Application of Super-Resolution Ultrasound (SRUS) in Liver Tumor

Overview

The macroscopic vascular supply of liver tumors varies considerably according to histological subtype, lesion size, and disease stage. Current clinical imaging modalities primarily characterize liver tumors based on their macroscopic vascular perfusion patterns. Conventional color Doppler ultrasonography enables qualitative assessment of tumor vascularity, facilitates the differentiation of benign from malignant hepatic lesions, delineates the anatomical relationship between tumors and major intrahepatic vessels, and detects vascular invasion. Nevertheless, these macroscopic vascular characteristics arise from complex microvascular architectures, including vascular distribution patterns, microvessel density, vessel morphology and tortuosity, blood flow velocity, and flow direction. Despite the critical role of tumor microcirculation in tumor progression and therapeutic response, the heterogeneity of microvascular hemodynamics among different liver tumors remains inadequately characterized. The emergence of Super Resolution Ultrasound Imaging (SRUS) has markedly advanced ultrasound imaging by overcoming the acoustic diffraction limit, enabling visualization of microvessels with diameters as small as approximately 20 μm. Unlike conventional ultrasound techniques, SRUS preserves the inherent advantages of ultrasound, including deep tissue penetration and a large field of view, while achieving an approximately tenfold improvement in spatial resolution. This unique combination effectively bridges the long-standing gap between imaging depth and spatial resolution in vascular imaging. Furthermore, by localizing and tracking individual circulating microbubbles,SRUS enables quantitative assessment of microvascular blood flow velocity over a broad dynamic range without Doppler angle dependence. Consequently, super-resolution ultrasound imaging offers an unprecedented opportunity to characterize and compare the microvascular hemodynamic features of benign and malignant liver lesions, thereby improving the accuracy of preoperative differential diagnosis, tumor staging, therapeutic response assessment, and prognostic evaluation.

Detailed description

The macroscopic vascular supply of liver tumors varies considerably according to histological subtype, lesion size, and disease stage. Current clinical imaging modalities primarily characterize liver tumors based on their macroscopic vascular perfusion patterns. Conventional color Doppler ultrasonography enables qualitative assessment of tumor vascularity, facilitates the differentiation of benign from malignant hepatic lesions, delineates the anatomical relationship between tumors and major intrahepatic vessels, and detects vascular invasion. Nevertheless, these macroscopic vascular characteristics arise from complex microvascular architectures, including vascular distribution patterns, microvessel density, vessel morphology and tortuosity, blood flow velocity, and flow direction. Despite the critical role of tumor microcirculation in tumor progression and therapeutic response, the heterogeneity of microvascular hemodynamics among different liver tumors remains inadequately characterized.

The emergence of Super Resolution Ultrasound Imaging (SRUS) has markedly advanced ultrasound imaging by overcoming the acoustic diffraction limit, enabling visualization of microvessels with diameters as small as approximately 20 μm. Unlike conventional ultrasound techniques, SRUS preserves the inherent advantages of ultrasound, including deep tissue penetration and a large field of view, while achieving an approximately tenfold improvement in spatial resolution. This unique combination effectively bridges the long-standing gap between imaging depth and spatial resolution in vascular imaging. Furthermore, by localizing and tracking individual circulating microbubbles,SRUS enables quantitative assessment of microvascular blood flow velocity over a broad dynamic range without Doppler angle dependence. Consequently, super-resolution ultrasound imaging offers an unprecedented opportunity to characterize and compare the microvascular hemodynamic features of benign and malignant liver lesions, thereby improving the accuracy of preoperative differential diagnosis, tumor staging, therapeutic response assessment, and prognostic evaluation.

Interventions

• Diagnostic test Perform super-resolution ultrasound imaging on the study population
  Perform super-resolution ultrasound imaging on the study population, record and calculate characteristic hemodynamic and morphological parameters, and analyze microvascular flow patterns.

Primary outcome measures

• Vascular parameters in different types of benign and malignant liver tumors [Time frame: At the time of initial diagnostic imaging (baseline), with pathological confirmation from subsequent surgical resection or biopsy obtained during the same hospitalization period.]

Secondary outcome measures (1)

• Differences in treatment effectiveness between patient subgroups [Time frame: From date of treatment initiation until the date of first documented pathological or imaging response assessment, assessed up to 12 months]

Eligibility criteria

Inclusion criteria

• Any gender, 18 years or older;
• People newly diagnosed with liver tumors, including:

① Hepatocellular carcinoma; ② Cholangiocarcinoma; ③ Liver metastases; ④ Liver hemangioma; ⑤ Focal nodular hyperplasia of the liver.

• Need to have a contrast-enhanced ultrasound as part of routine care;
• Willing to join this study and sign the informed consent after discussing it with the doctor.

Exclusion criteria

• During the data collection process, if the participant is unable to cooperate fully, preventing the collection from being completed;
• If the skin in the collection area is broken or scabbed, or if there's too much ascites in the abdominal cavity interfering with sound signal penetration, making data collection impossible;
• Previous puncture biopsy or other treatments for existing liver malignant tumors;
• Patients with a history of allergy, allergic constitution, or severe intolerance to sulfur hexafluoride or other components of the ultrasound contrast agent;
• Patients who refuse to participate in this study;
• Any uncontrollable comorbidities that could limit the patient's adherence to the study requirements or affect their ability to sign the written informed consent;
• Poor overall condition or inability to tolerate relevant examinations;
• Participants whom the researcher deems unsuitable for inclusion in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07707661 · EHBHK Y2024-H027-P001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