How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.

Early effects of an x-ray contrast medium on renal T(2) */T(2) MRI as compared to short-term hyperoxia, hypoxia and aortic occlusion in rats.

AIM: X-ray contrast media (CM) can cause acute kidney injury (AKI). Medullary hypoxia is pivotal in CM-induced AKI, as indicated by invasively and pin-point measured tissue oxygenation. MRI provides spatially resolved blood oxygenation level-dependent data using T2 * and T2 mapping. We studied CM effects on renal T2 */T2 and benchmarked them against short periods of hyperoxia, hypoxia and aortic occlusion (AO). METHODS: Rats were equipped with carotid artery catheters (tip towards aorta) and supra-renal aortic occluders. T2 */T2 mapping was performed using a 9.4-T animal scanner. CM (1.5 mL iodixanol) was injected into the thoracic aorta with the animal in the scanner followed by 2 h of T2 */T2 mapping. For T2 */T2 assessment, regions of interest in the cortex (C), outer medulla (OM), inner medulla (IM) and papilla (P) were determined according to morphological features. RESULTS: Hyperoxia increased T2 * in C (by 17%) and all medullary layers (25-35%). Hypoxia decreased T2 * in C (40%) and all medullary layers (55-60%). AO decreased T2 * in C (18%) and all medullary layers (30-40%). Upon injection of CM, T2 * increased transiently, then decreased, reaching values 10-20% below baseline in C and OM and 30-40% below baseline in IM and P. CONCLUSION: T2 * mapping corroborates data previously obtained with invasive methods and demonstrates that CM injection affects renal medullary oxygenation. CM-induced T2 * decrease in OM was small vs. hypoxia and aortic occlusion. T2 * decrease obtained for hypoxia was more pronounced than for AO. This indicates that T2 * may not accurately reflect blood oxygenation under certain conditions.

Linking non-invasive parametric MRI with invasive physiological measurements (MR-PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats.

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non-invasive MRI in an integrated hybrid setup (MR-PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi-modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation-dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR-PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.