Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study
Amber Nolan, Cathrine Petersen, Diego Iacono, Christine L. Mac Donald, Pratik Mukherjee, André van der Kouwe, Sonia Jain, Allison Stevens, Bram R. Diamond, Ruopeng Wang, Amy J. Markowitz, Bruce Fischl, Daniel P. Perl, Geoffrey T. Manley, C. Dirk Keene, Ramon Diaz‐Arrastia, Brian L. Edlow, the TRACK-TBI Investigators, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena G. Bodien, M. Ross Bullock, Randall M. Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann‐Christine Duhaime, Richard G. Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel C. Gardner, Etienne Gaudette, Joseph T. Giacino, Dana Goldman, Luis González, Shankar P. Gopinath, Rao P. Gullapalli, J. Claude Hemphill, Gillian Hotz, Frederick K. Korley, Joel H. Kramer, Natalie Kreitzer, Harvey S. Levin, Christopher J. Lindsell, Joan Machamer, Christopher J. Madden, Alastair J. Martin, Thomas W. McAllister, Michael McCrea, Randall E. Merchant, Lindsay D. Nelson, Laura B. Ngwenya, Florence Noël, David O. Okonkwo, Eva Palacios, Ava M. Puccio, Miri Rabinowitz, Claudia S. Robertson, Jonathan Rosand, Angelle M. Sander, Gabriella Satris, David M. Schnyer, Seth A. Seabury, Mark Sherer, Murray B. Stein, Sabrina R. Taylor, Nancy Temkin, Arthur W. Toga, Alex B. Valadka, Mary J. Vassar, Paul Vespa, Kevin Wang, John K. Yue, Esther L. Yuh, Ross Zafonte
Abstract
Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.