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Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

机译:脑血管细胞激活的超灵敏分子MRI可及早发现慢性中枢神经系统疾病

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摘要

Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuroinflammation.
机译:由于内皮细胞可以被较大的造影剂所靶向,因此脑血管细胞活化的分子成像非常有希望评估中枢神经系统(CNS)的潜在炎症。在这项研究中,我们旨在证明脑血管细胞激活的分子磁共振成像(MRI)可以在没有可见病变和症状的情况下揭示中枢神经系统疾病。为此,我们通过体外和体内实验优化了靶向血管细胞粘附分子1和MRI方案的对比剂携带颗粒。尽管对比前MRI图像无法揭示正在进行的病理,但对比增强MRI显示血管性痴呆的低灌注触发的中枢神经系统损伤,阿尔茨海默病的淀粉样蛋白诱导的脑血管激活未被掩盖,并允许在实验性自身免疫性脑脊髓炎期间监测疾病活动。此外,对比增强的MRI显示脑血管细胞活化与中枢神经系统疾病的已知危险因素有关,例如周围炎症,乙醇消耗,高血糖和衰老。通过提供比以前报道的方法和分子造影剂高得多的灵敏度,本研究中描述的技术为神经炎症领域的研究开辟了新途径。

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