A novel method for tracking nitrogen kinetics in vivo under hyperbaric conditions using radioactive nitrogen-13 gas and positron emission tomography.

Decompression sickness (DCS) is caused by gaseous nitrogen dissolved in tissues forming bubbles during decompression. To date, no method exists to identify nitrogen within tissues, but with advances in positron-emission tomography (PET) technology, it may be possible to track gaseous radionuclides into tissues. We aimed to develop a method to track nitrogen movement in vivo and under hyperbaric pressure that could then be used to further our understanding of DCS using nitrogen-13 (13N2). A single anesthetized female Sprague-Dawley rat was exposed to 625 kPa, composed of air, isoflurane, and 13N2 for 10 min. The PET scanner recorded 13N2 during the hyperbaric exposure with energy windows of 250-750 keV. The PET showed an increase in 13N2 concentration in the lung, heart, and abdominal regions, which all reached a plateau after ∼4 min. This showed that it is possible to gain noninvasive in vivo measurements of nitrogen kinetics through the body while at hyperbaric pressures. Tissue samples showed radioactivity above background levels in the blood, brain, liver, femur, and thigh muscle when assessed using a γ counter. The method can be used to evaluate an array of challenges to our understanding of decompression physiology by quantifying nitrogen load through γ counts of 13N2, and signal intensity of the PET. Further development of the method will improve the specificity of the measured outcomes, and enable it to be used with larger mammals, including humans.NEW & NOTEWORTHY This article describes a method for the in vivo quantification and tracking of nitrogen through the mammalian body whilst exposed to hyperbaric pressure. The method has the potential to further our understanding of decompression sickness, and quantitatively evaluate the effectiveness of both the treatment and prevention of decompression sickness.

Development and validation of a computational method to predict unintended auditory brainstem response during transcranial ultrasound neuromodulation in mice.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a promising noninvasive neuromodulation modality. The inadvertent and unpredictable activation of the auditory system in response to TUS obfuscates the interpretation of non-auditory neuromodulatory responses. OBJECTIVE: The objective was to develop and validate a computational metric to quantify the susceptibility to unintended auditory brainstem response (ABR) in mice premised on time frequency analyses of TUS signals and auditory sensitivity. METHODS: Ultrasound pulses with varying amplitudes, pulse repetition frequencies (PRFs), envelope smoothing profiles, and sinusoidal modulation frequencies were selected. Each pulse's time-varying frequency spectrum was differentiated across time, weighted by the mouse hearing sensitivity, then summed across frequencies. The resulting time-varying function, computationally predicting the ABR, was validated against experimental ABR in mice during TUS with the corresponding pulse. RESULTS: There was a significant correlation between experimental ABRs and the computational predictions for 19 TUS signals (R2 = 0.97). CONCLUSIONS: To reduce ABR in mice during in vivo TUS studies, 1) reduce the amplitude of a rectangular continuous wave envelope, 2) increase the rise/fall times of a smoothed continuous wave envelope, and/or 3) change the PRF and/or duty cycle of a rectangular or sinusoidal pulsed wave to reduce the gap between pulses and increase the rise/fall time of the overall envelope. This metric can aid researchers performing in vivo mouse studies in selecting TUS signal parameters that minimize unintended ABR. The methods for developing this metric can be adapted to other animal models.

Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain.

BACKGROUND: Moderate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound's effects on behavior and peripheral nerve structure. METHODS: Focused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy. RESULTS: Compared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for ≥4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy. DISCUSSION: Focused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes.

Changes in the Cerebello-Thalamo-Cortical Network After Magnetic Resonance-Guided Focused Ultrasound Thalamotomy.

Objective: In recent years, transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor (ET). So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in ET patients treated with tcMRgFUS thalamotomy. Methods: Eleven patients diagnosed with ET were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3 Tesla magnetic resonance imaging (3T MRI) including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed before the procedure as well as 1 year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus, and the corticospinal tract in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results: The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p < 0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r = -0.54, p = 0.04; MD: r = 0.57, p = 0.04); RD: r = 0.67, p = 0.036). Further, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r = 0.58; p = 0.062; MD: r = -0.52, p = 0.64; RD: r = -0.61 p = 0.090). Conclusions: Microstructural changes were detected within the CTCT after tcMRgFUS, and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism, and ultimately to improve targeting prospectively. Impact statement The results of this study demonstrate microstructural changes within the cerebello-thalamo-cortical pathways 1 year after MR-guided focused ultrasound thalamotomy. Even more, microstructural changes within the cerebello-thalamo-cortical pathways correlated significantly with clinical outcome. These findings do not only highly emphasize the need of new targeting strategies for MR-guided focused ultrasound thalamotomy but also help to elucidate the treatment mechanism of it.

