Application value of dual-phase cone-beam computed tomography during hepatic arteriography in the detection of ≤2 cm hypervascular hepatocellular carcinoma and its feeding arteries

Introduction

Primary liver cancer remains one of the most prevalent malignant neoplasms globally, ranking as the sixth most common cancer in terms of incidence and the fourth leading cause of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancer cases, imposing a heavy global disease burden (1,2). In China, HCC represents a major public health challenge, ranking fourth in cancer incidence and second in cancer-related death nationwide. The predominant risk factors for HCC in the Chinese population include chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, long-term alcohol intake, non-alcoholic steatohepatitis, and underlying cirrhosis (3,4).

Early diagnosis and precise localization of small HCC (SHCC; defined as lesions with a maximum diameter ≤2 cm) are pivotal to optimizing individualized treatment strategies, improving long-term clinical outcomes, and reducing postoperative tumor recurrence in HCC patients (5). While surgical resection and liver transplantation are the first-line curative treatments for early-stage HCC, transarterial chemoembolization (TACE) has been widely established as a safe and effective minimally invasive modality for unresectable HCC, particularly for SHCC patients who are ineligible for surgery (6). The technical success and therapeutic efficacy of TACE are highly dependent on the accurate identification of all viable tumor lesions and their corresponding feeding arteries, which is the prerequisite for superselective catheterization and targeted embolization to maximize tumor necrosis while sparing normal liver parenchyma (7).

At present, multiple imaging modalities are applied in the clinical workup of HCC, each with inherent advantages and limitations. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), a hepatobiliary-specific contrast-enhanced magnetic resonance imaging (MRI) technique, is widely recognized as one of the most sensitive non-invasive imaging modalities for HCC detection. Notably, EOB-MRI demonstrates particular superiority in detecting early-stage HCC and high-grade dysplastic nodules (HGDNs) through the hepatobiliary phase (HBP), where hepatocellular-specific uptake of the contrast agent enables identification of lesions with impaired hepatocyte function that may not exhibit prominent arterial enhancement (8,9). However, for very small hypervascular HCC lesions (<1.5 cm), the conspicuity of arterial-phase enhancement on EOB-MRI may be reduced due to factors such as transient respiratory motion artifacts and relatively lower arterial contrast concentration compared with direct intra-arterial contrast delivery, which can affect the detection of subtle arterial hyperenhancement features in these minute lesions (10,11). Contrast-enhanced ultrasound (CEUS) allows real-time dynamic evaluation of tumor perfusion, but its diagnostic performance is limited by inherent blind areas, respiratory motion artifacts, and intestinal gas interference, with a reported detection rate of as low as 55.9% for HCC lesions ≤1 cm in previous clinical studies (12,13). Digital subtraction angiography (DSA) has long been the conventional intraoperative imaging modality during TACE procedures; however, its inherent two-dimensional (2D) planar imaging property and relatively low contrast resolution restrict its ability to detect small lesions and their fine feeding arteries, especially for SHCC with faint tumor staining (14,15).

In recent years, cone-beam computed tomography (CBCT) technology has been increasingly integrated into clinical interventional oncology practice. Dual-phase CBCT during hepatic arteriography (CBCT-HA), which acquires both arterial and venous phase images via a single contrast medium injection, has been reported to achieve higher sensitivity for HCC detection compared with single-phase CBCT-HA and conventional DSA (16,17). More importantly, dual-phase CBCT-HA can simultaneously generate high-resolution three-dimensional (3D) images of tumor staining and vascular anatomy, which can be combined with dedicated embolization navigation software to assist superselective catheterization during TACE procedures (18).

However, existing clinical studies have rarely focused on the head-to-head comparison of the diagnostic performance of dual-phase CBCT-HA with EOB-MRI, CEUS, and DSA specifically for ≤2 cm SHCC, as well as its clinical value in feeding artery identification for these small lesions. Accordingly, the study aims to systematically analyze the application value of dual-phase CBCT-HA in the detection of ≤2 cm HCC and their corresponding feeding arteries. We present this article in accordance with the STARD reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0511/rc).

Methods

Study design and subjects

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Tianjin Second People’s Hospital (approval No. LL-BG-2024006). The written informed consent was obtained from the participants or their guardians. A total of 134 consecutive patients with HCC who underwent TACE at Tianjin Second People’s Hospital from February 2021 to April 2023 were enrolled in this study.

Inclusion criteria: (I) patients met the pathological or clinical diagnostic criteria for HCC; (II) complete clinical and imaging data, including EOB-MRI examination within 1 week before TACE and postoperative follow-up data; (III) all patients underwent DSA, dual-phase CBCT-HA, lipiodol TACE, and immediate lipiodol CBCT (L-CBCT) during the operation; and (IV) all target lesions were ≤2 cm in maximum diameter.

Exclusion criteria: (I) diffuse HCC; (II) vascular invasion; (III) concomitant arterioportal fistula; and (IV) poor breath-holding compliance with severe motion artifacts on images.

