Quantitative Dynamic Contrast‐Enhanced Ultrasound Confirms Renal Obstruction

Abstract

Objectives

To evaluate dynamic contrast‐enhanced ultrasound (DCEUS) potential for diagnosing ureteropelvic junction obstruction (UPJO). We hypothesize that DCEUS can identify differences in renal parenchymal microcirculation between normal and obstructed kidneys.

Materials and Methods

This prospective study included 8 subjects (16 kidneys) with unilateral renal obstruction clinically determined to need surgery and confirmed by nuclear medicine (NM) diuretic half‐time ($t_{1/2}\ge 20\min$). Subjects underwent pre‐ and post‐surgery DCEUS and NM imaging at a tertiary care institution (Dec 2021 to Oct 2024). DCEUS‐derived time‐intensity curves were analyzed to calculate mean‐transit time (MTT), time‐to‐peak (TTP), and full‐width at half‐maximum (FWHM). DCEUS MTT was compared between normal and affected kidneys and to NM $t_{1/2}$. Statistical significance was determined using two‐sided paired and unpaired Student t‐tests.

Results

MTT was significantly longer in obstructed kidneys compared to normal kidneys before surgery ($52\pm 7\mathrm{s}$ vs. $18\pm 3\mathrm{s};P=.002$) and normalized after pyeloplasty ($13\pm 3\mathrm{s}$ vs. $14\pm 2\mathrm{s};P=.8$). A point‐biserial correlation between DCEUS MTT and NM drainage time categories was found to be $r_{\mathit{pb}}=0.8$ ($P<.0001$). Similar patterns were observed for TTP and FWHM, however, they were not statistically significant. The results showed potential of DCEUS MTT in categorizing kidneys into delayed and normal, according to their NM drainage time (ROC AUC = 0.97, 95% CI = [0.9, 1.0]).

Conclusion

DCEUS MTT shows promise as a diagnostic tool for assessing UPJO, potentially serving as a stand‐alone or complementary modality to NM without additional ionizing radiation. Further trials with larger cohorts and those with non‐obstructing hydronephrosis are required to confirm its clinical utility.

Short abstract

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Abbreviations

AUC

area under the curve

CI

confidence interval

CT

computed tomography

DCEUS

dynamic contrast‐enhanced ultrasound

DRF

differential renal function

FDA

U.S. Food and Drug Administration

FWHM

full width at half‐maximum

HIPAA

health insurance portability and accountability act

IRB

institutional review board

MTT

mean‐transit time

NM

nuclear medicine

ROC

receiver operating characteristic

ROI

region of interest

TIC

time‐intensity curves

TTP

time‐to‐peak

UCAs

ultrasound contrast agents

UPJO

ureteropelvic junction obstruction

US

ultrasound

Hydronephrosis is a pathological condition characterized by the dilation of the upper urinary tract, often due to an obstruction that impedes the flow of urine from the kidneys to the bladder. ¹ This obstruction can be anatomical, for example, strictures or external compression, ² or functional, for example, impaired ureteral peristalsis. ³ A common cause of hydronephrosis is ureteropelvic junction obstruction (UPJO), which, if left untreated, can lead to renal damage, loss of function, and irreversible kidney failure. ⁴

Current diagnosis of UPJO involves multiple imaging modalities to assess renal anatomy and function. Ultrasound (US) and computed tomography (CT) visualize the anatomy, identifying structural abnormalities and hydronephrosis severity, while nuclear medicine (NM) dynamic renal scans, such as diuretic renography, evaluate differential renal function (DRF) and urinary drainage time. ⁵ NM renography uses radiotracers ⁶ that are filtered in the renal parenchyma and excreted into the urinary collecting system. ⁷ Urologists combine NM findings with anatomical imaging and clinical symptomatology to decide whether surgical intervention is necessary to relieve the obstruction.

The primary mechanism of renal parenchymal injury in UPJO is increased pressure in the pelvicalyceal system, which disrupts normal kidney function. ⁸ This elevated pressure presumably causes changes in perfusion by altering the balance of intravascular and extravascular pressures. Therefore, a more direct evaluation of parenchymal changes may offer a more accurate assessment of renal health in UPJO. Dynamic contrast‐enhanced ultrasound (DCEUS) offers a promising new way to achieve this by evaluating renal microvascular perfusion. Unlike the radiotracers used in NM imaging, ultrasound contrast agents (UCAs) are intravascular and not excreted by the kidneys. ⁹ Consequently, DCEUS, by directly looking at a cortical perfusion, offers a potentially better measurement of changes from obstruction.