A tool for monitoring cell type-specific focused ultrasound neuromodulation and control of chronic epilepsy.

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.

Benchmark problems for transcranial ultrasound simulation: Intercomparison of compressional wave models.

Computational models of acoustic wave propagation are frequently used in transcranial ultrasound therapy, for example, to calculate the intracranial pressure field or to calculate phase delays to correct for skull distortions. To allow intercomparison between the different modeling tools and techniques used by the community, an international working group was convened to formulate a set of numerical benchmarks. Here, these benchmarks are presented, along with intercomparison results. Nine different benchmarks of increasing geometric complexity are defined. These include a single-layer planar bone immersed in water, a multi-layer bone, and a whole skull. Two transducer configurations are considered (a focused bowl and a plane piston operating at 500 kHz), giving a total of 18 permutations of the benchmarks. Eleven different modeling tools are used to compute the benchmark results. The models span a wide range of numerical techniques, including the finite-difference time-domain method, angular spectrum method, pseudospectral method, boundary-element method, and spectral-element method. Good agreement is found between the models, particularly for the position, size, and magnitude of the acoustic focus within the skull. When comparing results for each model with every other model in a cross-comparison, the median values for each benchmark for the difference in focal pressure and position are less than 10% and 1 mm, respectively. The benchmark definitions, model results, and intercomparison codes are freely available to facilitate further comparisons.

Comparison between MR and CT imaging used to correct for skull-induced phase aberrations during transcranial focused ultrasound.

Transcranial focused ultrasound with the InSightec Exablate system uses thermal ablation for the treatment of movement and mood disorders and blood brain barrier disruption for tumor therapy. The system uses computed tomography (CT) images to calculate phase corrections that account for aberrations caused by the human skull. This work investigates whether magnetic resonance (MR) images can be used as an alternative to CT images to calculate phase corrections. Phase corrections were calculated using the gold standard hydrophone method and the standard of care InSightec ray tracing method. MR binary image mask, MR-simulated-CT (MRsimCT), and CT images of three ex vivo human skulls were supplied as inputs to the InSightec ray tracing method. The degassed ex vivo human skulls were sonicated with a 670 kHz hemispherical phased array transducer (InSightec Exablate 4000). 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. Targets at the geometric focus and 5 mm lateral to the geometric focus were investigated. There was no statistical difference between any of the metrics at either target using either MRsimCT or CT for phase aberration correction. As opposed to the MRsimCT, the use of CT images for aberration correction requires registration to the treatment day MR images; CT misregistration within a range of ± 2 degrees of rotation error along three dimensions was shown to reduce focal spot intensity by up to 9.4%. MRsimCT images used for phase aberration correction for the skull produce similar results as CT-based correction, while avoiding both CT to MR registration errors and unnecessary patient exposure to ionizing radiation.

Improving in situ acoustic intensity estimates using MR acoustic radiation force imaging in combination with multifrequency MR elastography.

PURPOSE: Magnetic resonance acoustic radiation force imaging (MR-ARFI) enables focal spot localization during nonablative transcranial ultrasound therapies. As the acoustic radiation force is proportional to the applied acoustic intensity, measured MR-ARFI displacements could potentially be used to estimate the acoustic intensity at the target. However, variable brain stiffness is an obstacle. The goal of this study was to develop and assess a method to accurately estimate the acoustic intensity at the focus using MR-ARFI displacements in combination with viscoelastic properties obtained with multifrequency MR elastography (MRE). METHODS: Phantoms with a range of viscoelastic properties were fabricated, and MR-ARFI displacements were acquired within each phantom using multiple acoustic intensities. Voigt model parameters were estimated for each phantom based on storage and loss moduli measured using multifrequency MRE, and these were used to predict the relationship between acoustic intensity and measured displacement. RESULTS: Using assumed viscoelastic properties, MR-ARFI displacements alone could not accurately estimate acoustic intensity across phantoms. For example, acoustic intensities were underestimated in phantoms stiffer than the assumed stiffness and overestimated in phantoms softer than the assumed stiffness. This error was greatly reduced using individualized viscoelasticity measurements obtained from MRE. CONCLUSION: We demonstrated that viscoelasticity information from MRE could be used in combination with MR-ARFI displacements to obtain more accurate estimates of acoustic intensity. Additionally, Voigt model viscosity parameters were found to be predictive of the relaxation rate of each phantom's time-varying displacement response, which could be used to optimize patient-specific MR-ARFI pulse sequences.

