Investigating the potential of catheter-assisted pulsed focused ultrasound ablation for atherosclerotic plaques.

BACKGROUND: Atherosclerosis is a condition in which an adhesive substance called plaque accumulates over time inside the arteries. Plaque buildup results in the constriction of arteries, causing a shortage of blood supply to tissues and organs. Removing atherosclerotic plaques controls the development of acute ischemic stroke and heart diseases. It remains imperative for positive patient outcomes. PURPOSE: This study sought to develop a minimally invasive technique for removing arterial plaques by applying focused ultrasound (FUS) energy on the metal surface of a nitinol catheter wire to induce inertial cavitation. The induced cavitation can deplete plaque mechanically inside the arteries, leading towards improved recanalization of blood vessels. METHODS: The enhanced cavitation effect induced by combining FUS with a metal catheter was first verified by exposing agar phantom gels with or without a 0.9-mm diameter nitinol wire to an acoustic field produced by a 0.5-MHz FUS transducer. The phenomenon was further confirmed in pork belly fat samples with or without a 3-mm diameter nitinol catheter wire. Cavitation was monitored by detecting the peaks of emitted ultrasound signals from the samples using a passive cavitation detector (PCD). Cavitation threshold values were determined by observing the jump in the peak amplitude of signals received by the PCD when the applied FUS peak negative pressure (PNP) increased. To simulate arterial plaque removal, FUS with or without a catheter was used to remove tissues from pork belly fat samples and the lipid cores of human atherosclerotic plaque samples using 2500-cycle FUS bursts at 10% duty cycle and a burst repetition rate of 20 Hz. Treatment outcomes were quantified by subtracting the weight of samples before treatment from the weight of samples after treatment. All measurements were repeated 5 times (n = 5) unless otherwise indicated, and paired t-tests were used to compare the means of two groups. A p-value of <0.05 will be considered significant. RESULTS: Our results showed that with a nitinol wire, the cavitation threshold in agar phantoms was reduced to 2.6 MPa from 4.3 MPa PNP when there was no nitinol wire in the focal region of FUS. For pork belly fat samples, cavitation threshold values were 1.0 and 2.0 MPa PNP, with and without a catheter wire, respectively. Pork belly fat tissues and lipid cores of atherosclerotic plaques were depleted at the interface between a catheter and the samples at 2 and 4 MPa FUS PNP, respectively. The results showed that with a catheter wire in the focal region of a 3-min FUS treatment session, 24.7 and 25.6 mg of lipid tissues were removed from pork belly fat and human atherosclerotic samples, respectively. In contrast, the FUS-only group showed no reduction in sample weight. The differences between FUS-only and FUS-plus-catheter groups were statistically significant (p < 0.001 for the treatment on pork belly samples, and p < 0.01 for the treatment on human atherosclerotic samples). CONCLUSION: This study demonstrated the feasibility of catheter-assisted FUS therapy for removing atherosclerotic plaques.

Real-Time Cavitation Monitoring During Optical Coherence Tomography Guided Photo-Mediated Ultrasound Therapy of the Retina.

OBJECTIVE: Photo-mediated ultrasound therapy (PUT) is a novel antivascular therapeutic modality based on cavitation-induced bioeffects. During PUT, synergistic combinations of laser pulses and ultrasound bursts are used to remove the targeted microvessels selectively and precisely without harming nearby tissue. In the current study, an integrated system combining PUT and spectral domain optical coherence tomography (SD-OCT) was developed, where the SD-OCT system was used to guide PUT by detecting cavitation in real time in the retina of the eye. METHOD: We first examined the capability of SD-OCT in detecting cavitation on a vascular-mimicking phantom and compared the results with those from a passive cavitation detector. The performance of the integrated system in treatment of choroidal microvessels was then evaluated in rabbit eyes in vivo. RESULTS: During the in vivo PUT experiments, several biomarkers at the subretinal layer in the rabbit eye were identified on OCT images. The findings indicate that, by evaluating biomarkers of treatment effect, real-time SD-OCT monitoring could help to avoid micro-hemorrhage, which is a potential major side effect. CONCLUSION: Real-time OCT monitoring can thus improve the safety and efficiency of PUT in removing the retinal and choroidal microvasculature.

Ultrasound-assisted laser therapy for selective removal of melanoma cells.

The current study explores the potential of ultrasound-assisted laser therapy (USaLT) to selectively destroy melanoma cells. The technology was tested on an ex vivo melanoma model, which was established by growing melanoma cells in chicken breast tissue. Ultrasound-only and laser-only treatments were used as control groups. USaLT was able to effectively destroy melanoma cells and selectively remove 66.41% of melanoma cells in the ex vivo tumor model when an ultrasound peak negative pressure of 2 MPa was concurrently applied with a laser fluence of 28 mJ/cm2 at 532 nm optical wavelength for 5 min. The therapeutic efficiency was further improved with the use of a higher laser fluence, and the treatment depth was improved to 3.5 mm with the use of 1,064 nm laser light at a fluence of 150 mJ/cm2. None of the laser-only and ultrasound-only treatments were able to remove any melanoma cells. The treatment outcome was validated with histological analyses and photoacoustic imaging. This study opens the possibility of USaLT for melanoma that is currently treated by laser therapy, but at a much lower laser fluence level, hence improving the safety potential of laser therapy.

Photoacoustic imaging of squirrel monkey cortical responses induced by peripheral mechanical stimulation.

Non-human primates (NHPs) are crucial models for studies of neuronal activity. Emerging photoacoustic imaging modalities offer excellent tools for studying NHP brains with high sensitivity and high spatial resolution. In this research, a photoacoustic microscopy (PAM) device was used to provide a label-free quantitative characterization of cerebral hemodynamic changes due to peripheral mechanical stimulation. A 5 × 5 mm area within the somatosensory cortex region of an adult squirrel monkey was imaged. A deep, fully connected neural network was characterized and applied to the PAM images of the cortex to enhance the vessel structures after mechanical stimulation on the forelimb digits. The quality of the PAM images was improved significantly with a neural network while preserving the hemodynamic responses. The functional responses to the mechanical stimulation were characterized based on the improved PAM images. This study demonstrates capability of PAM combined with machine learning for functional imaging of the NHP brain.