A total of 222 HCC lesions were identified in the 134 enrolled patients and were divided into two groups according to the maximum diameter: ≤1 cm group (n=100, 45.0%) and 1 cm < diameter ≤2 cm group (n=122, 55.0%). Among all patients, 99 cases with 146 lesions underwent preoperative CEUS simultaneously. The patient enrollment flowchart is shown in Figure 1.

Figure 1 Comparison of HCC detection performance among three imaging modalities. This stacked bar chart demonstrates the proportional distribution of positive (light beige) and negative (coral orange) diagnostic results for HCC detected by CBCT-HA, DSA, and EOB-MRI, respectively. Error bars indicate the standard error of the positive detection rate. Statistically significant differences were identified in the positive detection rate between CBCT-HA and DSA (P<0.001), as well as between EOB-MRI and DSA (P=0.005). CBCT-HA, cone-beam computed tomography during hepatic arteriography; DSA, digital subtraction angiography; EOB-MRI, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging; HCC, hepatocellular carcinoma..

Imaging examination protocols

EOB-MRI examination

Patients fasted for 6–8 hours before the examination. The scanning parameters were as follows: repetition time (TR) 3.76 ms, echo time (TE) 0.23 ms, field of view (FOV) 400 mm × 325 mm, matrix 176×288, slice thickness 3 mm, slice gap 0.6 mm, number of excitations (NEX) 1, flip angle 9°. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), in-phase (IP), out-of-phase (OP), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) sequences were acquired.

Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA; Bayer, Germany) was used as the hepatobiliary-specific contrast agent, administered at a dose of 0.1 mL/kg via intravenous bolus injection at a rate of 1 mL/s. HBP images were obtained 20 min after injection.

CEUS examination

Patients fasted for 6–8 hours before the examination. After conventional ultrasound assessment of the liver, 1.5–2.4 mL of sulfur hexafluoride microbubbles (SonoVue, Bracco, Italy) was injected via the cubital vein, followed by a 5 mL saline flush. The dynamic perfusion process of the lesions was recorded in real time for frame-by-frame analysis.

DSA examination

Intraoperative DSA was performed using a digital angiography system (Artis Zee Ceiling III, Siemens Healthineers, Erlangen, Germany). Using the modified Seldinger technique, the right femoral artery was punctured, and a 5-F catheter sheath was placed. For cases with unclear tumor staining or feeding arteries, a 1.98–2.7-F microcatheter was used for superselective angiography of the left or right hepatic artery.

Dual-phase CBCT-HA examination

The catheter tip was placed in the common or proper hepatic artery, and 20 mL of iohexol injection was injected at a rate of 2 mL/s. The first arterial phase acquisition was started 8 s after contrast injection, and the second venous phase acquisition was performed at 30 s. The scanning parameters were as follows: 8 s rotation time, 200° rotation, 8 ms pulse width, detector dose level 1.20 lGy/frame, acquisition matrix 660×480.

After 3D acquisition, images were automatically reconstructed at the workstation with a slice thickness of 1.8 mm and matrix size of 512×512×512. The EmboGuide embolization navigation software was used to automatically identify tumor feeding arteries and generate 3D navigation maps for superselective catheterization.

Immediate L-CBCT was performed after lipiodol emulsion embolization to evaluate the lipiodol deposition in the lesions, which was used as the imaging gold standard for the confirmation of HCC lesions in this study.

Image analysis and diagnostic criteria

All preoperative EOB-MRI images were transferred to the Picture Archiving and Communication System (PACS), and independently analyzed by two radiologists with more than 10 years of experience in abdominal imaging, who were blinded to the clinical and intraoperative imaging data. Typical HCC was defined as “fast-in and fast-out” enhancement pattern on dynamic contrast-enhanced sequences, with hypointensity on HBP, combined with other supportive signs such as capsule-like enhancement, intermediate signal on T2WI, and restricted diffusion (19).

CEUS images were analyzed by a senior ultrasonologist with more than 20 years of clinical experience. DSA and dual-phase CBCT-HA images were retrospectively analyzed by two interventional radiologists with more than 10 years of experience, and a consensus was reached in case of disagreement.

Diagnostic criteria for HCC on dual-phase CBCT-HA: meeting one of the following criteria: (I) nodular enhancement in the arterial phase with contrast washout in the venous phase, with or without typical “corona enhancement” (16); (II) well-demarcated nodular lipiodol deposition on L-CBCT; and (III) lipiodol deposition or tumor progression on follow-up imaging after embolization.

Criteria for positive feeding artery detection: (I) the artery directly connected to the tumor lesion on CBCT-HA or DSA images was defined as the tumor feeding artery; (II) positive detection was defined as clear visualization of all feeding arteries and their ostia, while negative detection was defined as unclear or undetermined feeding arteries; and (III) tumor opacification on angiography via the artery, or nodular lipiodol deposition on L-CBCT after embolization via the artery (20).

Statistical analysis

All statistical analyses were performed using R software (version 4.3.2). Categorical variables were presented as numbers (percentages), and continuous variables were presented as mean ± standard deviation. The Chi-squared (χ²) test was used to compare the detection rate of HCC lesions, patient-level positive diagnostic rate, and feeding artery detection rate between different imaging modalities.

Results

Baseline clinical characteristics of the enrolled patients

This retrospective study consecutively enrolled 134 patients with pathologically, radiologically, or clinically confirmed HCC, with a total of 222 target lesions with maximum diameter ≤2 cm. The enrolled patients had a mean age of 60.25 years (range, 33–82 years), predominantly male (108/134, 80.6%), and the main etiology was chronic HBV infection (104/134, 77.6%). Most patients had well-preserved liver function (Child-Pugh grade A: 107/134, 78.1%) and excellent performance status [Eastern Cooperative Oncology Group (ECOG) score 0: 133/134, 99.3%] (Table 1).

All 222 lesions were stratified by maximum diameter into the ≤1 cm group (n=100, 45.0%) and the 1 cm < diameter ≤2 cm group (n=122, 55.0%). The majority of lesions were located in the right hepatic lobe (155/222, 69.8%), followed by the left hepatic lobe (64/222, 28.8%) and caudate lobe (3/222, 1.4%) (Table 2). Among all patients, 99 cases with 146 lesions underwent simultaneous preoperative CEUS for subgroup analysis.

Comparison of HCC detection performance between dual-phase CBCT-HA, DSA, and EOB-MRI

At the lesion level, dual-phase CBCT-HA detected 217 of 222 lesions, with an overall sensitivity of 97.7% [95% confidence interval (CI): 94.6–99.2%], including 97 lesions in the ≤1 cm group (sensitivity =97.0%; 95% CI: 91.5–99.4%) and 120 lesions in the 1 cm < diameter ≤2 cm group (sensitivity =98.4%; 95% CI: 94.2–99.8%). In comparison, DSA detected 174 lesions (overall sensitivity =78.4%; 95% CI: 72.6–83.4%), while EOB-MRI detected 208 lesions (overall sensitivity =93.7%; 95% CI: 89.5–96.5%). Detailed sensitivity values for lesions of different sizes are shown in Tables 3-5. Specificity was not calculated in this study as the cohort comprised only patients with confirmed HCC lesions; future studies with control groups including benign lesions or healthy subjects would be needed to evaluate specificity.

For HCC lesions ≤1 cm, the detection rate of dual-phase CBCT-HA was 97.0% (97/100), which was significantly higher than that of EOB-MRI (86.0%, 86/100; χ²=7.78; P=0.005) and DSA (68.0%, 68/100; χ²=29.13; P<0.001) (Table 3). The stacked bar chart visually demonstrated the positive and negative detection rates of the three imaging modalities for ≤1 cm HCC lesions, and between-group comparisons confirmed the statistically significant superiority of dual-phase CBCT-HA over the other two modalities.

A representative case demonstrated the incremental value of dual-phase CBCT-HA in detecting additional SHCC lesions beyond those identified by preoperative EOB-MRI. In this case, dual-phase CBCT-HA detected two additional small nodules (7 and 5 mm) that were not visualized on preoperative EOB-MRI, and all three lesions showed dense lipiodol deposition on post-embolization L-CBCT with sustained treatment response at 12-month follow-up (Figure 2). Detailed clinical and imaging findings are provided in the figure caption.

Figure 2 Representative case of a 70-year-old female patient with post-hepatitis B cirrhosis and HCC. (A,B) Preoperative EOB-MRI identified a single 8.4 mm × 7.8 mm HCC nodule in S4 showing typical imaging features. (C) Intraoperative dual-phase CBCT-HA demonstrated the known S4 nodule with typical “corona” enhancement. (D,E,G,H) No abnormal signal was detected in S6 and S3 on preoperative EOB-MRI. (F,I) Dual-phase CBCT-HA additionally detected 7 and 5 mm nodules in S6 and S3, respectively, both showing characteristic “corona” enhancement. (J-L) Post-embolization L-CBCT showed dense lipiodol deposition in all three nodules. (M-O) Twelve-month follow-up CT showed persistent dense lipiodol deposition with reduced lesion sizes and no evidence of tumor viability. This case illustrates that dual-phase CBCT-HA can identify additional small hypervascular HCC lesions that are not detected by preoperative EOB-MRI. The yellow arrows indicate the hypervascular HCC nodules in segments S4, S6, and S3, and their corresponding dense lipiodol deposition after embolization. CBCT, cone-beam computed tomography; CBCT-HA, cone-beam computed tomography during hepatic arteriography; CT, computed tomography; DWI, diffusion-weighted imaging; EOB-MRI, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging; HCC, hepatocellular carcinoma; L-CBCT, lipiodol cone-beam computed tomography; S3, segment 3; S4, segment 4; S6, segment 6; T2WI, T2-weighted imaging.

For HCC lesions with 1 cm < diameter ≤2 cm, the detection rate of dual-phase CBCT-HA was 98.4% (120/122), which was comparable to that of EOB-MRI (100.0%, 122/122; χ²=2.02; P=0.16), and significantly higher than that of DSA (86.9%, 106/122; χ²=11.76; P<0.001) (Table 4). Two hypovascular HCC lesions detected by EOB-MRI were not identified by dual-phase CBCT-HA or DSA; these lesions showed no obvious arterial enhancement and presented with progressive enlargement during follow-up.

