Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model

Objectives Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. Methods The experiments involved 11 gravid sheep at 102–129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2–1-kHz pulse-repetition rate and 10–16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Results Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Conclusion Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83483/1/8880_ftp.pd

Image-guided focused ultrasound ablation of breast cancer: current status, challenges, and future directions

Image-guided focussed ultrasound (FUS) ablation is a non-invasive procedure that has been used for treatment of benign or malignant breast tumours. Image-guidance during ablation is achieved either by using real-time ultrasound (US) or magnetic resonance imaging (MRI). The past decade phase I studies have proven MRI-guided and US-guided FUS ablation of breast cancer to be technically feasible and safe. We provide an overview of studies assessing the efficacy of FUS for breast tumour ablation as measured by percentages of complete tumour necrosis. Successful ablation ranged from 20% to 100%, depending on FUS system type, imaging technique, ablation protocol, and patient selection. Specific issues related to FUS ablation of breast cancer, such as increased treatment time for larger tumours, size of ablation margins, methods used for margin assessment and residual tumour detection after FUS ablation, and impact of FUS ablation on sentinel node procedure are presented. Finally, potential future applications of FUS for breast cancer treatment such as FUS-induced anti-tumour immune response, FUS-mediated gene transfer, and enhanced drug delivery are discussed. Currently, breast-conserving surgery remains the gold standard for breast cancer treatment

Mechanobiological Modulation of Cytoskeleton and Calcium Influx in Osteoblastic Cells by Short-Term Focused Acoustic Radiation Force

Mechanotransduction has demonstrated potential for regulating tissue adaptation in vivo and cellular activities in vitro. It is well documented that ultrasound can produce a wide variety of biological effects in biological systems. For example, pulsed ultrasound can be used to noninvasively accelerate the rate of bone fracture healing. Although a wide range of studies has been performed, mechanism for this therapeutic effect on bone healing is currently unknown. To elucidate the mechanism of cellular response to mechanical stimuli induced by pulsed ultrasound radiation, we developed a method to apply focused acoustic radiation force (ARF) (duration, one minute) on osteoblastic MC3T3-E1 cells and observed cellular responses to ARF using a spinning disk confocal microscope. This study demonstrates that the focused ARF induced F-actin cytoskeletal rearrangement in MC3T3-E1 cells. In addition, these cells showed an increase in intracellular calcium concentration following the application of focused ARF. Furthermore, passive bending movement was noted in primary cilium that were treated with focused ARF. Cell viability was not affected. Application of pulsed ultrasound radiation generated only a minimal temperature rise of 0.1°C, and induced a streaming resulting fluid shear stress of 0.186 dyne/cm2, suggesting that hyperthermia and acoustic streaming might not be the main causes of the observed cell responses. In conclusion, these data provide more insight in the interactions between acoustic mechanical stress and osteoblastic cells. This experimental system could serve as basis for further exploration of the mechanosensing mechanism of osteoblasts triggered by ultrasound

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2020 was a pivotal year, with COVID-19 as an impetus for rethinking care delivery and business models within Health Systems. 2021 promises new strides in digital technology as an enabler for these new requirements - and for better meeting the needs of our patients. Join the discussion to learn more