In humans, the kidneys have the most abundant blood supply, receiving roughly 20–25% of cardiac output, and filter approximately 94% of this bloody supply through the cortex. RBF varies under different conditions. Under conditions such as hemorrhagic shock, low cardiac output, or redistribution of systemic blood flow, significant pre-renal arterial contractions lead to rapid and dramatic RBF reduction. CEUS can detect a 15% reduction in human RBF . Cagini et al considered that 2-2.5 min was the best time to observe renal injury after injection of contrast medium .
Currently, a nuclear medical scan can examine blood flow to the kidneys. However, its high cost and inability to delineate the dynamic changes of the cortical and medullary blood flow limit its clinical application as a routine test. CDFI has some diagnostic value in the assessment of vascular changes, but it cannot accurately measure blood perfusion in the renal arcuate and smaller arteries. Moreover, CDFI results may vary among different operators. Wei et al reported that CEUS not only detects early hemodynamic changes in a rabbit AKI model but also helps to delineate abnormal changes in renal blood distributions and hemodynamic . Jin et al. examined a number of patients before renal transplantation through contrast-enhanced ultrasound technology, and found that the enhanced parameters reflected certain advantages in monitoring the blood flow perfusion of transplanted kidney, and suggested that this technology may be able to early diagnose acute rejection of renal transplantation. This indicates that CEUS has certain potential in clinical diagnosis and efficacy evaluation of renal diseases, especially those with renal blood circulation changes, but further research is needed .
SonoVue is an ideal red-blood-cell tracer . SonoVue has a chemical composition of F6S, and a microbubble diameter similar to that of average red-blood-cell diameters; hence, it can flow to all organs and tissues and is then excreted through the respiratory system instead of the urinary system, making it safe for all tissues and organs . After the administration of contrast agent, a TIC can be produced for the ROI within the imaging plane. From the produced TIC, several temporal and amplitude features can be obtained, including AT, TTP, A, AUC, and the WIS [24–25].
These parameters quantitatively evaluate the real-time blood flow characteristics in the capillaries of the renal cortex. The value of AT, which represents the time interval between commencing of contrast-agent administration and when signals start to enhance in the ROI, is determined by the blood flow velocity in renal cortical microvessels. The value of TTP, which is the time interval between the commencing of contrast-agent administration and signals reaching their peaks in the ROI, is determined by the blood flow velocity in renal cortical blood vessels. In the present study, due to the short contrast-agent-filling time and the relatively small sample size, the temporal and amplitude changes of the echogenicity enhancement in the renal cortex were difficult to differentiate by direct visual inspection alone. Analysis of TICs indicated that the AT and TTP were the slowest at 3 d after I/R injury. This result suggested that it took a long time for the contrast agent to reach the renal capillaries as a consequence of increased resistance in the renal cortical microvasculature. Renal histopathological examinations showed that at 3 d after I/R injury, some of the renal tubular epithelial cells exhibited chromatin condensation, genomic DNA fragmentation, and dissolution of internal nuclear structure, all of which are characteristics of oncotic (coagulative) necrosis. Additionally, there was a congestive and inflammatory penumbra around the necrotic area. Cellular casts were seen in tubular lumens, with interstitial edema and numerous lymphocytic infiltrations. The pathological changes were most significant in the 3-d I/R kidneys. At 3 d after I/R injury, neutrophils and various metabolites not only accumulated within the blood-vessel lumen but also extravasated to cause extensive interstitial edema and to compress small blood vessels. The overall results were increased vascular resistance and reduced blood flow velocity in the microvasculature. WIS represents the average blood velocity and local tissue perfusion rate since the emergence of contrast agent in the ROI. Theoretically, as the TTP prolongs, the TIC curve becomes flat and the WIS is reduced. Changes in WIS are opposite to those of AT and TTP. Our present results further validated that as the AT and TTP were prolonged, the WIS decreased and the TIC became flattened. The WIS was lowest and the ascending of the curve was slowest in the 3-d I/R group, which was followed sequentially by the 24-h I/R group, 5-d I/R group, and the sham group. These results suggested that the value of WIS changed at different time points after I/R injury. The change of WIS showed an opposite trend to that of AT and TTP. The AUC is affected by blood flow velocity and the contrast-agent distribution volume, and is linearly correlated with the blood supply in the renal parenchyma . Theoretically, when the TTP is delayed, the AUC should increase as a result of an increased number of microbubbles entering the ROI. Our present results showed that the I/R groups had significantly greater AUCs than that of the sham-operation group, which were consistent with the aforementioned theory. This phenomenon might be explained by the numerous stagnant microbubbles in the renal capillaries as a result of swelling of the renal medulla, compression of small renal veins, and consequent increase of venous-return resistance. The stasis of renal cortical blood flow is the main reason for the reduced descending slope of the cortical blood-flow curve. The reduction of renal blood perfusion, together with stasis of cortical blood flow, leads to a significantly increased AUC value. In the present study, the AUC values did not significantly differ among the I/R groups, whereas the changes in RBF caused by AKI induced differential degrees of tissue damage among these groups. This discrepancy might be explained by several factors. First, within 5 d of I/R injury, a great number of activated neutrophils adhered to the endothelium of the renal parenchymal venule. Microbubbles could be phagocytosed and subsequently remain intact within these activated neutrophils. It has been demonstrated that phagocytosed microbubbles remain acoustically active and can be detected . Second, renal I/R injury is an irreversible process. The RBF only resumes when necrotic cells are absorbed, or when new blood vessels are formed. Due to the high permeability of neovasculature, reduced cortical blood-flow velocity, and interference from inflammatory cells, the accumulation of microbubbles is not significantly detectable via ultrasound imaging procedures. For these reasons, the AUC is not a suitable parameter for the quantitative evaluation of renal blood volume in renal AKI. In contrast, the A value, which denotes the change in the perfusion peak intensity during the contrast process, reflects the number of microbubbles in the renal cortex and the change of local blood flow. In the present study, the A value did not differ among the experimental groups, because the A value represented the transient signal intensity instead of an accumulative effect. Therefore, the A value is not a reliable quantitative parameter to monitor changes in blood perfusion following renal I/R injury.