Reproducibility and precision of renal perfusion quantification with contrast enhanced ultrasound in critically ill patients: a prospective observational study

Critical Care Ma et al. Critical Care (2025) 29:461 https://doi.org/10.1186/s13054-025-05692-1 Open Access RESEARCH Reproducibility and precision of renal perfusion quantification with contrast enhanced ultrasound in critically ill patients: a prospective observational study Hongye Ma1,2, Pierre Frossard3, Giuseppe Gullo3,4, Bastien Trächsel5, Jean-Yves Meuwly3,4 and Antoine G. Schneider2,4* Abstract Objective Contrast-enhanced ultrasound (CEUS) is a promising tool to assess renal microcirculation. However, its reproducibility has never been formally assessed. We aimed to assess the reproducibility and precision of CEUS measurements in critically ill patients. Methods We conducted an observational study in 20 critically ill patients in stable cardio-pulmonary condition. In group 1 (n = 10), to assess CEUS reproducibility, we performed three CEUS scans within a one-hour time frame in rigorously similar conditions and settings. In group 2 (n = 10), to assess the influence of ultrasound contrast agent rate, we performed two CEUS scans, one with standard settings and the second with a doubled ultrasound contrast agent rate. CEUS-derived parameters included relative blood volume (RBV), mean transit time (mTT) and perfusion index (PI). We used linear quantile mixed models to assess their reproducibility (stability across different time points), precision (variability of consecutive measurements), and the influence of a change in ultrasound contrast agent (UCA) infusion rate. Finally, we sought to determine patients’ related factors associated with signal instability. Results In Group 1, CEUS derived parameters remained similar across the three study timepoints (3 289 vs. 3 680 vs. 3 590 for RBV, 4.1 vs. 4.2 vs. 4.2 for mTT and 684 vs. 762 vs. 735 for PI, all p values > 0.05), indicating stability of these parameters within individual patients over time. Intra-measure coefficient of variability was 23.2% for RBV, 13.9% for mTT and 33.8% for PI. The median of five CEUS assessments yielded reliable estimates. In Group 2, doubling the UCA rate resulted in a significant increase in RBV (3 207 vs. 1 624, p = 0.01), and in PI (977 vs. 617, p = 0.01), while mTT remained stable (4.6 vs. 3.8, p = 0.08). No patients-related parameter could be significantly associated with CEUS parameters variability. Conclusions Under controlled conditions, CEUS derived parameters are reproducible and have a fair precision in critically ill patients in stable hemodynamic condition. mTT might be more reliable under varying infusion conditions. Further studies are required to establish the clinical utility of CEUS in critically ill patients. *Correspondence: Antoine G. Schneider Full list of author information is available at the end of the article © The Author(s) 2025. 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To view a copy of this licence, visit http://creati vecommons.org/licenses/by-nc-nd/4.0/. Ma et al. Critical Care (2025) 29:461 Page 2 of 10 Keywords Renal perfusion, Ultrasonography, Contrast enhanced imaging, Destruction replenishment sequences, Reproducibility, Precision Background Acute kidney injury (AKI) is a common and severe complication in patients admitted to the intensive care unit (ICU) [1]. To date the contribution of renal perfusion alterations to its pathophysiology remains poorly understood [2]. This is largely related to the absence of an adequate tool to evaluate renal perfusion in critical illness. Imaging techniques (scintigraphy, blood oxygen level-dependent magnetic resonance imaging (BOLD MRI)) are expensive and require extensive and prolonged patients’ mobilization which limits its usability in ICU [3]. Experiments have been conducted with renal vein catheterization, however, this procedure is too invasive to be used outside the context of a study [4]. A reproducible, quick and easy method allowing assessment of renal microcirculation could improve our understanding of renal perfusion alterations during AKI and facilitate its management. Contrast-enhanced ultrasound (CEUS) is an ultrasound based imaging modality, which makes use of dedicated contrast agents [5, 6]. CEUS enables blood flow visualisation and techniques have been proposed to quantify organ perfusion [7–9] including the kidney [5, 10]. Such techniques have been shown to be safe and feasible even in critically ill patients [11–14]. CEUS is applicable at the bedside and could enable to study renal perfusion in critical illness [15]. Such technology could guide fluid or vasopressors management in critically ill patients with or without AKI. However, before this technique enters clinical practice several practical elements need to be clarified. Issues have been raised about the repeatability of CEUS measurements. Indeed, previous experiments [16] were associated with high variability in results. Measurement variability can be explained by minute changes in ultrasound probe angle (patient or investigator movement), the evaluation of a different area of the kidney or simply inadequate image quality. This can be minimized by thorough quality criteria for image selection, precise anatomical landmarks and probe position and the use of median values as final output. Another difficulty is associated with the fact that CEUS cannot deliver absolute measure of flow. Indeed, in the absence of a reference value, CEUS is only able to perform semi-quantification. Hence, patients cannot be compared to each other but only changes between two measurements can be informative. To date, no standardized dosing protocols for UCA have been made available. While some studies have suggested a variety of infusion rates [17], others have proposed alternative parameters [18, 19]. Given the relatively high cost of contrast agents, optimizing infusion protocols to balance dosage reduction and measurement reliability is relevant. However, the impact of infusion rate variations on CEUS-derived parameters remains unclear. Accordingly, we designed a prospective observational study to evaluate the reproducibility (stability across different time points for a gi (...truncated)