Advanced Ultrasound in Diagnosis and Therapy ›› 2025, Vol. 9 ›› Issue (4): 375-387.doi: 10.26599/AUDT.2025.250094
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Guan Xina,1, Hu Xinyuanb,1, Han Hongb, Zhang Dezhic,*(
), Xu Huixionga,*()
Received:2025-09-12
Revised:2025-09-24
Accepted:2025-10-20
Online:2025-12-30
Published:2025-11-06
Contact:
Abdominal Ultrasound Department, Diagnostic Ultrasound Center, First Hospital of Jilin University, Jilin, P. R. China (Dezhi Zhang), e-mail: dezhi@jlu.edu.cn (DZ Z);Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361000, China (Huixiong Xu),e-mail: xuhuixiong@126.com (HX X).,
About author:1Xin Guan and Xinyuan Hu contributed equally to this study.
Guan Xin, Hu Xinyuan, Han Hong, Zhang Dezhi, Xu Huixiong. The Evolving Application of Ultrasound in the Precision Management of Small Hepatocellular Carcinoma. Advanced Ultrasound in Diagnosis and Therapy, 2025, 9(4): 375-387.
Figure 1
Emerging ultrasound techniques and algorithms for the management of small HCC. US, ultrasound; CEUS, contrast-enhanced ultrasound; LI-RADS, liver imaging reporting and data system; TRA, treatment response assessment; HCC, hepatocellular carcinoma. Reproduced with permission from [57,60] and [67]."
Table 1
Comparison of major clinical guidelines for the diagnosis of small HCC"
| Guidelines | EASL | AASLD | APASL | CSH | KLCA | JSH |
| EASL, the European Association for the Study of the Liver; AASLD, the American Association for the Study of Liver Diseases; APASL, the Asia-Pacific Association for the Study of the Liver; CSH, the Chinese Society for the Study of the Liver; KLCA-NCC, the Korean Liver Cancer Association-National Cancer Center; JSH, the Japanese Society for the Study of the Liver; CT, computed tomography; MRI, magnetic resonance imaging; CEUS, con trast-enhanced ultrasound; HBA, hepatobiliary agents; LI-RADS, Liver Imaging Reporting and Data System. | ||||||
| Imaging modality | CT/MRI | CT/MRI | CT/MRI/CEUS | CT/MRI/CEUS | CT/MRI/CEUS | CT/MRI/CEUS |
| CEUS role | Secondary | Secondary | First-line | First-line | First-line | First-line |
| HBA-MRI role | Recognized, optional | Recognized, optional | Recognized, optional | Recommended, widely used | Integral to algorithm | Integral to algorithm |
| Diagnostic algorithm | EASL Criteria | LI-RADS | APASL Criteria | China Criteria | KLCA Criteria | JSH Criteria |
| Diagnosis for ≤ 2 cm nodule | Typical pattern on 1 technique | Typical pattern on 1 technique | Typical pattern on 1 technique | Typical pattern on 1 technique | Typical pattern on 1 technique | Often typical pattern on 1 technique |
| Biopsy for atypical ≤ 2 cm nodule | Recommended | Recommended | Consider alternative imaging first | Consider alternative imaging first | Consider alternative imaging first | Consider alternative imaging first |
Figure 2
Major pathologic changes of liver nodules during hepatocarcinogenesis and associated ultrasonographic manifestations. RN, regenerative nodule; LGDN, low-grade dysplastic nodule; HGDN, high-grade dysplastic nodule; HCC, hepatocellular carcinoma; US, ultrasound; APHE, arterial phase hyper enhancement; KP, Kupffer phase."