Dose-dependent effects of high intensity focused ultrasound on compound action potentials in an ex vivo rodent peripheral nerve model: comparison to local anesthetics.

BACKGROUND: In animal models, focused ultrasound can reversibly or permanently inhibit nerve conduction, suggesting a potential role in managing pain. We hypothesized focused ultrasound's effects on action potential parameters may be similar to those of local anesthetics. METHODS: In an ex vivo rat sciatic nerve model, action potential amplitude, area under the curve, latency to 10% peak, latency to 100% peak, rate of rise, and half peak width changes were assessed after separately applying increasing focused ultrasound pressures or concentrations of bupivacaine and ropivacaine. Focused ultrasound's effects on nerve structure were examined histologically. RESULTS: Increasing focused ultrasound pressures decreased action potential amplitude, area under the curve, and rate of rise, increased latency to 10% peak, and did not change latency to 100% peak or half peak width. Increasing local anesthetic concentrations decreased action potential amplitude, area under the curve, and rate of rise and increased latency to 10% peak, latency to 100% peak, and half peak width. At the highest focused ultrasound pressures, nerve architecture was altered compared with controls. DISCUSSION: While some action potential parameters were altered comparably by focused ultrasound and local anesthetics, there were small but notable differences. It is not evident if these differences may lead to differences in clinical pain effects when focused ultrasound is applied in vivo or if focused ultrasound pressures that result in clinically relevant changes damage nerve structures. Given the potential advantages of a non-invasive technique for managing pain conditions, further investigation may be warranted in an in vivo pain model.

Transcranial focused ultrasound phase correction using the hybrid angular spectrum method.

The InSightec Exablate system is the standard of care used for transcranial focused ultrasound ablation treatments in the United States. The system calculates phase corrections that account for aberrations caused by the human skull. This work investigates whether skull aberration correction can be improved by comparing the standard of care InSightec ray tracing method with the hybrid angular spectrum (HAS) method and the gold standard hydrophone method. Three degassed ex vivo human skulls were sonicated with a 670 kHz hemispherical phased array transducer (InSightec Exablate 4000). Phase corrections were calculated using four different methods (straight ray tracing, InSightec ray tracing, HAS, and hydrophone) and were used to drive the transducer. 3D raster scans of the beam profiles were acquired using a hydrophone mounted on a 3-axis positioner system. Focal spots were evaluated using six metrics: pressure at the target, peak pressure, intensity at the target, peak intensity, positioning error, and focal spot volume. For three skulls, the InSightec ray tracing method achieved 52 ± 21% normalized target intensity (normalized to hydrophone), 76 ± 17% normalized peak intensity, and 0.72 ± 0.47 mm positioning error. The HAS method achieved 74 ± 9% normalized target intensity, 81 ± 9% normalized peak intensity, and 0.35 ± 0.09 mm positioning error. The InSightec-to-HAS improvement in focal spot targeting provides promise in improving treatment outcomes. These improvements to skull aberration correction are also highly relevant for the applications of focused ultrasound neuromodulation and blood brain barrier opening, which are currently being translated for human use.

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery.

BACKGROUND: Trans-cranial MR guided focused ultrasound (tcMRgFUS) ablation targets are <5mm from critical neurological structures, creating a need for improved MR imaging and thermometry. The purpose of this study was to evaluate the performance of a dual-channel radiofrequency receive-only head coil designed specifically for integrated use in tcMRgFUS. METHODS: Imaging used a 3 T MRI and the ExAblate Neuro System (INSIGHTEC Inc., Israel). Sensitivity maps determined receive-only coil uniformity. The head coil was compared to the volume body coil at the level of the thalamus using 1) T2-weighted imaging and 2) multi-echo MR thermometry of volunteers in the transducer helmet. Thermal sonications (40 W, 24s) were acquired in a heating phantom. Thermal maps in were constructed to evaluate temperature uncertainty, focal heating, and temperature evolution. RESULTS: The normalized signal intensity showed up to a 35% variation. On T2wFSE images the SNR with the head coil is improved by 4x in the axial plane, and 3x in sagittal and coronal planes. The head coil provided better visualization of the thalamus and globus pallidus (axial), and of the anterior/posterior commissure, and brain stem/cerebellum (sagittal) compared to the body coil. MR thermometry showed a 4x gain in SNR in the thalamus. Thermometry showed a preserved focal spot with 20 °C temperature rise. The average temperature uncertainty (mean ± std) was reduced from σ T = 0.96 °C ± 0.55 °C for the body coil to σ T = 0.41 °C ± 0.24 °C for the head coil. CONCLUSIONS: Greater SNR from the dual-channel head coil provides access to better treatment day visualization for treatment planning and higher precision intra-operative thermometry.

