title: Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains.
abstract: 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 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-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, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) 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, RM(0)(B) 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. RM(0)(B) 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 RM(0)(B) 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.
authors: Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, via Ardeatina 306, 00179 Rome, Italy. giulietti.giovanni@gmail.com
authors: Giovanni
authors: G
authors: Giulietti
authors: Marco
authors: M
authors: Bozzali
authors: Viviana
authors: V
authors: Figura
authors: Barbara
authors: B
authors: Spanò
authors: Roberta
authors: R
authors: Perri
authors: Camillo
authors: C
authors: Marra
authors: Giordano
authors: G
authors: Lacidogna
authors: Franco
authors: F
authors: Giubilei
authors: Carlo
authors: C
authors: Caltagirone
authors: Mara
authors: M
authors: Cercignani
mesh_terms: D000368:Aged; D000465:Algorithms; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009474:Neurons / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity