Ex vivo T2 relaxation: associations with age-related neuropathology and cognition

The transverse relaxation time constant, T(2), is sensitive to brain tissue's free water content and the presence of paramagnetic materials such as iron. In this study, ex vivo magnetic resonance imaging was used to investigate alterations in T(2) related to Alzheimer's disease (AD) pathology and other types of neuropathology common in old age, as well as the relationship between T(2) alterations and cognition. Cerebral hemispheres were obtained from 371 deceased older adults. Using fast spin-echo imaging with multiple echo times, T(2) maps were produced and warped to a study-specific template. Hemispheres underwent neuropathologic examination for identification of AD pathology and other common age-related neuropathologies. Voxelwise linear regression was carried out to detect regions of pathology-related T(2) alterations and, in separate analyses, regions in which T(2) alterations were linked to antemortem cognitive performance. AD pathology was associated with T(2) prolongation in white matter of all lobes and T(2) shortening in the basal ganglia and insula. Gross infarcts were associated with T(2) prolongation in white matter of all lobes, and in the thalamus and basal ganglia. Hippocampal sclerosis was associated with T(2) prolongation in the hippocampus and white matter of the temporal lobe. After controlling for neuropathology, T(2) prolongation in the frontal lobe white matter was associated with lower performance in the episodic, semantic, and working memory domains. In addition, voxelwise analysis of in vivo and ex vivo T(2) values indicated a positive relationship between the two, though further investigation is necessary to accurately translate findings of the present study to the in vivo case.