Boiling Histotripsy as a Non-Invasive Non-Thermal Approach for Treatment of Human Colon Cancer Tumors: An Ex Vivo Proof-of-Concept.

OBJECTIVES

Colorectal cancer (CRC) is the third most common cancer globally and is frequently diagnosed at metastatic stages. As an alternative to the current standard of care, a novel high-intensity-focused ultrasound (HIFU)-based boiling histotripsy (BH) method has the potential to provide an ultrasound (US)-guided approach for non-invasive mechanical fractionation of CRC metastases and enhancement of anti-tumor immune response for inoperable primary CRC.

METHODS

Young's modulus of the autopsy human sigmoid colon cancer was first measured using shear wave elastography. Volumetric BH lesion was then produced in the cancer sample ex vivo using a 2-MHz 9-element annular array (67.5° focusing angle) targeting a 3D-grid (5 × 5 foci across 2 transverse layers with 1-mm spacing) under B-mode US guidance. Each focus received 150 pulses of 1-ms duration (peak positive/negative pressures and shock amplitude P+/P/As = 91/-13/78 MPa, acoustic power and initial intensity within the pulse W0 = 125.5 W and I0 = 2.7 W/cm2) delivered at 0.1-s intervals (1% duty cycle). The obtained lesion was analyzed via B-mode imaging and histologically with hematoxylin-eosin and Masson's trichrome.

RESULTS

Young's modulus of the autopsy CRC sample was 38 ± 10 kPa and aligned with clinical values for rectal adenocarcinomas. BH treatment was successfully guided in real-time using B-mode US: the treated area was hyperechoic during BH and hypoechoic post-treatment. Histology confirmed the presence of intact mucinous colon carcinoma outside the BH lesion, and fractionated cells and damaged stroma with disrupted collagen fibers within the lesion.

CONCLUSIONS

This ex vivo pilot study demonstrates the potential of BH for non-invasive non-thermal US-guided treatment for CRC and metastases.