Additionally, DCEUS offers several other benefits over NM, including the absence of ionizing radiation, higher spatial resolution, shorter imaging duration, and high safety profiles. ⁹ It is also a cost‐effective modality¹ with easier access in underserved areas.

In this study, we aim to quantitatively evaluate UPJO by DCEUS time‐intensity curves (TICs). We compare DCEUS perfusion metrics with NM drainage time to demonstrate the correlation between the two. We hypothesize that DCEUS can identify differences in renal parenchymal microcirculation between normal and obstructed kidneys. Being radiation‐free, DCEUS enables safe, repeated imaging for monitoring obstruction. Our ultimate goal is to explore its potential to detect early kidney microvascular changes before significant functional loss occurs.

Materials and Methods

Human Subjects

This prospective study included 8 subjects (16 kidneys), approved by the Institutional Review Board, IRBMED‐ID: HUM00193843, and conducted in compliance with the Health Insurance Portability and Accountability Act (HIPAA). Written informed consent was obtained from all participants.

Adult patients ($\ge 18\text{years}$) diagnosed with unilateral renal obstruction, including a NM MAG3 diuretic $t_{1/2}\ge 20\min$ and $\mathrm{DRF}\ge 15\%$, and elected for surgical correction via pyeloplasty or proximal ureteroureterostomy, were eligible for inclusion. Patients were excluded if they had a solitary kidney, abnormalities in the contralateral collecting system, or vesicoureteral reflux. Other exclusions included the presence of a ureteral stent or percutaneous nephrostomy tube in the obstructed kidney, absence of NM imaging, or previous hypersensitivity to a UCA. Pregnant or breastfeeding females, patients with a body mass index ≥40 without prior US confirming adequate kidney visualization, individuals with chronic kidney disease (stages 4 and 5), and those with unstable cardiopulmonary conditions were also excluded. This strict inclusion and exclusion criteria were necessary for this pilot study to minimize confounding factors, allowing for a focused evaluation of DCEUS performance as an alternative to NM in patients undergoing surgical correction for UPJO.

All subjects meeting the inclusion criteria were identified and offered participation in the study by a single urologist (S. N. A). Upon consent, subjects were scheduled for a preoperative DCEUS exam. The NM exams were performed as part of the subjects' routine clinical care and followed our institution's standard protocol for diuretic renography using 99mTc‐MAG3, which also required pre‐exam hydration (see Section S.1 for the detailed protocol). All subjects received intravenous furosemide (Lasix) as part of the NM exam to facilitate urinary drainage. A similar hydration protocol was used for DCEUS—subjects were instructed to drink 500 mL of water within 1 h prior to the study. They subsequently underwent surgery (pyeloplasty) with ureteral stent removal ~3–6 weeks after surgery. Subjects were scheduled for a follow‐up visit with NM and DCEUS repeats ~3 months after stent removal.

It was not necessary to perform preoperative or postoperative NM and DCEUS exams on the same day, as scheduling depended on clinical availability and other logistical factors (see Table S.2.1 for the relative timing of these exams with respect to surgery).

After each DCEUS imaging session, subjects were monitored on‐site for 30 min to assess for any immediate adverse events. Additional follow‐up evaluation was conducted 1–10 days after the study to monitor for any delayed reactions.

Ultrasound Imaging

Schematics of human kidneys are shown in Figure 1, A and B. An example of a US image in B‐ and contrast‐modes is shown in Figure 1, C and D, respectively.

Figure 1.

A, Schematic of the human kidney, showing its position and orientation. The ultrasound probe is positioned in the lower subcostal space along the midaxillary line, imaging the mid‐sagittal plane of the kidney. B, Magnified view of the kidneys from panel (A), detailing the major anatomical components. C and D, Representative B‐mode (C) and contrast‐enhanced mode (D) ultrasound images of a normal kidney obtained in this study.

