The combination of ex-vivo MRI and neuropathology of human brain tissue can enhance investigation of the neuropathological correlates of brain abnormalities and assist in the development of biomarkers of various age-related neuropathologies. Ex-vivo MRI provides images at essentially the same time as histological examination of the tissue, ensuring that no additional pathology develops between imaging and histology. Furthermore, ex-vivo MRI allows imaging independent of frailty level. We have developed a unique large, longitudinal, clinical, pathologic, ex-vivo MRI database including data from community-dwelling older adults. Through these studies we have revealed novel MRI signatures of various age-related neuropathologies.

  • We have mapped the effects of Alzheimer's pathology and hippocampal sclerosis on the shape of the hippocampus, and demonstrated for the first time that hippocampal atrophy is more substantial in hippocampal sclerosis than Alzheimer's.
  • We have generated the signatures of Alzheimer's and hippocampal sclerosis on regional brain volumes, and showed for the first time that hippocampal sclerosis is associated with atrophy not only in temporal lobe regions in the vicinity of the hippocampus, but also in frontal lobe regions with strong connections to the hippocampus.
  • We have shown that regional volumes in the temporal lobe, as well as T2 values in temporal and frontal lobe regions explain a substantial portion of the variance in cognition above and beyond what is explained by demographics and neuropathologies.
  • We have generated the signatures of Alzheimer's pathology, hippocampal sclerosis and gross infarcts on T2 constants.
  • We have generated for the first time the signature of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) on regional brain volumes.
  • We have shown that white matter hyperintensities are associated not only with vascular pathologies, but also with Alzheimer's pathology.
  • We have shown that enlarged perivascular spaces are associated with infarcts and diabetes independent of other age-related neuropathologies.
  • We have presented for the first time the signature of LATE-NC on brain R2.
Also see our research on: Translational Ex-Vivo MRI

Selected Related Publications

  • Dawe RJ, Bennett DA, Schneider JA, Arfanakis K. Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study. PLoS One 2011;6:e26286.
  • Dawe RJ, Bennett DA, Schneider JA, Leurgans SE, Kotrotsou A, Boyle PA, Arfanakis K. Ex vivo T2 relaxation: associations with age-related neuropathology and cognition. Neurobiol Aging 2014;35:1549-1561.
  • Kotrotsou A, Schneider JA, Bennett DA, Leurgans SE, Dawe RJ, Boyle PA, Golak T, Arfanakis K. Neuropathologic correlates of regional brain volumes in a community cohort of older adults. Neurobiol Aging 2015;36:2798-2805.
  • Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, Rademakers R, Alafuzoff I, Attems J, Brayne C, Coyle-Gilchrist ITS, Chui HC, Fardo DW, Flanagan ME, Halliday G, Hokkanen SRK, Hunter S, Jicha GA, Katsumata Y, Kawas CH, Keene CD, Kovacs GG, Kukull WA, Levey AI, Makkinejad N, Montine TJ, Murayama S, Murray ME, Nag S, Rissman RA, Seeley WW, Sperling RA, White Iii CL, Yu L, Schneider JA. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 2019;142:1503-1527.
  • Arfanakis K, Evia AM, Leurgans SE, Cardoso LFC, Kulkarni A, Alqam N, Lopes LF, Vieira D, Bennett DA, Schneider JA. Neuropathologic Correlates of White Matter Hyperintensities in a Community-Based Cohort of Older Adults. J Alzheimers Dis. 2020;73:333-345.
  • Javierre-Petit C, Schneider JA, Kapasi A, Makkinejad N, Tamhane AA, Leurgans SE, Mehta RI, Barnes LL, Bennett DA, Arfanakis K. Neuropathologic and Cognitive Correlates of Enlarged Perivascular Spaces in a Community-Based Cohort of Older Adults. Stroke. 2020;51:2825-2833.
  • Tazwar M, Evia AM, Tamhane AA, Ridwan AR, Leurgans SE, Bennett DA, Schneider JA, Arfanakis K. Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with lower R2 relaxation rate: an ex-vivo MRI and pathology investigation. Neurobiol Aging. 2022;117:128-138.
AD path MR volumetry signature
LATE-NC volumetry signature
Alzheimer's path T2 signature
LATE-NC signature on brain R2