MRI of kidney size matters.

OBJECTIVE: To highlight progress and opportunities of measuring kidney size with MRI, and to inspire research into resolving the remaining methodological gaps and unanswered questions relating to kidney size assessment. MATERIALS AND METHODS: This work is not a comprehensive review of the literature but highlights valuable recent developments of MRI of kidney size. RESULTS: The links between renal (patho)physiology and kidney size are outlined. Common methodological approaches for MRI of kidney size are reviewed. Techniques tailored for renal segmentation and quantification of kidney size are discussed. Frontier applications of kidney size monitoring in preclinical models and human studies are reviewed. Future directions of MRI of kidney size are explored. CONCLUSION: MRI of kidney size matters. It will facilitate a growing range of (pre)clinical applications, and provide a springboard for new insights into renal (patho)physiology. As kidney size can be easily obtained from already established renal MRI protocols without the need for additional scans, this measurement should always accompany diagnostic MRI exams. Reconciling global kidney size changes with alterations in the size of specific renal layers is an important topic for further research. Acute kidney size measurements alone cannot distinguish between changes induced by alterations in the blood or the tubular volume fractions-this distinction requires further research into cartography of the renal blood and the tubular volumes.

In vivo monitoring of renal tubule volume fraction using dynamic parametric MRI.

PURPOSE: The increasing incidence of kidney diseases is a global concern, and current biomarkers and treatments are inadequate. Changes in renal tubule luminal volume fraction (TVF) serve as a rapid biomarker for kidney disease and improve understanding of renal (patho)physiology. This study uses the amplitude of the long T2 component as a surrogate for TVF in rats, by applying multiexponential analysis of the T2-driven signal decay to examine micromorphological changes in renal tissue. METHODS: Simulations were conducted to identify a low mean absolute error (MAE) protocol and an accelerated protocol customized for the in vivo study of T2 mapping of the rat kidney at 9.4 T. We then validated our bi-exponential approach in a phantom mimicking the relaxation properties of renal tissue. This was followed by a proof-of-principle demonstration using in vivo data obtained during a transient increase of renal pelvis and tubular pressure. RESULTS: Using the low MAE protocol, our approach achieved an accuracy of MAE < 1% on the mechanical phantom. The T2 mapping protocol customized for in vivo study achieved an accuracy of MAE < 3%. Transiently increasing pressure in the renal pelvis and tubules led to significant changes in TVF in renal compartments: ΔTVFcortex = 4.9%, ΔTVFouter_medulla = 4.5%, and ΔTVFinner_medulla = -14.6%. CONCLUSION: These results demonstrate that our approach is promising for research into quantitative assessment of renal TVF in in vivo applications. Ultimately, these investigations have the potential to help reveal mechanism in acute renal injury that may lead to chronic kidney disease, which will support research into renal disorders.

Noninvasive Assessment of Diabetic Kidney Disease With MRI: Hype or Hope?

Owing to the increasing prevalence of diabetic mellitus, diabetic kidney disease (DKD) is presently the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early identification and disease interception is of paramount clinical importance for DKD management. However, current diagnostic, disease monitoring and prognostic tools are not satisfactory, due to their low sensitivity, low specificity, or invasiveness. Magnetic resonance imaging (MRI) is noninvasive and offers a host of contrast mechanisms that are sensitive to pathophysiological changes and risk factors associated with DKD. MRI tissue characterization involves structural and functional information including renal morphology (kidney volume (TKV) and parenchyma thickness using T1- or T2-weighted MRI), renal microstructure (diffusion weighted imaging, DWI), renal tissue oxygenation (blood oxygenation level dependent MRI, BOLD), renal hemodynamics (arterial spin labeling and phase contrast MRI), fibrosis (DWI) and abdominal or perirenal fat fraction (Dixon MRI). Recent (pre)clinical studies demonstrated the feasibility and potential value of DKD evaluation with MRI. Recognizing this opportunity, this review outlines key concepts and current trends in renal MRI technology for furthering our understanding of the mechanisms underlying DKD and for supplementing clinical decision-making in DKD. Progress in preclinical MRI of DKD is surveyed, and challenges for clinical translation of renal MRI are discussed. Future directions of DKD assessment and renal tissue characterization with (multi)parametric MRI are explored. Opportunities for discovery and clinical break-through are discussed including biological validation of the MRI findings, large-scale population studies, standardization of DKD protocols, the synergistic connection with data science to advance comprehensive texture analysis, and the development of smart and automatic data analysis and data visualization tools to further the concepts of virtual biopsy and personalized DKD precision medicine. We hope that this review will convey this vision and inspire the reader to become pioneers in noninvasive assessment and management of DKD with MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Dynamic parametric MRI and deep learning: Unveiling renal pathophysiology through accurate kidney size quantification.

