The Evolving Application of Ultrasound in the Precision Management of Small Hepatocellular Carcinoma

doi:10.26599/AUDT.2025.250094

Abstract

Abstract:

Early detection of hepatocellular carcinoma (HCC) is crucial, as patient outcomes depend largely on clinical stage and treatment options at diagnosis. Currently most clinical guidelines emphasize non-invasive cross-sectional imaging for HCC diagnosis and evaluation, yet the full potential of ultrasound is often underexplored. With the development of emerging ultrasound techniques and diagnostic algorithms in recent years, the diagnostic ability of ultrasound for HCC smaller than 3 cm has been substantially improved and is increasingly emphasized in the management of small HCC. Following sequential clinical scenarios, this review discusses the state-of-the-art of ultrasound-related techniques and algorithms for preoperative screening and diagnosis, intraoperative guidance and monitoring as well as posttreatment efficacy evaluation of small HCC. By highlighting how advanced ultrasound complements and enhances standard practices, this review aims to promote ultrasound as an indispensable, versatile, and dynamic tool in the precision management of small HCC.

Key words: Ultrasound; Contrast-enhanced ultrasound; Small hepatocellular carcinoma; Diagnosis and treatment; Fusion imaging

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.

Figures/Tables 4

Figure 1

Table 1

Figure 2

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

Table 2

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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