For DCEUS, Definity (Lantheus Medical Imaging N. Billerica, MA)—approved by the U.S. Food and Drug Administration (FDA) for intravenous (IV) administration in echocardiography—was used off‐label. For each kidney examination, a bolus dose of 0.3 mL Definity was injected into the antecubital vein via a straight IV line catheter (20‐gauge or larger), followed by a 10 mL saline flush. The normal kidney was imaged first. To image the affected kidney, a second 0.3 mL bolus dose (followed by another 10 mL saline flush) was administered after ~15 min, once the contrast from the first bolus had cleared. This resulted in a total Definity dose of 0.6 mL per subject, remaining within the FDA‐approved limit of $20\mathrm{\mu L}/\mathrm{kg}$. All IV administrations were performed by a trained nurse as a standard IV push at a rate consistent with clinical practice.

Prior to DCEUS, B‐mode and color flow US were acquired from both kidneys to optimize the image quality. The ultrasound imaging sequence began at the start of the saline flush and continued for at least 100 s thereafter.

In this study, we were consistently able to visualize the entire kidney in a single imaging plane. However, in rare cases where the entire kidney cannot be imaged—such as in cases of massive dilation—a representative ROI in the renal parenchyma, for example, the interpolar region, can be selected for analysis without compromising the integrity of the perfusion measurements.

All DCEUS examinations were performed by two radiologists (M. Z. and R. M.), with clinical ultrasound scanners: GE LE 9 or LE 10 (General Electric Healthcare, Wauwatosa, WI, USA) and C2‐9 or C1‐6 curvilinear probes, displaying B‐ and CEUS‐mode images simultaneously. The CEUS cine loops were stored with Digital Imaging and Communications in Medicine (DICOM) standard format for offline analysis.

Image Analysis

The TIC analysis generally followed published literature, ¹⁰ with several modifications to address application‐specific challenges, primarily imaging motion due to factors such as respiratory kidney movement. A custom tracking software ¹¹ was developed to manage two key tasks: (i) eliminating frames where the scanning plane had shifted due to motion, and (ii) tracking kidney motion throughout the imaging sequence. This motion correction was critical for reliable analysis of contrast flow dynamics (Video S1).

The region of interest (ROI) selection process is shown in Figure 2. Specifically, Figure 2A shows an example of ROIs on a normal kidney, while Figure 2B illustrates ROI placement in a dilated kidney. The cortical ROIs for contrast signal extraction were translated by the renal pelvis B‐mode ROI motion.

Figure 2.

Regions of interest (ROIs) used in dynamic contrast‐enhanced ultrasound (DCEUS) imaging for tracking and signal extraction in normal (A) and obstructed (B) kidneys. An ROI on the renal sinus (blue polygon) in B‐mode (left) is used to track kidney motion during imaging for time‐intensity curve (TIC) analysis. In DCEUS mode (right), 20 circular ROIs (each with a radius of 10 pixels) on the renal cortex are used to extract the contrast signal. The example corresponds to $\text{Subject}05$, with the left and right kidneys being the clinically normal and obstructed kidneys, respectively.

The pixel intensities were filtered, linearized, averaged, smoothed ¹² and normalized to the maximum value in the cine loop. They were then fitted to the standard lognormal distribution, which has been shown to outperform other indicator dilution models. ¹⁰ During the fitting process, greater weights were applied to the data corresponding to the primary pass of the contrast agent, minimizing the effect of contrast recirculation.

Among the different tissue perfusion parameters, we focused on time‐related ones, as these have been shown to be the most reproducible. ¹³ Specifically, we examined time‐to‐peak (TTP), full‐width at half‐maximum (FWHM), and mean‐transit time (MTT) (Figure 3).

Figure 3.

Schematic representation of a typical TIC curve, illustrating key parameters used for quantitative analysis. FWHM, full‐width at half‐maximum; MTT, mean‐transit time; PI, peak intensity; TTP, time to peak.

