TY - JOUR
T1 - Manganese-Enhanced Magnetic Resonance Imaging as a Diagnostic and Dispositional Tool after Mild-Moderate Blast Traumatic Brain Injury
AU - Rodriguez, Olga
AU - Schaefer, Michele L.
AU - Wester, Brock
AU - Lee, Yi Chien
AU - Boggs, Nathan
AU - Conner, Howard A.
AU - Merkle, Andrew C.
AU - Fricke, Stanley T.
AU - Albanese, Chris
AU - Koliatsos, Vassilis E.
N1 - Funding Information:
Acknowledgments: We would like to acknowledge Dr. Ibolja Cernak, University of Alberta, Canada, for the pioneering ideas behind the projects' inception and funding. Blast experiments were performed in the Applied Physics Laboratory at Johns Hopkins University. All imaging experiments were performed in the Georgetown-Lombardi Comprehensive Cancer Center's Preclinical Imaging Research Laboratory, partially supported by the Cancer Center Support Grant P30 CA51008-21. Animal importation into the Preclinical Imaging Research Laboratory was assisted by the Division of Comparative Medicine at Georgetown University Medical Center. Funding provided by: DOD DM102465 (Cernak, PI, Albanese, subcontract PI), NIH P30 CA51008-18 (Weiner) and ABC2 (Albanese); Maryland Stem Cell Research Fund 2011-MSCRF-22-0067-00 (Koliatsos).
Publisher Copyright:
Copyright © 2016 Mary Ann Liebert, Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Traumatic brain injury (TBI) caused by explosive munitions, known as blast TBI, is the signature injury in recent military conflicts in Iraq and Afghanistan. Diagnostic evaluation of TBI, including blast TBI, is based on clinical history, symptoms, and neuropsychological testing, all of which can result in misdiagnosis or underdiagnosis of this condition, particularly in the case of TBI of mild-to-moderate severity. Prognosis is currently determined by TBI severity, recurrence, and type of pathology, and also may be influenced by promptness of clinical intervention when more effective treatments become available. An important task is prevention of repetitive TBI, particularly when the patient is still symptomatic. For these reasons, the establishment of quantitative biological markers can serve to improve diagnosis and preventative or therapeutic management. In this study, we used a shock-tube model of blast TBI to determine whether manganese-enhanced magnetic resonance imaging (MEMRI) can serve as a tool to accurately and quantitatively diagnose mild-to-moderate blast TBI. Mice were subjected to a 30 psig blast and administered a single dose of MnCl2 intraperitoneally. Longitudinal T1-magnetic resonance imaging (MRI) performed at 6, 24, 48, and 72 h and at 14 and 28 days revealed a marked signal enhancement in the brain of mice exposed to blast, compared with sham controls, at nearly all time-points. Interestingly, when mice were protected with a polycarbonate body shield during blast exposure, the marked increase in contrast was prevented. We conclude that manganese uptake can serve as a quantitative biomarker for TBI and that MEMRI is a minimally-invasive quantitative approach that can aid in the accurate diagnosis and management of blast TBI. In addition, the prevention of the increased uptake of manganese by body protection strongly suggests that the exposure of an individual to blast risk could benefit from the design of improved body armor.
AB - Traumatic brain injury (TBI) caused by explosive munitions, known as blast TBI, is the signature injury in recent military conflicts in Iraq and Afghanistan. Diagnostic evaluation of TBI, including blast TBI, is based on clinical history, symptoms, and neuropsychological testing, all of which can result in misdiagnosis or underdiagnosis of this condition, particularly in the case of TBI of mild-to-moderate severity. Prognosis is currently determined by TBI severity, recurrence, and type of pathology, and also may be influenced by promptness of clinical intervention when more effective treatments become available. An important task is prevention of repetitive TBI, particularly when the patient is still symptomatic. For these reasons, the establishment of quantitative biological markers can serve to improve diagnosis and preventative or therapeutic management. In this study, we used a shock-tube model of blast TBI to determine whether manganese-enhanced magnetic resonance imaging (MEMRI) can serve as a tool to accurately and quantitatively diagnose mild-to-moderate blast TBI. Mice were subjected to a 30 psig blast and administered a single dose of MnCl2 intraperitoneally. Longitudinal T1-magnetic resonance imaging (MRI) performed at 6, 24, 48, and 72 h and at 14 and 28 days revealed a marked signal enhancement in the brain of mice exposed to blast, compared with sham controls, at nearly all time-points. Interestingly, when mice were protected with a polycarbonate body shield during blast exposure, the marked increase in contrast was prevented. We conclude that manganese uptake can serve as a quantitative biomarker for TBI and that MEMRI is a minimally-invasive quantitative approach that can aid in the accurate diagnosis and management of blast TBI. In addition, the prevention of the increased uptake of manganese by body protection strongly suggests that the exposure of an individual to blast risk could benefit from the design of improved body armor.
KW - blast injury
KW - blast-induced neurotrauma
KW - manganese-enhanced MRI (MEMRI)
KW - traumatic brain injury
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U2 - 10.1089/neu.2015.4002
DO - 10.1089/neu.2015.4002
M3 - Article
C2 - 26414591
AN - SCOPUS:84964790961
SN - 0897-7151
VL - 33
SP - 662
EP - 671
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 7
ER -