Aikaterini Kotrotsou PhD, Abstract Co-Author: Nothing to Disclose

David A. Bennett MD, Abstract Co-Author: Nothing to Disclose

Julie A. Schneider MD, Abstract Co-Author: Nothing to Disclose

Sue Leurgans, Abstract Co-Author: Nothing to Disclose

Tom Golak, Abstract Co-Author: Nothing to Disclose

Konstantinos Arfanakis PhD, Presenter: Nothing to Disclose

Brain atrophy is a hallmark of aging and neurodegenerative diseases. To determine the macrostructural signatures of age-related neuropathologies, MRI findings must be combined with pathology. Only a few studies have examined the association of brain volumes with neuropathology, and those studies suffered from low numbers of participants, long intervals between imaging and death, and low detail in terms of the spatial patterns of brain atrophy. The objective of this study was to determine the neuropathologic correlates of regional brain volumes by combining ex-vivo MR volumetry and pathology on a large cohort of older persons.

Cerebral hemispheres were obtained from 166 deceased participants of two longitudinal, clinical-pathologic cohort studies of aging. All hemispheres were imaged ex-vivo, while immersed in 4% formaldehyde solution, on a 3T MRI scanner. A multi-atlas approach was used to segment ex-vivo MRI data into white and gray matter; 34 cortical and 8 subcortical regions. All volumes were normalized by the height of the participants. Following imaging, hemispheres underwent neuropathologic examination. The pathologies considered in analyses were: Alzheimer’s disease (AD) pathology, Lewy bodies, hippocampal sclerosis (HS), gross and microscopic chronic infarcts, and cerebral amyloid angiopathy. Multiple linear regression was used to investigate the association between volumes and age-related neuropathologies across participants, controlling for age at death, sex, education, postmortem interval to fixation and to imaging. False Discovery Rate was used to correct for multiple comparisons.

Fig. 1 shows brain regions with significant negative correlation (p<0.05, FDR-corrected) between their volume and AD pathology (Fig.1A), and HS (Fig.1B). No other pathologies showed significant correlations with the volume of the segmented regions.

This study provides detailed spatial patterns of brain regions with volumes that are negatively correlated with age-related neuropathologies. These patterns may allow development of MR biomarkers of AD and HS. To our knowledge, this is the largest MR volumetry pathology investigation to date, and the only assessing a high number of brain regions.

This study provides information on the neuropathologic correlates of regional brain volumes, and may assist in the detection of AD pathology and hippocampal sclerosis in-vivo.

Kotrotsou, A, Bennett, D, Schneider, J, Leurgans, S, Golak, T, Arfanakis, K, Neuropathologic Correlates of Brain Atrophy: An MRI – Pathology Study in a Community Cohort of Older Adults.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14015009.html