How do tau PET and amyloid PET imaging markers correlate to changes in grey matter microstructure as detected by diffusion MRI?

• Published in: Alzheimer's & dementia Vol. 17; no. S4
• Main Authors: Kullakanda, Durga Prasad, Chen, Jenny, Ades‐Aron, Benjamin, Osorio, Ricardo, Fieremans, Els
• Format: Journal Article
• Language: English
• Published: 01.12.2021
• DOI: 10.1002/alz.052815
• ISSN: 1552-5260

Background Diffusion MRI (dMRI) allows non‐invasive mapping of microstructural changes in the brain. In this study, we assess the relationship between amyloid and tau deposition and grey matter microstructure as detected with diffusion kurtosis imaging (DKI) [1,2]. We hypothesize that inflammation associated with amyloid deposits might result in more restricted diffusion and neuronal death associated with tau pathology might result in less restricted diffusion. Method 38 cognitively healthy subjects received 3‐T PET‐MR imaging, each including anatomical MPRAGE, DKI and static PET scans either with 18F‐Florbetaben (n=20, 12 females, age = 67.20±5.75 years) or 18F‐MK‐6240 tracer (n=18, 14 females, age = 66.56±5.23 years) to probe amyloid or tau deposition, respectively. For each subject, regions of interest (ROIs) were automatically segmented on MPRAGE using Freesurfer, combined and narrowed down to 4 regions of interest: primary motor cortex as a control, anterior/posterior cingulate cortex as high amyloid regions, and entorhinal cortex as a high tau region. The standardized uptake values in these ROIs normalized to grey matter cerebellum yielded cortical relative SUV (SUVR). DKI processing provided parametric maps of the mean diffusivity (MD), kurtosis (MK) and fractional anisotropy (FA). Pearson correlation between tau PET SUVR/amyloid PET SUVR and MD, FA, and MK was calculated with significance testing. Result Correlation analysis (Tables 1, 2) showed positive correlations between amyloid PET SUVR and MD in posterior cingulate cortex, tau PET SUVR and MD in anterior cingulate cortex and posterior cingulate cortex, and tau PET SUVR and MK in primary motor cortex. Negative correlation was observed between PET SUVR and FA in entorhinal cortex. Conclusion Increased amyloid and tau burden on PET correlated with less restricted diffusion as indicated by higher MD and lower FA, suggesting sensitivity of dMRI to cortical atrophy and late‐stage neuronal death, as previously observed in cortex and white matter tracts [2, 3]. The current study of healthy controls is limited by the narrow range of amyloid and tau burden. Future work will extend to subjects with mild cognitive impairment. References: [1] Jensen & Helpern, NMR Biomed., 2010(23):698‐710; [2] Dong et al, Neurobiol. Aging 2020(89):118‐128; [3] Montal et al, Alzheimer’s Dement., 2017(14):340‐351.