TY  - JOUR
PY  - 2018//
TI  - Multimodal characterization of the late effects of TBI (LETBI): a methodological overview of the LETBI project
JO  - Journal of neurotrauma
A1  - Edlow, Brian L.
A1  - Keene, C. Dirk
A1  - Perl, Daniel
A1  - Iacono, Diego
A1  - Folkerth, Rebecca
A1  - Stewart, William
A1  - Macdonald, Christine L.
A1  - Augustinack, Jean
A1  - Diaz-Arrastia, Ramon
A1  - Estrada, Camilo
A1  - Flannery, Elissa
A1  - Gordon, Wayne
A1  - Grabowski, Tom
A1  - Hansen, Kelly
A1  - Hoffman, Jeanne
A1  - Kroenke, Christopher
A1  - Larson, Eric
A1  - Lee, Patricia
A1  - Mareyam, Azma
A1  - McNab, Jennifer A.
A1  - McPhee, Jeanne
A1  - Moreau, Allison L.
A1  - Renz, Anne
A1  - Richmire, KatieRose
A1  - Stevens, Allison
A1  - Tang, Cheuk Y.
A1  - Tirrell, Lee S.
A1  - Trittschuh, Emily
A1  - van der Kouwe, Andre
A1  - Varjabedian, Ani
A1  - Wald, Lawrence L.
A1  - Wu, Ona
A1  - Yendiki, Anastasia
A1  - Young, Liza
A1  - Zollei, Lilla
A1  - Fischl, Bruce
A1  - Crane, Paul K.
A1  - Dams-O'connor, Kristen
SP  - 1604
EP  - 1619
VL  - 35
IS  - 14
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 and Parkinson's disease (AD and 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 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.<p />  <p>Language: en</p>
LA  - en
SN  - 0897-7151
UR  - http://dx.doi.org/10.1089/neu.2017.5457
ID  - ref1
ER  -