MRI-Guided Focused Ultrasound of Osseous Metastases: Treatment Parameters Associated With Successful Pain Reduction.

BACKGROUND: A phase 3 multicenter trial demonstrated that magnetic resonance imaging (MRI)-guided focused ultrasound (US) is a safe, noninvasive treatment that alleviated pain from bone metastases. However, outcomes varied among institutions (from 0%-100% treatment success). PURPOSE: The aim of this study was to identify patient selection, technical treatment, and imaging parameters that predict successful pain relief of osseous metastases after MRI-guided focused US. MATERIALS AND METHODS: This was a secondary analysis of a phase 3 clinical study that included participants who received MRI-guided focused US treatment for painful osseous metastases. Noncontrast CT was obtained before treatment. T2-weighted and T1-weighted postcontrast MRIs at 1.5 T or 3 T were obtained before, at the time of, and at 3 months after treatment. Numerical Rating Scale pain scores and morphine equivalent daily dose data were obtained over a 3-month follow-up period. At the 3-month endpoint, participants were categorized as pain relief responders or nonresponders based on Numerical Rating Scale and morphine equivalent daily dose data. Demographics, technical parameters, and imaging features associated with pain relief were determined using stepwise univariable and multivariable models. Responder rates between the subgroup of participants with all predictive parameters and that with none of the parameters were compared using Fisher exact test. RESULTS: The analysis included 99 participants (mean age, 59 ± 14 years; 56 women). The 3 variables that predicted successful pain relief were energy density on the bone surface (EDBS) (P = 0.001), the presence of postprocedural periosteal devascularization (black band, BB+) (P = 0.005), and female sex (P = 0.02). The subgroup of participants with BB+ and EDBS greater than 5 J/mm2 had a larger decrease in mean pain score (5.2; 95% confidence interval, 4.6-5.8) compared with those without (BB-, EDBS ≤ 5 J/mm2) (1.1; 95% confidence interval, 0.8-3.0; P < 0.001). Participants with all 3 predictive variables had a pain relief responder rate of 93% compared with 0% in participants having none of the predictive variables (P < 0.001). CONCLUSIONS: High EDBS during treatment, postprocedural periosteal devascularization around the tumor site (BB+), and female sex increased the likelihood of pain relief after MRI-guided focused US of osseous metastasis.

A rapid beam simulation framework for transcranial focused ultrasound.

Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor.

OBJECTIVE: Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs. METHODS: In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria. RESULTS: Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups. CONCLUSIONS: MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

Enhanced microbubble contrast agent oscillation following 250 kHz insonation.

Microbubble contrast agents are widely used in ultrasound imaging and therapy, typically with transmission center frequencies in the MHz range. Currently, an ultrasound center frequency near 250 kHz is proposed for clinical trials in which ultrasound combined with microbubble contrast agents is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuation compared to higher frequencies. However, the microbubble vibrational response has not yet been carefully evaluated at this low frequency (an order of magnitude below the resonance frequency of these contrast agents). In the past, it was assumed that encapsulated microbubble expansion is maximized near the resonance frequency and monotonically decreases with decreasing frequency. Our results indicated that microbubble expansion was enhanced for 250 kHz transmission as compared with the 1 MHz center frequency. Following 250 kHz insonation, microbubble expansion increased nonlinearly with increasing ultrasonic pressure, and was accurately predicted by either the modified Rayleigh-Plesset equation for a clean bubble or the Marmottant model of a lipid-shelled microbubble. The expansion ratio reached 30-fold with 250 kHz at a peak negative pressure of 400 kPa, as compared to a measured expansion ratio of 1.6 fold for 1 MHz transmission at a similar peak negative pressure. Further, the range of peak negative pressure yielding stable cavitation in vitro was narrow (~100 kPa) for the 250 kHz transmission frequency. Blood brain barrier opening using in vivo transcranial ultrasound in mice followed the same trend as the in vitro experiments, and the pressure range for safe and effective treatment was 75-150 kPa. For pressures above 150 kPa, inertial cavitation and hemorrhage occurred. Therefore, we conclude that (1) at this low frequency, and for the large oscillations, lipid-shelled microbubbles can be approximately modeled as clean gas microbubbles and (2) the development of safe and successful protocols for therapeutic delivery to the brain utilizing 250 kHz or a similar center frequency requires consideration of the narrow pressure window between stable and inertial cavitation.