Renal pathologies often manifest as alterations in kidney size, providing a valuable avenue for employing dynamic parametric MRI as a means to derive kidney size measurements for the diagnosis, treatment, and monitoring of renal disease. Furthermore, this approach holds significant potential in supporting MRI data-driven preclinical investigations into the intricate mechanisms underlying renal pathophysiology. The integration of deep learning algorithms is crucial in achieving rapid and precise segmentation of the kidney from temporally resolved parametric MRI, facilitating the use of kidney size as a meaningful (pre)clinical biomarker for renal disease. To explore this potential, we employed dynamic parametric T2 mapping of the kidney in rats in conjunction with a custom-tailored deep dilated U-Net (DDU-Net) architecture. The architecture was trained, validated, and tested on manually segmented ground truth kidney data, with benchmarking against an analytical segmentation model and a self-configuring no new U-Net. Subsequently, we applied our approach to in vivo longitudinal MRI data, incorporating interventions that emulate clinically relevant scenarios in rats. Our approach achieved high performance metrics, including a Dice coefficient of 0.98, coefficient of determination of 0.92, and a mean absolute percentage error of 1.1% compared with ground truth. The DDU-Net enabled automated and accurate quantification of acute changes in kidney size, such as aortic occlusion (-8% ± 1%), venous occlusion (5% ± 1%), furosemide administration (2% ± 1%), hypoxemia (-2% ± 1%), and contrast agent-induced acute kidney injury (11% ± 1%). This approach can potentially be instrumental for the development of dynamic parametric MRI-based tools for kidney disorders, offering unparalleled insights into renal pathophysiology.

Comprehensive Analysis of the Spatial Distribution of Gadolinium, Iron, Manganese, and Phosphorus in the Brain of Healthy Rats After High-Dose Administrations of Gadodiamide and Gadobutrol.

OBJECTIVES: After the administration of gadolinium-based contrast agents (GBCAs), residual gadolinium (Gd) has been detected in a few distinct morphological structures of the central nervous system (CNS). However, a systematic, comprehensive, and quantitative analysis of the spatial Gd distribution in the entire brain is not yet available. The first aim of this study is to provide this analysis in healthy rats after administration of high GBCA doses. The second aim is to assess the spatial distributions and possible Gd colocalizations of endogenous iron (Fe), manganese (Mn), and phosphorus (P). In addition, the presence of Gd in proximity to blood vessels was assessed by immunohistochemistry. MATERIALS AND METHODS: Male rats were randomly assigned to 3 groups (n = 3/group): saline (control), gadodiamide (linear GBCA), and gadobutrol (macrocyclic GBCA) with cumulative Gd doses of 14.4 mmol/kg of body mass. Five weeks after the last administration, the brains were collected and cryosectioned. The spatial distributions of Gd, Fe, Mn, and P were analyzed in a total of 130 sections, each covering the brain in 1 of the 3 perpendicular anatomical orientations, using laser ablation coupled with inductively coupled plasma mass spectrometry. Quantitative spatial element maps were generated, and the concentrations of Gd, Fe, and Mn were measured in 31 regions of interest covering various distinct CNS structures. Correlation analyses were performed to test for possible colocalization of Gd, Fe, and Mn. The spatial proximity of Gd and blood vessels was studied using metal-tagged antibodies against von Willebrand factor with laser ablation coupled with inductively coupled plasma mass spectrometry. RESULTS: After administration of linear gadodiamide, high Gd concentrations were measured in many distinct structures of the gray matter. This involved structures previously reported to retain Gd after linear GBCA, such as the deep cerebellar nuclei or the globus pallidus, but also structures that had not been reported so far including the dorsal subiculum, the retrosplenial cortex, the superior olivary complex, and the inferior colliculus. The analysis in all 3 orientations allowed the localization of Gd in specific subregions and layers of certain structures, such as the hippocampus and the primary somatosensory cortex. After macrocyclic gadobutrol, the Gd tissue concentration was significantly lower than after gadodiamide. Correlation analyses of region of interest concentrations of Gd, Fe, and Mn revealed no significant colocalization of Gd with endogenous Fe or Mn in rats exposed to either GBCA. Immunohistochemistry revealed a colocalization of Gd traces with vascular endothelium in the deep cerebellar nuclei after gadobutrol, whereas the majority of Gd was found outside the vasculature after gadodiamide. CONCLUSIONS: In rats exposed to gadodiamide but not in rats exposed to gadobutrol, high Gd concentrations were measured in various distinct CNS structures, and structures not previously reported were identified to contain Gd, including specific subregions and layers with different cytoarchitecture and function. Knowledge of these distinct spatial patterns may pave the way for tailored functional neurological testing. Signs for the localization of the remaining Gd in the vascular endothelium were prominent for gadobutrol but not gadodiamide. The results also indicate that local transmetalation with endogenous Fe or Mn is unlikely to explain the spatial patterns of Gd deposition in the brain, which argues against a general role of these metals in local transmetalation and release of Gd ions in the CNS.

