Functional MRI of the kidney: tools for translational studies of pathophysiology of renal disease

Abstract

Magnetic resonance imaging (MRI) provides exquisite anatomic detail of various organs and is capable of providing additional functional information. This combination allows for comprehensive diagnostic evaluation of pathologies such as ischemic renal disease. Noninvasive MRI techniques could facilitate translation of many studies performed in controlled animal models using technologies that are invasive to humans. Such a translation is being recognized as essential because many proposed interventions and drugs that prove efficacious in animal models fail to do so in humans. In this article, we review the state-of-the-art functional MRI technique as applied to the kidneys.

Fig. 1

Renal perfusion magnetic resonance imagery (MRI) by arterial spin labeling (ASL). A: method of acquiring MRI following ASL. The vertical stripe illustrates the labeling radio frequency (RF) pulse applied so that all the spins in the descending aorta are inverted. The horizontal stripe is a representation of the transverse slice of interest through the kidneys. The thick hatched slab (right) represents a presaturation pulse applied to avoid any venous contribution to the observed signal intensity and to minimize any artifacts due to peristaltic motion in the abdomen. Two acquisitions were performed, one with and one without the labeling pulse. The difference image would then be a representation of all the labeled blood that enters the slice of interest. Obviously, this varies as a function of time delay between the labeling pulse and the acquisition. B: set of transverse (difference) images through the kidneys obtained after different delay times in a swine model with a chronic renal artery stenosis in the left kidney (right). Based on this set of data, it is possible to estimate absolute perfusion (115).

Fig. 2

Gadolinium (Gd)-diethylenetriamine pentaacetic acid (DTPA)-enhanced first-pass perfusion imaging in a human subject following extracorporeal shock wave lithotripsy (ESWL). Shown is a representative perfusion image (A) along with the regions of interest used for signal intensity vs. time plots (B). The blurring of corticomedullary differentiation in the lower pole of the right kidney indicates where the ESWL was focused. Note that the cortical curve in the affected region (Ab Cor) is lower than normal (Nor Cor), whereas the medullary curve in the affected region (Ab Med) is higher than normal (Nor Med). With the use of the slope of these curves as a relative perfusion index, it was shown that there is a reduction in cortical flow (~30%) with a concomitant increase in the medullary flow (34 ± 14%) in the region where ESWL in focused. Reprinted from Ref. with permission.

Fig. 3

Use of intravascular contrast agents for perfusion MRI. Shown is a representative series of kidney images in a rabbit obtained using gradient echo sequence (TR/TE/FA = 15/3 ms/10⁰) with a temporal resolution of 2 s (right to left and top to bottom). Ferumoxytol at a dose of 1 mg/kg was administered as a bolus through an ear vein, and the acquisition of MRI was simultaneously initiated. Marked in the 1st time frame (precontrast) are the abdominal aorta (solid arrow) and vena cava (solid arrowhead), respectively. Note in the 3rd time frame that the aorta goes completely dark. In the next time frame, the cortex gets dark (arrow), and by the 7th time frame the medulla goes completely dark whereas cortex recovers, and by the 13th time frame the vena cava becomes dark. Based on this type of dynamic scanning, one can obtain concentration vs. time profiles and fit them to appropriate mathematical models to extract various perfusion indexes (140).

Fig. 4

Illustration of renal function as evaluated by dynamic MRI following administration of Gd-DTPA, a positive contrast agent (i.e., with higher concentrations, the signal is increased). Shown are longitudinal relaxation (T₁)-weighted MR images obtained in a chronic renal artery stenosis model in swine at representative time points following Gd-DTPA (0.05 mmol/kg) and following administration of captopril (118). The top row was obtained 1 wk postsurgical placement of an MRI-compatible ameroid constrictor around the renal artery (seen on the X-ray angiograms on the right). The bottom row was obtained in the same animal 5 wk later. Note the severity of the renal artery stenosis, especially the poststenotic vessel dilatation, a classic sign of hemodynamically significant stenosis. Whereas at week 1, the contrast washout is almost complete and symmetrical, at week 6, with the progression of stenosis to a point of being hemodynamically significant, the washout in the affected kidney is rather limited. Figure reproduced from Ref. with permission from RSNA.

Fig. 5

A: blood oxygenation level-dependent (BOLD) MRI data in human kidney. Shown are data acquired with a 3D sequence where the entire kidney in the coronal plane can be covered within a single breath-hold interval. Shown are images from 1 representative slice (of 6 acquired). Left: first image of 8 echo images acquired. Right: corresponding calculated rate of spin dephasing (R₂*)map. The corticomedullary differentiation on both the anatomic image and R₂* map are remarkable. The medulla appears darker on the T₁-weighted anatomic images, whereas on the R₂* maps it appears bright (signifying relatively low regional blood and hence tissue P_O2). B: set of pre- and postpharmaceutical R₂* maps in rat kidneys in the axial plane (500-μm in-plane and 3-mm slice thickness). While this was not performed to address any specific scientific question, it is a very nice demonstration of the advantage and efficacy of the technique. These images were all acquired within ~1 h, with about 10 min between administration of different agents. Furosemide stops the reabsorptive function along the medullary thick ascending limbs and thereby reduces the oxygen consumption in the medullary segments. Thus one can observe a reduction in the brightness of R₂* maps in the medulla (lower R₂* implies better oxygenation). ANG II is a vasoconstrictor that is commonly used, and we observed little effect on the R₂* maps. However, following subsequent administration of N ^ω-nitro-L-arginine methyl ester (L-NAME) and norepinephrine (potent vasoconstrictors), there was a significant increase in R₂*, predominantly in the renal medulla. C: BOLD MRI data in a mouse kidney. Shown are data acquired in a 24-g mouse using a dedicated 2-cm surface coil on a standard 3.0-T whole body scanner (same as for A and B). This figure provides clear indication of the power of the technology in terms of its scaling and how observations could be translated from a mouse models to humans very easily. Shown are 1 representative image (left; of 6 individual echo images) obtained in the coronal plane (160-μm in-plane and 500-μm slice thickness) and the calculated R₂* map (right). CO, cortex; OM, outer medulla.

Fig. 6

A: illustration of individual changes post-L-NAME in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The average (means ± SE) of all points acquired at least 20 min after L-NAME administration was used as postmaneuver R₂*. Mean R₂* values pre- and post-L-NAME in the renal medulla were averaged over all rats of each strain. WKY rats showed significant response to L-NAME in the medulla, as evaluated by BOLD MRI measurements. SHRs did not show significant response to L-NAME. Also, note that the pre-L-NAME, R₂* in SHRs is similar in magnitude to post-L-NAME in WKY. Figure reproduced from Ref. with permission from Wiley InterScience. B: illustration of individual changes posttempol in SHR and WKY rats. Average (means ± SE) of all points acquired at least 20 min after tempol administration was used as postmaneuver R₂*. Mean R₂* values pre- and posttempol in the renal medulla were averaged over all rats of each strain. SHR showed significant response to tempol in medulla, as evaluated by BOLD MRI measurements. WKY rats did not show significant response to tempol. Figure reproduced from Ref. with permission from Wiley InterScience.