Renal cortex blood perfusion contrast‐enhanced ultrasound: Assisting diagnosis and treatment of renal artery disease

Renal cortical blood perfusion CEUS can evaluate the structure and microcirculation of renal cortex, which is expected to provide a safer and more convenient evaluation system for clinicians in the diagnosis and treatment of early renal artery disease.


| RENAL CORTE X B LOOD PERFUS I ON CEUS AND PAR AME TER S
The kidneys are highly vascularized organs, with a rich distribution of cortical blood vessels that provide favorable conditions for perfusion assessment.Renal cortex blood perfusion CEUS enables sequential visualization of perfusion, beginning from the main blood vessels and extending to the small vessels.During the early arterial phase, the renal cortex is initially visualized, followed by the medulla.
Corticomedullary differentiation increases, peaks at 20-40 s after injection, then diminishes and disappears within 2 min, resulting in a dynamic change in echo intensity and forming a time-intensity curve (TIC). 3Each point on the TIC curve represents the ultrasound signal intensity at a specific moment.The ascending part of the curve signifies the dispersion of the contrast agent in the bloodstream, while the descending part indicates its clearance (Figure 1).Time-related parameters and signal intensity-related parameters reflecting tissue hemodynamic characteristics are derived from the shape and slope of the curve, including those utilized for evaluating renal perfusion (Figure 2).Abnormalities in these parameters can serve as early indicators of renal function and pathological changes, preceding alterations in biochemical markers such as blood creatinine. 4

| APPLI C ATI ON OF RENAL CORTE X B LOOD PERFUS I ON CEUS IN THE D IAG NOS IS AND TRE ATMENT OF RENAL ARTERY D IS E A S E S
The current guidelines for diagnosing renal artery stenosis recommend renal artery ultrasound as the initial approach, primarily using the peak blood flow velocity to assess the extent of vascular stenosis. 5In contrast, CEUS of renal cortex blood perfusion and renal contrast enhanced renal artery ultrasound offer a comprehensive evaluation of the lesion morphology and perfusion, aiding in identifying patients who may benefit from intervention (Figure 3). 6In cases of suspected renal infarction, CEUS reveals wedge-shaped non-enhancing areas in the infarcted region, clearly distinguishing infarction from cortical ischemic areas, with diagnostic performance comparable to CTA. 7 Furthermore, parameters of renal cortex blood perfusion can be utilized to assess the prognosis of patients with renal artery stenosis.Ran et al. developed a prognostic model by measuring various parameters of renal artery cortex perfusion combined with machine learning, demonstrating that CEUS scoring of renal cortex blood perfusion is one of the prognostic factors for hypertension following renal artery angioplasty. 8In another study, Li and colleagues constructed a prognosis model using data on renal cortex blood perfusion and serum creatinine from 497 patients, revealing that the area under the washout phase AUC is associated with the 1-year decline in renal function outcome for these patients. 9ditionally, the assessment of renal artery stenosis in transplant kidneys presents another suitable application scenario

for CEUS. Graft renal artery stenosis typically becomes evident
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.© 2024 The Author(s).Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd. between 3 months and 2 years following renal transplantation, with an incidence as high as 23%. 10 The AUC value and PI value were found to be effective predictors of the benefits of improving renal function following endovascular treatment for transplant renal artery stenosis. 11

| ADVANTAG E S AND LIMITATI ON S OF RENAL CORTE X B LOOD PERFUS I ON CEUS
The primary benefit of renal cortex blood perfusion CEUS lies in its early diagnostic capability.In addition, it is safe and non-invasive.
Unlike radiotracers, iodine agents, and gadolinium agents, ultrasonic imaging intensifiers avoid the adverse impact of these drugs on the kidneys and reduce the incidence of allergic reactions. 5Furthermore, it provides a comprehensive assessment, as it can be combined with renal artery contrast-enhanced ultrasound for simultaneous evaluation of renal artery structure.Lastly, CEUS is efficient and convenience, enabling bedside examinations with shorter exam times, particularly beneficial for elderly patients who may not be suitable

R E FE R E N C E S
Compared to the native kidney vasculature, the location of transplant renal arteries is more superficial, which facilitates the use of renal artery CEUS and renal cortex blood perfusion CEUS with less technical challenges.Furthermore, there are no concerns regarding nephrotoxicity associated with digital subtraction angiography (DSA) or CTA contrast agents, making it an ideal method for monitoring perioperative renal function in transplant kidneys.12

F I G U R E 1
Contrast agent diffusion resulting in the generation of a time-intensity curve (TIC) within a specific region of interest (ROI).

