Comparison of micro-flow imaging and contrast-enhanced ultrasonography in assessing segmental congestion after right living donor liver transplantation
Article information
Abstract
Purpose
This study aimed to determine whether micro-flow imaging (MFI) offers diagnostic performance comparable to that of contrast-enhanced ultrasonography (CEUS) in detecting segmental congestion among patients undergoing living donor liver transplantation (LDLT).
Methods
Data from 63 patients who underwent LDLT between May and December 2022 were retrospectively analyzed. MFI and CEUS data collected on the first postoperative day were quantified. Segmental congestion was assessed based on imaging findings and laboratory data, including liver enzymes and total bilirubin levels. The reference standard was a postoperative contrast-enhanced computed tomography scan performed within 2 weeks of surgery. Additionally, a subgroup analysis examined patients who underwent reconstruction of the middle hepatic vein territory.
Results
The sensitivity and specificity of MFI were 73.9% and 67.5%, respectively. In comparison, CEUS demonstrated a sensitivity of 78.3% and a specificity of 75.0%. These findings suggest comparable diagnostic performance, with no significant differences in sensitivity (P=0.655) or specificity (P=0.257) between the two modalities. Additionally, early postoperative laboratory values did not show significant differences between patients with and without congestion. The subgroup analysis also indicated similar diagnostic performance between MFI and CEUS.
Conclusion
MFI without contrast enhancement yielded results comparable to those of CEUS in detecting segmental congestion after LDLT. Therefore, MFI may be considered a viable alternative to CEUS.
Introduction
Living donor liver transplantation (LDLT) utilizing the right lobe is widely accepted as a safe and effective approach for adult-to-adult transplantation [1]. Optimal hepatic vein outflow is crucial for the success of LDLT. Insufficient hepatic venous drainage can leave a transplanted living donor liver graft susceptible to congestion and subsequent damage from excessive portal inflow [2,3]. While the right hepatic vein (RHV) serves as the primary venous outflow vessel for right lobe grafts, venous blood from the anterior sector often drains into the middle hepatic vein (MHV) as well [3,4].
Early detection of postoperative outflow obstruction is also essential. Timely recognition of hepatic venous obstruction allows for interventions like balloon angioplasty or stent placement, which are key to improving graft survival [5,6]. Clinical indicators of hepatic vein outflow obstruction include elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, as well as increased ascites and pleural effusion. However, these signs are often nonspecific, making radiological evaluation essential for the management of patients with suspected obstruction [7-11].
Contrast-enhanced ultrasonography (CEUS) and computed tomography (CT) are common imaging modalities for detecting hepatic congestion [11,12]. However, CT poses challenges due to radiation exposure and the potential nephrotoxicity of contrast agents [13]. CEUS represents a bedside alternative that avoids these risks. This technique has gained popularity for monitoring vascular complications following LDLT [14]. Despite the benefits of CEUS, concerns have been raised about the repeated use of ultrasound contrast agents in intensive care settings and the high operator dependence for diagnosis. Furthermore, the need for expensive and sophisticated equipment can increase the overall cost of the procedure [15]. Micro-flow imaging (MFI) is an emerging technology capable of detecting small vessel flow with high resolution and minimal artifacts [16]. It allows for visualization of the microvasculature comparable to that of CEUS [17]. To date, the utility of MFI in patients with LDLT remains unestablished. Therefore, this study compared the performance of MFI and CEUS in diagnosing segmental congestion in patients with LDLT and examined correlations with laboratory data.
Materials and Methods
Compliance with Ethical Standards
This retrospective study received approval from the relevant institutional review board of Samsung Medical Center (IRB No. 2023-09-031-001), and the requirement for informed consent was waived.
