Project Summary/Abstract (Description) Motivation: There is growing evidence that impaired renal oxygenation (an increased ratio of oxygen consumption to oxygen delivery) is a common characteristic of deteriorated kidney function. This includes conditions such as acute kidney injury (AKI), chronic kidney disease (CKD), the transition from AKI to CKD, and further progression to end-stage renal disease. Approximately half of all patients undergoing chemotherapeutic treatment benefit from platinum-based antineoplastic drugs. However, these drugs are nephrotoxic, which limits both the dosage that can be safely administered and the population that can receive it. Noninvasive monitoring and repeatable measurement of intrarenal tissue oxygenation, an area that continues to present an unmet clinical need, will enhance the clinical management of AKI, CKD, and the determination of dosage and selection of chemotherapeutic regimens in cancer patients. The renal oxygen extraction fraction (OEF), expressed as the ratio of the difference between arterial and venous oxygen saturation to arterial oxygen saturation, can serve as a quantitative biomarker of renal tissue oxygen tension. An increased OEF suggests impaired tissue oxygenation, implying a decrease in renal oxygen tension, assuming that blood oxygen tension is in balance with the surrounding tissue. MRI has the potential to offer 3D volumetric, voxel-by-voxel noninvasive quantification of deoxyhemoglobin concentration and OEF through advanced signal modeling. However, there are major challenges to overcome: 1) respiratory and/or bulk motion in the abdomen, 2) flow-induced errors, 3) the presence of large susceptibility and fat, and 4) the lack of advanced algorithms that effectively calculate OEF. This project aims to address these major challenges. Approach: This project is highly focused on the technological development of MRI. Aim 1 intends to enable a fully flow-compensated multi-echo 3D non-Cartesian MRI method that is robust to respiratory motion. This MRI technique will continuously acquire a navigation signal from which respiratory and/or bulk motion can be extracted, thereby enabling robust retrospective motion-resolved kidney image reconstruction. Aim 2 will focus on the development of: 1) joint multi-echo and respiratory motion-resolved image reconstruction, 2) total field inversion for renal quantitative susceptibility mapping (QSM), and 3) OEF mapping from a signal model that combines the magnitude-based quantitative blood oxygen level dependent (qBOLD) and the phase-based QSM. Aim 3 will evaluate the sensitivity of the developed renal OEF mapping method on healthy subjects before and after an induced alteration in renal oxygenation. Significance: This work will lead to free-breathing renal functional MRI that enables noninvasive voxel-by-voxel quantification of renal OEF. This technique will facilitate its widespread use as a quantitative imaging biomarker of renal tissue oxygen tension in both research and clinical settings.

Project Narrative Impaired kidney oxygenation is often identified as a common denominator of deteriorated kidney function in a variety of kidney diseases, such as acute kidney injury, chronic kidney disease, and its transition to end-stage renal failure. Noninvasive measurement and quantification of renal tissue oxygenation is crucial for clinical management and treatment. This work will develop motion-robust, fully ungated free-breathing abdominal MRI for quantification of renal oxygen extraction fraction.