Data Processing and Statistical Analysis

The standard errors for each DCEUS parameter were computed by an error propagation method ¹⁴ from fitted lognormal TICs. Statistical significance was determined by two‐sided paired and unpaired Student t‐test, with $P<.05$ indicating a statistically significant difference. Point‐biserial correlation was used to assess the relationship between continuous DCEUS MTT and the categorical NM drainage groups (delayed and normal based on $t_{1/2}>20\min$). Unless noted otherwise, mean and standard error of the mean are reported throughout the study. Data processing, plotting and statistical analysis were done with Python. Specifically, NumPy, ¹⁵ SciPy, ¹⁶ Pandas, ¹⁷ Matplotlib ¹⁸ and seaborn ¹⁹ Python libraries were used for scientific computation, plotting and statistical analysis. The Pydicom ²⁰ library was used to access and read the DICOM files. All these libraries are open‐source and available in the public domain.

Receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value, based on the point closest to $\left(0,1\right)$ on the ROC curve, representing 100% sensitivity and 100% specificity. The confidence interval (CI) reported for the ROC AUC was obtained using 1000 bootstrapped samples with replacement. All statistical analysis was confirmed by a dedicated statistician (S. D. N.).

Results

Eight subjects participated in the study. One participant ($\text{Subject}1$) was lost to follow‐up, and therefore, no post‐surgery results are presented. The low enrollment rate was due to strict inclusion/exclusion criteria enforced to ensure minimizing effects of other possible confounding factors. The mean (±standard deviation) age of participants was $54\pm 20\text{years}$ (Table 1). Participants required only one administration of the contrast agent per kidney in a given examination, and no adverse reactions to the agent were reported. The demographic characteristics of the subjects, along with NM diuretic $t_{1/2}$ and DRF for each kidney, are presented in Table 1.

Table 1.

Demographic information and pre‐ and post‐operative measurements for normal and obstructed kidneys.

S	G	Age	eGFR	O	DCEUS MTT (s)				NM t1/2 (min)				NM DRF (%)
					Pre		Post		Pre		Post		Pre		Post
					N	O	N	O	N	O	N	O	N	O	N	O
1 a	F	73	52	Left	10	73	na	na	7	1000 b	na	na	67	33	na	na
2	F	29	85	Left	19	72	11	9	7	30	8	7	81	19	75	25
3	F	76	79	Left	41	72	11	25	3	41	6	5	55	45	55	45
4	F	27	123	Left	14	30	17	11	5	1000 b	4	4	55	45	55	45
5	F	58	78	Right	15	39	11	9	8	28	12	6	46	54	45	55
6	F	70	65	Left	15	23	13	15	4	1000 b	10	5	64	36	62	38
7	F	41	114	Left	17	42	29	57	8	78	6	39 c	50	50	51	49
8	M	58	80	Right	14	63	21	10	14	1000 b	17	7	54	46	55	45

Note: Age column is in years.

Abbreviations: DCEUS, dynamic contrast‐enhanced ultrasound; DRF, differential renal function; eGFR, estimated glomerular filtration rate ($\mathrm{mL}/\min /1.73{\mathrm{m}}^2$); F, female; G, gender assigned at birth; M, male; MTT, mean‐transit time; N, normal; NA, not available; NM, nuclear medicine; O, obstructed; S, subject.

^a The subject lost to follow‐up.

^b Placeholder for no drainage during NM study.

^c Post‐pyeloplasty NM continued to have $t_{1/2}>20\min$ and is being monitored closely for persistent obstruction.

Representative TICs of normal and affected kidneys before and after surgical correction of the obstructed kidney for $\text{Subject}2$ are shown in Figure 4. MTT, TTP, and FWHM values are shown in the insets of each panel. As shown, the TICs demonstrate distinct differences between the normal and affected kidneys, both pre‐ and post‐surgery.

Figure 4.

Representative examples of time‐intensity curves of normal (A and C) and affected (B and D) kidneys, before pyeloplasty of the obstructed kidney (A and B) and after pyeloplasty of the obstructed kidney (C and D). FWHM, full‐width at half‐maximum; MTT, mean‐transit time; TTP, time to peak.