Data Collection
At the authors’ institution, patients are routinely assessed on the first postoperative day (POD) after LDLT using Doppler ultrasound, MFI, and CEUS. MFI and CEUS data were obtained from patients who underwent LDLT between May 2022 and December 2022. Patients were excluded if they did not undergo MFI assessment or if they exhibited poor image quality due to deep positioning of the liver graft (Fig. 1). The analysis included patient characteristics, time between CEUS/MFI and CT scans, surgical records, indications for surgery, and any anastomosis of MHV tributaries V5 and V8. To more fully understand segmental congestion, preoperative and postoperative (PODs 1, 3, 5, 7, and 9) laboratory values were also collected for AST, ALT, and total bilirubin levels.
Ultrasound Examination
A radiologist (W.K.J., with 26 years of experience in abdominal ultrasound) performed CEUS and MFI using an EPIQ 7 Ultrasound system (Philips Healthcare, Eindhoven, Netherlands) equipped with a C2-9 convex probe. B-mode imaging was initially used to evaluate parenchymal changes in the transplanted livers and to identify thrombi in the grafted veins. Doppler ultrasound was employed to assess vascularity. The resistance index and systolic acceleration time of the hepatic artery, as well as blood flow at the portal vein anastomotic site and at sites pre- and post-anastomosis, were measured using pulsed Doppler ultrasound. The waveform of the RHV was analyzed, and in cases involving reconstruction of the MHV tributaries (V5 and V8), the waveforms of V5 and/or V8 were also assessed in reference to the surgical records.
MFI data were then acquired using the same equipment. The edge of the anterior segment of the transplanted liver, representing the expected drainage area of the MHV, was distinctly visible in the intercostal view. MFI of the anterior segment was captured with P5 positioned as the central landmark. The examination was conducted with the gain set at 45% to provide adequate visualization of vascularity and ensure reproducibility. The same operator then evaluated the patients using CEUS with the contrast agent Sonovue (sulfur hexafluoride, Bracco Diagnostics, Milan, Italy), which was diluted with saline. A 2.4-mL bolus was injected into the left antecubital vein. Real-time CEUS was initiated with a low mechanical index (0.079), and video clips were recorded for 60 seconds immediately following the injection of the contrast agent. The hepatic graft and blood vessels were monitored, and segmental congestion was assessed by examining arterial and portal venous phase intrahepatic echoes in the transplanted liver through the intercostal spaces.
Image Analysis
Quantitative vascular parameters were evaluated on MFI, specifically the vascular area index (VAI), which is the ratio (%) of pixels in the Doppler signal to those within the target area. To minimize potential recall bias, this analysis was conducted at least 1 month after the ultrasound examination on POD 1. A radiologist (T.H., with 3 years of experience in abdominal ultrasound) manually traced the boundaries of the target areas on two-dimensional MFI images three times. The VAI was calculated for each image using ImageJ (National Institutes of Health, Bethesda, MD, USA), and the average of these three VAI values was used for the analysis [18]. The target area was manually delineated on the anterior segment of the transplanted liver graft, with the RHV serving as the boundary and P5 as the central anatomical landmark. This encompassed the entire region corresponding to the drainage areas of the MHV tributaries (V5). If the RHV was not clearly distinguishable, an imaginary line extending from the RHV was used as the right margin. The depth was set at 4 cm from the liver capsule to accommodate the region where posterior attenuation of the Doppler signal typically occurs, as this has been found to be the sole factor impacting the diagnostic performance of MFI (Fig. 2) [16].