Subgroup analysis in patients with simultaneous preoperative CEUS

In the subgroup of 99 patients who underwent simultaneous CEUS, 146 target lesions were included, with 55 lesions in the ≤1 cm group and 91 lesions in the 1 cm < diameter ≤2 cm group. In this cohort, dual-phase CBCT-HA detected 144 lesions (overall detection rate 98.6%), DSA detected 119 lesions (81.5%), EOB-MRI detected all 146 lesions (100.0%), while CEUS detected only 94 lesions (64.4%).

For lesions ≤1 cm in this subgroup, the detection rate of dual-phase CBCT-HA reached 100.0% (55/55), which was comparable to EOB-MRI (100.0%; χ²=0; P>0.99), and significantly higher than DSA (70.9%; χ²=18.7; P<0.001) and CEUS (49.1%; χ²=37.6; P<0.001) (Table 6). CEUS presented obvious diagnostic blind spots for ≤1 cm micro-HCC, with some lesions undetectable due to respiratory motion interference and intestinal gas obscuration, while intraoperative dual-phase CBCT-HA achieved full liver coverage without significant detection limitations.

A representative case illustrated the superior diagnostic performance of dual-phase CBCT-HA over CEUS for micro-HCC located in the hepatic dome. A 43-year-old male with chronic hepatitis B-related cirrhosis presented with a slightly elevated serum alpha-fetoprotein (AFP) level of 16.02 ng/mL, raising clinical suspicion of HCC.

Preoperative EOB-MRI detected a 9.3 mm × 8.4 mm nodule near the hepatic dome in segment 2 (S2) of the left hepatic lobe, which exhibited typical imaging features of HCC, including hyperintensity on T2WI and DWI, arterial-phase hyperenhancement, and hepatobiliary-phase hypointensity with ill-defined margins (Figure 3A-3D). However, preoperative CEUS failed to identify any abnormal perfusion nodules in the corresponding anatomical region (Figure 3E), which was attributed to the interference of respiratory motion and acoustic shadowing from the lung base at the hepatic dome.

Figure 3 A 43-year-old male patient with post-hepatitis B cirrhosis and an AFP level of 16.02 ng/mL. (A-D) Preoperative EOB-MRI showed a small nodule in S2 of the left hepatic lobe near the hepatic dome, which presented hyperintensity on T2WI and DWI, marked enhancement in the arterial phase, and obvious hypointensity in the HBP with ill-defined borders, measuring approximately 9.3 mm × 8.4 mm, suggestive of HCC. (E) CEUS showed no obvious abnormal perfusion nodule in the corresponding area on MRI. (F,G) Intraoperative dual-phase CBCT-HA during TACE showed a markedly enhancing nodule in S2 of the left hepatic lobe near the hepatic dome in the early phase, with decreased enhancement in the late phase, presenting typical “corona enhancement”, suggestive of HCC. (H) After superselective embolization with lipiodol emulsion during TACE, auxiliary L-CBCT showed uniform and dense lipiodol deposition in the nodule in S2 of the left hepatic lobe near the hepatic dome. (I,J) Contrast-enhanced CT reexamination 1 month after TACE showed good lipiodol deposition in the nodule, no obvious enhancement in all enhanced phases, no obvious tumor activity, and the AFP level decreased to normal (3.8 ng/mL). The yellow arrows indicate the HCC nodule in S2 of the left hepatic lobe near the hepatic dome. AFP, alpha-fetoprotein; CBCT, cone-beam computed tomography; CBCT-AP, cone-beam computed tomography during apical periodontitis; CBCT-HA, cone-beam computed tomography during hepatic arteriography; CEUS, contrast-enhanced ultrasound; CT, computed tomography; DWI, diffusion-weighted imaging; EOB-MRI, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging; HBP, hepatobiliary phase; HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging; L-CBCT, lipiodol cone-beam computed tomography; S2, segment 2; T2WI, T2-weighted imaging; TACE, transarterial chemoembolization.

During TACE, intraoperative dual-phase CBCT-HA clearly visualized the target nodule, which showed marked nodular enhancement in the arterial phase and gradual washout in the venous phase, presenting the characteristic “corona enhancement” pattern of hypervascular HCC (Figure 3F,3G). Based on the 3D localization provided by dual-phase CBCT-HA, superselective catheterization of the tumor feeding artery was successfully performed, followed by embolization with lipiodol emulsion. Immediate post-embolization L-CBCT confirmed uniform and dense lipiodol deposition within the entire nodule, indicating complete targeting of the lesion (Figure 3H).

At 1-month follow-up, contrast-enhanced computed tomography (CT) showed persistent good lipiodol retention in the nodule without evidence of residual enhancement, and the serum AFP level normalized to 3.8 ng/mL (Figure 3I,3J). The patient subsequently underwent left lateral hepatectomy for curative intent. Pathological examination of the resected specimen confirmed the diagnosis of moderately differentiated HCC with locally well-differentiated components, and the nodule showed extensive coagulative necrosis with only a small number of residual tumor cell clusters. This case demonstrated that intraoperative dual-phase CBCT-HA can reliably detect micro-HCC missed by CEUS and guide accurate superselective embolization, leading to favorable early therapeutic outcomes.

