Quantification of renal perfusion using an intravascular contrast agent (part 1): Results in a canine model

Abstract

In this work absolute values of regional renal blood volume (rRBV) and flow (rRBF) are assessed by means of contrastenhanced (CE) MRI using an intravascular superparamagnetic contrast agent. In an animal study, eight foxhounds underwent dynamic susceptibility-weighted MRI upon injection of contrast agent. Using principles of indicator dilution theory and deconvolution analysis, parametric images of rRBV, rRBF, and mean transit time (MTT) were computed. For comparison, wholeorgan blood flow was determined invasively by means of an implanted flow probe, and the weight of the kidneys was evaluated postmortem. A mean rBV value of 28 ml/100 g was found in the renal cortex, with a corresponding mean rBF value of 524 ml/100 g/min and an average MTT of about 3.4 s. Although there was a systematic difference between the absolute blood flow values determined by MRI and the ultrasonic probe, a significant correlation (r s ‫؍‬ 0.72, P < 0.05) was established. The influence of the arterial input function (AIF), T 1 relaxation effects, and repeated measurements on the precision of the perfusion quantitation is discussed.Magn Key words: kidney; perfusion; susceptibility contrast; intravascular contrast agent; dynamic T* 2 -weighted imaging; time series deconvolutionIt has been shown that absolute values of regional cerebral blood volume and flow can be determined from T* 2 -weighted dynamic MR images acquired during the passage of a paramagnetic contrast agent (1-4). However, with the use of a conventional diffusible MR contrast agent (such as Gd-DTPA), this method is limited to tissue regions with an intact blood-brain barrier, wherein the contrast agent remains within the intravascular space (5). Recently, ultrasmall superparamagnetic iron oxide (USPIO) particles, which can be employed as intravascular contrast agents, have become available (6). These agents generate a strong transient decrease in signal intensity when delivered as a bolus, and enable determination of both blood flow and volume in extracranial tissues (7).Absolute quantification of tissue perfusion by dynamic MRI appears to be highly promising in the evaluation of diseases of the kidney, since MRI has already been established as a valuable tool for the assessment of renovascular disease through the combination of morphologic and functional imaging (8,9). As renoparenchymal damage is often caused by a long-standing renal artery stenosis, the challenge for an MR perfusion technique is to differentiate hemodynamically significant stenoses from nonsignificant stenoses. Renoparenchymal perfusion would provide a valuable parameter for deciding whether a stenosis is hemodynamically relevant, in the context of a reduction in renal blood flow.The primary objective of this study was to investigate whether quantification of regional renal blood flow (rRBF) and regional renal blood volume (rRBV) is feasible by means of T* 2 -weighted dynamic MRI with an intravascular contrast agent. To this end, eight foxhounds under physiologic conditions underwent dynamic MRI upon in...

Quantification of renal perfusion abnormalities using an intravascular contrast agent (part 2): Results in animals and humans with renal artery stenosis

“…The MR perfusion data was analyzed offline by a physicist on a workstation, as described in Part 1 (35). For each degree of renal artery stenosis, regional renal blood volume (rRBV), regional renal blood flow (rRBF), and mean transit time (MTT) were calculated from the measured signal-time curves (Fig.…”

“…In addition, five patients were evaluated as part of a phase 2 study. For all measurements, the intravascular USPIO contrast agent NC100150 (Clariscan ® ; Amersham Health, Oslo, Norway) was used as described in Part 1 of the present study (35). This contrast agent is cleared from the blood solely by uptake in the reticuloendothelial system, and is not filtrated in the kidney at all.…”

“…Chronically instrumented dogs were used as described in Part 1 (35). Different degrees of renal artery stenosis were created by graded inflation of an implanted cuff placed around the artery downstream of the flow probe (19).…”

“…On the day of the experiment, the chronically instrumented dogs were anesthetized as described in Part 1 (35). The animals were placed in a supine position.…”

“…Dynamic T* 2 -weighted perfusion measurements were performed in the renal arteries downstream of the implanted cuff, as described in Part 1 (35) (Fig. 1).…”