Congestion and Non-congestion Groups
Two radiologists (W.K.J. and J.S., with 26 and 7 years of experience in abdominal radiology, respectively) assessed postoperative hepatic congestion using CT, which represents the reference standard. Then, the diagnostic performance and laboratory findings of CEUS and MFI were compared between patients with and without congestion. Typically, patients underwent routine assessment within 2 weeks of surgery via postoperative contrast-enhanced CT. However, those with suspected complications received CT evaluations earlier than the standard protocol dictated. Segmental congestion was defined as an area in the liver graft where the hepatic parenchyma, corresponding to the drainage areas of the MHV tributaries, exhibited consistent hypoattenuation across all phases of CT imaging [19,20]. Congestion was defined on CEUS as either early arterial hyperenhancement or low echogenicity of the involved parenchyma during the portal venous phase [20]. For MFI, congestion was identified when the VAI value fell below the cutoff determined by receiver operating characteristic (ROC) curve analysis, which established the thresholds for diagnosing congestion. To ensure a precise comparison, assessments were primarily focused on the V5 drainage area of the liver graft. Furthermore, due to the temporal discrepancy between the reference standard CT and the MFI examination, an analysis was also performed using CEUS on the same day as MFI as an alternative reference standard. The representative case is shown in Figs. 3 and 4.
Statistical Analysis
The clinical characteristics of patients with and without congestion were compared using the t-test. The chi-square test was also employed to compare proportions. The diagnostic performance of CEUS and MFI was evaluated against that of CT. The capacities of MFI and CEUS to detect segmental congestion were compared using the McNemar test. Laboratory data for the two groups, based on CT, CEUS, and MFI findings, were examined using repeated measures analysis of variance. A subgroup of patients with reconstructed MHV territories underwent additional analysis. All data were statistically analyzed using SPSS version 29 (IBM Corp., Armonk, NY, USA). P-values of less than 0.05 were considered to indicate statistical significance.
Results
Among 95 patients, 32 were excluded due to the absence of MFI data (n=28), poor ultrasound image quality resulting from deep positioning of the liver graft (n=2), or suboptimal MFI results following CEUS (n=2). Consequently, data were analyzed from 63 patients who had undergone LDLT. Table 1 summarizes the demographic and clinical characteristics of these individuals. Segmental congestion was detected in 23 of the 63 patients (36.5%), of whom 14 (60.9%) did not undergo MHV reconstruction. In contrast, 13 of the 40 patients (32.5%) without congestion did not receive MHV reconstruction. Furthermore, the segmental congestion group had a higher proportion of liver transplants due to liver cirrhosis compared to hepatocellular carcinoma, whereas the group without segmental congestion had a higher proportion of transplants due to hepatocellular carcinoma compared to liver cirrhosis (P=0.035).
The average time difference between CEUS and MFI, performed on POD 1, and the subsequent CT scan was 10.9 days (range, 2 to 14 days). No significant difference in this parameter was observed between the groups with and without segmental congestion (P=0.808). Among a subgroup of 36 patients who underwent reconstruction of the MHV territories, the majority (58.3%) received reconstruction of the V5 branch. Pulsed Doppler ultrasound conducted on POD 1 revealed that the reconstructed MHV tributaries primarily exhibited a biphasic or triphasic flow pattern in 28 patients (77.8%). The presence of biphasic or triphasic flow was significantly more common in patients without segmental congestion than in those with congestion (P=0.021). Only two patients exhibited changes in the pulsed Doppler ultrasound waveform by the time of the CT scan (Table 1).
The CEUS assessment revealed that 28 of the 63 patients exhibited congestion. Additionally, the mean VAI for the entire patient cohort was 10.72%, with a standard deviation (SD) of 8.49%. Patients with segmental congestion exhibited a VAI of 6.28%±5.89% (mean±SD), while those without congestion had a VAI of 13.28%±8.75% (mean±SD). The optimal cutoff value for VAI, determined using the Youden J index from the ROC analysis, was 9.07%. This value corresponded to the largest area under the ROC curve, which was 0.683. Additionally, congestion was identified in 30 of the 63 patients by MFI (47.6%). The sensitivities of MFI and CEUS were 73.9% and 78.3%, respectively, while the specificities were 67.5% and 75.0%, respectively (Table 2). These findings indicate no significant differences between MFI and CEUS in sensitivity (P=0.655), specificity (P=0.257), and accuracy (P=0.387). When CEUS was used as the reference standard, the sensitivity and specificity of MFI were 64.3% and 85.7%, respectively, as reported in Supplementary Table 1.
