Expanding the Role of Contrast-Enhanced Ultrasound in the Diagnosis and Management of HCC

Hepatocellular carcinoma (HCC) remains one of the most consequential challenges in abdominal imaging. Incidence continues to rise worldwide, driven by chronic liver disease related to viral hepatitis, alcohol use, and an increasing burden of metabolic-associated liver disease. Because prognosis declines sharply once disease is detected at an advanced stage, early and accurate diagnosis is critical to guiding appropriate therapy and improving patient outcomes.

Recently, Applied Radiology sat down with leading radiologists to discuss the evolving role of contrast-enhanced ultrasound (CEUS) in the diagnosis and management of patients with suspected HCC, and how it fits alongside CT and MRI across the imaging and treatment continuum.

The conversation was hosted by Applied Radiology Group Publisher Kieran Anderson and featured David Fetzer, MD, Associate Professor of Radiology and Medical Director of Ultrasound at UT Southwestern Medical Center and Parkland Health; Rajan Gupta, MD, Professor of Radiology and Vice Chair of Clinical Affairs at Duke Radiology; and Louis Mazzarelli, MD, Chairman, Department of Radiology, Lawrence and  Memorial and Westerly Hospitals, Yale New Haven Health

The Diagnostic Stakes in HCC

As Dr. Fetzer explained, HCC is now the most common primary liver cancer worldwide and one of the leading causes of cancer-related mortality. “Unlike breast cancer or prostate cancer, where we’re making strides in reducing mortality, the incidence and mortality in HCC are actually going up,” he said. HCC is most often associated with chronic liver disease, and the growing prevalence of obesity and diabetes has further accelerated disease burden.

Dr. Gupta emphasized that diagnostic certainty is especially important because downstream management decisions, most notably liver transplantation, depend on it. “Before you transplant a liver, you absolutely need to make sure that the lesion you’re transplanting for is hepatocellular carcinoma,” he noted. As a result, radiologists rely heavily on imaging-based diagnosis using ultrasound, CT, and MRI.

Where CEUS Adds Value in the Imaging Pathway

All three experts described CEUS as a complementary, problem-solving modality that enhances, not replaces, cross-sectional imaging. Dr. Fetzer outlined two primary scenarios where CEUS provides added clinical value. In some practices, lesions detected on screening ultrasound can be evaluated immediately with CEUS during the same visit. “At least in our practice, we can do a same-day diagnosis,” he said. “That’s cost-effective, very satisfying for patients, and it expedites care for clinicians.”

CEUS also plays an important role when CT or MRI findings are inconclusive. “If CT was only single-phase or MRI images were degraded by artifact, CEUS can help improve confidence, or even make the diagnosis when CT or MRI couldn’t,” Dr. Fetzer explained.

Dr. Gupta noted that CEUS is particularly useful when lesions demonstrate arterial hyperenhancement but remain indeterminate on CT or MRI. In these cases, CEUS can help clarify enhancement patterns and support more confident LI-RADS categorization, especially when other imaging lacks sufficient criteria for a definitive diagnosis.

Improving Confidence with CEUS-LI-RADS

A consistent theme was the importance of LI-RADS® in standardizing interpretation and increasing diagnostic confidence. Dr. Fetzer highlighted evidence showing that CEUS performs comparably to CT and MRI for definitive HCC diagnosis. “We found that the positive predictive value and specificity were just as high as CT and MRI,” he said. “When you call an LR-5 lesion on CEUS, you have that same diagnostic confidence.”

Importantly, CEUS is now recognized within U.S. transplant criteria. “Any of the diagnostic modalities, CT, MRI, or CEUS, can now be used to diagnose HCC and help qualify patients for transplantation,” Dr. Fetzer said. “That’s a big deal.”

Dr. Mazzarelli added that having LI-RADS criteria across CT, MRI, and CEUS allows clinicians to tailor imaging strategies to individual patients, often within multidisciplinary tumor boards. “They’re wonderful tools individually,” he said, “but they’re even more powerful when combined.”

Beyond Diagnosis: Interventional and Follow-Up Applications

CEUS is increasingly used beyond diagnosis, particularly in interventional radiology. Dr. Fetzer described its value in biopsy and ablation procedures, where it can help identify viable tumors within partially necrotic lesions and confirm accurate needle placement. “It improves diagnostic yield and allows immediate confirmation of successful therapy,” he said.

Dr. Mazzarelli emphasized CEUS’s role in treatment response assessment. Because microbubble contrast agents remain strictly intravascular, CEUS provides a true depiction of enhancement. “What we see is real enhancement,” he said. “Not pseudo-enhancement or delayed effects.” This allows earlier detection of residual or recurrent disease compared with CT or MRI, enabling timely retreatment when necessary.

Patient-Centered Advantages and Practice Integration

All three experts highlighted CEUS as a patient-friendly modality. It avoids ionizing radiation, is safe for patients with renal dysfunction, and can be repeated multiple times due to the short half-life of microbubble contrast agents. “By eight to ten minutes, the contrast is washed out and you can give another dose,” Dr. Fetzer noted, an advantage not feasible with CT or MRI.

Dr. Mazzarelli described CEUS as helping to “democratize imaging,” offering an option for patients who cannot undergo CT or MRI because of contrast allergies, kidney disease, or breath-holding limitations. “We never want to restrict patients from having an alternative for a life-changing diagnosis,” he said.

Looking Ahead

Looking forward, the panelists agreed that education and local champions will be key to broader adoption in the United States. “Contrast-enhanced ultrasound is fundamentally a problem-solving technique,” Dr. Gupta said. “And we all like solutions to hard problems.” Dr. Mazzarelli pointed to emerging post-processing and microvascular imaging techniques as the next frontier. “Contrast-enhanced ultrasound allows us to look at tumors from a vascular perspective in a way we’ve never seen before,” he said.

Together, these discussions underscore CEUS as a versatile, patient-centered modality with expanding evidence and growing clinical relevance, one that is increasingly earning its place alongside CT and MRI in the diagnosis and management of HCC.