For lesions with 1 cm < diameter ≤2 cm in this subgroup, the detection rate of dual-phase CBCT-HA was 97.8% (89/91), which was not significantly different from EOB-MRI (100.0%; χ²=2.0; P=0.16), but significantly higher than DSA (87.9%; χ²=6.7; P=0.009) and CEUS (73.6%; χ²=21.7; P<0.001) (Table 7).

Patient-level positive diagnostic rate

At the patient level, among all 134 enrolled patients, dual-phase CBCT-HA yielded a positive HCC diagnosis in 132 cases (98.5%), DSA in 117 cases (87.3%), and EOB-MRI in all 134 cases (100.0%). There was no significant difference in the patient-level positive diagnostic rate between dual-phase CBCT-HA and EOB-MRI (χ²=2.02; P>0.05), while the diagnostic rate of dual-phase CBCT-HA was significantly higher than that of DSA (χ²=12.75; P<0.001) (Table 8).

In the 99 patients who underwent simultaneous CEUS, dual-phase CBCT-HA achieved a positive diagnostic rate of 98.9% (98/99), which was comparable to EOB-MRI (100.0%; χ²=1.01; P>0.05), and significantly higher than DSA (87.9%; χ²=9.96; P<0.05) and CEUS (67.7%; χ²=34.95; P<0.001) (Table 9).

Comparison of tumor feeding artery detection between dual-phase CBCT-HA and DSA

Among all 222 lesions, dual-phase CBCT-HA identified positive tumor feeding arteries in 83 lesions (83.0%) of the ≤1 cm group (among 97 detected lesions) and 111 lesions (91.0%) of the 1 cm < diameter ≤2 cm group (among 120 detected lesions), with an overall feeding artery detection rate of 87.4% (194/222). In comparison, DSA identified positive feeding arteries in only 30 lesions (44.1%) of the ≤1 cm group (among 68 detected lesions) and 70 lesions (66.0%) of the 1 cm < diameter ≤2 cm group (among 106 detected lesions), with an overall detection rate of 45.0% (100/222). The detection rate of positive tumor feeding arteries by dual-phase CBCT-HA was significantly higher than that of DSA in both size groups (all P<0.001). The bar charts directly compared the feeding artery detection rates of the two modalities for ≤1 cm lesions (Figure 4A) and 1 cm < diameter ≤2 cm lesions (Figure 4B), confirming the significant superiority of dual-phase CBCT-HA in identifying fine tumor feeding vessels.

Figure 4 Comparison of the detection rates of positive feeding arteries of HCC lesions with diameter ≤1 cm and 1 cm < diameter ≤2 cm by dual-phase CBCT-HA and DSA. (A) Statistical bar chart of the detection rates of positive feeding arteries for ≤1 cm HCC lesions by the two methods, with the detection rate of dual-phase CBCT-HA significantly higher than DSA (P<0.001). (B) Statistical bar chart of the detection rates of positive feeding arteries for 1 cm < diameter ≤2 cm HCC lesions by the two methods, with the detection rate of dual-phase CBCT-HA significantly higher than DSA (P<0.001). CBCT-HA, cone-beam computed tomography during hepatic arteriography; DSA, digital subtraction angiography; HCC, hepatocellular carcinoma.

With the assistance of EmboGuide navigation software based on dual-phase CBCT-HA images, which automatically identifies tumor feeding arteries and generates 3D navigation maps, superselective segmental or subsegmental embolization was successfully performed in 70 of 83 (84.3%) ≤1 cm lesions and 106 of 111 (95.5%) 1 cm < diameter ≤2 cm lesions with identified feeding arteries. A representative case of a 15.2 mm HCC lesion in hepatic S2 is presented in Figure 5.

Figure 5 A 68-year-old female patient with post-hepatitis B cirrhosis. (A,B) Preoperative EOB-MRI revealed a nodule in S2 of the left hepatic lobe, which presented slightly hyperintense signals on T2WI and DWI, mild enhancement in the arterial phase, and obvious hypointensity in the HBP, measuring approximately 15.2 mm × 14.6 mm, suggestive of HCC. The yellow arrows indicate the HCC nodule in S2 of the left hepatic lobe. (C) Intraoperative dual-phase CBCT-HA during TACE showed a nodule in S6 of the right hepatic lobe with prominent enhancement in the early phase and reduced enhancement in the late phase, showing heterogeneous “corona” enhancement, suggestive of HCC. The yellow arrows indicate the HCC nodule in S6 of the right hepatic lobe. (D) Coronal MIP images of CBCT-HA clearly displayed tumor staining (yellow arrow) and the small feeding arterial branches entering the tumor (red arrow). (E) On VR images, the tumor and its feeding arteries were automatically identified by the EmboGuide navigation technology. (F) DSA showed tumor staining in the left lateral lobe of the liver (yellow arrow), while the tumor-feeding arteries were slender and poorly visualized. (G) The 3D navigation path image planned by the EmboGuide navigation software guided the operator to perform superselective catheterization to the distal branches of the tumor-feeding artery; lipiodol emulsion was infused with visible lipiodol deposition in the tumor. (H) L-CBCT demonstrated dense lipiodol deposition in the S2 nodule of the left hepatic lobe; contrast-enhanced CT at 1 month after TACE showed good lipiodol deposition in the nodule. The yellow arrows indicate dense lipiodol deposition within the S2 HCC nodule. (I) EOB-MRI at 1 month after TACE revealed no obvious tumor viability in the S2 nodule of the left hepatic lobe with a significant reduction in the lesion size. The yellow arrows indicate the treated S2 nodule with no obvious residual tumor viability. (J) Contrast-enhanced CT at 10 months after TACE showed persistent good lipiodol deposition in the S2 nodule of the left hepatic lobe, without obvious enhancement and a significant reduction in the lesion size. The yellow arrows indicate persistent lipiodol deposition in the S2 nodule without tumor enhancement. 3D, three-dimensional; CBCT-HA, cone-beam computed tomography during hepatic arteriography; CT, computed tomography; DSA, digital subtraction angiography; DWI, diffusion-weighted imaging; EOB-MRI, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging; HBP, hepatobiliary phase; HCC, hepatocellular carcinoma; L-CBCT, lipiodol cone-beam computed tomography; MIP, maximum intensity projection; S2, segment 2; S6, segment 6; T2WI, T2-weighted imaging; TACE, transarterial chemoembolization; VR, volume rendering.

