Improved contrast-enhanced ultrasound imaging for the preclinical assessment of liver cancer treatment with transarterial chemoembolization

Hepatocellular carcinoma (HCC) represents a significant disease burden and mortality risk worldwide. Transarterial chemoembolization (TACE) is a minimally invasive treatment procedure that restricts tumor blood flow after local injection of an embolization agent and anticancer drug mixture. Assessment of tumor response to TACE is currently determined by using magnetic resonance imaging (MRI) or computed tomography (CT) at 4 to 6
$\mathbf{wk}$
. Recently, it was shown that contrast-enhanced ultrasound (CEUS) imaging at 1 to 2 wk may result in a similarly if not better effective assessment while giving an earlier indication of tumor response and improving treatment management. However, measurement of tumor perfusion levels is limited by conventional processing of CEUS images and could be improved by adapting methods used for super-resolution ultrasound (SRUS) imaging. The overall goal of this research was to develop an improved CEUS-based assessment of liver cancer response to TACE therapy. Using a rat model of HCC, tumors were treated with TACE or a shame procedure (
$(N=3$
per group). Immediately following tail vein injection of a microbubble (MB) contrast agent, CEUS imaging was performed using a preclinical ultrasound system (Vevo 3100, FUJIFILM VisualSonics Inc) equipped with a 15 MHz linear transducer. Imaging was performed in anesthetized animals at baseline before TACE and again 7 and 14 d thereafter. Improved CEUS images were generated by applying spatiotemporal filtering followed by MB detection and localization. Microvessel density (MVD) was calculated from CEUS images as a percentage of tumor area with microvascular structures. On average, MVD decreased by 56.0 % in the TACE treated animals after 1 wk, versus 11.9 % in the control animals. Tumor diameter decreased by 20.3 % in the treated group animals after 1 wk, while tumors grew 12.1 % in the control group. The level of microvascular detail in the CEUS images provided insight into treatment efficacy within only 2 wk of a single TACE procedure.