SFB 1340: In vivo Visualization of Extracellular Matrix Pathology „Matrix in Vision“

所有生物组织对炎症、损伤或肿瘤侵袭的反应都是通过局部细胞外基质(ECM)的适应性反应而失去平衡。这个过程被称为ECM重塑，涉及生化成分、结构和物理机械特性的变化。基质蛋白、蛋白多糖和糖胺多聚糖(GAG)的定量和定性修饰始于疾病发展的早期阶段，并随着疾病的进展而继续。由于ECM组分在病变组织中发生了根本性的数量和质量变化，ECM作为检测、表征和监测疾病的活体成像靶点引起了人们的兴趣。在第一个资助期内，CRC“Matrix in Vision”利用分子和生物物理的体外和体内磁共振成像方法，利用动脉粥样硬化、主动脉瘤、尿毒症心肌病、多发性硬化症、肠道和肝脏的炎症情况以及瘤周炎症的模型证实了这一点。在第二个资助期，目的是调查迄今建立的体内成像方法如何适用于在已建立的疾病模型中检测治疗反应，以及成像可以提供关于细胞外基质成分及其在治疗过程中变化的信息。为此，研究中心将进一步推进包括元素显微镜在内的物理和生化分析技术。一个中心目标是分析分子成像探针(基于Gd的非特异性和特异性造影剂、氧化铁纳米颗粒)与ECM组件之间的相互作用。这里的重点是GAG，这是一个重要的目标，因为它们可以与带正电的成像探针或其带正电的组件形成络合物。使用临床批准的基于Gd的成像探针对MR成像中炎症组织增强的潜在机制的预期洞察将影响对临床对比增强MRI的解释。成像研究将包括对ECM的机械结构元素进行多尺度量化，范围从微观蛋白质和GAG网络到通过临床诊断弹性成像研究的宏观机械参数。结果还将立即转化为临床应用。通过这种方式，CRC 1340首次将放射学中的生物分子方法与对机械组织参数在疾病发展和治疗反应监测中的作用的新见解相结合。此外，CRC 1340还将首次实现分子和生物物理医学成像中ECM结构和信号产生关系的研究，以开发新的成像方法，从而在放射学中进行定量的疾病特异性诊断。

All biological tissues react to inflammation, injury, or tumor invasion by an adaptive response of the local extracellular matrix (ECM) with a loss of equilibrium. This process is known as ECM remodeling and involves changes in the biochemical composition, architecture, and physicomechanical properties. Quantitative and qualitative modification of matrix proteins, proteoglycans, and glycosaminoglycans (GAGs) begins in the early phase of disease development and continues with disease progression. Because of the fundamental quantitative and qualitative changes the ECM components undergo in diseased tissue, the ECM has attracted our interest as an vivo imaging target for the detection, characterization, and monitoring of disease. During the first funding period CRC „Matrix in Vision“ confirmed this using models of atherosclerosis, aortic aneurysm, uremic cardiomyopathy, multiple sclerosis, inflammatory conditions of the bowel and liver, and peritumoral inflammation using methods of molecular and biophysical ex vivo and in vivo MR imaging. During the second funding period, the aims are to investigate how the methods of in vivo imaging established so far are suitable to detect treatment responses in established disease models and what information imaging can provide on ECM composition and its changes during treatment. To this end, the CRC will further advance physical and biochemical analytical techniques including element microscopy. A central aim is to analyze interactions between molecular imaging probes (gadolinium (Gd)-based nonspecific and specific contrast agents, iron oxide nanoparticles) and ECM components. The focus here is on GAGs, which are an important target because they can form complexes with positively charged imaging probes or their positively charged components. The expected insights into mechanisms underlying the enhancement of inflammatory tissue in MR imaging using clinically approved Gd-based imaging probes will affect the interpretation of clinical contrast-enhanced MRI. Imaging studies will include multiscale quantification of mechanical structural elements of the ECM, ranging from microscopic protein and GAG networks to macroscopic mechanical parameters investigated by clinical diagnostic elastography. The results will also translate into immediate clinical applications.In this way, CRC 1340 for the first time combines biological molecular methods in radiology with new insights into the role of mechanical tissue parameters in the development of disease and the monitoring of treatment responses. Also for the first time, CRC 1340 will thus enable the investigation of relationships of ECM structure and signal generation in molecular and biophysical medical imaging towards the development of new imaging approaches allowing quantitative, disease-specific diagnosis in radiology.