PROJECT SUMMARY Chronic kidney disease (CKD) is one of the leading causes of morbidity and mortality in the United States, affecting approximately 15% of the adult population. One of the best prognostic indicators of CKD progression and outcomes is kidney fibrosis, for which new treatments are being developed. Noninvasive methods to detect and quantify fibrosis, as well as monitor disease progression and/or the response to these treatments, are urgently needed. Fibrosis occurs when excess collagen accumulates in the kidney. Collagen contains a large amount of amide protons. While current magnetic resonance imaging (MRI) methods are insensitive to these amide protons, a technique called amide proton transfer (APT) contrast imaging detects signals from amide protons and, therefore, is expected to be able to detect and quantify kidney fibrosis. Kidneys present a unique imaging challenge due to inherent motion and limited spatial coverage, which can be mitigated with 3D radial acquisition techniques. The long-term goal of this project is to develop a noninvasive, noncontrast MRI method to quantify kidney fibrosis. Our objectives in this proposal are to implement and test a fast 3D radial MRI imaging and reconstruction method for quantifying kidney fibrosis. Our hypothesis is that APT contrast imaging will allow the accurate quantitation of kidney fibrosis. Our rationale is that eventually APT contrast can be used clinically to detect CKD earlier, monitor disease progression, and assess treatment efficacy in patients. We will complete the following specific aims: 1) implement a novel 3D radial acquisition strategy for acquiring whole kidney APT contrast data; and 2) test the ability of APT contrast imaging compared to existing MRI methods to quantify fibrosis in pediatric kidney transplant patients with CKD. All imaging metrics will be correlated with qualitative and quantitative histological measures at matching time points. The proposed research is innovative because it will develop a rapid 3D, noncontrast and noninvasive method of quantifying fibrosis throughout the entire kidney. These results are significant because they will provide a means of detecting, quantifying, and following renal fibrosis early in the disease process, when it may be most reversible, and monitoring response to medical treatments. This work will have an immediate positive impact by providing a novel means of assessing efficacy in treatment trials as well as providing a clinical method for evaluating disease progression and therapy response.

PROJECT NARRATIVE This project will develop a novel, noninvasive, noncontrast, motion insensitive imaging method to quantify fibrosis in the kidneys of children and adults. The objectives of this highly innovative proposal will catalyze new scientific endeavors by providing a new biomarker for chronic kidney disease (CKD) assessment for clinical care and pharmaceutical trials. The proposed research is relevant to the growing public health concern of CKD because it will develop a new method for early diagnosis, longitudinal monitoring, and therapeutic assessment, which could ultimately lead to personalized CKD therapies, prevention of progression, and reduced morbidity and mortality.