Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains

Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD).The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach.We recruited 19 AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0 T including a T1-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T1 and B1 maps. The T1-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM0B, showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM0B differences between AD and HS groups, adjusting for local GM atrophy.Widespread areas of reduced RM0B were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex.These results indicate that, among qMT parameters, RM0B is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid β deposition. RM0B might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM0B and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.

► Voxel-wise whole-brain qMT parameteric maps are analysed in AD for the first time. ► Among qMT parameters, RM0B is the most sensitive to AD pathology. ► RM0B is reduced in cortical areas known to be involved by AD pathology. ► RM0B is interpreted as an index of metabolic change.