Understanding and monitoring renal microvascular remodeling in CKD by super-resolution ultrasound.

病理性微血管重构和微血管功能障碍是进行性慢性肾脏疾病（CKD）的常见表现和促进因素，但体内成像方法无法对其进行量化。最近，我们开发了一种超分辨率超声方法，可以在形态和功能水平上对组织进行非常详细的微血管表征。该方法依赖于注射临床使用的充气微泡作为造影剂，并使用GPS和雷达已知的算法进行跟踪。生成的轨迹以与定位精度相对应的分辨率显示，这远远超出了超声设备的分辨率限制。此外，该方法还可以量化单个毛细血管内的血流速度和方向，即微血管动力学的功能分析。我们的目标是开发用于实验和临床肾脏病学的超分辨率超声来分析肾脏疾病的微血管改变。我们的初步数据表明，肾脏血管系统可以在小鼠和人类中以超分辨率可视化，但需要对扫描方案、数据处理和图像分析进行重大修改，以达到与肿瘤或大脑相同的质量。我们的目标是：(1)修改方案以分析小鼠和人类的肾脏微血管；(2)研究从急性肾损伤（AKI）到慢性肾病（CKD）转变过程中的肾脏微血管重塑。作为一项概念验证研究，我们将分析巨噬细胞迁移抑制因子（MIF）在微血管重塑中的作用。为了完成这项任务，我们的团队结合了成像（Kiessling）、数据分析（Schmitz）和转化肾病学（Djudjaj）的专家。超分辨率超声波是一种非侵入性的方法，我们已经在乳腺癌患者的临床试验中使用了它。通过与联盟内的临床肾病学家合作，我们还致力于（iii）对不同阶段的CKD患者进行首次临床试验。最后，我们将（iv）进行放射学分析，以评估从超分辨率超声数据中提取的参数的额外好处。

Pathological microvascular remodeling and microvascular dysfunction are common findings and contributing factors in progressive chronic kidney diseases (CKD), but in-vivo imaging methods that allow for their quantification are not available. Recently, we developed a super-resolution ultrasound method, enabling a highly detailed microvascular characterization of tissues at the morphologic and functional level. The method relies on the injection of clinically used gas-filled microbubbles as contrast agents and their tracking with algorithms known from GPS and radar. The resulting tracks are displayed at a resolution corresponding to the localization accuracy, which goes far beyond the resolution limits of the ultrasound devices. In addition, the method allows for quantification of blood velocity and direction within single capillaries, i.e. functional analyses of microvascular dynamics. We here aim to develop super-resolution ultrasound for experimental and clinical nephrology to analyze microvascular alterations in kidney diseases. Our preliminary data show that kidney vasculature can be visualized at super-resolution in mice and humans, but significant modifications of the scanning protocol, data processing and image analysis will be required to achieve the same quality as in tumors or the brain. Our aims are to (i) modify the protocol to analyze the renal microvasculature in mice and humans and to (ii) investigate renal microvascular remodeling during the transition from acute kidney injury (AKI) to CKD. As a proof-of-concept study we will analyze the role of macrophage migration inhibitory factor (MIF) on microvascular remodeling. To achieve this task, our team combines experts in imaging (Kiessling), data analysis (Schmitz) and translational nephrology (Djudjaj). Super-resolution ultrasound is a non-invasive method and we already used it in a clinical trial on breast cancer patients. In cooperation with clinical nephrologists within the consortium we also aim to (iii) perform a first clinical trial with patients with different stages of CKD. Finally, we will (iv) perform radiomic analyses to evaluate the additional benefit of parameters extracted from super-resolution ultrasound data.