Consistent with our hypothesis, MTT exhibited a statistically significant difference between normal and obstructed kidneys before surgery. This is further illustrated in Figure 5, violin plots of MTT for normal and obstructed kidneys before and after surgical correction of the obstructed kidney. Preoperatively, MTT was significantly longer in obstructed kidneys ($52\pm 7\mathrm{s}$) compared to normal kidneys ($\mathrm{MTT}=18\pm 3\mathrm{s};P=.002$; paired t‐test). Successful pyeloplasty resolved this difference, with MTT values in previously obstructed kidneys ($13\pm 3\mathrm{s}$) becoming comparable to those of normal kidneys ($\mathrm{MTT}=14\pm 2\mathrm{s};P=.8$; paired t‐test). Additionally, there was no significant difference in MTT for normal kidneys before and after pyeloplasty of the obstructed kidney ($P=.34$; paired t‐test), suggesting the presence of a stable baseline for MTT in normal kidneys. Detailed MTT values for each individual subject, both before and after surgery, are presented in Table 1.

Figure 5.

Dynamic contrast‐enhanced ultraound (DCEUS) mean‐transit time (MTT) is significantly different between normal and obstructed kidneys before pyeloplasty of the obstructed kidney, and this difference is resolved after successful pyeloplasty. The distribution of MTT values is shown, comparing normal and obstructed kidneys before pyeloplasty of the obstructed kidneys ($n=8$) and normal and previously obstructed kidneys after pyeloplasty of the obstructed kidney ($n=6$). Results from subjects 1 and 7 are excluded from the post‐pyeloplasty group. $\text{Subject}1$ did not show up for post‐surgery screening. $\text{Subject}7$ NM $t_{1/2}$ drainage time was greater than 20 minutes, indicating persistent obstruction (see Table 1 for details). Mean values are marked by horizontal lines across violin plots, and statistically significant differences between groups are noted by the P‐values displayed above the plots (paired two‐tailed t‐test). Outliers, calculated as data points outside of $1.5\mathrm{IQR}$ (interquartile range), are shown as individual points.

While MTT showed the largest difference between obstructed and normal kidneys, FWHM and TTP followed a similar pattern, although these differences were not statistically significant. The FWHM for normal kidneys was $13\pm 1\mathrm{s}$, compared to $27\pm 6\mathrm{s}$ in obstructed kidneys ($P=.06$). Similarly, the TTP for normal kidneys was $6\pm 1\mathrm{s}$, while obstructed kidney had a TTP of $9\pm 3\mathrm{s}$ ($P=.4$), see Figure S4.1 for more details.

Pyeloplasty did not resolve obstruction in one subject ($\text{Subject}7$), as evident by NM $t_{1/2}$ in Table 1. Interestingly, this persistence of obstruction was reflected in DCEUS MTT as well, making this the only subject without a decrease in MTT after pyeloplasty. This further reinforces the reliability of DCEUS MTT in assessing UPJO. The fact that MTT remained elevated, consistent with the NM results, underscores DCEUS potential to provide valuable insight when pyeloplasty is unsuccessful in resolving the obstruction.

A comparison of NM diuretic drainage $t_{1/2}$ and DCEUS MTT is presented in Figure 6. The violin plot in Figure 6A shows DCEUS MTT values for all kidneys grouped by NM drainage time, with a cutoff of $t_{1/2}=20\min$ (total of 30 instances; 21 with $t_{1/2}<20$ and 9 with $t_{1/2}>20$). A significant difference in MTT was observed between the normal drainage group ($16\pm 2\mathrm{s}$) and the delayed drainage group ($52\pm 6\mathrm{s};P<.001$, unpaired t‐test). DCEUS MTT strongly correlated with NM drainage time categories (point‐biserial correlation, $r_{\mathit{pb}}=0.8$, $P<.0001$).

Figure 6.

Comparison of NM drainage time and DCEUS MTT showing strong correlation between the two metric. A, Violin plot of DCEUS MTT for kidneys categorized into normal and delayed drainage based on NM $t_{1/2}$. The mean values are represented by white horizontal lines across the violin plots. A significant difference in MTT is observed between the two groups ($P<.001$, unpaired t‐test). A strong point‐biserial correlation is found between NM drainage categories and MTT ($r_{\mathit{pb}}=0.8,P<.0001$). B, ROC curve showing the diagnostic performance of MTT in distinguishing between normal and delayed drainage, with an optimal threshold of 30 s determined by the closest point to (0, 1). C, Scatter plot comparing DCEUS MTT with NM $t_{1/2}$. Data points associated with kidneys with no drainage ($t_{1/2}>1000\min$ in Table 1) are indicated by upward arrows. The plot is divided into four quadrants: top‐right (obstruction agreement, shaded yellow) and bottom‐left (no obstruction agreement, shaded green) show where NM and DCEUS results align; the top‐left and bottom‐right quadrants represent false negatives and false positives, respectively.

