Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer's disease patients and healthy subjects

Abstract

Purpose: AV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer's disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations.

Methods: We recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed.

Results: White matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter.

Conclusion: These results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1

Pipeline for histogram creation. CT scan was registered on the T1 scan (1) and the transformation matrix applied to the PET AV-45 scan (2). T1 was segmented in grey and white matter (3) and the binary masks of the tissues were applied to the PET AV-45 scan in T1 space (4). Intensity histograms were extracted from the tissues (5).

Figure 2

Mean histograms shapes. Upper row: grey and white matter mean histograms for (a) HC and (b) AD groups. Lower row: grey and white matter mean histograms for (c) subjects classified in cluster 1 and (d) subjects classified in cluster 2 (cf. the Cluster Analysis section). Arrows in (a) show shape difference relative to (c); arrow in (b) shows shape difference relative to (d), see Cluster Analysis below.

Figure 3

Upper panel. Spider web plots of the 7 histogram indices for (HC) and AD patients. Blue line = HC, red line = AD. Lower panel. Comparison of the histogram indexes in grey matter and in white matter between AD patients and HC subjects groups. Mean and (standard deviation) are mentioned for each index. Threshold significance for p=.05. Significant p values are mentioned with an asterisk.

Figure 4

Histogram shape of misclassified subjects. a) Grey matter mean histograms of the 2 AD patients classified as HC (red stars and red crosses) and the 2 HC classified as AD (empty blue squares and diamonds) in the discriminant analysis performed on grey matter histogram parameters plotted against the mean grey matter histogram of the correctly classified AD (filled red square) and HC (blue filled square). b) White matter mean histograms of 2 (out of 3) AD patients classified as HC (red stars and red crosses) and the 2 (out of 7) HC classified as AD (empty blue squares and diamonds) in the discriminant analysis performed on white matter histogram parameters, plotted against the mean white matter histogram of the correctly classified AD (filled red square) and HC (blue filled square). 1 out of 3 misclassified AD and 5 out of 7 misclassified HC are not shown for easiness of presentation, see supplementary Figure 2. Vertical pointed-dashed lines in both a and b panels mark 25th and 75th percentiles of histograms.