Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood–brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood–brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies.

中文翻译：

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慢速的血脑运输是美国足球运动员持久的障碍功能障碍的基础。

在报道了慢性外伤性脑病（一种进行性的tauopathy）之后，美式足球运动员的反复轻度外伤性脑损伤已引起公众越来越多的关注。尽管尚不清楚重复性轻度颅脑外伤引起的神经退行性病变的机制，并且尚未进行死前诊断测试，但神经病理学研究提示微血管损伤（尤其是血脑屏障功能障碍）具有致病作用。因此，我们的主要目的是证明改进的动态对比增强MRI方法的有效性，该方法已经开发出来，可以检测脑微血管功能的损害。为此，我们扫描了42名成年男性业余美式足球运动员和一个对照组，其中包括27名从事非接触式运动的运动员和26名非运动员。MRI扫描还对51例涉及血脑屏障的脑部疾病的患者进行了检查，即脑部恶性肿瘤，缺血性中风和出血性创伤性挫伤。根据长时间扫描的数据，我们生成了可直观显示每个大脑体素的通透性值的地图。我们的渗透性图显示，一部分业余美式足球运动员的血脑传输速度有所增加，但在与性别和年龄相匹配的对照组中却没有。渗透率的增加是区域特异性的（白质，中脑梗，红色核，颞叶皮层），并且与白质的变化相关，这通过扩散张量成像得以证实。此外，从淡季和淡季都进行了扫描的球员可以看出，通透性的提高持续了几个月。对患有脑病的患者进行检查后发现，示踪剂的缓慢积累是损伤核心周围区域的特征，该区域经常显示出快速的血脑运输。接下来，我们在两种啮齿动物模型中验证了我们的方法：遭受反复轻度闭合头撞击伤害的大鼠和小鼠，以及因光血栓形成而导致血管损伤的大鼠。在这两种模型中，均观察到血液到大脑的缓慢运输，这与神经病理学改变相关。最后，对反复发作或局灶性脑血管损伤的大鼠脑中Evans蓝白蛋白复合物运输的计算模拟和直接成像表明，细胞运输增加是观察到的缓慢的血脑运输基础。在一起