The diagnostic performance of DCEUS MTT in distinguishing normal from delayed drainage is illustrated by the ROC curve in Figure 6B. The area under the curve of $\mathrm{AUC}=0.97$ ($95\%\mathrm{CI}=\left[\mathrm{0.9,1.0}\right]$) indicates excellent diagnostic accuracy. The optimal threshold for DCEUS MTT was determined to be 30 s, although this threshold is preliminary and primarily demonstrates the potential of DCEUS. Further clinical studies with larger sample sizes and greater statistical power are needed for validation.

Using an MTT threshold of 30 s to diagnose UPJO offers an interesting perspective on the outliers observed in Figure 5. One such case is $\text{Subject}3$ whose normal kidney had an $\mathrm{MTT}=41\mathrm{s}$, above the 30 s threshold. This would falsely categorize the kidney as obstructed, representing a potential false positive. Similarly, $\text{Subject}6$ may represent a false negative, as their obstructed kidney had an $\mathrm{MTT}=23\mathrm{s}$, below the assumed threshold of 30 s.

A scatter plot of NM $t_{1/2}$ and DCEUS MTT is shown in Figure 6C, with four quadrants: top‐right and bottom‐left indicate alignment between the two metrics, top‐left shows false negatives, and bottom‐right shows false positives. Consistent with Figure 6, A and B, the clustering of points in the top‐right and bottom‐left quadrants suggests a strong agreement between NM $t_{1/2}$ and DCEUS MTT.

In addition to being radiation‐free, another significant advantage of DCEUS over NM renography is the considerable difference in imaging duration. NM studies required approximately 45 min (for both kidneys) to measure drainage time, while ~100 s cine loops of DCEUS imaging are sufficient for each kidney (totaling around 200 s).

Discussion

UPJO is one of the most common causes of hydronephrosis and, if left untreated, can lead to severe renal damage and eventual kidney failure. Surgical intervention, typically pyeloplasty, is the primary treatment for resolving UPJO. Currently, NM is the standard method to evaluate differential renal function and diagnose UPJO. In this study, we proposed DCEUS as an alternative to NM for evaluating UPJO. Unlike NM renography, which tracks the filtration and excretion of radiotracers through the renal collecting system, DCEUS uses UCAs, purely vascular agents that circulate within the renal parenchyma and are not excreted. This direct assessment of parenchymal changes and microvascular alterations, instead of the urine drainage time, is the major difference between the two modalities and may serve as a better indicator of potential future renal damage.

We confirmed that DCEUS MTT differs significantly between normal and obstructed kidneys and that successful pyeloplasty resolves this difference. Additionally, the lack of a significant difference in MTT in normally draining kidneys suggests a stable normal baseline. This is further confirmed by observed variability in MTT in the groups. Obstructed kidneys show greater variability compared to normally draining kidneys. This baseline could be used to establish threshold values, similar to those in NM studies, to categorize kidneys as “unobstructed,” “indeterminate,” or “obstructed.”

One important functional limitation of NM is its inability to quantify drainage and, therefore, quantitatively evaluate obstruction when there is no excretion, ²¹ labeled as $t_{1/2}>1000\min$. However, this is not a limitation for DCEUS, as it does not rely on excretion but instead evaluates renal microvascular perfusion and can, therefore, quantitatively assess even severe cases of obstruction.

The DCEUS faster imaging time should improve patient experience, even though our assessment focused on imaging time and did not consider factors such as IV access, injection time, and finding an appropriate imaging plane. Quantifying patient experience and measuring total procedure time will be the focus of our future studies.

Beyond imaging time, DCEUS offers several other key advantages: it is radiation‐free, making it safer for repeated use, especially in pediatric populations or patients requiring multiple follow‐up exams. It is less expensive than NM, does not require diuretics, and it is more accessible in resource‐limited settings where advanced imaging facilities and radiotracers may not be available. Given these benefits, DCEUS has the potential to become a more practical, safer, and cost‐effective alternative to NM renography for assessing renal obstruction.

