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Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow (RBF) is mediated by the rapid myogenic response, by the slower tubuloglomerular feedback (TGF) mechanism, and, possibly, by an even slower third mechanism. To evaluate the individual contribution of these mechanisms to RBF autoregulation, we analyzed the response of RBF to a step increase in RPP. In anesthetized rats, the suprarenal aorta was occluded for 30 s, and then the occlusion was released to induce a step increase in RPP. Three dampened oscillations were observed; their oscillation periods ranged from 9.5 to 13 s, from 34.2 to 38.6 s, and from 100.5 to 132.2 s, respectively. The two faster oscillations correspond with previously reported data on the myogenic mechanism and the TGF. In accordance, after furosemide, the amplitude of the intermediate oscillation was significantly reduced. Inhibition of nitric oxide synthesis by [N.sup.[omega]]-nitro-L-arginine methyl ester significantly increased the amplitude of the 10-s oscillation. It is concluded that the parameters of the dampened oscillations induced by the step increase in RPP reflect properties of autoregulatory mechanisms. The oscillation period characterizes the individual mechanism, the dampening is a measure for the stability of the regulation, and the square of the amplitudes characterizes the power of the respective mechanism. In addition to the myogenic response and the TGF, a third rather slow mechanism of RBF autoregulation exists. myogenic reaction; tubuloglomerular feedback; furosemide; [N.sup.[omega]]-nitro-L-arginine methyl ester.

Optimal ventriculoaortic coupling includes tuning of elastic properties. The ratio of effective arterial elastance and left ventricular endsystolic elastance is often taken as a measure for mechanical and energetical efficiency. The present study determined the time course of ventricular and aortic volume elasticity (VE = dp/dV) throughout a complete heartbeat. This was achieved by using changes of eigenfrequency of two catheter-transducer systems under closed chest conditions in rabbits. Short-term VE modulation was studied by a baroreflex response, as induced by pressure changes applied to the carotid sinus. Long-term changes were studied in atherosclerotic rabbits (12 wk of high-cholesterol feeding). The time course and mean values of ventricular and aortic VE were changed by the baroreflex stimulus. Cholesterol feeding diminished the response. The degree of ventriculoaortic coupling, as quantified by V[E.sub.Aorta]/V[E.sub.ventricle] ratio, varied during a single ejection period. The large span allows either maximal energetical efficiency or maximal stroke work. Although normal rabbits adjusted their ventriculoaortic coupling during baroreflex input, the cholesterol-fed rabbits failed to do so. compliance; ventriculoarterial coupling; eigenfrequency; cholesterol; atherosclerosis

Wronski, T., P. B. Persson, E. Seeliger, A. Harnath, and B. Flemming. Coupling of left ventricular and aortic volume elasticity in the rabbit. Am J Physiol Regulatory Integrative Comp Physiol 279: R539-R547, 2000.--Changes in volume elasticity (VE) of the left ventricle and aorta could be important for blood flow. A procedure is presented to rapidly assess VE of the left ventricle and aorta by analyzing changes in the eigenfrequency. Six control rabbits and 11 rabbits with atheromatosis (12 wk of high-cholesterol feeding) were studied. In control rabbits, during the first half of the systole, left ventricular VE continuously increased to +43% (P [is less than] 0.05). Then VE gradually declined to an end-diastolic minimum (20% of the average systolic levels, P [is less than] 0.05). Aortic VE changes were in the opposite direction to the ventricle. Aortic VE continuously decreased throughout the systole; the last value was 20% lower than at the beginning of the systole (P [is less than] 0.05). Conversely, diastolic VE of the aorta took on greater values. This inverse time course between ventricle and aorta may reduce energy requirements for conveying blood. High cholesterol-fed rabbits did not reveal the inverse behavior of ventricular and aortic VE, e.g., aortic VE increased during the systole (119%, P [is less than] 0.05). heart; aorta; compliance; left ventricular-arterial coupling; eigenfrequency; cholesterol; atherosclerosis

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. [ABSTRACT FROM AUTHOR]

Mapping the effective transverse relaxation time T2* represents an emerging MRI tool for non-invasive myocardial tissue characterization and holds the promise to provide means for assessing myocardial (patho)physiology in vivo. This work takes advantage of the linear increase of susceptibility effects with magnetic field strength which renders it appealing to perform T2* mapping at ultrahigh magnetic fields and enables temporally resolved T2* mapping. Recognizing this potential this study examines the applicability of myocardial CINE T2* mapping in healthy volunteers and hypertrophic cardiomyopathy (HCM) patients at 7.0 Tesla and investigates its capability to distinguish between healthy myocardium and myocardium affected by HCM.

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., (© 2024. The Author(s).)

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 T 2 component as a surrogate for TVF in rats, by applying multiexponential analysis of the T 2 -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 T 2 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 T 2 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: ΔTVF cortex  = 4.9%, ΔTVF outer&#95;medulla  = 4.5%, and ΔTVF inner&#95;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., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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 T 2 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., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

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., Competing Interests: Conflicts of interest and sources of funding: T.F., J.B., and H.P. are employees of Bayer AG. L.H. was an employee of Bayer AG during part of the investigations., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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 (MTR asym ), 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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-699/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

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., (© 2023 International Society for Magnetic Resonance in Medicine.)

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 (ADC cortex ) , ADC in the renal medulla (ADC medulla ) and difference between ADC cortex and ADC medulla (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: ADC cortex presented superior performance in discriminating DKD with normal and declined estimated glomerular filtration rate (eGFR) over ADC medulla , 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 ADC cortex 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: ADC cortex is a valuable imaging marker for the diagnosis and prediction of renal function decline in DKD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-149/coif). WW was supported by grants from the National Natural Science Foundation of China (Nos. 82170731 and 81470974) and the High-level Hospital Construction Project of Guangdong Province (No. DFJH201908). ZL was supported by grants from the Key Area Research and Development Program of Guangdong Province (No. 2021B0101420006), Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (No. U22A20345), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No. 2022B1212010011), and High-level Hospital Construction Project of Guangdong Province (No. DFJHBF202105). Erdmann Seeliger was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft) Collaborative Research Center (1365 “Renoprotection” Project B04). ZW reports being a full-time employee of Philips (2020-now) during the conduct of the study. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aim: Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T 2 and T 2 * 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 T 2 * and T 2 changes in acute pathophysiological scenarios., Methods: KS was determined from T 2 *, T 2 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 O 2 saturation of hemoglobin from changes in T 2 * and KS., Results: Upon aortic occlusion KS decreased; this correlated with a decrease in T 2 *, T 2 . Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T 2 *, T 2 . Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T 2 *, T 2 . Hypoxemia induced mild reductions in KS and T 2 *, T 2 . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T 2 *, T 2 followed by a decrease. Furosemide caused T 2 *, T 2 elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T 2 *., Conclusion: Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T 2 *, T 2 . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies., (© 2022 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)