P.J. White

Enhanced ultrasound transmission through the human skull using shear mode conversion

A new transskull propagation technique, which deliberately induces a shear mode in the skull bone, is investigated. Incident waves beyond Snells critical angle experience a mode conversion from an incident longitudinal wave into a shear wave in the bone layers and then back to a longitudinal wave in the brain. The skulls shear speed provides a better impedance match, less refraction, and less phase alteration than its longitudinal counterpart. Therefore, the idea of utilizing a shear wave for focusing ultrasound in the brain is examined. Demonstrations of the phenomena, and numerical predictions are first studied with plastic phantoms and then using an ex vivo human skull. It is shown that at a frequency of 0.74 MHz the transskull shear method produces an amplitude on the order of--and sometimes higher than--longitudinal propagation. Furthermore, since the shear wave experiences a reduced overall phase shift, this indicates that it is plausible for an existing noninvasive transskull focusing method [Clement, Phys. Med. Biol. 47(8), 1219-1236 (2002)] to be simplified and extended to a larger region in the brain.

Local frequency dependence in transcranial ultrasound transmission

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

A full-wave Helmholtz model for continuous-wave ultrasound transmission

A full-wave Helmholtz model of continuous-wave (CW) ultrasound fields may offer several attractive features over widely used partial-wave approximations. For example, many full-wave techniques can be easily adjusted for complex geometries, and multiple reflections of sound are automatically taken into account in the model. To date, however, the full-wave modeling of CW fields in general 3D geometries has been avoided due to the large computational cost associated with the numerical approximation of the Helmholtz equation. Recent developments in computing capacity together with improvements in finite element type modeling techniques are making possible wave simulations in 3D geometries which reach over tens of wavelengths. The aim of this study is to investigate the feasibility of a full-wave solution of the 3D Helmholtz equation for modeling of continuous-wave ultrasound fields in an inhomogeneous medium. The numerical approximation of the Helmholtz equation is computed using the ultraweak variational formulation (UWVF) method. In addition, an inverse problem technique is utilized to reconstruct the velocity distribution on the transducer which is used to model the sound source in the UWVF scheme. The modeling method is verified by comparing simulated and measured fields in the case of transmission of 531 kHz CW fields through layered plastic plates. The comparison shows a reasonable agreement between simulations and measurements at low angles of incidence but, due to mode conversion, the Helmholtz model becomes insufficient for simulating ultrasound fields in plates at large angles of incidence.

Transcranial Focused Ultrasound Surgery

The development of high-intensity ultrasound technology into a system for performing image-guided noninvasive ultrasound neurosurgery has developed at a relatively rapid pace in the past few years. Magnetic resonance imaging has contributed significantly to this development by providing a modality by which percutaneous ultrasound treatments can be preoperatively planned, intraoperatively guided and postoperatively evaluated for safety and efficacy. Especially in the case of transcranial ultrasound therapies, the structural identification and thermal monitoring of cortical structures is essential to avoid overheating at the skull-brain interface and to avoid the sonication of critical structures. This chapter briefly describes the physics of transmitting ultrasound through the skull and the technological advances that circumvented the physical limits imposed by the skull bone. The integration of magnetic resonance guidance and monitoring is detailed, along with an overview of ongoing studies with a commercially developed magnetic resonance imaging-compatible hemispherical transducer array.

The Effects of Desiccation on Skull Bone Sound Speed in Porcine Models

Pre- and postdesiccation sound speeds through ex vivo porcine skull specimens were determined by time-of-flight measurements with propagated broadband pulses centered at 0.97 MHz (Phis12.7 mm, -6-dB bandwidth = 58%). The measured longitudinal sound speed in the 13 porcine samples (predesiccation average sound speed = 1727 plusmn 57 ms-1) changed by a statistically significant +2.3% after deionized water reconstitution (paired t-test, alpha = 0.05, p = 0.0332).

Two-Dimensional Localization with a Single Diffuse Ultrasound Field Excitation

Traditional ultrasound imaging methods rely on the bandwidth and center frequency of transduction to achieve axial and radial image resolution, respectively. In this study, a new modality for spatially localizing scattering targets in a two-dimensional field is presented. In this method, the bandwidth of field excitation is high, and the center frequency is lowered such that the corresponding wavelengths are substantially larger than the target profiles. Furthermore, full two-dimensional field measurements are obtained with single send-receive sequences, demonstrating a substantial simplification of the traditional scanning techniques. Field reconstruction is based on temporal-spectral cross-correlations between measured backscatter data and a library of region of interest (ROI) backscatter data measured a priori. The transducer design is based upon a wedge-shaped geometry, which was shown to yield spatially frequency-separated bandwidths of up to 156% with center frequencies of 1.38 MHz. Initial results with these send-and-receive transducer parameters and cylindrical reflection targets in a 10-mm times 10-mm ROI demonstrate two-dimensional target localization to within 0.5 mm. Spatial localization of point scatterers is demonstrated for single and multiple scattering sites.

