We read with great interest the commentary titled, "Reversible Neuroinhibition Does Not Require a Thermal Mechanism" in response to our article "Reversible Neuroinhibition by Focused Ultrasound is mediated by a Thermal Mechanism." [1] We are grateful that the authors highlight an important and complex point of ongoing discussion in the literature about the underlying mechanism(s) of FUS-mediated neuromodulation.
Transcranial focused ultrasound (tFUS) is capable of providing subtherapeutic and therapeutic ablative treatments for a variety of brain disorders. A major challenge towards widespread use of tFUS-based therapies stems from the complexity of the skull that could result in severe loss of focusing gain. Using extensive hydrophone scan measurements in plain water as well as transskull, we have documented a range of tFUS beam distortions for a variety of target points and access angles. In this paper, we present quantitative measurements of tFUS distortions due to skull aberrations at different operating frequencies. In addition, refocusing results for a variety of target points at different frequencies within the transducer bandwidth are presented in terms of improvement in focusing gain. Dual-mode ultrasound array (DMUA) prototype (64 elements, concave with 40-mm radius of curvature) was used. Skull samples were extracted from animal subjects that have undergone tFUS treatments using the DMUA prototype were utilized. Experiments were performed at a set of 31 discrete frequencies in the range 2.0 MHz–5.0 MHz. A needle hydrophone was used to measure the pressure waveforms at the target locations. The element transmission efficiency varied as a function of frequency in a nonmonotonic manner with a range of 5–15 dB variation for the different target points. The array focusing gain also varied nonmonotonically suggesting the need for broadband refocusing.
carotid bodies (cBs) are chemoreceptors that monitor and register changes in the blood, including the levels of oxygen, carbon dioxide, and pH, and regulate breathing. enhanced activity of cBs was shown to correlate with a significant elevation in the blood pressure of patients with hypertension. CB removal or denervation were previously shown to reduce hypertension. Here we demonstrate the feasibility of a dual-mode ultrasound array (DMUA) system to safely ablate the cB in vivo in a spontaneously hypertensive rat (SHR) model of hypertension. DMUA imaging was used for guiding and monitoring focused ultrasound (FUS) energy delivered to the target region. In particular, 3D imaging was used to identify the carotid bifurcation for targeting the cBs. intermittent, high frame rate imaging during image-guided fUS (igfUS) delivery was used for monitoring the lesion formation. DMUA imaging provided feedback for closed-loop control (cLc) of the lesion formation process to avoid overexposure. The procedure was tolerated well in over 100 SHR and normotensive rats that received unilateral and bilateral treatments. the measured mean arterial pressure (MAp) exhibited measurable deviation from baseline 2-4 weeks post IgFUS treatment. The results suggest that the direct unilateral FUS treatment of the CB might be sufficient to reduce the blood pressure in hypertensive rats and justify further investigation in large animals and eventually in human patients.
Multiple-focus pattern synthesis using ultrasound arrays has been previously demonstrated. Furthermore, an optimal synthesis method was shown to provide well-behaved solutions. This method creates predefined focus patterns at a single frequency for an ultrasonic array operating in continuous wave. In this paper, we extend the approach to the broadband case using orthogonal frequency-division multiplexing (OFDM). A broadband multiple-focus pattern is formed by summing the results of the synthesis algorithm at a set of discrete frequencies within the transducer bandwidth. The OFDM approach allows for achieving a predictable focusing gain at the target point(s) due to the waveform orthogonality. Outside the target region, the different frequency components can be expected to provide a larger degree of destructive interference. Hydrophone scans of multiple-focus patterns in plain water as well as transskull were performed using a phased array with a multichannel arbitrary waveform generator. The array has a 3.5 MHz center frequency with a 6-dB bandwidth in the range 2.2 MHz–4.8 MHz. The skull samples were obtained from 300 to 350 g rats that were used in other in vivo experiments. The results show greater focus resolution than for any single frequency pattern while reducing the interference patterns outside the target region.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.