This case involved a 68-year-old female patient with HCC complicating post-hepatitis B cirrhosis. Preoperative EOB-MRI identified a nodule in S2 of the left hepatic lobe, which presented slightly hyperintense signals on T2WI and DWI, mild enhancement in the arterial phase, and obvious hypointensity in the HBP, measuring approximately 15.2 mm × 14.6 mm, consistent with the imaging features of HCC (Figure 5A,5B). During TACE, intraoperative dual-phase CBCT-HA revealed a nodule in segment 6 (S6) of the right hepatic lobe with prominent enhancement in the early phase and reduced enhancement in the late phase, showing heterogeneous “corona” enhancement suggestive of HCC (Figure 5C). Coronal maximum intensity projection (MIP) images of CBCT-HA clearly displayed tumor staining (yellow arrow) and the small feeding arterial branches entering the tumor (red arrow) (Figure 5D). On volume rendering (VR) images, the EmboGuide navigation technology automatically identified the tumor and its feeding arteries (Figure 5E). In contrast, DSA only showed tumor staining in the left lateral lobe of the liver (yellow arrow), while the tumor-feeding arteries were slender and poorly visualized (Figure 5F). The 3D navigation path image planned by the EmboGuide navigation software guided the operator to perform superselective catheterization to the distal branches of the tumor-feeding artery, and lipiodol emulsion was infused with visible lipiodol deposition in the tumor (Figure 5G). L-CBCT demonstrated dense lipiodol deposition in the S2 nodule of the left hepatic lobe (Figure 5H). A contrast-enhanced CT reexamination at 1 month after surgery showed good lipiodol deposition in the nodule, and EOB-MRI revealed no obvious tumor viability with a significant reduction in the lesion size (Figure 5I). A contrast-enhanced CT follow-up at 10 months after surgery showed persistent good lipiodol deposition in the S2 nodule of the left hepatic lobe, without obvious enhancement and a further significant reduction in the lesion size (Figure 5J). This finding confirms that dual-phase CBCT-HA combined with EmboGuide navigation technology can accurately identify tumor-feeding arteries that are not clearly displayed by DSA, improve the success rate of superselective embolization, and achieve effective therapeutic outcomes for SHCC lesions.

This case involved a 51-year-old male patient with HCC complicating post-hepatitis B cirrhosis. Preoperative EOB-MRI identified two nodules in S6 of the right hepatic lobe, measuring 17.6 mm × 15.3 mm and 8.2 mm × 6.9 mm, respectively, with imaging features suggestive of HCC. During TACE, intraoperative dual-phase CBCT-HA clearly visualized both nodules in S6 of the right hepatic lobe, which exhibited prominent enhancement in the early phase and reduced enhancement in the late phase with the typical “corona” enhancement sign, consistent with the imaging characteristics of HCC (Figure 6A-6D). In contrast, DSA showed tumor staining in the right hepatic lobe (yellow arrow), yet the tumor-feeding arteries were slender and overlapped anteroposteriorly, resulting in poor visualization (Figure 6E). On VR images of CBCT-HA, the EmboGuide navigation technology accurately and automatically identified the two HCC nodules and their corresponding feeding arteries (Figure 6F). The 3D navigation path images planned by the EmboGuide navigation software guided the operator to perform precise superselective catheterization to the tumor-feeding arteries; subsequent angiography confirmed obvious tumor staining, and lipiodol emulsion was infused with clear lipiodol deposition observed in both nodules (Figure 6G,6H). Immediate post-embolization L-CBCT revealed obvious heterogeneous lipiodol deposition in the two nodules in S6 of the right hepatic lobe (Figure 6I,6J). A contrast-enhanced CT reexamination at 1 month after TACE showed good lipiodol deposition in both nodules with no obvious enhancement in all enhanced phases (Figure 6K,6L). This finding further verifies that dual-phase CBCT-HA combined with EmboGuide navigation technology can effectively identify multiple SHCC lesions (≤2 cm) in the same hepatic segment and their feeding arteries that are poorly visualized on DSA, realize accurate superselective embolization, and achieve sustained and effective therapeutic outcomes for such multiple SHCC lesions.

