Simultaneous Measurement of Kidney Function by Dynamic Contrast Enhanced MRI and FITC-Sinistrin Clearance in Rats at 3 Tesla: Initial Results

Abstract

Glomerular filtration rate (GFR) is an essential parameter of kidney function which can be measured by dynamic contrast enhanced magnetic resonance imaging (MRI-GFR) and transcutaneous approaches based on fluorescent tracer molecules (optical-GFR). In an initial study comparing both techniques in separate measurements on the same animal, the correlation of the obtained GFR was poor. The goal of this study was to investigate if a simultaneous measurement was feasible and if thereby, the discrepancies in MRI-GFR and optical-GFR could be reduced. For the experiments healthy and unilateral nephrectomised (UNX) Sprague Dawley (SD) rats were used. The miniaturized fluorescent sensor was fixed on the depilated back of an anesthetized rat. A bolus of 5 mg/100 g b.w. of FITC-sinistrin was intravenously injected. For dynamic contrast enhanced perfusion imaging (DCE-MRI) a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence was used. By means of a one compartment model the excretion half-life (t1/2) of FITC-sinistrin was calculated and converted into GFR. GFR from DCE-MRI was calculated by fitting pixel-wise a two compartment renal filtration model. Mean cortical GFR and GFR by FITC-sinistrin were compared by Bland-Altman plots and pair-wise t-test. Results show that a simultaneous GFR measurement using both techniques is feasible. Mean optical-GFR was 4.34±2.22 ml/min (healthy SD rats) and 2.34±0.90 ml/min (UNX rats) whereas MRI-GFR was 2.10±0.64 ml/min (SD rats) and 1.17±0.38 ml/min (UNX rats). Differences between healthy and UNX rats were significant (p<0.05) and almost equal percentage difference (46.1% and 44.3%) in mean GFR were assessed with both techniques. Overall mean optical-GFR values were approximately twice as high compared to MRI-GFR values. However, compared to a previous study, our results showed a higher agreement. In conclusion, the possibility to use the transcutaneous method in MRI may have a huge impact in improving and validating MRI methods for GFR assessment in animal models.

Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

“…Early functional changes have previously been investigated in several models of ischemia reperfusion AKI following the administration of Gd‐based contrast agents. Most of these studies addressed the quantification of renal perfusion and estimation of glomerular filtration rate both at preclinical and clinical levels . DCE‐MRI methods are less time consuming and costly than methods based on the clearance of injected tracers, and do not involve radiation issues, as in radionuclide renography .…”

Transcutaneous Assessment of Renal Function in Conscious Rodents

“…One of them is the independence from blood and urine sampling which leads to great savings in terms of consumables, time and, of course, animal stress. Table 2, the exogenous renal marker FITC-sinistrin and the measurement of its elimination kinetics through the skin allow the impact of renal pathologies on kidney function to be studied 9,10,[14][15][16][17][18] . The serial collection of blood samples required to assess plasma clearance or biomarkers of renal disease are stressful for the animal, cumbersome and time-consuming for the researchers.…”

Simplified Method to Measure Glomerular Filtration Rate by Iohexol Plasma Clearance in Conscious Rats

“…The approach has some limitations, since it requires almost complete immobilization during the procedure, which in animals usually requires an anesthetic. This may result in errors in GFR estimation, as shown by Zöllner et al [35]. Their findings demonstrated that the mean GFR values determined in rats using MRI were about half those found through transcutaneous FITC-sinistrin clearances.…”