Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage

Abstract

The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are >0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p<0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.

Fig. 1

Interpolated weight vectors for (A) GM, (B) WM and (C) CSF overlaid on the corresponding custom template. Color scale indicates the weight i.e. the importance of the voxel location for classification.

Fig. 2

Anatomic patterns with maximum discriminative power between AD and controls are overlaid on the corresponding custom T1 template. Color scale used to indicate the frequency of occurrence of the voxel in multiple tissue maps. Yellow: voxel location used in all three tissues (GM, WM and CSF); orange: voxel location used in at least two tissues and red: voxel location used in one tissue only.

Fig. 3

aSTAND-score categorized according to pathological Braak NFT stage. Subjects A and B are outlier cases with aSTAND score – Braak stage discordance discussed in the paper.

Fig. 4

The percentage of subjects in each Braak stage classified based on (A) clinical diagnosis and (B) diagnosis using aSTAND-score at the time of the MRI scan.

Fig. 5

Scatter plot showing relationship between aSTAND-score and hippocampal W score. For convenience, reference lines at a W score of zero and aSTAND-score of 0 have been added to the plot.