Usability of Functional MRI in Clinical Studies for Fast and Reliable Assessment of Renal Perfusion and Quantification of Hemodynamic Effects on the Kidney

Abstract

The purpose of this study was to evaluate contrast-media-free arterial spin labeling, a technique of functional magnetic resonance imaging (MRI), for assessment of kidney perfusion in a clinical study. We examined renal perfusion by arterial spin labeling in 15 healthy adults using a clinical 1.5-T MRI system, twice under baseline conditions and 60 minutes after a single oral dose of 50 mg captopril. Data evaluation included assessment of interstudy and interrater reproducibility in addition to the pharmacological effect of captopril on kidney perfusion and a sample size calculation for potential application of the technique in pharmacological intervention studies. Interstudy reproducibility of cortical and medullary kidney perfusion was excellent (intraclass correlation coefficients 0.77 and 0.83, respectively). Interrater reproducibility was excellent in the cortex and good in the medulla (intraclass correlation coefficients 0.97 and 0.66, respectively). Ingestion of 50 mg captopril was associated with an 11% drop of systolic blood pressure and a rise in kidney perfusion by 22% in the cortex (369 ± 48 vs 452 ± 56 mL/[min·100 g], P < .001) and 26% in the medulla (157 ± 39 to 198 ± 45 ml/[min·100 g]; P < .01). Statistical power analysis revealed that a small sample size of only 6 participants is needed in a clinical trial to capture an equal change in kidney perfusion to the one induced by 50 mg captopril with a statistical power of 82% and an α error of 0.05. In conclusion, funtional MRI with arterial spin labeling is a reliable method for quantification of kidney perfusion and for fast assessment of pharmacologically induced renal perfusion changes, allowing low case numbers.

Non-Invasive Renal Perfusion Imaging Using Arterial Spin Labeling MRI: Challenges and Opportunities

“…For example, RBF has been shown to increase during aliskiren therapy and return to original levels after withdrawal of the drug [ 36 ]. Others include telmisartan [ 28 ], furosemide [ 37 ], losartan [ 53 ] and captopril [ 54 ]. The effects of renal denervation (RDN) on RBF in a group of patients with treatment-resistant hypertension were also assessed with ASL (no changes detected up to 3 months after RDN) [ 38 ].…”

“… Number of renal ASL publications in humans per year since the introduction of the technique (excluding cancer studies and conference proceedings) [ 11 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ] ( n = 50). …”

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging

“…Previous studies showed lower inter-reader reproducibility of perfusion measurements with ASL in the renal medulla than perfusion measurement in the renal cortex. [21] Last but not least, the administered dose of diclofenac is much lower than the one used in clinical practice.…”

“…In the mentioned work by Getzin et al ., a power calculation was performed for different scenarios with small pharmacological effects on renal perfusion. A sample size calculation for potential application of functional MRI in pharmacological intervention studies revealed a sample size of 6 for a mean±SD perfusion difference of 82.8 ± 56.1 ml/min/100 g (effect size 1.48) and a sample size of 17 for a perfusion difference of 41.4 ± 56.1 ml/min/100 g (effect size 0.74) …”

“…[19,20] Compared to CEUS, ASL is less investigator-dependent. [21] Compared to PAH clearance, the gold standard renal blood flow measurement, ASL can detect rapid changes of renal perfusion as acquisition time is below 5 min. [19,21] To our knowledge, this is the first study to investigate changes of renal perfusion after diclofenac administration using functional MRI.…”