Global sonication of the human intracranial space via a jumbo planar transducer.

Contrary to conditioning a Focused Ultrasound (FUS) beam to sonicate a localized region of the human brain, the goal of this investigation was to explore the prospect of distributing homogeneous ultrasound energy over the entire brain space with a large cranium-wide ultrasound beam. Recent ultrasound preclincal studies utilizing large or whole brain stimulation regions create a demand for expanding the treatment envelope of transcranial pulsed-low intensity ultrasound towards Global Brain Sonication (GBS) for potential human investigation. Here, we conduct ultrasound field characterizations when transmitting pulsed ultrasound through human skull specimens using a 1-3 piezocomposite planar transducer operating at 464 kHz with an active single-element surface of 30 × 30 cm. Through computational simulation and hydrophone scanning methodology, ultrasound wave behavior and dose homogeneity in the brain space were evaluated under various trajectories of sonication using the planar transducer. Clinically relevant pulse parameters used for transcranial therapeutic ultrasound applications were used in the experiments. Simulations and empirical testing revealed that dose homogeneity and acoustic intensity over the brain space are influenced by sonication trajectory, skull lens effects, and acoustic wave reflections. The transducer can emit a spatial peak pulse average intensity of 4.03 W/cm2 (0.24 MPa) measured in the free-field at 464 kHz with electrical power of 1 kW. The simulation showed that approximately 99 % of the cranial volume was exposed with <30 % of the maximum external acoustic intensity being transmitted into the skull. The transmission loss across all sonication trajectories is similar to previously reported FUS studies. A marker for GBS dose homogeneity is introduced to score the ultrasound pressure field uniformity in the intracranial space. Results of this study identify the initial challenges of exposing the entire human brain space with ultrasound using a large cranium-wide sonication beam intended for global brain therapeutic modulation.

Feasibility of Upper Cranial Nerve Sonication in Human Application via Neuronavigated Single-Element Pulsed Focused Ultrasound.

Sonicating deep brain regions with pulsed focused ultrasound using magnetic resonance imaging-guided neuronavigation single-element piezoelectric transducers is a new area of exploration for neuromodulation. Upper cranial nerves such as the trigeminal nerve and other nerves responsible for sensory/motor functions in the head may be potential targets for ultrasound pain therapy. The location of upper cranial nerves close to the skull base poses additional challenges when compared with conventional cortical or middle brain targets. In the work described here, a series of computational and empirical testing methods using human skull specimens were conducted to assess the feasibility of sonicating the trigeminal pathway near the sphenoid bone region. The results indicate a transducer with a focal length of 120 mm and diameter of 85 mm (350 kHz) can deliver sonication to upper cranial nerve regions with spatial accuracy comparable to that of focused ultrasound brain targets used in previous human studies. Temperature measurements in cortical bone and in the skull base with embedded thermocouples yield evidence of minimal bone heating. Conventional pulse parameters were found to cause reverberation interference patterns near the cranial floor; therefore, changes in pulse cycles and pulse repetition frequency were examined for reducing standing waves. Limitations and considerations for conducting ultradeep focal targeting in human applications are discussed.

Focused Ultrasound Platform for Investigating Therapeutic Neuromodulation Across the Human Hippocampus.

Pulsed low-intensity focused ultrasound (PLIFUS) has shown promise in inducing neuromodulation in several animal and human studies. Therefore, it is of clinical interest to develop experimental platforms to test repetitive PLIFUS as a therapeutic modality in humans with neurologic disorders. In the study described here, our aim was to develop a laboratory-built experimental device platform intended to deliver repetitive PLIFUS across the hippocampus in seizure onset zones of patients with drug-resistant temporal lobe epilepsy. The system uses neuronavigation targeting over multiple therapeutic sessions. PLIFUS (548 kHz) was emitted across multiple hippocampal targets in a human subject with temporal lobe epilepsy using a mechanically steered piezoelectric transducer. Stimulation was delivered up to 2.25 W/cm2 spatial peak temporal average intensity (free-field equivalent), with 36%-50% duty cycle, 500-ms sonications and 7-s inter-stimulation intervals lasting 140 s per target and repeated for multiple sessions. A first-in-human PLIFUS course of treatment was successfully delivered using the device platform with no adverse events.

Virtual Brain Projection for Evaluating Trans-skull Beam Behavior of Transcranial Ultrasound Devices.

