High intensity focused ultrasound and microbubbles induce targeted mild hyperthermia suitable for enhanced drug delivery

Abstract

High intensity focused ultrasound (HIFU) can elevate the temperature leading to tissue ablation (>60 °C). Mild hyperthermia (39–45 °C) can enhance drug delivery such as in the activation of thermosensitive liposomes for chemotherapy and in radiotherapy. The addition of microbubbles during HIFU could greatly enhance the heating process and increase the treatment area while operating at lower intensities. Here, we present a parametric study of microbubble-enhanced mild hyperthermia with HIFU in ex vivo porcine liver. A 30-s treatment at 0.9 MHz, 372 000 cycles, 82% duty cycle was used, and at estimated non-derated (water) pressures of 0.63, 1.25, 2.50 and 3.75 MPa. The microbubbles were injected locally in the treatment area. The measured temperature rise was greater with microbubbles than without at low acoustic pressures (0.63 and 1.25 MPa). At higher pressures (2.50 and 3.75 MPa), the presence of microbubbles did not have an effect on the measured temperature rise possibly due to inertial cavitation. Our results agree with predictions from a numerical model that solves the coupled acoustic-bubble flow fields with a two-way coupled Euler–Lagrange model. Future work will utilize the numerical model and new measurements to optimize targeted mild hyperthermia before applying it to enhanced drug delivery.

Tumor growth inhibition and tumor specific immunity enhancement in endometrial carcinoma by high intensity focused ultrasound

“…HIFU is a new tumor therapy [7]. In this method of treating tumor, the ultrasound localization kills tumor cells in the target area without damaging the surrounding normal tissue.…”

“…This method can activate the body's immune system, however it does not involve radiations and chemical damage [16]. HIFU has been suitable for treating solid tumors in tissues and organs including liver, bone, breast, pancreas, prostate, kidney, soft tissue, uterine fibroids, adenomyosis, benign prostatic hyperplasia, and retroperitoneal or abdominal pelvis [7]. Herein, HIFU suppresses EC progression in mice as found by constructing in vivo tumor growth model of EC.…”

“…High Intensity Focused Ultrasound (HIFU) is a safe treatment method because of its non-ionizing and non-invasive characteristics [6]. Studies show that HIFU is an oncological treatment which is repeatable with low complications [7]. In breast cancer, the HIFU combined with nanoparticles improves drug delivery and minimizes the side effects of treating tumors by drugs [8].…”