Sustained modulation of primate deep brain circuits with focused ultrasonic waves

Background: Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects. Objective: Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates. Methods: Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first. While the animals performed the task, we recorded intracranial EEG from occipital screws. The ultrasound was delivered into the deep brain targets daily for a period of more than 6 months. Results: The brief stimulation induced effects on choice behavior that persisted up to 15 minutes and were specific to the sonicated target. Stimulation of the left/right LGN increased the proportion of rightward/leftward choices. These effects were accompanied by an increase in gamma activity over visual cortex. The contralateral effect on choice behavior and the increase in gamma, compared to sham stimulation, suggest that the stimulation excited the target neural circuits. There were no detrimental effects on the animals' discrimination performance over the months-long course of the stimulation. Conclusion: This study demonstrates that brief, 30-s ultrasonic stimulation induces neuroplastic effects specifically in the target deep brain circuits, and that the stimulation can be applied daily without detrimental effects. These findings encourage repeated applications of transcranial ultrasound to malfunctioning deep brain circuits in humans with the goal of providing a durable therapeutic reset

Evaluation of acoustic-thermal simulations of in vivo magnetic resonance guided focused ultrasound ablative therapy

AbstractPurpose To evaluate numerical simulations of focused ultrasound (FUS) with a rabbit model, comparing simulated heating characteristics with magnetic resonance temperature imaging (MRTI) data collected during in vivo treatment.Methods A rabbit model was treated with FUS sonications in the biceps femoris with 3D MRTI collected. Acoustic and thermal properties of the rabbit muscle were determined experimentally. Numerical models of the rabbits were created, and tissue-type-specific properties were assigned. FUS simulations were performed using both the hybrid angular spectrum (HAS) method and k-Wave. Simulated power deposition patterns were converted to temperature maps using a Pennes’ bioheat equation-based thermal solver. Agreement of pressure between the simulation techniques and temperature between the simulation and experimental heating was evaluated. Contributions of scattering and absorption attenuation were considered.Results Simulated peak pressures derived using the HAS method exceeded the simulated peak pressures from k-Wave by 1.6 ± 2.7%. The location and FWHM of the peak pressure calculated from HAS and k-Wave showed good agreement. When muscle acoustic absorption value in the simulations was adjusted to approximately 54% of the measured attenuation, the average root-mean-squared error between simulated and experimental spatial-average temperature profiles was 0.046 ± 0.019 °C/W. Mean distance between simulated and experimental COTMs was 3.25 ± 1.37 mm. Transverse FWHMs of simulated sonications were smaller than in in vivo sonications. Longitudinal FWHMs were similar.Conclusions Presented results demonstrate agreement between HAS and k-Wave simulations and that FUS simulations can accurately predict focal position and heating for in vivo applications in soft tissue

Development and characterization of a tissue mimicking psyllium husk gelatin phantom for ultrasound and magnetic resonance imaging

Purpose To develop and characterize a tissue-mimicking phantom that enables the direct comparison of magnetic resonance (MR) and ultrasound (US) imaging techniques useful for monitoring high-intensity focused ultrasound (HIFU) treatments. With no additions, gelatin phantoms produce little if any scattering required for US imaging. This study characterizes the MR and US image characteristics as a function of psyllium husk concentration, which was added to increase US scattering. Methods Gelatin phantoms were constructed with varying concentrations of psyllium husk. The effects of psyllium husk concentration on US B-mode and MR imaging were evaluated at nine different concentrations. T1, T2, and T2* MR maps were acquired. Acoustic properties (attenuation and speed of sound) were measured at frequencies of 0.6, 1.0, 1.8, and 3.0 MHz using a through-transmission technique. Phantom elastic properties were evaluated for both time and temperature dependence. Results Ultrasound image echogenicity increased with increasing psyllium husk concentration while quality of gradient-recalled echo MR images decreased with increasing concentration. For all phantoms, the measured speed of sound ranged between 1567–1569 m/s and the attenuation ranged between 0.42–0.44 dB/(cm·MHz). Measured T1 ranged from 974–1051 ms. The T2 and T2* values ranged from 97–108 ms and 48–88 ms, respectively, with both showing a decreasing trend with increased psyllium husk concentration. Phantom stiffness, measured using US shear-wave speed measurements, increased with age and decreased with increasing temperature. Conclusions The presented dual-use tissue-mimicking phantom is easy to manufacture and can be used to compare and evaluate US-guided and MR-guided HIFU imaging protocols

Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability

Spinal cord injury (SCI) affects thousands of people every year in the USA, and most patients are left with some permanent paralysis. Therapeutic options are limited and only modestly affect outcome. To address this issue, we used magnetic resonance imaging-guided focused ultrasound (MRgFUS) as a non-invasive approach to increase permeability in the blood-spinal cord barrier (BSCB). We hypothesize that localized, controlled sonoporation of the BSCB by MRgFUS will aid delivery of therapeutics to the injury. Here, we report our preliminary findings for the ability of MRgFUS to increase BSCB permeability in the thoracic spinal cord of a normal rat model. First, an excised portion of normal rat spinal column was used to characterize the acoustic field and to estimate the insertion losses that could be expected in an MRgFUS blood spinal cord barrier opening. Then, in normal rats, MRgFUS was applied in combination with intravenously administered microbubbles to the spinal cord region. Permeability of the BSCB was indicated as signal enhancement by contrast administered prior to T1-weighted magnetic resonance imaging and verified by Evans blue dye. Neurological testing using the Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10 rats tested. Two rats showed minor impairment indicating need for further refinement of parameters. No gross tissue damage was evident by histology. In this study, we have opened successfully the blood spinal cord barrier in the thoracic region of the normal rat spine using magnetic resonance-guided focused ultrasound combined with microbubbles