title: Manganese-Enhanced Magnetic Resonance Imaging as a Diagnostic and Dispositional Tool after Mild-Moderate Blast Traumatic Brain Injury.
abstract: 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.
authors.affiliation: 1 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington, DC.
authors.forename: Olga
authors.initials: O
authors.lastname: Rodriguez
authors.affiliation: 2 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Schaefer
authors.affiliation: 3 Research and Exploratory Development Department, Johns Hopkins University, Applied Physics Laboratory , Laurel, Maryland.
authors.forename: Brock
authors.initials: B
authors.lastname: Wester
authors.affiliation: 4 Department of Oncology, Georgetown University Medical Center , Washington DC.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lee
authors.affiliation: 3 Research and Exploratory Development Department, Johns Hopkins University, Applied Physics Laboratory , Laurel, Maryland.
authors.forename: Nathan
authors.initials: N
authors.lastname: Boggs
authors.affiliation: 3 Research and Exploratory Development Department, Johns Hopkins University, Applied Physics Laboratory , Laurel, Maryland.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Conner
authors.affiliation: 3 Research and Exploratory Development Department, Johns Hopkins University, Applied Physics Laboratory , Laurel, Maryland.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Merkle
authors.affiliation: 5 Pediatric and Integrative Systems Biology, George Washington University , Washington, DC.
authors.forename: Stanley T
authors.initials: ST
authors.lastname: Fricke
authors.affiliation: 4 Department of Oncology, Georgetown University Medical Center , Washington DC.|6 Department of Pathology, Georgetown University Medical Center , Washington DC.
authors.forename: Chris
authors.initials: C
authors.lastname: Albanese
authors.affiliation: 7 Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, Maryland.|8 Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Vassilis E
authors.initials: VE
authors.lastname: Koliatsos
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000000981:diagnostic imaging*; D000070642:Brain Injuries, Traumatic / Q000000981:diagnostic imaging*; D003287:Contrast Media; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D003287:Contrast Media; D008345:Manganese
keywords: blast injury; blast-induced neurotrauma; manganese-enhanced MRI (MEMRI); traumatic brain injury