing the 3D profile of
local volumetric expansion and compression.We compared the anatomical distribution of atrophy in 165 AD
patients (age: 75.6±7.6 years), 330 MCI subjects (74.8±7.5), and 181 controls (75.9±5.1). Brain atrophy in
selected regions-of-interest was correlated with clinical measurements – the sum-of-boxes clinical dementia
rating (CDR-SB), mini-mental state examination (MMSE), and the logical memory test scores – at voxel level
followed by correction for multiple comparisons. Baseline temporal lobe atrophy correlated with current
cognitive performance, future cognitive decline, and conversion from MCI to AD over the following year; it
predicted future decline even in healthy subjects. Over half of the AD and MCI subjects carried the ApoE4
(apolipoprotein E4) gene, which increases risk for AD; they showed greater hippocampal and temporal lobe
deficits than non-carriers. ApoE2 gene carriers – 1/6 of the normal group – showed reduced ventricular
expansion, suggesting a protective effect. As an automated image analysis technique, TBM reveals 3D
correlations between neuroimaging markers, genes, and future clinical changes, and is highly efficient for
large-scale MRI studies.