Hearing out Ultrasound Neuromodulation.

Many neuroscientists are excited regarding the potential of ultrasound to yield spatiotemporally precise and noninvasive modulation of arbitrary brain regions. Here, Guo et al. (2018) and Sato et al. (2018) show that applying ultrasound to rodent brains activates acoustic responses more prominently than eliciting neuromodulation directly, suggesting potential confounds of ultrasound neuromodulation experiments.

Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound.

In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are focused through the body to selectively ablate difficult to access lesions and tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the temperature increase throughout the tissue to guide the therapy. In clinical MRI, tightly fitted hardware comprised of multichannel coil arrays are required to capture high quality images at high spatiotemporal resolution. Ablating tissue requires a clear path for acoustic energy to travel but current array materials scatter and attenuate acoustic energy. As a result coil arrays are placed outside of the transducer, clear of the beam path, compromising imaging speed, resolution, and temperature accuracy of the scan. Here we show that when coil arrays are fabricated by additive manufacturing (i.e., printing), they exhibit acoustic transparency as high as 89.5%. This allows the coils to be placed in the beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms and volunteers. We also characterize printed coil materials properties over time when submerged in the water required for acoustic coupling. These arrays offer high SNR and acceleration capabilities, which can address current challenges in treating head and abdominal tumors allowing MRgFUS to give patients better outcomes.

High sensitivity MR acoustic radiation force imaging using transition band balanced steady-state free precession.

PURPOSE: MR acoustic radiation force imaging (MR-ARFI) provides a method to visualize the focal spot of a focused ultrasound (FUS) beam without introducing a significant temperature rise. With conventional spoiled MR-ARFI pulse sequences, the ARFI phase always equals the motion-encoded phase. In this work, MR-ARFI using transition band balanced steady-state free precession (bSSFP) is presented, which improves the sensitivity of MR-ARFI with high acquisition speed. THEORY AND METHODS: Motion-encoding gradients (MEG) are inserted into bSSFP sequences for MR-ARFI. By applying an ultrasound pulse during the MEG, motion-encoded phase is generated, which leads to an amplified change in the image phase when operating in the bSSFP transition band. MR-ARFI was performed on a homemade gel phantom using both the proposed technique and a spoiled gradient echo ARFI sequence with identical MEG and FUS, and ARFI images were compared. RESULTS: The bSSFP-ARFI sequence generated an ARFI image phase that is more than 5 times larger than the motion-encoded phase in a few seconds with 2DFT readout. By keeping FUS pulses as short as 1.45 ms, temperature rise was insignificant during the measurement. CONCLUSION: bSSFP-ARFI has enhanced sensitivity compared with conventional MR-ARFI pulse sequences and could provide an efficient way to visualize the focal spot. Magn Reson Med 79:1532-1537, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A spiral-based volumetric acquisition for MR temperature imaging.

PURPOSE: To develop a rapid pulse sequence for volumetric MR thermometry. METHODS: Simulations were carried out to assess temperature deviation, focal spot distortion/blurring, and focal spot shift across a range of readout durations and maximum temperatures for Cartesian, spiral-out, and retraced spiral-in/out (RIO) trajectories. The RIO trajectory was applied for stack-of-spirals 3D imaging on a real-time imaging platform and preliminary evaluation was carried out compared to a standard 2D sequence in vivo using a swine brain model, comparing maximum and mean temperatures measured between the two methods, as well as the temporal standard deviation measured by the two methods. RESULTS: In simulations, low-bandwidth Cartesian trajectories showed substantial shift of the focal spot, whereas both spiral trajectories showed no shift while maintaining focal spot geometry. In vivo, the 3D sequence achieved real-time 4D monitoring of thermometry, with an update time of 2.9-3.3 s. CONCLUSION: Spiral imaging, and RIO imaging in particular, is an effective way to speed up volumetric MR thermometry. Magn Reson Med 79:3122-3127, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome.

BACKGROUND: Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor. PURPOSE/HYPOTHESIS: To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor. STUDY TYPE: Retrospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T. FIELD STRENGTH/SEQUENCE: T2 -weighted images were acquired immediately and at 1 year posttreatment at 3T. ASSESSMENT: An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year. STATISTICAL TESTS: Statistical significance was assessed using the Wilcoxon two-tailed rank test. RESULTS: The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure - posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure. DATA CONCLUSION: In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.