Assessment of rhabdomyolysis-induced acute kidney injury with chemical exchange saturation transfer magnetic resonance imaging.

Background: Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. Methods: AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Results: Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. Conclusions: The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

Diagnostic and prognostic performance of renal compartment volume and the apparent diffusion coefficient obtained from magnetic resonance imaging in mild, moderate and severe diabetic kidney disease.

Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). There are unmet needs for noninvasive diagnosis and prognosis prediction of DKD in clinical practice. This study examines the diagnostic and prognostic value of magnetic resonance (MR) markers of renal compartment volume and the apparent diffusion coefficient (ADC) for mild, moderate, and severe DKD. Methods: This study was registered at the Chinese Clinical Trial Registry Center (registration number: ChiCTR-RRC-17012687). Sixty-seven DKD patients were prospectively randomly enrolled and underwent clinical examination and diffusion-weighted magnetic resonance imaging (DW-MRI). Patients with comorbidities that affected renal volumes or components were excluded. Ultimately, 52 DKD patients were included in the cross-sectional analysis. The ADC in the renal cortex (ADCcortex), ADC in the renal medulla (ADCmedulla) and difference between ADCcortex and ADCmedulla (ΔADC) were measured using a twelve-layer concentric objects (TLCO) approach. Renal compartment volumes of the parenchyma and pelvis were derived from T2-weighted MRI. Due to lost contact or ESRD diagnosed before follow-up (n=14), only 38 DKD patients remained for follow-up (median period =8.25 years) to investigate the correlations between MR markers and renal outcomes. The primary outcomes were the composite of doubling of the primary serum creatinine concentration or ESRD. Results: ADCcortex presented superior performance in discriminating DKD with normal and declined estimated glomerular filtration rate (eGFR) over ADCmedulla, ΔADC and renal compartment volumes with an AUC of 0.904 (sensitivity of 83% and specificity of 91%) and was moderately correlated with the clinical biomarkers eGFR and proteinuria (P<0.05). The Cox survival analysis demonstrated that ADCcortex rather than ΔADC is a predictor of renal outcomes with a hazard ratio of 3.4 (95% CI: 1.1-10.2, P<0.05) independent of baseline eGFR and proteinuria. Conclusions: ADCcortex is a valuable imaging marker for the diagnosis and prediction of renal function decline in DKD.

Renal MRI: From Nephron to NMR Signal.

