Optimization of MR-ARFI for Human Transcranial Focused Ultrasound.

Magnetic resonance acoustic radiation force imaging (MR-ARFI) is an exceptionally promising technique to non-invasively confirm targeting accuracy and estimate exposure of low-intensity transcranial focused ultrasound stimulation. MR-ARFI uses magnetic field motion encoding gradients to visualize the MR phase changes generated by microscopic displacements at the ultrasound focus. Implementing MR-ARFI in the human central nervous system has been hindered by 1) phase distortion caused by subject motion, and 2) insufficient signal-to-noise ratio at low (<1.

The relationship between parameters and effects in transcranial ultrasonic stimulation.

Transcranial ultrasonic stimulation (TUS) is rapidly gaining traction for non-invasive human neuromodulation, with a pressing need to establish protocols that maximise neuromodulatory efficacy. In this review, we aggregate and examine empirical evidence for the relationship between tunable TUS parameters and in vitro and in vivo outcomes. Based on this multiscale approach, TUS researchers can make better informed decisions about optimal parameter settings.

Focal Volume, Acoustic Radiation Force, and Strain in Two-Transducer Regimes.

Transcranial focused ultrasound stimulation (TUS) holds promise for non-invasive neural modulation in treating neurological disorders. Most clinically relevant targets are deep within the brain (near or at its geometric center), surrounded by other sensitive regions that need to be spared clinical intervention. However, in TUS, increasing frequency with the goal of improving spatial resolution reduces the effective penetration depth.

Focal Volume, Acoustic Radiation Force, and Strain in Two-Transducer Regimes.

Transcranial ultrasound stimulation (TUS) holds promise for noninvasive neural modulation in treating neurological disorders. Most clinically relevant targets are deep within the brain (near or at its geometric center), surrounded by other sensitive regions that need to be spared clinical intervention. However, in TUS, increasing frequency with the goal of improving spatial resolution reduces the effective penetration depth.

Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology.

Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent, we found that optimal parameters for excitation or inhibition are highly distinct, the effects of which are generally conserved across brain regions and cell types.

The relationship between parameters and effects in transcranial ultrasonic stimulation.

Transcranial ultrasonic stimulation (TUS) is rapidly gaining traction for non-invasive human neuromodulation, with a pressing need to establish protocols that maximise neuromodulatory efficacy. In this review, we aggregate and examine empirical evidence for the relationship between tunable TUS parameters and in vitro and in vivo outcomes. Based on this multiscale approach, TUS researchers can make better informed decisions about optimal parameter settings.

Biophysical effects and neuromodulatory dose of transcranial ultrasonic stimulation.

Transcranial ultrasonic stimulation (TUS) has the potential to usher in a new era for human neuroscience by allowing spatially precise and high-resolution non-invasive targeting of both deep and superficial brain regions. Currently, fundamental research on the mechanisms of interaction between ultrasound and neural tissues is progressing in parallel with application-focused research. However, a major hurdle in the wider use of TUS is the selection of optimal parameters to enable safe and effective neuromodulation in humans.

ITRUSST consensus on standardised reporting for transcranial ultrasound stimulation.

As transcranial ultrasound stimulation (TUS) advances as a precise, non-invasive neuromodulatory method, there is a need for consistent reporting standards to enable comparison and reproducibility across studies. To this end, the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST) formed a subcommittee of experts across several domains to review and suggest standardised reporting parameters for low intensity TUS, resulting in the guide presented here. The scope of the guide is limited to reporting the ultrasound aspects of a study.

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 (N).

ITRUSST Consensus on Standardised Reporting for Transcranial Ultrasound Stimulation.

As transcranial ultrasound stimulation (TUS) advances as a precise, non-invasive neuromodulatory method, there is a need for consistent reporting standards to enable comparison and reproducibility across studies. To this end, the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST) formed a subcommittee of experts across several domains to review and suggest standardised reporting parameters for low intensity TUS, resulting in the guide presented here. The scope of the guide is limited to reporting the ultrasound aspects of a study.

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.

Three-layer model with absorption for conservative estimation of the maximum acoustic transmission coefficient through the human skull for transcranial ultrasound stimulation.

Transcranial ultrasound stimulation (TUS) has been shown to be a safe and effective technique for non-invasive superficial and deep brain stimulation. Safe and efficient translation to humans requires estimating the acoustic attenuation of the human skull. Nevertheless, there are no international guidelines for estimating the impact of the skull bone.

Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose-response relationship with MR-ARFI.

Neuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. The purpose of this study was to confirm that MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) in the intact large animal; and to study the impact on cortical brain oscillations. The LGN on one side was identified with T2-weighted MRI in sheep (all male, n = 9).

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.

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.

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.

Improving Transcranial Acoustic Targeting: The Limits of CT-Based Velocity Estimates and the Role of MR.

Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) enables the noninvasive treatment of the deep brain. This capacity relies on the ability to focus acoustic energy through the in-tact skull, a feat that requires accurate estimates of the acoustic velocity in individual patient skulls. In current practice, these estimates are generated using a pretreatment computed tomography (CT) scan and then registered to a magnetic resonance (MR) dataset on the day of the treatment.

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.

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

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.

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.

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.

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.

Acoustic Attenuation: Multifrequency Measurement and Relationship to CT and MR Imaging.

Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) is gaining significant acceptance as a noninvasive treatment for motion disorders and shows promise for novel applications such as blood-brain barrier opening for tumor treatment. A typical procedure relies on CT-derived acoustic property maps to simulate the transfer of ultrasound through the skull. Accurate estimates of the acoustic attenuation in the skull are essential to accurate simulations, but there is no consensus about how attenuation should be estimated from CT images and there is interest in exploring MR as a predictor of attenuation in the skull.

A preclinical study of diffusion-weighted MRI contrast as an early indicator of thermal ablation.

Purpose: Intraoperative T -weighted (T2-w) imaging unreliably captures image contrast specific to thermal ablation after transcranial MR-guided focused ultrasound surgery, impeding dynamic imaging feedback. Using a porcine thalamotomy model, we test the unproven hypothesis that intraoperative DWI can improve dynamic feedback by detecting lesioning within 30 minutes of transcranial MR-guided focused ultrasound surgery.

Methods: Twenty-five thermal lesions were formed in six porcine models using a clinical transcranial MR-guided focused ultrasound surgery system.