Rodriguez Olga, Schaefer Michele L, Wester Brock, Lee Yi-Chien, Boggs Nathan, Conner Howard A, Merkle Andrew C, Fricke Stanley T, Albanese Chris, Koliatsos Vassilis E
1 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington, DC.
2 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
J Neurotrauma. 2016 Apr 1;33(7):662-71. doi: 10.1089/neu.2015.4002. Epub 2015 Dec 14.
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.
由爆炸弹药导致的创伤性脑损伤(TBI),即爆炸型TBI,是伊拉克和阿富汗近期军事冲突中的典型损伤。TBI(包括爆炸型TBI)的诊断评估基于临床病史、症状和神经心理学测试,所有这些都可能导致对这种病症的误诊或漏诊,尤其是在轻度至中度严重程度的TBI病例中。目前,预后由TBI的严重程度、复发情况和病理类型决定,当有更有效的治疗方法时,临床干预的及时性也可能会对预后产生影响。一项重要任务是预防重复性TBI,尤其是当患者仍有症状时。基于这些原因,建立定量生物学标志物有助于改善诊断以及预防或治疗管理。在本研究中,我们使用爆炸型TBI的冲击管模型来确定锰增强磁共振成像(MEMRI)是否可作为一种工具,用于准确、定量地诊断轻度至中度爆炸型TBI。对小鼠施加30磅力/平方英寸的爆炸冲击,并腹腔注射单剂量的MnCl2。在6、24、48和72小时以及14和28天进行的纵向T1磁共振成像(MRI)显示,与假手术对照组相比,几乎在所有时间点,遭受爆炸冲击的小鼠大脑中都有明显的信号增强。有趣的是,当小鼠在爆炸暴露期间用聚碳酸酯身体护盾进行保护时,对比度的显著增加得到了预防。我们得出结论,锰摄取可作为TBI的定量生物标志物,并且MEMRI是一种微创定量方法,可有助于准确诊断和管理爆炸型TBI。此外,身体保护可防止锰摄取增加,这强烈表明,改进防弹衣的设计可能会使个人免受爆炸风险的影响。