Anthony Daniel C, Sibson Nicola R, McAteer Martina A, Davis Ben, Choudhury Robin P
Department of Pharmacology, University of Oxford, Oxford, UK.
Methods Mol Biol. 2011;686:213-27. doi: 10.1007/978-1-60761-938-3_9.
Contrast agents are widely used with magnetic resonance imaging (MRI) to increase the contrast between regions of interest and the background signal, thus providing better quality information. Such agents can work in one of two ways, either to specifically enhance the signal that is produced or to localize in a specific cell type of tissue. Commonly used image contrast agents are typically based on gadolinium complexes or super-paramagnetic iron oxide, the latter of which is used for imaging lymph nodes. When blood-brain barrier (BBB) breakdown is a feature of central nervous system (CNS) pathology, intravenously administered contrast agent enters into the CNS and alters contrast on MR scans. However, BBB breakdown reflects downstream or end-stage pathology. The initial recruitment of leukocytes to sites of disease such as multiple sclerosis (MS), ischemic lesions, or tumours takes place across an intact, but activated, brain endothelium. Molecular imaging affords the ability to obtain a "non-invasive biopsy" to reveal the presence of brain pathology in the absence of significant structural changes. We have developed smart contrast agents that target and reversibly adhere to sites of disease and have been used to reveal activated brain endothelium when images obtained by conventional MRI look normal. Indeed, our selectively targeted micro-particles of iron oxide have revealed the early presence of cerebral malaria pathology and ongoing MS-like plaques in clinically relevant models of disease.
造影剂在磁共振成像（MRI）中被广泛使用，以增加感兴趣区域与背景信号之间的对比度，从而提供质量更好的信息。此类造影剂可通过两种方式之一发挥作用，要么特异性增强所产生的信号，要么定位于特定的细胞类型或组织中。常用的图像造影剂通常基于钆配合物或超顺磁性氧化铁，后者用于淋巴结成像。当中枢神经系统（CNS）病理学的一个特征是血脑屏障（BBB）破坏时，静脉注射的造影剂会进入中枢神经系统并改变磁共振扫描的对比度。然而，血脑屏障破坏反映的是下游或终末期病理学。白细胞最初募集到诸如多发性硬化症（MS）、缺血性病变或肿瘤等疾病部位，是通过完整但已激活的脑内皮进行的。分子成像能够进行“非侵入性活检”，以在无明显结构变化的情况下揭示脑病理学的存在。我们已经开发出了智能造影剂，它们靶向并可逆地附着于疾病部位，并且在常规MRI获得的图像看起来正常时，已被用于揭示激活的脑内皮。实际上，我们的选择性靶向氧化铁微粒已经在临床相关疾病模型中揭示了脑疟疾病理学的早期存在以及持续存在的类似MS的斑块。