Renal diseases pose a significant socio-economic burden on healthcare systems. The development of better diagnostics and prognostics is well-recognized as a key strategy to resolve these challenges. Central to these developments are MRI biomarkers, due to their potential for monitoring of early pathophysiological changes, renal disease progression or treatment effects. The surge in renal MRI involves major cross-domain initiatives, large clinical studies, and educational programs. In parallel with these translational efforts, the need for greater (patho)physiological specificity remains, to enable engagement with clinical nephrologists and increase the associated health impact. The ISMRM 2022 Member Initiated Symposium (MIS) on renal MRI spotlighted this issue with the goal of inspiring more solutions from the ISMRM community. This work is a summary of the MIS presentations devoted to: 1) educating imaging scientists and clinicians on renal (patho)physiology and demands from clinical nephrologists, 2) elucidating the connection of MRI parameters with renal physiology, 3) presenting the current state of leading MR surrogates in assessing renal structure and functions as well as their next generation of innovation, and 4) describing the potential of these imaging markers for providing clinically meaningful renal characterization to guide or supplement clinical decision making. We hope to continue momentum of recent years and introduce new entrants to the development process, connecting (patho)physiology with (bio)physics, and conceiving new clinical applications. We envision this process to benefit from cross-disciplinary collaboration and analogous efforts in other body organs, but also to maximally leverage the unique opportunities of renal physiology. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

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.

Parametric MRI Detects Aristolochic Acid Induced Acute Kidney Injury.

Exposure to aristolochic acid (AA) is of increased concern due to carcinogenic and nephrotoxic effects, and incidence of aristolochic acid nephropathy (AAN) is increasing. This study characterizes renal alterations during the acute phase of AAN using parametric magnetic resonance imaging (MRI). An AAN and a control group of male Wistar rats received administration of aristolochic acid I (AAI) and polyethylene glycol (PEG), respectively, for six days. Both groups underwent MRI before and 2, 4 and 6 days after AAI or PEG administration. T2 relaxation times and apparent diffusion coefficients (ADCs) were determined for four renal layers. Serum creatinine levels (sCr) and blood urea nitrogen (BUN) were measured. Tubular injury scores (TIS) were evaluated based on histologic findings. Increased T2 values were detected since day 2 in the AAN group, but decreased ADCs and increased sCr levels and BUN were not detected until day 4. Significant linear correlations were observed between T2 of the cortex and the outer stripe of outer medulla and TIS. Our results demonstrate that parametric MRI facilitates early detection of renal injury induced by AAI in a rat model. T2 mapping may be a valuable tool for assessing kidney injury during the acute phase of AAN.

Continuous diffusion spectrum computation for diffusion-weighted magnetic resonance imaging of the kidney tubule system.

BACKGROUND: The use of rigid multi-exponential models (with a priori predefined numbers of components) is common practice for diffusion-weighted MRI (DWI) analysis of the kidney. This approach may not accurately reflect renal microstructure, as the data are forced to conform to the a priori assumptions of simplified models. This work examines the feasibility of less constrained, data-driven non-negative least squares (NNLS) continuum modelling for DWI of the kidney tubule system in simulations that include emulations of pathophysiological conditions. METHODS: Non-linear least squares (LS) fitting was used as reference for the simulations. For performance assessment, a threshold of 5% or 10% for the mean absolute percentage error (MAPE) of NNLS and LS results was used. As ground truth, a tri-exponential model using defined volume fractions and diffusion coefficients for each renal compartment (tubule system: Dtubules , ftubules ; renal tissue: Dtissue , ftissue ; renal blood: Dblood , fblood ;) was applied. The impact of: (I) signal-to-noise ratio (SNR) =40-1,000, (II) number of b-values (n=10-50), (III) diffusion weighting (b-rangesmall =0-800 up to b-rangelarge =0-2,180 s/mm2), and (IV) fixation of the diffusion coefficients Dtissue and Dblood was examined. NNLS was evaluated for baseline and pathophysiological conditions, namely increased tubular volume fraction (ITV) and renal fibrosis (10%: grade I, mild) and 30% (grade II, moderate). RESULTS: NNLS showed the same high degree of reliability as the non-linear LS. MAPE of the tubular volume fraction (ftubules ) decreased with increasing SNR. Increasing the number of b-values was beneficial for ftubules precision. Using the b-rangelarge led to a decrease in MAPE ftubules compared to b-rangesmall. The use of a medium b-value range of b=0-1,380 s/mm2 improved ftubules precision, and further bmax increases beyond this range yielded diminishing improvements. Fixing Dblood and Dtissue significantly reduced MAPE ftubules and provided near perfect distinction between baseline and ITV conditions. Without constraining the number of renal compartments in advance, NNLS was able to detect the (fourth) fibrotic compartment, to differentiate it from the other three diffusion components, and to distinguish between 10% vs. 30% fibrosis. CONCLUSIONS: This work demonstrates the feasibility of NNLS modelling for DWI of the kidney tubule system and shows its potential for examining diffusion compartments associated with renal pathophysiology including ITV fraction and different degrees of fibrosis.