As mentioned earlier, we identified one false positive and one false negative when applying the preliminary 30 s MTT threshold. One factor explaining these discrepancies could be different hydration statuses on the day of each study because of the time gap (days) between NM scan and DCEUS. It is well known from NM studies that normal kidneys can show prolonged drainage times under suboptimal hydration conditions. ²² We are not sure of the effect of hydration status on DCEUS.

In both false positive and false negative cases, a repeat test may help clarify the result, which is a current clinical practice using NM. This is particularly appealing for DCEUS, given its low burden as discussed above. Alternatively, DCEUS could serve as a screening tool, flagging cases as “indeterminate” for further confirmation with NM or other methods. This approach positions DCEUS as either a standalone diagnostic tool or as a screening test to identify which patients would benefit from a NM examination. It is worth noting that even with NM, the current reference standard, ~15% of cases are categorized as “indeterminate,” ²³ , ²⁴ , ²⁵ , ²⁶ and treatment decisions in these cases are often guided by other factors.

The above discussion assumes that NM provides the true measurement, but this is not always the case. For example, conventional NM DRF calculations can sometimes yield inaccurate estimations due to differences in kidney size. ²⁷ As another example, in some instances, what appears to be an obstructed response in NM may actually result from volume expansion induced by the diuretic, rather than a true obstruction. ²⁸ Therefore, the observed differences between DCEUS and NM studies may lead to a stronger reference standard, which is the topic of our future studies.

Limitations

A primary limitation of this study is its small sample size, limiting its statistical power. However, despite this, the difference between MTT of normal and obstructed kidneys was strong enough to be statistically significant. While FWHM and TTP showed similar patterns, they were not statistically significant, likely due to limited sample size. This is relevant because determining the initial time in TIC can be challenging, making FWHM—a metric independent of initial time—a potentially more robust option. Additionally, the strict inclusion and exclusion criteria, while necessary to minimize confounding factors, may have limited the generalizability of our findings. While we excluded subjects with stage 4 or 5 chronic kidney disease, we acknowledge that longstanding UPJO may lead to irreversible vascular changes that could affect renal perfusion. Future studies with broader inclusion criteria and multivariate analysis will assess the impact of renal function and glomerular filtration rate on DCEUS parameters. This pilot study aimed to reduce variability and focus on evaluating DCEUS performance under controlled conditions, which is a critical step before expanding to broader cohorts. Another limitation is the lack of direct measure of DRF using DCEUS, an important piece of diagnostic information obtained with NM. The duration of timing between NM and DCEUS imaging could also introduce variability due to changes in the patient's hydration status or other physiological factors. Finally, 8 of 9 subjects were female, another potential factor that could limit the generalizability of the findings to a broader population. These factors should be addressed in future studies with larger cohorts and more controlled imaging conditions.

Conclusions

Dynamic contrast‐enhanced ultrasound (DCEUS) offers viable potential for evaluating ureteropelvic junction obstruction (UPJO). This study demonstrates that DCEUS‐derived mean‐transit time (MTT) can effectively distinguish between obstructed and normal kidneys, correlate with nuclear medicine (NM) drainage times, and normalize following successful pyeloplasty. With its radiation‐free nature, shorter imaging duration, and easier access, DCEUS could serve as a stand‐alone or complementary modality to NM.

Supporting information

Figure S4.1. Bar plots and corresponding violin plots for (a) mean‐transit time (MTT), (b) full‐width at half‐maximum (FWHM), and (c) time to peak (TTP). The bar plots show data for normal and affected kidneys, before and after pyeloplasty of the obstructed kidneys. Violin plots aggregate the data, with statistical comparisons indicated by P‐values above the plots. Mean values are marked by horizontal lines across the violin plots. Statistically significant differences between groups are noted by the P‐values displayed above the plots (paired two‐tailed t‐test).

Video S1. Example of B‐mode and contrast‐enhanced ultrasound (CEUS) cine loops of the kidney used for time‐intensity curve (TIC) analysis in the evaluation of ureteropelvic junction obstruction (UPJO). Circular regions of interest (ROIs) on the cortex are used for contrast signal extraction, while a polygonal ROI on the renal sinus in B‐mode is used to track kidney motion during the imaging sequence.

Supplementary Material

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.