Characterization and Ex Vivo evaluation of an extracorporeal high‐intensity focused ultrasound (HIFU) system

Abstract

Background: High-intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required.Methods: The acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo.Results: Acoustic pressure mapping showed the insignificant presence of side/grating lobes and pre-or post-focal peaks (≤−12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of −11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20-mm target, which suggests the well-controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750-1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling.Conclusions: Our characterization and ex vivo evaluation protocol met the IDE requirement. The in-situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets.

Experimental and Computational Analysis of HIFU Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids

“…Our model showed that the temperature of the spheroids was uniform throughout the culture medium with no significant temperature gradient within the focal region. Similar observations were obtained by Zhou et al (53), where the center of the ablated cancer appeared analogous to viable cells after H&E staining. These cells maintained their characteristics of cytologic staining and nuclear chromatin without any signs of breakdown.…”

“…These cells maintained their characteristics of cytologic staining and nuclear chromatin without any signs of breakdown. However, electron microscopy revealed that the cytoplasm of those normal-appearing cancer cells contained vacuoles, where the cell membranes were disintegrated with unidentified organelle structures, suggesting an irreversible cell death with the preservation of cellular structure induced by thermal fixation instead of incomplete coagulation necrosis (53). Add to that, the central part of the ablated tumor resisted degradation since the wound-healing process could not extend to this region right after HIFU treatment.…”

Experimental and Computational Analysis of High-Intensity Focused Ultrasound Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids

“…Our model showed that the temperature of the spheroids was uniform throughout the culture medium with no significant temperature gradient within the focal region. Similar observations were obtained by Zhou et al [65], where the center of the ablated cancer appeared analogous to viable cells after H&E staining. These cells retained their cytologic staining and nuclear chromatin features with no evidence of deterioration.…”

Nanomaterial-Based Drug Delivery System Targeting Lymph Nodes

“…When low ultrasound frequency (within the KHz range) is applied, the cavitation effect dominates, and it can be used to trigger drug release, perfluorocarbon nanoemulsions are used to overcome the limitations of bubble lifetime and extravasation, and to promote cell uptake and/or drug release at the tumor site [ 315 , 316 , 317 ]. Another possibility is to use high-intensity focused ultrasound to increase the temperature, which can also promote drug release [ 318 , 319 , 320 ]. J.L.…”