F I G U R E 2
Illustration of the TIC curve and the parameters.
Time-related Parameters Rise time,RT Time from ROI initiation to peak (arrival of contrast agent) Mean transit time, MTT -Time to peak,TTP TTP Time from injection of contrast agent to reaching peak intensity Fall time, FT T ime for signal decrease from ROI (contrast agent outflow time) Signal Intensity Parameters Mean intensity,Meanlin Mean signal intensity Peak intensity,PI Maximum signal intensity Wash-in rate,WiR Maximum slope in wash -in phase of curve Wash-out rate,WoR Maximum slope in wash -out phase of curve Wash-in Area Under Curve,WiAUC Area under curve between TI end and TTP end Wash-out Area Under Curve,WoAUC Area under curve between TTP end and TO Total Area Under Curve, WiWoAUC WiAUC+WoAUC

F I G U R E 3 4 |
for MRI exams or have mobility issues.Moreover, it helps reduce excessive medical costs for patients and provides convenience for follow-up and clinical care.Despite these advantages, CEUS also has inherent limitations compared to traditional ultrasound.First, in obese patients, factors such as susceptibility to respiratory motion, abdominal fat, intestinal gas, and rib shadows may compromise image quality.Second, it may produce false positives or false negatives in the presence of complex, tortuous, or variant lesions.Additionally, unlike CT or MRI which offer comprehensive imaging capabilities, ultrasound measurements are limited to single-layer sections and may not fully Routine ultrasound and CEUS (A) and DSA (B) showed 85% localized stenosis of the right renal artery with impaired renal cortical blood perfusion (C), which significantly improved after stent implantation (D).6 capture the overall renal cortex blood flow situation.Consequently, values obtained from different sections may result in poor reproducibility of parameters.Almushayt's study suggest that time-related parameters have more diagnostic significance than intensity-related parameters.13Furthermore, current guidelines do not provide reference ranges for different parameters, which is particularly important for patients with bilateral renal lesions.For patients with unilateral renal lesions, normal reference ranges are often derived from the contralateral normal kidney.This variability is due to differences in parameter definitions based on different instrument settings and analysis platforms, as well as a lack of sufficient research correlating these parameters with renal biopsy results or renal eGFR levels to determine the optimal guiding parameters.PROS PEC TS Compared to traditional ultrasound and other imaging modalities such as CTA or MRA, the efficient and convenient advantages of CEUS provide crucial support for its widespread application in the early diagnosis and treatment of renal vascular diseases.With continuous technological advancements, renal cortex CEUS can serve as a more sophisticated, valuable, and safe non-invasive imaging tool, offering essential information on renal artery structure and microcirculation for clinicians to make informed decisions.It still holds promising prospects for application in the following areas: (1) Supplementary information for intervention indications in renal artery stenosis is essential.Currently, guidelines primarily rely on peak systolic velocity (PSV) values from Doppler ultrasound for intervention indications of renal artery stenosis.As the research content of this technology continues to expand, it may effectively complement existing guidelines for intervention indications in patients with renal artery stenosis.(2) Evaluation and treatment guidance for complex renal vascular diseases is crucial.In complex renal vascular disorders such as abdominal aortic aneurysm or dissection involving renal arteries, kidney perfusion plays a critical role in patient prognosis.If renal cortex blood perfusion CEUS can provide more detailed clinical information for perioperative reconstruction strategies and renal function assessment in these cases, patients will benefit significantly.Future technological advancements are anticipated to further mitigate current limitations.First, the development of microbubble contrast agents tailored for specific organs holds the potential to extend imaging duration and eliminate the need for repeated injections.For example, a liver-specific ultrasound contrast agent has already demonstrated prolonged imaging times and significantly enhanced spatial resolution for small lesions.14Similarly, kidneyspecific contrast agents in development are expected to facilitate more comprehensive and sequential assessments of both kidneys simultaneously.Second, the integration of deep learning and artificial intelligence (AI) is projected to leverage CEUS data to refine diagnostic models.15These algorithms may also enable the fusion of images from various scanning modalities, thus offering a more holistic evaluation of renal structures and aiding in the determination of optimal reference parameters.In the future, such advancements are expected to significantly enhance early screening, diagnosis, preoperative evaluation, and intraoperative monitoring of clinical renal artery stenosis.In conclusion, renal cortex blood perfusion CEUS shows promising application prospects in the diagnosis and treatment of renal artery diseases, providing important clinical guidance for vascular surgeons.Further clinical study in the related field is needed to establish a solid foundation for the optimal utilization of this technology in management of renal artery diseases.Zhang Wayne W, Division of Vascular and Endovascular Surgery, Department of Surgery University of Washington, Seattle, WA, USA.Email: wwzhang@uw.eduYoungjun Li and Wayne W. Zhang contributed equally to this article and are designated corresponding authors.