TY - JOUR
T1 - Multimodal Characterization of the Late Effects of Traumatic Brain Injury
T2 - A Methodological Overview of the Late Effects of Traumatic Brain Injury Project
AU - Edlow, Brian L.
AU - Keene, C. Dirk
AU - Perl, Daniel P.
AU - Iacono, Diego
AU - Folkerth, Rebecca D.
AU - Stewart, William
AU - Mac Donald, Christine L.
AU - Augustinack, Jean
AU - Diaz-Arrastia, Ramon
AU - Estrada, Camilo
AU - Flannery, Elissa
AU - Gordon, Wayne A.
AU - Grabowski, Thomas J.
AU - Hansen, Kelly
AU - Hoffman, Jeanne
AU - Kroenke, Christopher
AU - Larson, Eric B.
AU - Lee, Patricia
AU - Mareyam, Azma
AU - McNab, Jennifer A.
AU - McPhee, Jeanne
AU - Moreau, Allison L.
AU - Renz, Anne
AU - Richmire, Katierose
AU - Stevens, Allison
AU - Tang, Cheuk Y.
AU - Tirrell, Lee S.
AU - Trittschuh, Emily H.
AU - Van Der Kouwe, Andre
AU - Varjabedian, Ani
AU - Wald, Lawrence L.
AU - Wu, Ona
AU - Yendiki, Anastasia
AU - Young, Liza
AU - Zöllei, Lilla
AU - Fischl, Bruce
AU - Crane, Paul K.
AU - Dams-O'Connor, Kristen
N1 - Publisher Copyright:
Copyright © 2018, Mary Ann Liebert, Inc. 2018.
PY - 2018/7/15
Y1 - 2018/7/15
N2 - Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.
AB - Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.
KW - dementia; MRI; neurodegeneration; neuropathology; traumatic brain injury
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U2 - 10.1089/neu.2017.5457
DO - 10.1089/neu.2017.5457
M3 - Article
C2 - 29421973
AN - SCOPUS:85049310610
SN - 0897-7151
VL - 35
SP - 1604
EP - 1619
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 14
ER -