The impact of segmental congestion on the early laboratory findings was assessed. Between groups with and without segmental congestion, no significant differences were found in preoperative and postoperative laboratory values for total bilirubin (P=0.069), AST (P=0.050), and ALT (P=0.068). Additionally, when comparisons were made between CEUS and MFI, preoperative and postoperative laboratory results for total bilirubin (P=0.648 and P=0.162, respectively), AST (P=0.050 and P=0.397), and ALT (P=0.455 and P=0.361) showed no significant differences (Supplementary Table 2).
Further analysis was conducted of a subgroup of 36 patients with reconstructed MHV territories, of whom nine exhibited segmental congestion. Within this subgroup, congestion was identified in 13 of the 36 patients by both CEUS and MFI. The mean VAI was 12.22%, with an SD of 8.12%. For CEUS compared to MFI, the sensitivity values were 88.9% versus 77.8% (P=0.564), the specificity values were 81.5% versus 77.8% (P=0.655), and the accuracy was similar (P=0.109). These results suggest that MFI and CEUS do not differ significantly in diagnostic performance (Table 2). When CEUS was used as the reference standard, the sensitivity and specificity of MFI were 69.2% and 82.6%, respectively, as detailed in Supplementary Table 1. Preoperative and postoperative laboratory values for AST and ALT showed significant differences based on the presence or absence of segmental congestion (AST, P=0.039; ALT, P=0.036). However, in the results obtained using MFI, only ALT demonstrated a significant difference (total bilirubin, P=0.160; AST, P=0.065; ALT, P=0.021). Conversely, preoperative and postoperative laboratory values for total bilirubin (P=0.557), AST (P=0.362), and ALT (P=0.394) did not show significant differences based on the presence or absence of segmental congestion as identified by CEUS (Supplementary Table 3).
Discussion
In patients who underwent LDLT, an association was found between MFI findings and segmental congestion, indicated by reduced vascularity. The diagnostic performance of MFI did not differ significantly from that of CEUS. The sensitivity, specificity, and accuracy for detecting segmental congestion were 73.9%, 67.5%, and 69.8%, respectively. In the subgroup analysis of MHV territory reconstruction, MFI and CEUS demonstrated similar diagnostic capabilities. Preoperative and postoperative laboratory values did not show significant differences between congestion groups categorized using each imaging modality. However, within the subgroup that underwent MHV territory reconstruction, significant differences in liver enzyme levels were found when using MFI for assessment. Therefore, MFI can be used to diagnose segmental congestion in patients with LDLT.
Ultrasound is a real-time imaging modality used to assess vascularity. While color and power Doppler imaging techniques are commonly employed to indirectly quantify vascularity, evaluating microvessels remains challenging [21-23]. Newer ultrasound MFI addresses these challenges. The clutter suppression algorithm in MFI can accurately detect slow blood flow signals, enabling differentiation between motion artifacts and actual slow flow [24,25]. Additionally, MFI can detect a greater number of microvessels and characterize their morphological details [16]. Increased venous pressure, caused by segmental congestion, is transmitted to the hepatic veins and sinusoids. This leads to decreased venous flow and reduced vascularity during slow flow conditions, which MFI can identify [26,27].
The capacity of CEUS to detect obstruction of the MHV after right liver LDLT was previously evaluated [20]. The qualitative data from CEUS have displayed good accuracy in detecting hepatic venous obstruction [28]. In the present study, the accuracy of CEUS in diagnosing segmental congestion was moderate. The sensitivity, specificity, and accuracy of MFI were 78.3%, 75.0%, and 76.2%, respectively. These results indicate that the diagnostic performance of MFI is comparable to that of CEUS. Additionally, MFI has several advantages over CEUS: it can be performed repeatedly, like Doppler imaging, and does not require intravenous injections or specific patient preparation [16]. Consequently, it is less influenced by the patient’s condition. Therefore, MFI provides practical benefits and can be considered a viable alternative to CEUS, particularly in situations where CEUS is not feasible. Incorporating MFI as a preliminary step before proceeding to CEUS could overcome some of the limitations associated with the latter technique. This strategy holds promise for improving the diagnosis of segmental congestion following LDLT.
