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Histotripsy for the Treatment of Cholangiocarcinoma Liver Tumors: In Vivo Feasibility and Ex Vivo Dosimetry Study.

ABSTRACT: Histotripsy is a noninvasive, nonionizing, and nonthermal focused ultrasound ablation method that is currently being developed for the treatment of liver cancer. Promisingly, histotripsy has been shown for ablating primary [hepatocellular carcinoma (HCC)] and metastatic [colorectal liver metastasis (CLM)] liver tumors in preclinical and early clinical studies. The feasibility of treating cholangiocarcinoma (CC), a less common primary liver tumor that arises from the bile ducts, has not been explored previously. Given that prior work has established that histotripsy susceptibility is based on tissue mechanical properties, there is a need to explore histotripsy as a treatment for CC due to its dense fibrotic stromal components. In this work, we first investigated the feasibility of histotripsy for ablating CC tumors in vivo in a patient-derived xenograft mouse model. The results showed that histotripsy could generate CC tumor ablation using a 1-MHz small animal histotripsy system with treatment doses of 250, 500, and 1000 pulses/point. The second set of experiments compared the histotripsy doses required to ablate CC tumors to HCC and CLM tumors ex vivo. For this, human tumor samples were harvested after surgery and treated ex vivo with a 700-kHz clinical histotripsy transducer. Results demonstrated that significantly higher treatment doses were required to ablate CC and CLM tumors compared to HCC, with the highest treatment dose required for CC tumors. Overall, the results of this study suggest that histotripsy has the potential to be used for the ablation of CC tumors while also highlighting the need for tumor-specific treatment strategies.

SUBMITTER: Hendricks-Wenger A

PROVIDER: S-EPMC9297335 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Histotripsy is a therapeutic ultrasound modality under development to liquefy tissue mechanically via bubble clouds. Image guidance of histotripsy requires both quantification of the bubble cloud activity and accurate delineation of the treatment zone. In this study, magnetic resonance (MR) and diagnostic ultrasound imaging were combined to assess histotripsy treatment in vitro and ex vivo. Mechanically ablative histotripsy pulses were applied to agarose phantoms or porcine livers. Bubble cloud emissions were monitored with passive cavitation imaging (PCI), and hyperechogenicity via plane wave imaging. Changes in the medium structure due to bubble activity were assessed with diagnostic ultrasound using conventional B-mode imaging and T 1-, T 2-, and diffusion-weighted MR images acquired at 3 Tesla. Liquefaction zones were correlated with diagnostic ultrasound and MR imaging via receiver operating characteristic (ROC) analysis and Dice similarity coefficient (DSC) analysis. Diagnostic ultrasound indicated strong bubble activity for all samples. Histotripsy-induced changes in sample structure were evident on conventional B-mode and T 2-weighted images for all samples, and were dependent on the sample type for T 1- and diffusion-weighted imaging. The greatest changes observed on conventional B-mode or MR imaging relative to baseline in the samples did not necessarily indicate the regions of strongest bubble activity. Areas under the ROC curve for predicting phantom or liver liquefaction were significantly greater than 0.5 for PCI power, plane wave and conventional B-mode grayscale, T 1, T 2, and ADC. The acoustic power mapped via PCI provided a better prediction of liquefaction than assessment of the liquefaction zone via conventional B-mode or MR imaging for all samples. The DSC values for T 2-weighted images were greater than those derived from conventional B-mode images. These results indicate diagnostic ultrasound and MR imaging provide complimentary sets of information, demonstrating that multimodal imaging is useful for assessment of histotripsy liquefaction.

Dataset Information

Histotripsy for the Treatment of Cholangiocarcinoma Liver Tumors: In Vivo Feasibility and Ex Vivo Dosimetry Study.

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