Clinical translation of abdominal histotripsy: a review of preclinical studies in large animal models

Abstract

Histotripsy is an emerging noninvasive, non-thermal, and non-ionizing focused ultrasound (US) therapy that can be used to destroy targeted tissue. Histotripsy has evolved from early laboratory prototypes to clinical systems which have been comprehensively evaluated in the preclinical environment to ensure safe translation to human use. This review summarizes the observations and results from preclinical histotripsy studies in the liver, kidney, and pancreas. Key findings from these studies include the ability to make a clinically relevant treatment zone in each organ with maintained collagenous architecture, potentially allowing treatments in areas not currently amenable to thermal ablation. Treatments across organ capsules have proven safe, including in anticoagulated models which may expand patients eligible for treatment or eliminate the risk associated with taking patients off anti-coagulation. Treatment zones are well-defined with imaging and rapidly resorb, which may allow improved evaluation of treatment zones for residual or recurrent tumor. Understanding the effects of histotripsy in animal models will help inform physicians adopting histotripsy for human clinical use.

Keywords: Histotripsy; abdomen; ablation; kidney; liver; pancreas; renal; tumor.

Figure 1:

Histopathologic comparison of tissue destruction modalities. Differences in procedural application and mechanism of action between histotripsy, high intensity focused ultrasound (HIFU), microwave ablation (MW), radiofrequency ablation (RF), cryoablation, and irreversible electroporation (IRE) are illustrated in the pictograms under each modality. Histotripsy uses cavitation to mechanically destroy tissue. HIFU, MW, RF and cryoablation use thermal mechanisms to create coagulative necrosis and IRE uses electricity to disrupt the cell membrane potential. Pathologic differences are illustrated below each modality. Images have been reprinted with permission and license numbers can be found in the Acknowledgements section.

Figure 2:

MRI and gross pathology images of a histotripsy treatment (white arrows) in a porcine liver. A) Axial T2-weighted fat-saturated MRI following histotripsy of a healthy swine liver. B) Axial T1 weighted MRI before the administration of IV contrast. C) Axial T1 weighted MRI after the administration of a gadolinium-based contrast, shown in the portal venous phase. A patent vessel runs through the treatment zone (yellow arrow). D) Corresponding gross pathology of histotripsy treatment with patent vessel.

Figure 3:

MRI and gross pathology images of a histotripsy treatment (white arrow) in a porcine kidney. A) Axial T2-weighted fat-saturated MRI following histotripsy of a healthy swine kidney. B) Axial T1 weighted MRI with IV contrast (gadobenate dimeglumine) in the corticomedullary phase after treatment (white arrow). C) Coronal MRI with contrast 13 minutes after administering IV contrast. Note the wedge-shaped perfusion defect (yellow arrow) extending peripheral to the treatment zone (white arrows), causing the treatment zone to appear larger. D) Corresponding gross image demonstrating the central area of treatment (white arrows) with adjacent perfusion deficit (yellow arrow).