Figure 6 A 51-year-old male patient with HCC complicating post-hepatitis B cirrhosis. Preoperative EOB-MRI revealed two nodules in S6 of the right hepatic lobe (measuring 17.6 mm × 15.3 mm and 8.2 mm × 6.9 mm, respectively), suggestive of HCC. (A-D) Intraoperative dual-phase CBCT-HA during TACE showed two nodules with obvious enhancement in the early phase and reduced enhancement in the late phase in S6 of the right hepatic lobe, presenting the typical “corona” enhancement sign, suggestive of HCC. The yellow arrows indicate the two hypervascular HCC nodules in S6 of the right hepatic lobe with typical “corona” enhancement; the red arrow indicates the fine feeding arterial branches supplying the two tumor nodules. (E) DSA showed tumor staining in the right hepatic lobe (yellow arrow), while the tumor-feeding arteries were slender and overlapped anteroposteriorly with poor visualization. The red arrow indicates the slender and anteroposteriorly overlapped tumor-feeding arteries with poor visualization. (F) On VR images, the two tumors and their corresponding feeding arteries were automatically identified by the EmboGuide navigation technology. (G,H) The 3D navigation path images planned by the EmboGuide navigation software guided the operator to perform superselective catheterization to the tumor-feeding arteries; angiography confirmed tumor staining, and lipiodol emulsion was infused with visible lipiodol deposition in the tumors. The yellow arrow indicates lipiodol deposition within the tumor nodules after superselective embolization. (I,J) L-CBCT showed obvious heterogeneous lipiodol deposition in the two nodules in S6 of the right hepatic lobe. The yellow arrows indicate heterogeneous lipiodol deposition in the two S6 HCC nodules. (K,L) Contrast-enhanced CT reexamined at 1 month after TACE showed good lipiodol deposition in the two nodules with no obvious enhancement. The yellow arrows indicate persistent good lipiodol deposition in the two nodules without residual tumor enhancement. 3D, three-dimensional; CBCT-HA, cone-beam computed tomography during hepatic arteriography; CT, computed tomography; DSA, digital subtraction angiography; DWI, diffusion-weighted imaging; EOB-MRI, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging; HCC, hepatocellular carcinoma; L-CBCT, lipiodol cone-beam computed tomography; S6, segment 6; T2WI, T2-weighted imaging; TACE, transarterial chemoembolization; VR, volume rendering.

Discussion

Early detection and precise localization of ≤2 cm HCC, especially ≤1 cm micro-HCC, is critical to improve the curative effect and long-term prognosis of patients (5,6). In this retrospective study, we systematically evaluated the diagnostic performance of intraoperative dual-phase CBCT-HA for ≤2 cm HCC and its feeding arteries, in comparison with conventional imaging modalities including EOB-MRI, CEUS, and DSA.

Our findings demonstrate that dual-phase CBCT-HA exhibits high diagnostic sensitivity for hypervascular HCC lesions ≤2 cm in diameter, with a sensitivity of 97.0% for ≤1 cm lesions and 98.4% for 1–2 cm lesions. For 1–2 cm hypervascular HCC, the sensitivity of dual-phase CBCT-HA was comparable to that of EOB-MRI, which is widely recognized as the most sensitive non-invasive imaging modality for HCC detection. More importantly, for ≤1 cm hypervascular micro-HCC, dual-phase CBCT-HA showed a significantly higher detection rate than EOB-MRI (97.0% vs. 86.0%, P<0.001). This result is consistent with previous studies by Marrero et al. (17) and Hwang et al. (21), which reported that intraprocedural CBCT-HA had superior detection ability for small hypervascular HCC compared with preoperative MRI, especially for lesions <1 cm. The superior performance of dual-phase CBCT-HA for micro-HCC may be attributed to several factors. First, direct intra-arterial contrast injection maximizes the enhancement difference between tumor lesions and background liver parenchyma, avoiding the influence of systemic circulation on contrast concentration. Second, CBCT-HA is not affected by respiratory motion artifacts to the same degree as dynamic MRI, which can cause blurring and reduced conspicuity of small arterial-enhancing lesions (10,11). Third, the dual-phase acquisition protocol captures both early arterial and late venous phases, providing comprehensive hemodynamic information that facilitates identification of small hypervascular nodules (16,22). It is important to emphasize that this advantage pertains specifically to hypervascular lesions; EOB-MRI remains the superior non-invasive modality for detecting hypovascular early HCC and HGDN through the HBP. In addition, dual-phase acquisition provides both arterial enhancement and venous washout information, which is the key imaging feature for the diagnosis of hypervascular HCC, even in very small lesions (16,22).