Previous studies have indicated that patients with congestive hepatopathy typically exhibit a mild increase in serum aminotransferase levels and the presence of unconjugated hyperbilirubinemia [27]. Similarly, levels of AST, ALT, and C-reactive protein are elevated in patients with LDLT who experience segmental congestion [29]. However, the present findings did not reveal any significant differences in clinical outcomes, such as laboratory findings, between patients with and without segmental congestion. In patients who undergo MHV territory reconstruction, segmental congestion may occur if the draining veins are insufficient. Correspondingly, the absence of segmental congestion in these patients may be due to adequate venous drainage [30,31]. Furthermore, a subgroup analysis of patients with MHV territory reconstruction revealed that, in line with previous research, AST and ALT levels were higher in patients with segmental congestion than in those without congestion [29].
This study had several limitations. First, interobserver variability was not assessed, as all MFI assessments were conducted by a single operator at one center. Second, a discrepancy in timing existed between the ultrasound assessment and CT imaging, which served as the reference standard. Despite this, patients underwent periodic ultrasound assessments during the study, and changes were observed in only two of the 63 patients. Additionally, regarding 10 cases where congestion was detected on CEUS but not on subsequent CT, these may represent rapid hemodynamic adjustments in the right anterior section, potentially accompanied by the formation of adequate intrahepatic collaterals [32,33]. Conversely, in the five cases in which congestion was detected on CT but not in the initial CEUS findings, serial ultrasound examinations, including several pulsed Doppler studies conducted within a 2-day interval, showed no significant changes. Upon re-reviewing the CT images, it was determined that in two cases, the areas of congestion were small and not included in the sonic window, and in one case, congestion was attributed to thrombosis in the graft veins. Thus, the use of CT as a reference standard for assessing segmental congestion was considered acceptable. Although further analysis was not performed due to the small number of cases, this should be considered in future studies, particularly regarding the extent of the congestion area on CT. The retrospective design of the present study introduced additional limitations that may impact the generalizability of the findings. In this effort to gain a comprehensive understanding of segmental congestion, only preoperative and postoperative laboratory values were analyzed, and the impact of segmental congestion on patient survival and outcomes was not assessed. Future research should include additional data on factors such as graft size, ABO incompatibility, degree of graft steatosis, and other complications such as rejection, vascular complications, or biliary complications.
In conclusion, MFI without contrast enhancement yielded results that were not significantly different from those obtained with CEUS in detecting segmental congestion after LDLT. Therefore, MFI may be considered a viable alternative to CEUS.
Notes
Author Contributions
Conceptualization: Han T, Jeong WK, Shin J. Data acquisition: Han T, Jeong WK, Gu K, Rhu J, Kim JM, Choi GS. Data analysis or interpretation: Han T, Jeong WK, Cha DI. Drafting of the manuscript: Han T, Jeong WK. Critical revision of the manuscript: Jeong WK, Shin J, Cha DI, Gu K, Rhu J, Kim JM, Choi GS. Approval of the final version of the manuscript: all authors.
Woo Kyoung Jeong serves as Editor for the Ultrasonography, but has no role in the decision to publish this article. All remaining authors have declared no conflicts of interest.
Supplementary Material
References
Article information Continued
Notes
Key point
The utility in diagnosing segmental congestion in patients after living donor liver transplantation (LDLT) is comparable between micro-flow imaging (MFI) and contrast-enhanced ultrasonography. MFI offers a practical diagnostic alternative that minimally impacts patient status while facilitating rapid and accurate clinical assessment. The incorporation of MFI can be considered in clinical and surgical decision-making for patients undergoing LDLT.