Reliable kidney size determination by magnetic resonance imaging in pathophysiological settings.

AIM: Kidney diseases constitute a major health challenge, which requires noninvasive imaging to complement conventional approaches to diagnosis and monitoring. Several renal pathologies are associated with changes in kidney size, offering an opportunity for magnetic resonance imaging (MRI) biomarkers of disease. This work uses dynamic MRI and an automated bean-shaped model (ABSM) for longitudinal quantification of pathophysiologically relevant changes in kidney size. METHODS: A geometry-based ABSM was developed for kidney size measurements in rats using parametric MRI (T2 , T2 * mapping). The ABSM approach was applied to longitudinal renal size quantification using occlusion of the (a) suprarenal aorta or (b) the renal vein, (c) increase in renal pelvis and intratubular pressure and (d) injection of an X-ray contrast medium into the thoracic aorta to induce pathophysiologically relevant changes in kidney size. RESULTS: The ABSM yielded renal size measurements with accuracy and precision equivalent to the manual segmentation, with >70-fold time savings. The automated method could detect a ~7% reduction (aortic occlusion) and a ~5%, a ~2% and a ~6% increase in kidney size (venous occlusion, pelvis and intratubular pressure increase and injection of X-ray contrast medium, respectively). These measurements were not affected by reduced image quality following administration of ferumoxytol. CONCLUSION: Dynamic MRI in conjunction with renal segmentation using an ABSM supports longitudinal quantification of changes in kidney size in pathophysiologically relevant experimental setups mimicking realistic clinical scenarios. This can potentially be instrumental for developing MRI-based diagnostic tools for various kidney disorders and for gaining new insight into mechanisms of renal pathophysiology.

Recommendations for Preclinical Renal MRI: A Comprehensive Open-Access Protocol Collection to Improve Training, Reproducibility, and Comparability of Studies.

Renal MRI holds incredible promise for making a quantum leap in improving diagnosis and care of patients with a multitude of diseases, by moving beyond the limitations and restrictions of current routine clinical practice. Clinical and preclinical renal MRI is advancing with ever increasing rapidity, and yet, aside from a few examples of renal MRI in routine use, it is still not good enough. Several roadblocks are still delaying the pace of progress, particularly inefficient education of renal MR researchers, and lack of harmonization of approaches that limits the sharing of results among multiple research groups.Here we aim to address these limitations for preclinical renal MRI (predominantly in small animals), by providing a comprehensive collection of more than 40 publications that will serve as a foundational resource for preclinical renal MRI studies. This includes chapters describing the fundamental principles underlying a variety of renal MRI methods, step-by-step protocols for executing renal MRI studies, and detailed guides for data analysis. This collection will serve as a crucial part of a roadmap toward conducting renal MRI studies in a robust and reproducible way, that will promote the standardization and sharing of data.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Animal Models of Renal Pathophysiology and Disease.

Renal diseases remain devastating illnesses with unacceptably high rates of mortality and morbidity worldwide. Animal models are essential tools to better understand the pathomechanisms of kidney-related illnesses and to develop new, successful therapeutic strategies. Magnetic resonance imaging (MRI) has been actively explored in the last decades for assessing renal function, perfusion, tissue oxygenation as well as the degree of fibrosis and inflammation. This chapter aims to provide a comprehensive overview of animal models of acute and chronic kidney diseases, highlighting MRI-specific considerations, advantages, and pitfalls, and thus assisting the researcher in experiment planning.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Preparation and Monitoring of Small Animals in Renal MRI.