Focused ultrasound single-element piezoelectric transducers constitute a promising method to deliver ultrasound to the brain in low-intensity applications, but are subject to defocusing and high attenuation because of transmission through the skull. Here, a novel virtual brain projection method is used to superimpose a magnetic resonance image of the brain in ex vivo human skulls to provide targets during trans-skull focused ultrasound single-element piezoelectric transducer pressure field mapping. Positions of the transducer, skull and hydrophone are tracked in real time using a stereoscopic navigation camera and 3-D Slicer software. Virtual targets of the left dorsolateral prefrontal cortex, left hippocampus and cerebellar vermis were chosen to illustrate the method's flexibility in evaluating focal-zone beam distortion and attenuation. The regions are of interest as non-invasive brain stimulation targets in the treatment of neuropsychiatric disorders via repeated ultrasound exposure. The technical approach can facilitate the assessment of transcranial ultrasound device operator positioning reliability, intracranial beam behavior and computational model validation.

Scalp sensor for simultaneous acoustic emission detection and electroencephalography during transcranial ultrasound.

Focused ultrasound is now capable of noninvasively penetrating the intact human skull and delivering energy to specific areas of the brain with millimeter accuracy. The ultrasound energy is supplied in high-intensities to create brain lesions or at low-intensities to produce reversible physiological interventions. Conducting acoustic emission detection (AED) and electroencephalography (EEG) during transcranial focused ultrasound may lead to several new brain treatment and research applications. This study investigates the feasibility of using a novel scalp senor for acquiring concurrent AED and EEG during clinical transcranial ultrasound. A piezoelectric disk is embedded in a plastic cup EEG electrode to form the sensor. The sensor is coupled to the head via an adhesive/conductive gel-dot. Components of the sensor prototype are tested for AED and EEG signal quality in a bench top investigation with a functional ex vivo skull phantom.

Simultaneous magnetic resonance and optical elastography acquisitions: Comparison of displacement images and shear modulus estimations using a single vibration source.

The mechanical properties of tissue are sensitive to pathological changes, which is the basis for using dynamic elastography as a diagnostic tool. The purpose of this study is a concurrent cross-modality comparison of two dynamic elastography methods, Magnetic Resonance Elastography (MRE) and Scanning Laser Doppler Vibrometry (SLDV) using a single vibration source method. Cylindrical soft tissue mimicking specimens of Plastisol and Ecoflex are stimulated with 60, 100, 150, and 250 Hz sinusoidal vibration during imaging. Specimen stiffness was also varied by adjusting the softener amount in each material. Displacement fields acquired using the two methods show similarity in wave front geometry at all frequencies. Magnetic Resonance Elastography (MRE) with 3D inversion and Optical Elastography (OE) with averaged 1D curve fitting were used to derive complex shear moduli from each imaging modality. MRE and OE shear storage modulus (n = 3) results were closest at 150 Hz with Plastisol G' (MRE) = 9.03 ±â€¯0.43 kPa and G' (OE) = 8.46 ±â€¯0.14 kPa while Ecoflex was G' (MRE) = 15.71 ±â€¯0.95 kPa and G' (OE) = 13.71 ±â€¯0.03 kPa. Correlation between MRE and OE complex shear moduli related by all 36 coupled scans performed during this study yield a Pearson's correlation of ρ = 0.88 with p < 0.001 for G' (storage modulus) and ρ = 0.85 with p < 0.001 for G" (loss modulus). The simultaneous imaging approach yields stiffness values within the same range and acceptable error margins for MRE and OE.

A dual-mode hemispherical sparse array for 3D passive acoustic mapping and skull localization within a clinical MRI guided focused ultrasound device.

Previous work has demonstrated that passive acoustic imaging may be used alongside MRI for monitoring of focused ultrasound therapy. However, past implementations have generally made use of either linear arrays originally designed for diagnostic imaging or custom narrowband arrays specific to in-house therapeutic transducer designs, neither of which is fully compatible with clinical MR-guided focused ultrasound (MRgFUS) devices. Here we have designed an array which is suitable for use within an FDA-approved MR-guided transcranial focused ultrasound device, within the bore of a 3 Tesla clinical MRI scanner. The array is constructed from 5 × 0.4 mm piezoceramic disc elements arranged in pseudorandom fashion on a low-profile laser-cut acrylic frame designed to fit between the therapeutic elements of a 230 kHz InSightec ExAblate 4000 transducer. By exploiting thickness and radial resonance modes of the piezo discs the array is capable of both B-mode imaging at 5 MHz for skull localization, as well as passive reception at the second harmonic of the therapy array for detection of cavitation and 3D passive acoustic imaging. In active mode, the array was able to perform B-mode imaging of a human skull, showing the outer skull surface with good qualitative agreement with MR imaging. Extension to 3D showed the array was able to locate the skull within ±2 mm/2° of reference points derived from MRI, which could potentially allow registration of a patient to the therapy system without the expense of real-time MRI. In passive mode, the array was able to resolve a point source in 3D within a ±10 mm region about each axis from the focus, detect cavitation (SNR ~ 12 dB) at burst lengths from 10 cycles to continuous wave, and produce 3D acoustic maps in a flow phantom. Finally, the array was used to detect and map cavitation associated with microbubble activity in the brain in nonhuman primates.