Testing the efficacy of Contrast Enhanced Ultrasound in detecting transplant rejection using a murine model of heart transplantation

One of the key unmet needs to improve long‐term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast‐enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High‐resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next‐generation imaging approaches to diagnose transplant rejection.

A pre-treatment planning strategy for high-intensity focused ultrasound (HIFU) treatments

Most operational protocols for HIFU procedures do not incorporate a pre-treatment planning stage comparable to the rigorous pre-treatment planning that is mandated for other modalities of radiation therapy. Ongoing studies investigating pre-treatment strategies that would improve the efficiency and effectiveness of HIFU treatments are complex in nature. Most are based on the incorporation of predictive phase-aberration corrections of propagation-path-specific phase changes. We have shown that the substantially simpler method of optimizing HIFU source placement in relation to layered tissue structures can have a significant effect on focal integrity, and that MRI scans and a wave-vector time-domain linear propagation model can potentially be used to plan for optimized source orientation. Five ex vivo bovine tissue specimens with heterogeneous tissue structures were each mounted in rigid frames with acoustic windows for HIFU transmission. A spherically-focused HIFU source (F0 = 1.502 MHz, D = 100 mm, Rc = 100 mm) was positioned to transmit though each specimen at pre-selected orientations, and the transmitted ultrasound pressure fields were scanned for a series of orientations, followed by a series of MRI scans. Ultrasound transmission simulations were performed and compared with experimental results. Analyses performed on the acoustic field scans to quantify the level of focal distortion [distortion index (DI) = 1- (the ratio between the acoustic energy within a focal zone and the total acoustic energy within the measured area] demonstrated that over the 5 specimens, at least an average of 7.3% (range 5.6% to 12.3%, SD = 2.8%) improvement in DI could be expected by source placement optimization. The accurate simulation of ultrasound propagation through heterogeneous tissue layers using MRI data was also achieved.

Transcranial ultrasound-optical transmission correlation

Although the transmission of ultrasound (US) through the skull bone has been demonstrated for both therapeutic and imaging applications, the clinical efficacy of certain transcranial US applications remains limited by the highly attenuating properties of skull bone. For those applications, the ability to pre-procedurally determine those areas of the skull that are less attenuating to US could be a tremendous asset for improving the use of US in the brain. To present a possible solution, we have hypothesized that the optical transmission intensity at points across the skull surface can be correlated with the local US transmission efficiency. The demonstration of this correlation would potentially allow for the use of integrated lasers and photodetectors within a HIFU system to create a patient-specific transmission map of the skull. We have statistically investigated the relationship between transmitted optical and US intensities over multiple points across several ex vivo human calvaria to demonstrate thi...

A pre‐treatment planning strategy for high‐intensity focused ultrasound treatments.

Most operational protocols for HIFU procedures do not incorporate a pre-treatment planning stage comparable to the rigorous pre-treatment planning that is mandated for other modalities of radiation therapy. Ongoing studies investigating pre-treatment strategies that would improve the efficiency and effectiveness of HIFU treatments are complex in nature. Most are based on the incorporation of predictive phase-aberration corrections of propagation-path-specific phase changes. We have shown that the substantially simpler method of optimizing HIFU source placement in relation to layered tissue structures can have a significant effect on focal integrity, and that MRI scans and a wave-vector time-domain linear propagation model can potentially be used to plan for optimized source orientation. Five ex vivo bovine tissue specimens with heterogeneous tissue structures were each mounted in rigid frames with acoustic windows for HIFU transmission. A spherically-focused HIFU source (F0 = 1.502 MHz, D = 100 mm, Rc = 100 mm) was positioned to transmit though each specimen at pre-selected orientations, and the transmitted ultrasound pressure fields were scanned for a series of orientations, followed by a series of MRI scans. Ultrasound transmission simulations were performed and compared with experimental results. Analyses performed on the acoustic field scans to quantify the level of focal distortion [distortion index (DI) = 1- (the ratio between the acoustic energy within a focal zone and the total acoustic energy within the measured area] demonstrated that over the 5 specimens, at least an average of 7.3% (range 5.6% to 12.3%, SD = 2.8%) improvement in DI could be expected by source placement optimization. The accurate simulation of ultrasound propagation through heterogeneous tissue layers using MRI data was also achieved.