Neuropathologic correlates of brain macrostructure.

摘要

Alzheimer's disease (AD), the most common form of dementia, is a degenerative disorder of the brain that leads to memory loss. Clinical diagnostic techniques in use rely on behavioral and neuropsychological criteria and only provide diagnoses of possible or probable AD. However, lately it has become clear that clinical-pathological correspondence is not always consistent. A definitive diagnosis of AD is only possible via histology. Thus, the development of a reliable neuroimaging technique that allows detection of AD-pathology during life is needed. This method would be noninvasive, and could allow detection and monitoring of the disease through time.;The purpose of this work was to investigate the use of magnetic resonance imaging (MRI) as diagnostic tool for AD-pathology and other age-related neuropathologies that are common in older persons. To uncover the anatomical origins and determine the macrostructural signatures of age-related neuropathologies, it is necessary to link MRI findings with pathology on the same individuals. In this work, we focused on imaging cerebral hemispheres ex-vivo, when a complete pathology report was available from a board-certified neuropathologist. The main difference between this work and any other study is the abundance of ex-vivo imaging data paired with pathology in a relatively large pool of subjects.;First, we developed and validated a protocol to perform ex-vivo MR volumetry. By using this protocol it was shown that: (a) regional brain volumes measured with this approach remain relatively unchanged for a period of 6 months postmortem, and (b) a linear correspondence was detected between in-vivo and ex-vivo measurements, suggesting that this approach captures information linked to antemortem macrostructural brain characteristics.;Using this approach, we combined ex-vivo MR volumetry with pathology on the same adults. AD-pathology was negatively correlated with volumes of cortical and subcortical gray matter regions, and whole-hemisphere white matter. A negative correlation was shown between hippocampal sclerosis and volumes of hippocampus, as well as other temporal and frontal gray matter regions.;Finally, we performed a morphometric MRI study to investigate associations of brain volumes with pathology. AD-pathology was negatively associated with regions of gray matter and white matter located in temporal, frontal and parietal lobes.