Our study also found that dual-phase CBCT-HA significantly outperformed CEUS in the detection of ≤2 cm HCC, with a detection rate of 100.0% vs. 49.1% for ≤1 cm lesions and 97.8% vs. 73.6% for 1–2 cm lesions. The low detection rate of CEUS for small lesions is mainly due to the influence of respiratory motion, intestinal gas interference, and diagnostic blind areas in the hepatic dome, as well as the reduced frequency of typical enhancement patterns in micro-HCC (12,13,23). In contrast, intraoperative dual-phase CBCT-HA is not affected by the above factors and can provide whole-liver coverage with high spatial resolution, enabling the detection of small and occult lesions that are missed by CEUS.

As the conventional imaging modality during TACE, DSA showed a significantly lower detection rate for ≤2 cm HCC compared with dual-phase CBCT-HA in our study, especially for ≤1 cm lesions (68.0% vs. 97.0%). This is mainly due to the inherent limitations of DSA, including 2D planar imaging, overlapping of vascular structures, and low contrast resolution, which make it difficult to identify small lesions with faint tumor staining (14,15). Dual-phase CBCT-HA provides 3D volumetric images with multiplanar reconstruction, which can eliminate the interference of vascular overlap and clearly show the enhancement pattern of small lesions, thus significantly improving the detection rate of SHCC.

Another key finding of our study is that dual-phase CBCT-HA significantly improved the detection rate of tumor feeding arteries for ≤2 cm HCC, with a detection rate of 85.6% for ≤1 cm lesions and 91.0% for 1–2 cm lesions, which was significantly higher than DSA. Accurate identification of feeding arteries is the prerequisite for superselective TACE, which is the key to improve the curative effect, reduce normal liver tissue damage, and decrease tumor recurrence (7,24). The 3D reconstruction images of dual-phase CBCT-HA can clearly show the origin, course, and branching of the feeding arteries, even for the fine and tortuous feeding arteries of micro-HCC. Combined with the EmboGuide navigation system, dual-phase CBCT-HA can generate a 3D navigation map to guide superselective catheterization, which achieved a high success rate of superselective embolization in our study (84.3% for ≤1 cm lesions and 95.5% for 1–2 cm lesions). This is of great clinical significance for the implementation of precise TACE for SHCC, which is recommended as an important quality control indicator for HCC TACE treatment (25).

Limitation

This study has several limitations that should be acknowledged. First, the reference standard used in this study—combining immediate post-embolization L-CBCT with nodular lipiodol deposition and follow-up imaging—has inherent limitations. While this composite reference standard is widely accepted in interventional oncology for the diagnosis of small hypervascular HCC (26), it may not capture all true HCC lesions. Specifically, hypovascular or poorly vascularized HCC lesions that are detectable on EOB-MRI (particularly via the HBP) but do not show arterial enhancement on angiographic imaging would not be identified by L-CBCT, potentially leading to underestimation of the true disease burden and overestimation of the sensitivity of angiography-based modalities. In our cohort, we identified 2 such lesions (both in the 1–2 cm size group) that were detected by EOB-MRI but not by dual-phase CBCT-HA or DSA; these were classified as true positives for EOB-MRI and false negatives for the angiographic modalities in our statistical analysis. This phenomenon may partially explain the slightly higher detection rate of EOB-MRI (100.0%) compared with dual-phase CBCT-HA (98.4%) for 1–2 cm lesions. Second, most of the included lesions were diagnosed by imaging and clinical criteria rather than histopathology, which is difficult to obtain for micro-HCC due to the high risk of puncture biopsy and the clinical practice of treating small lesions based on imaging diagnosis alone. Third, this is a single-center retrospective study, and the results need to be validated in multi-center prospective cohorts with larger sample sizes. Fourth, there is no unified standard for dual-phase CBCT-HA image acquisition protocols across different centers, which may affect the consistency and generalizability of the results. Finally, our study focused exclusively on hypervascular HCC lesions amenable to detection via hepatic arteriography; the findings cannot be extrapolated to hypovascular early-stage HCC or HGDN, for which EOB-MRI remains the superior diagnostic modality.

Conclusions

For hypervascular HCC lesions ≤2 cm in diameter, dual-phase CBCT-HA demonstrates significantly higher sensitivity than CEUS and DSA, with performance comparable to EOB-MRI for 1–2 cm lesions and higher sensitivity for ≤1 cm micro-HCC. These findings should be interpreted within the context of the study focus on hypervascular lesions detectable via hepatic arteriography; EOB-MRI remains the preferred non-invasive modality for the detection of hypovascular early-stage HCC and HGDN. In addition, dual-phase CBCT-HA can significantly improve the detection rate of feeding arteries of ≤2 cm HCC, especially for lesions ≤1 cm, which facilitates accurate identification of tumor feeding arteries and successful superselective embolization during TACE. Therefore, dual-phase CBCT-HA is a valuable imaging modality for the detection of SHCC and guidance of precise TACE treatment.

Acknowledgments

The authors sincerely thank the medical staff of the Interventional Department and Imaging Department of Tianjin Second People’s Hospital for their contributions to this study.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0511/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0511/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0511/prf

Funding: This study was supported by the Natural Science Foundation of Tianjin (No. 23JCYBJC00950) and the Tianjin Key Medical Discipline Construction Project (No. TJYXZDXK-3-019B).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0511/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Tianjin Second People’s Hospital (approval No. LL-BG-2024006). The written informed consent was obtained from the participants or their guardians.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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