Effect of Bifidobacterium-induced changes in tumor tissue acoustic properties on efficacy of high-intensity focused ultrasound ablation

Abstract

To investigate the effects of Bifidobacterium on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice. Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (n=20) and control group (n=20) for intravenous injection of Bifidobacterium suspension (200 μL, 4 × 108 cfu/mL) and PBS (200 μL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining. In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. Bifidobacterium colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (P=0.01); the acoustic velocity (P=0.001) and the acoustic attenuation (P=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (P=0.0006) and larger coagulative necrosis volume (P=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (P=0.0134). Bifidobacterium can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.