Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Amber Nolan; Cathrine Petersen; Diego Iacono; Christine L. Mac Donald; Pratik Mukherjee; Andre J. W. van der Kouwe; Sonia Jain; Allison A. Stevens; Bram R. Diamond; Ruopeng Wang; Amy J. Markowitz; Bruce R. Fischl; Daniel P. Perl; Geoffrey T. Manley; Christopher Dirk Keene; Ramon R. Diaz-Arrastia; Brian L. Edlow; the TRACK-TBI Investigators; Opeolu M Adeoye; Neeraj Badjatia; Kim Boase; Jason K. Barber; Yelena G. Bodien; M. Ross Bullock; Randall Matthew Chesnut; John D. Corrigan; Karen L. Crawford; SUREYYA S. DIKMEN; Ann‐Christine Duhaime; Richard G. Ellenbogen

doi:10.1089/neu.2020.7373

NeuroscienceJournal of NeurotraumaJan 8, 2021

Peer-reviewed journal article

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Amber Nolan iD, Cathrine Petersen iD, Diego Iacono iD, Christine L. Mac Donald iD, Pratik Mukherjee iD, Andre J. W. van der Kouwe iD, Sonia Jain iD, Allison A. Stevens iD, Bram R. Diamond iD, Ruopeng Wang iD, Amy J. Markowitz iD, Bruce R. Fischl iD, Daniel P. Perl iD, Geoffrey T. Manley iD, Christopher Dirk Keene iD, Ramon R. Diaz-Arrastia iD, Brian L. Edlow iD, the TRACK-TBI Investigators, Opeolu M Adeoye iD, Neeraj Badjatia iD, Kim Boase, Jason K. Barber iD, Yelena G. Bodien iD, M. Ross Bullock, Randall Matthew Chesnut iD, , ROSS D. ZAFONTE iD

Abstract

Diffusion tractography MRI can infer changes in network connectivity in patients with traumatic brain injury (TBI), but pathological substrates of disconnected tracts have not been well-defined due to a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750 m resolution, followed by histopathologic 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 and 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 neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

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