High-Dimensional Medial Lobe Morphometry: An Automated MRI Biomarker for the New AD Diagnostic Criteria

Abstract

Introduction. Medial temporal lobe atrophy assessment via magnetic resonance imaging (MRI) has been proposed in recent criteria as an in vivo diagnostic biomarker of Alzheimer's disease (AD). However, practical application of these criteria in a clinical setting will require automated MRI analysis techniques. To this end, we wished to validate our automated, high-dimensional morphometry technique to the hypothetical prediction of future clinical status from baseline data in a cohort of subjects in a large, multicentric setting, compared to currently known clinical status for these subjects. Materials and Methods. The study group consisted of 214 controls, 371 mild cognitive impairment (147 having progressed to probable AD and 224 stable), and 181 probable AD from the Alzheimer's Disease Neuroimaging Initiative, with data acquired on 58 different 1.5 T scanners. We measured the sensitivity and specificity of our technique in a hierarchical fashion, first testing the effect of intensity standardization, then between different volumes of interest, and finally its generalizability for a large, multicentric cohort. Results. We obtained 73.2% prediction accuracy with 79.5% sensitivity for the prediction of MCI progression to clinically probable AD. The positive predictive value was 81.6% for MCI progressing on average within 1.5 (0.3 s.d.) year. Conclusion. With high accuracy, the technique's ability to identify discriminant medial temporal lobe atrophy has been demonstrated in a large, multicentric environment. It is suitable as an aid for clinical diagnostic of AD.

Figure 1

Cohort flow diagram.

Figure 2

Intensity standardization example for an ADNI subject. From left to right: (a) reference image; (b) original image; (c) standardized image using the Nyul et al. histogram-matching technique [41]; and (d) standardized image using our tissue derived, spatially constrained intensity matching technique [42]. The color map was chosen to increase contrast.

Figure 3

Overview of (a) medial temporal lobe volume of interest; (b) whole brain mask; and (c) temporal lobe volume of interest.

Figure 4

Significant structural differences within the medial temporal lobe related to the discrimination task between (a, b) CTRL versus probable AD and (c, d) CTRL versus MCI-P. Left images represent grey matter concentration differences, while right images represent deformation differences. For each map, we present the covarying voxels associated with the top three eigenvectors in each discriminating function, color-coded with respect to their negative or positive distance from the center and normalized to the maximum absolute value in the VOI.