Lu-Ping Li

Early changes with diabetes in renal medullary hemodynamics as evaluated by fiberoptic probes and BOLD magnetic resonance imaging.

Objective:We sought to evaluate the influence of streptozotocin (STZ)-induced diabetes on renal outer medullary pO2 and blood flow by invasive microprobes and to demonstrate feasibility that blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) can monitor these changes. Materials and Methods:A total of 60 Wistar-Furth rats were used. Diabetes was induced by STZ in 48. Animals were divided into OxyLite group (n = 30) and BOLD MRI groups (n = 30) each with a 5 subgroups of 6 animals: control and 2, 5, 14, and 28 days after induction of diabetes. Outer renal medullary oxygen tension and blood flow were measured by the combined OxyLite/OxyFlo probes. Results:Both OxyLite and BOLD MRI showed a significant increase in the renal hypoxia levels after STZ at all time points. However, no changes were observed in the outer renal medullary oxygen tension and blood flow between diabetic and control groups. Conclusions:These preliminary results suggest that hypoxic changes can be detected as early as 2 days in rat kidneys with diabetes by BOLD MRI and that these early changes are not dependent on blood flow.

Evaluation of the Reproducibility of Intrarenal and Measurements Following Administration of Furosemide and During Waterload

To estimate the reproducibility of BOLD MRI measurements in the evaluation of intrarenal oxygenation levels.

Blood Oxygen Level-Dependent MR Imaging of the Kidneys

Oxygenation status plays a major role in renal physiology and pathophysiology, and thus has attracted considerable attention in recent years. While much of the early work and a significant amount of present work is based on invasive methods or ex vivo analysis, and is therefore restricted to animal models, blood oxygen level-dependent (BOLD) MR imaging has been shown to extend these findings to human beings. BOLD MR imaging is most useful in monitoring effects of physiologic or pharmacologic maneuvers. Several teams around the world have demonstrated reproducible data and have illustrated several useful applications. Studies supporting the use of renal BOLD MR imaging in characterizing disease with prognostic value have also been reported. This article provides an overview of current state-of-the art of renal BOLD MR imaging.

Evaluation of intrarenal oxygenation by BOLD MRI at 3.0T

To examine the benefit of using higher field strengths for BOLD MRI to detect changes in renal medullary oxygenation following pharmacological maneuvers.

Kidneys in hypertensive rats show reduced response to nitric oxide synthase inhibition as evaluated by BOLD MRI.

To examine whether the noninvasive technique of blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) can detect changes in renal medullary oxygenation following administration of a nitric oxide (NO) synthase inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME). Hypertension is associated with endothelial dysfunction and is characterized by a lack of response to endothelial‐dependent vasoactive substances, including nitric oxide synthase inhibitors. We hypothesized that the magnitude of the change would be reduced in the kidneys of hypertensive subjects relative to normal controls.

Effect of nitric oxide synthase inhibition on intrarenal oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging.

Objective:To investigate the feasibility of studying renal effects of nitric oxide synthase inhibition (NOSi) in humans by blood oxygenation level-dependent (BOLD) MRI. Nitric oxide (NO) is known to play a key role in the pathophysiology of hypertension and previous reports suggest reduced bioavailability of NO in the kidneys of hypertensive rats and hence show reduced response to NOSi using BOLD MRI. Ability to perform similar studies in humans could potentially lead to detection of early changes before development of symptoms, and to monitor novel interventions targeted toward improved NO bioavailability. The specific goals for this study were: (1) to examine whether lower doses and dose rate of administration of NOSi such as those previously used in humans can be detected by BOLD MRI in rat kidneys, (2) to compare changes in R2* to direct measures of renal medullary oxygen levels and blood flow using invasive probes (OxyLite/OxyFlo), and (3) to examine for the first time the effect of NOSi on intrarenal oxygenation in humans. Material and Methods:In rat kidneys, acute changes in renal tissue oxygenation induced by different doses (2, 4, and 10 mg/kg) of N-nitro-l-arginine methyl ester were studied in 36 Sprague Dawley rats, which were equally divided into BOLD MRI and OxyLite/OxyFlo groups. Similarly in humans, acute changes in renal oxygenation were induced by 2 different NOS inhibitors NG-monomethyl-l-arginine (4.25 mg/kg) in 7 volunteers and N-nitro-l-arginine methyl ester (2 mg/kg and 4 mg/kg) in 6 healthy young volunteers. A multiple gradient echo sequence was used in both rats (TE = 4.4–57.8 milliseconds with 3.6 milliseconds interecho spacing) and humans (TE = 6.4–40.8 milliseconds with a 2.3 milliseconds interecho spacing) to acquire 16 T2*-weighted images. R2* maps were constructed by fitting a single exponential decay to the image data on pixel by pixel basis. R2* measurements in the cortex and medulla were performed by regions of interest analysis. Measurements were performed before and during infusion of NOSi. Results:In rats, NOSi decreased medullary pO2 and blood flow in a dose-dependent manner, and BOLD MRI showed an increase in medullary R2* consistent with the invasive pO2 measurements. In humans, BOLD MRI similarly showed an increase in medullary and cortical R2* after NOSi in a dose-dependent manner. In both rats and humans, the R2* values fell back toward baseline before the end of the infusion period. Conclusion:Comparison of BOLD MRI measurements with those using invasive probes suggests that changes in blood flow are at least partly responsible for observed changes with BOLD MRI. Monitoring changes after NOSi by renal BOLD MRI in vivo in human kidneys are feasible, and preliminary findings are consistent with observations in rat kidneys. Future studies are warranted to fully understand the apparent reversal in R2* changes during the infusion of NOSi.

Evaluation of Intrarenal Oxygenation at 3.0 T Using 3-Dimensional Multiple Gradient-Recalled Echo Sequence

Objective:The objective of this study was to validate quantitation of R2* and &Dgr;R2* measurements obtained with a 3-dimensional (3-D) multiple gradient-recalled echo (mGRE) sequence for evaluating intrarenal oxygenation in humans. Materials and Methods:Validation was accomplished (1) by comparing R2* values with previously established 2-D techniques (n = 5, mean age = 33.6 years) and (2) by measuring change in &Dgr;R2* after furosemide (20 mg intravenously) administration (n = 5, mean age = 22 years). Additional pre- and postfurosemide scans were done at 1.5 T for comparison purposes. Results:R2* measurements with the 3-D technique showed good agreement with the 2-D techniques. The baseline medullary R2* at 3.0 T was about twice the value found at 1.5 T. Furosemide-induced change in R2* was observed within 5 minutes after administration. Conclusions:R2* measurements with 3-D mGRE were comparable with those reported using 2-D techniques. The 3-D implementation facilitates observation of temporal changes in the medullary oxygenation without compromising spatial coverage.

Effect of free radical scavenger (tempol) on intrarenal oxygenation in hypertensive rats as evaluated by BOLD MRI.

To demonstrate a differential response following administration of a free radical scavenger, tempol, in kidneys of hypertensive compared to normotensive rats.

Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole-body scanner†

To extend observations on intra‐renal oxygenation with blood oxygen level‐dependent (BOLD) MRI in human and rats to mouse kidneys imaged with a human whole‐body scanner.

Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose.

To compare the effects of osmolality versus viscosity of radio‐contrast media on intra‐renal oxygenation as determined by blood oxygenation level‐dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN).