Object. High-intensity focused ultrasonography is known to induce controlled and selective noninvasive destruction of tissues by focusing ultrasonic beams within organs, like a magnifying glass concentrating enough sunlight to burn a hole in paper. Such a technique should be highly interesting for the treatment of deep-seated lesions in the brain. Nevertheless, ultrasonic tissue ablation in the brain has long been hampered by the defocusing effect of the skull bone. Methods. In this in vivo study, the authors used a high-power time-reversal mirror specially designed for noninvasive ultrasonic brain treatment to induce thermal lesions through the skulls of 10 sheep. The sheep were divided into three groups and, depending on group, were killed 1, 2, or 3 weeks after treatment. The thermal lesions were confirmed based on findings of posttreatment magnetic resonance imaging and histological examinations. After treatment, the basic neurological functions of the animals were unchanged: the animals recovered from anesthesia without any abnormal delay and did not exhibit signs of paralysis or coma. No major behavioral change was observed. Conclusions. The results provide striking evidence that noninvasive ultrasonographic brain surgery is feasible. Thus the authors offer a novel noninvasive method of performing local brain ablation in animals for behavioral studies. This technique may lead the way to noninvasive and nonionizing treatment of brain tumors and neurological disorders by selectively targeting intracranial lesions. Nevertheless, sheep do not represent a good functional model and extensive work will need to be conducted preferably on monkeys to investigate the effects of this treatment.

In vivo transcranial brain surgery with an ultrasonic time reversal mirror

In order to find out whether high intensity focused ultrasound (HIFU) might be useful against hepatocellular carcinoma, we analyzed the effect of a microbubble agent (Levovist) on the temperature rise and tissue necrosis induced by HIFU. Rabbits were given 7 ml Levovist (300 mg/ml) or saline intravenously. Up to six areas per rabbit liver were exposed to HIFU for 60 s (2.18 MHz, ISPTA=400 W/cm2). The volume of the tissue coagulated by HIFU was measured 10 min after the start of HIFU. HIFU-induced lesions were larger in the animals given Levovist: (mm3, Levovist versus saline) 371±104 versus 166±71 (P<0.001). Temperatures in the animals given Levovist were also higher 60 s after the start of exposure: (°C, Levovist versus saline) 20.3±3.5 versus 13.2±3.8 (P<0.001). The amount of damage differed greatly, but the pathological changes caused by HIFU with Levovist were the same as those caused by HIFU with saline. Hemorrhagic areas and implosion cysts were seen, and many cells had been disrupted or destroyed. Microbubble agents developed for diagnostic uses could also be used in anticancer therapy.

Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue.

Purpose. To investigate the safety, efficacy and feasibility of using high-intensity focused ultrasound (HIFU) as a non-invasive treatment for patients with breast cancer. Patients and Methods. Twenty-two patients with breast cancer were enrolled into this non-randomized prospective trial. Disease TNM stage was classified as stage I in 4 patients, stage IIA in 9 patients, stage IIB in 8 patients, and stage IV in 1 patient. Tumor size ranged from 2 to 4.8 cm in diameter (mean 3.4 cm). All patients received chemotherapy, radiation and tamoxifen, following HIFU for the primary lesions. Outcome measures included radiological and pathologic assessment of the treated tumor, cosmesis, and local recurrence. A cumulative survival rate is calculated by using the Kaplan–Meier method. Results. No severe complications were encountered after HIFU. Post-operative imaging demonstrated positive response and regression of all treated lesions. Follow-up biopsy revealed coagulation necrosis of target tumor and subsequent replacement by fibroblastic tissue. After a median follow-up of 54.8 months, 1 patient died, 1 was lost to follow-up, and 20 were still alive. Two of 22 patients developed local recurrence. Five-year disease-free survival and recurrence-free survival were 95% and 89%, respectively. Cosmetic result was judged as good to excellent in 94% of patients. Conclusions. HIFU treatment is safe, effective, and feasible for patients with breast cancer. But, large-scale, multiple-center clinical trials will be needed to determine the future role of this novel modality.

Extracorporeal high intensity focused ultrasound treatment for patients with breast cancer

Au-nanoparticle coated mesoporous silica nanocapsule-based multifunctional platform for ultrasound mediated imaging, cytoclasis and tumor ablation.

Methods for the bulk ablation of soft tissue using intense ultrasound, with potential applications in the thermal treatment of focal tumors, are presented An approximate analytic model for bulk ablation predicts the progress of ablation based on tissue properties, spatially averaged ultrasonic heat deposition, and perfusion The approximate model allows the prediction of threshold acoustic powers required for ablation in vivo as well as the comparison of cases with different starting temperatures and perfusion characteristics, such as typical in vivo and ex vivo experiments In a full three-dimensional numerical model, heat deposition from array transducers is computed using the Fresnel approximation and heat transfer in tissue is computed by finite differences, accounting for heating changes caused by boiling and thermal dose-dependent absorption Similar ablation trends due to perfusion effects are predicted by both the simple analytic model and the full numerical model Comparisons with experimental results show the efficacy of both models in predicting tissue ablation effects Phenomena illustrated by the simulations and experiments include power thresholds for in vivo ablation, differences between in vivo and ex vivo lesioning for comparable source conditions, the effect of tissue boiling and absorption changes on ablation depth, and the performance of a continuous rotational scanning method suitable for interstitial bulk ablation of soft tissue

Bulk ablation of soft tissue with intense ultrasound: modeling and experiments.

High intensity focused ultrasound (HIFU) can raise the temperature of abnormal tissue to over 70℃ within a few milliseconds, which results in coagulation necrosis of abnormal tissues. This is a noninvasive and effective approach with great potential for the treatment of tumors. Experimental HIFU research on animals, clinical applications and therapeutic systems are reviewed and current problems are analyzed. Further application prospects are forecast.

Wang Hong

Papers

High intensity focused ultrasound for tumor treatment