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

所有生物组织通过局部细胞外基质（ECM）的适应性反应对炎症、损伤或肿瘤侵袭作出反应，失去平衡。这个过程被称为ECM重塑，涉及生物化学组成、结构和物理力学性质的变化。基质蛋白、蛋白聚糖和糖胺聚糖（GAG）的定量和定性修饰始于疾病发展的早期阶段，并随着疾病进展而持续。由于ECM组分在患病组织中经历的基本的定量和定性变化，ECM作为用于疾病的检测、表征和监测的体内成像靶吸引了我们的兴趣。在第一个资助期内，CRC“Matrix in Vision”使用动脉粥样硬化、主动脉瘤、尿毒症心肌病、多发性硬化、肠道和肝脏炎症以及肿瘤周围炎症的模型，使用分子和生物物理离体和体内MR成像方法证实了这一点。在第二个资助期内，目的是研究迄今为止建立的体内成像方法如何适用于检测已建立疾病模型的治疗反应，以及成像可以提供ECM成分及其在治疗期间变化的信息。为此，CRC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。主要目的是分析分子成像探针（钆（Gd）为基础的非特异性和特异性造影剂，氧化铁纳米粒子）和ECM成分之间的相互作用。这里的重点是GAG，这是一个重要的目标，因为它们可以形成复合物与带正电荷的成像探针或其带正电荷的组件。使用临床批准的Gd成像探头在MR成像中增强炎症组织的潜在机制的预期见解将影响临床对比增强MRI的解释。成像研究将包括ECM的机械结构元素的多尺度定量，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。结果也将转化为直接的临床应用。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将首次使ECM结构与分子和生物物理医学成像中信号生成的关系的研究能够朝着新的成像方法的发展，从而允许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.