Development and Validation of Radiation-Free Pediatric Renal Function Quantification

项目摘要 动机：慢性肾脏疾病（CKD）影响着5亿多人。儿童通常会发展 CKD来自泌尿系统阻塞性疾病和肾毒性治疗，然后遭受严重的生长衰竭，高血压， 紧张、心血管风险和神经认知缺陷，最终导致终末期肾病。准确 肾功能定量将改善肾积水（1/100婴儿）和dos的临床管理， 在肿瘤患者中的化疗方案的制定/选择。 肾小球滤过率（GFR）是肾功能的生物标志物，来自血液或尿液检查。这些 检测仅提供总体GFR，准确性有限，尤其是在儿童中，儿童更是如此 得了癌症MRI提供了极好的解剖描绘，没有电离辐射，因此是儿科的理想选择。 肾脏成像然而，MRI尚未被广泛用于儿童肾功能评价，由于缺乏 可靠性和繁琐的工作流程。这些障碍源于这样一个事实，即所需的关键组件 用于全球和区域GFR计算，包括高时空分辨率、血浆流速和动脉输入 功能，难以获得，肾脏（皮质和髓质）的准确图像分割是劳动 密集。另外，虽然相同的造影剂注射可以用于阻塞评估，但是某些造影剂注射可以用于阻塞评估。 使用标准MRI采集技术时，由于肾脏的高密度， 造影剂浓度。该项目解决了自动化综合 儿童肾功能评价。 方法：该项目有三个开发目标，并通过临床研究进行了验证。目标1将使 新型自由呼吸时间分辨3D动态对比增强MRI，同时提供准确的 GFR计算和肾血浆流速。这是通过结合自导航运动补偿来实现的， 利用并行成像和压缩感测的快速采集，以及相位衬度湍流成像。第二 目的是开发多种新的图像分析方法来提取GFR和肾血浆流量（RPF）， Aim 1的新的数据流，以及自动化的新机器学习图像处理技术， 肾脏的分割以及最终的全局和区域GFR计算。在目标3中，我们将开发和 集成超短回波时间技术，以解决由于高对比度的T2* 效应导致的MRI信号丢失 为阻塞患者提供集中的治疗，并进一步结合运动补偿和加速成像， 本发明提供了能够实现时间分辨的高分辨率动态MRI以用于造影剂洗脱动力学分析的方法， 目标4将确定这些方法在临床环境中的性能。 意义：这项工作将带来强大的、自动化的全面儿科肾脏MRI， 准确评估儿童肾功能。这些技术将有利于在通信领域的广泛应用。 社区环境，并允许对儿童和成人的肾功能进行稳健的评估。

Project Abstract Motivation: Chronic kidney disease (CKD) affects more than 500 million people. Children commonly develop CKD from urinary obstructive diseases and nephrotoxic therapies, and then suffer severe growth failure, hyper- tension, cardiovascular risks, and neurocognitive deficits, and eventually end-stage kidney disease. Accurate renal function quantification will improve clinical management of hydronephrosis (1 in 100 babies) and dos- ing/selection of chemotherapeutic regimens in oncology patients. Glomerular filtration rate (GFR), the biomarker of renal function, is derived from blood or urine tests. These tests only provide global GFR and are limited in accuracy, especially in children, and even more so in children with cancer. MRI offers superb anatomic delineation without ionizing radiation, and is thus ideal for pediatric kidney imaging. However, MRI has not been widely adopted for pediatric renal function evaluation due to lack of reliability and cumbersome workflow. These hurdles stem from the fact that the critical components required for global and regional GFR calculation, including high spatiotemporal resolution, plasma flow and arterial input function, are difficult to obtain, and that accurate image segmentation of kidneys (cortex and medulla) is labor intensive. Additionally, although the same contrast agent injection can be used for obstruction evaluation, certain areas of the kidney suffer from significant signal loss using standard MRI acquisition techniques due to high contrast agent concentrations. This project addresses these major challenges for automated comprehensive renal function evaluation in children. Approach: The project has three development aims, which are validated by clinical studies. Aim 1 will enable novel free-breathing time-resolved 3D dynamic contrast enhanced MRI that simultaneously provides accurate GFR calculation and renal plasma flow. This is achieved by incorporating self-navigated motion compensation, fast acquisition with parallel imaging and compressed sensing, and phase-contrast flow imaging. The second aim is to develop multiple new image analysis methods to extract GFR and renal plasma flow (RPF) that lever- age novel flow data of Aim 1, as well as automated new machine-learning image processing techniques for the segmentation of kidneys and ultimately global and regional GFR calculation. In Aim 3, we will develop and integrate ultrashort-echo-time techniques to address the MRI signal loss due to T2* effects from high contrast concentration for patients with obstruction, and further incorporate motion compensation and accelerated imag- ing methods to enable time-resolved high-resolution dynamic MRI for contrast washout kinetics analysis in the same MR exam. Aim 4 will determine the performance of these methods in a clinical setting. Significance: This work will lead to robust, automated comprehensive pediatric renal MRI for safer and more accurate renal function evaluation in children. The techniques will facilitate widespread application in the com- munity setting and permit robust evaluation of renal function, for both children and adults.