Profiling Renal Oxygenation with MRI Step Response Analysis: Imaging Signatures for Acute Kidney Injury

• Applicants: Dr. Kathleen Cantow; Professor Thoralf Niendorf, Ph.D.
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 547591347

Rationale and unmet needs: The kidney is a unique organ: renal blood supply drives renal oxygen consumption and determines the functional state of the kidney. The unique relationship of renal O2 delivery/O2 consumption contributes to low partial pressure of O2 in renal tissue, meaning that the kidney is always at the brink of O2 deprivation and hypoxia. Lack of O2 and renal tissue hypoxia are key early elements in the genesis of acute kidney injury (AKI), which is a global health crisis hidden in plain sight. Current clinical markers fail to meet this challenge – they are not sensitive to hypoxia and do not reflect the complexity of AKI. Imagine if there was a way to observe renal oxygenation in vivo – a way to classify kidney oxygenation states as poor, healthy or just right. Imagine if physicians could image renal oxygenation and detect signatures of hypoxia with relevant diagnostic information, to intercept disease at the earliest stages, before the onset of manifest injury. Aims and hypotheses: This project aims at profiling renal oxygenation using dynamic MRI of the kidney’s response to an abrupt change of the inspiratory fractions of O2/CO2. We hypothesize that MRI profiling of renal oxygenation can provide i) signatures of the functional states of the kidney, ii) clear distinction between healthy kidneys and AKI, iii) differentiation of moderate and severe AKI and iv) facilitates swift translation from pre-clinical research to human application. Approach and novel aspects: Perturbation of renal oxygenation triggers adjustments that either restore equilibrium, or establish a new equilibrium. The impact, temporal course and frequency response of these adjustments vary depending on the state of the kidney. Recognizing this potential we put forward renal step response analysis (SRA) using (sub)second dynamic MRI and MR line scanning in conjunction with readouts of integrative physiology. By unravelling the characteristics of the kidney’s response to steep and abrupt changes in inspiratory gas fractions, we enter an entirely new research field of kidney health and disease. To reach these goals, we will examine MR oximetry involving mapping renal oxygenation, renal size, renal tubular water and renal blood volume fraction, analyzing these measures using sophisticated analytic and machine learning approaches. Clinical translation: Owing to the non-invasive nature of MR, this project promotes swift translation, bridging renal MR oximetry in in vivo studies in rats with a pilot study in healthy humans. Expected outcome: Renal step response analysis using dynamic MRI provides identifiers for renal health and AKI. Signatures derived from step response analysis of renal oxygenation facilitate clear distinction between moderate and severe AKI. Insights from the renal step response methodology form a springboard to ultimately inform on renal pathophysiology, improve prediction of renal disease, intercept progression and evaluate treatment.

• DFG Programme: Research Grants