Table 2
Comparison of emerging ultrasound techniques and algorithms for the management of small HCC"
| Modalities | Function | Advantages | Limitations |
| US, ultrasound; LI-RADS, Liver Imaging Reporting and Data System; HCC, hepatocellular carcinoma; CEUS, contrast-enhanced ultrasound; CT, computed tomography; MRI, magnetic resonance imaging; APHE, arterial phase hyperenhancement; TRA, treatment response assessment. | |||
| B-mode US | To detect and characterize lesion as well as to assess adjacent invasion | First-line tool for screening | Suboptimal sensitivity Suboptimal specificity Influenced by patient, operator and ultrasonic device conditions |
| US LI-RADS | To standardize B-mode US interpretation, reporting and treatment recommendations in patients at high-risk of HCC | US category score determines follow-up management US visualization score conveys expected sensitivity level of US test Moderate-to-good intra-observer agreement | Lack of management recommendations based on visualization scores Confounding factors: overweight, Child-Pugh class B disease, and moderate to severe fatty liver |
| Traditional Doppler US | To visualize the nature, direction and velocity of blood flow as well as to display its adjacency to intrahepatic vessels | Resistance index aids in differential diagnosis of malignancy | Hard to detect fine blood flow High false negative rate Heartbeat interference |
| Microvascular US | To detect slow-velocity flow and to visualize smaller vessel flow | High vascular sensitivity High spatial resolution Excellent interobserver agreement Reduced motion artifact | Angle dependent Cannot provide directional flow and quantitative evaluation Confounding factors (patient body habitus and motion, deep lesion) |
| CEUS | To observe lesion microperfusion dynamically | The only US technique recommended for HCC diagnosis Detect eHCC that invisible on B-mode US Suitable for CT/MRI contradication No renal toxicity | Few lesions can be characterized at one session Lower sensitivity than CT/MRI Confounding factors (respiration, lesion visualization and operator experience) |
| CEUS LI-RADS | To stratify the likelihood of HCC by imaging appearance on CEUS and lesion size | High interobserver consistency in assessing APHE High specificity for CEUS LR-5 The most widely applied CEUS reference for HCC diagnosis | Poor to moderate interobserver consistency in assessing washout CEUS LR-3 reduces the HCC diagnostic probability Poor sensitivity for CEUS LR-5 Current version not available for Sonazoid contrast agent |
| Super resolution US | To precisely localize and track microbubble for ultrahigh-resolution vascular imaging | 10 times better spatial resolution than CEUS Wide flow velocity measurement range mm/s to cm/s and independent of Doppler angle | Slow imaging speeds Susceptibility to probe or tissue motion Fails to resolve the complete capillary bed |
| US elastography | To detect tissue stiffness by measuring the elasticity coefficient | Good reproducibility with same device Accuracy for liver fibrosis staging High liver stiffness is related to HCC occurrence | Overlap of stiffness value for benign and malignant lesions Confounding factors (sampling bias, lesion depth, necroinflammation, congestion, manufacture) |
| US radiomics | To extract imaging features from US images in a high throughput manner | Detect information unrecognizable to naked eye Avoid interpretation subjectivity | Poor interpretability and generalization Input data may vary from different device and operators Lack of standardization |
| Intraoperative US | To provide high-resolution imaging by directly placing transducer on liver surface | High sensitivity in detecting small lesions High spatial resolution High diagnostic accuracy Unaffected by gas, ribs and other structures Immediate imaging and interpretation | Operators need to be experienced Some lesions remain difficult to visualize Difficult to show the whole liver |
| US fusion imaging | To fuse and reconstruct US/CEUS image with previous cross-sectional images in real time | Detect invisible lesions on B-mode US or CEUS High positioning accuracy High technical success rate Low complication rate | Operation complexity Operator dependent Not suitable for patient with anatomical abnormality |
| LI-RADS CEUS nonradiation TRA v2024 | To provide instructions for tumor viability evaluation after non-radiation locoregional therapy | Evaluation based on both intralesional and perilesional contrast enhancement Broader criteria for intralesional enhancement and stricter criteria are used for perilesional enhancement | LR-TR Nonviable does not imply complete pathologic response Indications only include partial locoregional treatment Limited current studies |
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