Renal diseases remain devastating illnesses with unacceptably high rates of mortality and morbidity worldwide. Animal models are essential tools to better understand the pathomechanism of kidney-related illnesses and to develop new, successful therapeutic strategies. Magnetic resonance imaging (MRI) has been actively explored in the last decades for assessing renal function, perfusion, tissue oxygenation as well as the degree of fibrosis and inflammation. This chapter aims to provide an overview of the preparation and monitoring of small animals before, during, and after surgical interventions or MR imaging. Standardization of experimental settings such as body temperature or hydration of animals and minimizing pain and distress are essential for diminishing nonexperimental variables as well as for conducting ethical research.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Reversible (Patho)Physiologically Relevant Test Interventions: Rationale and Examples.

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe test interventions that are used to study the control of renal hemodynamics and oxygenation in experimental animals in the context of kidney-specific control of hemodynamics and oxygenation. The rationale behind the use of the individual tests, the physiological responses of renal hemodynamics and oxygenation, the use in preclinical studies, and the possible application in humans are discussed.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Quantitative Assessment of Renal Perfusion and Oxygenation by Invasive Probes: Basic Concepts.

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe basic principles of methodology to quantify renal hemodynamics and tissue oxygenation by means of invasive probes in experimental animals. Advantages and disadvantages of the various methods are discussed in the context of the heterogeneity of renal tissue perfusion and oxygenation.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by a separate chapter describing the experimental procedure and data analysis.

MRI Mapping of the Blood Oxygenation Sensitive Parameter T2* in the Kidney: Basic Concept.

The role of hypoxia in renal disease and injury has long been suggested but much work still remains, especially as it relates to human translation. Invasive pO2 probes are feasible in animal models but not for human use. In addition, they only provide localized measurements. Histological methods can identify hypoxic tissue and provide a spatial distribution, but are invasive and allow only one-time point. Blood oxygenation level dependent (BOLD) MRI is a noninvasive method that can monitor relative oxygen availability across the kidney. It is based on the inherent differences in magnetic properties of oxygenated vs. deoxygenated hemoglobin. Presence of deoxyhemoglobin enhances the spin-spin relaxation rate measured using a gradient echo sequence, known as R2* (= 1/T2*). While the key interest of BOLD MRI is in the application to humans, use in preclinical models is necessary primarily to validate the measurement against invasive methods, to better understand physiology and pathophysiology, and to evaluate novel interventions. Application of MRI acquisitions in preclinical settings involves several challenges both in terms of logistics and data acquisition. This section will introduce the concept of BOLD MRI and provide some illustrative applications. The following sections will discuss the technical issues associated with data acquisition and analysis.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Monitoring Renal Hemodynamics and Oxygenation by Invasive Probes: Experimental Protocol.

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe methods to study control of renal hemodynamics and tissue oxygenation by means of invasive probes in anesthetized rats. Step-by-step protocols are provided for two setups, one for experiments in laboratories for integrative physiology and the other for experiments within small-animal magnetic resonance scanners.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by a separate chapter describing the basic concepts of quantitatively assessing renal perfusion and oxygenation with invasive probes.

Subsegmentation of the Kidney in Experimental MR Images Using Morphology-Based Regions-of-Interest or Multiple-Layer Concentric Objects.

Functional renal MRI promises access to a wide range of physiologically relevant parameters such as blood oxygenation, perfusion, tissue microstructure, pH, and sodium concentration. For quantitative comparison of results, representative values must be extracted from the parametric maps obtained with these different MRI techniques. To improve reproducibility of results this should be done based on regions-of-interest (ROIs) that are clearly and objectively defined.Semiautomated subsegmentation of the kidney in magnetic resonance images represents a simple but very valuable approach for the quantitative analysis of imaging parameters in multiple ROIs that are associated with specific anatomic locations. Thereby, it facilitates comparing MR parameters between different kidney regions, as well as tracking changes over time.Here we provide detailed step-by-step instructions for two recently developed subsegmentation techniques that are suitable for kidneys of small rodents: i) the placement of ROIs in cortex, outer and the inner medulla based on typical kidney morphology and ii) the division of the kidney into concentrically oriented layers.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.