Monitoring kidney size to interpret MRI-based assessment of renal oxygenation in acute pathophysiological scenarios.

AIM: Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T2 and T2 * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here, we used dynamic MRI to monitor KS for physiological interpretation of T2 * and T2 changes in acute pathophysiological scenarios. METHODS: KS was determined from T2 *, T2 mapping in rats. Six interventions that acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions that change the blood and/or tubular volume. A biophysical model was used to estimate changes in O2 saturation of hemoglobin from changes in T2 * and KS. RESULTS: Upon aortic occlusion KS decreased; this correlated with a decrease in T2 *, T2 . Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T2 *, T2 . Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T2 *, T2 . Hypoxemia induced mild reductions in KS and T2 *, T2 . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T2 *, T2 followed by a decrease. Furosemide caused T2 *, T2 elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T2 *. CONCLUSION: Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T2 *, T2 . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies.

MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis.

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum-a region with predominant inflammation in this model-is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS.