P. Jason White

500-Element Ultrasound Phased Array System for Noninvasive Focal Surgery of the Brain: A Preliminary Rabbit Study With Ex Vivo Human Skulls

The aim of this study was to test a prototype MRI‐compatible focused ultrasound phased array system for trans‐skull brain tissue ablation. Rabbit thigh muscle and brain were sonicated with a prototype, hemispherical 500‐element ultrasound phased array operating at frequencies of 700–800 kHz. An ex vivo human skull sample was placed between the array and the animal tissue. The temperature elevation during 20–30‐sec sonications was monitored using MRI thermometry. The induced focal lesions were observed in T2 and contrast‐enhanced T1‐weighted fast spin echo images. Whole brain histology evaluation was performed after the sonications. The results showed that sharp temperature elevations can be produced both in the thigh muscle and in the brain. High‐power sonications (600–1080 W) produced peak temperatures up to 55°C and focal lesions that were consistent with thermal tissue damage. The lesion size was found to increase with increasing peak temperature. The device was then modified to operate in the orientation that will be used in the clinic and successfully tested in phantom experiments. As a conclusion, this study demonstrates that it is possible to create ultrasound‐induced lesions in vivo through a human skull under MRI guidance with this large‐scale phased array. Magn Reson Med 52:100–107, 2004.

A Magnetic Resonance Imaging–Compatible, Large-Scale Array for Trans-Skull Ultrasound Surgery and Therapy

Advances in ultrasound transducer array and amplifier technologies have prompted many intriguing scientific proposals for ultrasound therapy. These include both mildly invasive and noninvasive techniques to be used in ultrasound brain surgery through the skull. In previous work, it was shown how a 500‐element hemisphere‐shaped transducer could correct the wave distortion caused by the skull with a transducer that operates at a frequency near 0.8 MHz. Because the objective for trans‐skull focusing is its ultimate use in a clinical context, a new hemispheric phased‐array system has now been developed with acoustic parameters that are optimized to match the values determined in preliminary studies.

An Intraoperative Brain-shift Monitor Using Shear-mode Transcranial Ultrasound: Preliminary Results

A device that uses the shear mode of transcranial ultrasound transmission for intraoperative monitoring has been designed, constructed, and tested with 10 human subjects. Magnetic resonance (MR) images were obtained with the device spatially registered to the MR reference coordinates. Peaks in both the ultrasound and MR signals were identified and analyzed both for spatial localization and signal-to-noise ratio (SNR). The first results aimed towards validating the prototype device against MRI have demonstrated excellent correlation (n = 38, R2 = 0.9962) between the structural localization abilities of the two modalities. In addition, the overall SNR of the ultrasound backscatter signals (n = 38, SNR = 25.4plusmn5.2 dB) was statistically equivalent to that of the MR data (n = 38, SNR = 22.5plusmn4.8 dB).

Nonthermal ablation of deep brain targets: A simulation study on a large animal model

Purpose: Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low-duty-cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood–brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects. Methods: The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI-guided FUS system. Low-duty-cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models. Results: The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive cavitation detector was used to measure the inertial cavitation threshold and to determine the pressure amplitude to use for ablation. Simulations of the detector’s acoustic field suggest that its maximum sensitivity was in the lower part of the main beam, which may have led to excessive exposure levels in the experiments that may have contributed to damage in the prefocal area. Conclusions: Overall, these results suggest that case-specific full wave simulations before the procedure can be useful to predict the focal and the prefocal side lobes and the extent of the resulting bioeffects produced by nonthermal ablation. Such simulations can also be used to optimally position passive cavitation detectors. The disagreement between the simulations and the experiments in the postfocal region may have been due to shielding of the ultrasound field due to microbubble activity in the focal region. Future efforts should include the effects of microbubble activity and vascularization on the pressure field.

Two-dimensional image reconstruction with spectrally-randomized ultrasound signals

An ultrasound imaging method using unfocused frequency-randomized transmissions and image reconstruction from data received by a single element is experimentally demonstrated. The elements of an ultrasound imaging array are randomly assigned different frequencies and driven by a multicycle sinusoidal burst. The resulting acoustic field is spectrally unique and target localization is possible based on the a priori knowledge of this field. A 64-element phased array driven by arbitrary waveform generators is used in the experiments. Transmission frequencies range from 2.00 to 2.64 MHz with 10 kHz resolution. One element of the array is reserved for receiving backscattered signals and an image is reconstructed from the signals received by this single element. Reconstruction is based on cross-correlation of the received data with transmitted bursts to obtain radial elliptical projections. Multiple projections are obtained from single received data, which are back-projected to obtain an image. Successful target localization is made possible through multiple frequency-randomized acquisitions. The performance of the method is measured using images of a single point target. These images are quantified and analyzed in terms of their point spread function (PSF) and SNR. Optimum imaging parameters, such as the number of acquisitions, transmit burst length, and number of possible receivers, are obtained through further analysis of SNR. Images obtained with the frequency-randomized transmission method compared well with the performance measurements of a typical B-mode acquisition. It is demonstrated that the frequencyrandomized method provides images superior to B-mode images in terms of PSF. The two-point discrimination threshold is measured to be 2 mm in the lateral and azimuth directions.

The feasibility of noninvasive image‐guided treatments of brain disorders by focused ultrasound

Brain disorders, such as tumors, functional problems, etc., are difficult to treat and the invasive interventions often disturb surrounding brain tissue, resulting in complications. In addition, the delivery of therapeutic agents to the brain via the blood supply is often impossible because the blood brain barrier protects the brain tissue from foreign molecules. Our hypothesis has been that transcranial therapeutic ultrasound exposures can be delivered with an optimized phased‐array system. We have demonstrated that highly focused therapeutic ultrasound beams can be accurately delivered through an intact human skull noninvasively. Furthermore, we demonstrated using ex vivo human skulls that we can use CT‐derived information to predict the phase shifts required for correcting the wave distortion. We have also developed a method to focally disrupt the blood brain barrier without damaging the neurons in the targeted tissue volume. This may allow delivery of therapeutic or diagnostic agents into image‐specif...

Frequency‐dependent ultrasound transmission through the human skull

The development of large‐aperture multiple‐source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled acoustic energy delivery into the brain parenchyma. 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. To determine the efficacy of frequency modulation with such a device, this study examines the frequency dependence of ultrasound transmission in the range of 0.6–1.4 MHz through a series of seven points on each of three ex vivo human calvaria. Using broadband pulses, it is shown that the reflected spectra from the skull reveal information regarding the transmission energies at specific frequencies. In fact, there exists an inverse correlation between the reflected pressure amplitude and the transmitted pressure amplitude such that, f...

Feasibility of shear‐mode transcranial ultrasound imaging

Despite ultrasound’s potential to provide a low cost method for imaging blood flow and diagnosing certain brain disorders, distortion and low signal to noise ratios caused by the skull have severely limited the use of existing clinical devices, such as trancranial Doppler sonography. Presently we investigate the potential to propagate ultrasound through the skull with reduced distortion and higher signal amplitudes by using high incident angles. In such cases the ultrasound angle of entry is set beyond Snell’s critical angle for the longitudinal pressure wave, so that propagation in the bone is purely due to a shear wave. This wave then converts back to a longitudinal acoustic wave in the brain. This conversion from a longitudinal wave (skin) to a shear wave (skull) and again to a longitudinal wave (brain) does not necessarily produce a highly distorted or small‐amplitude wave. Basic images and measurements of shear speed‐of‐sound and attenuation values for ex vivo human skull bone will be presented for f...

Focusing ultrasound through bone and tissue layers in the wave vector frequency domain

A planar projection algorithm is combined with ray theory to propagate ultrasound through an arbitrary number of randomly oriented isotropic tissue layers. The propagation information can then be used for beam aberration correction. This method, which is intended for applications in therapeutic ultrasound, calculates or measures the space–time pressure field in a plane and uses wave vector frequency‐domain methods to project the field through the media. The approach requires information obtained a priori from MRI or CT images and is valid for longitudinal propagation through tissue and bone layers at low incident angles. The algorithm is verified by propagating fields created by a 1.5 MHz, 104‐element therapy array through a combination of layered materials, including plastic phantoms, fresh porcine fat‐muscle layers, and ex vivo human bone samples.

A structure function constraint for stable least‐squares inversion of reflection data

High‐frequency seismic profiles often indicate that the near‐surface sediments in shallow water are layered on scales larger than about 0.5 m but not on smaller scales. Consequently, for a meaningful least‐squares inversion of reflection data using a horizontally stratified sediment model, the wavelengths in the insonifying wave should be long enough to ‘‘average out’’ the small‐scale sediment structure. With such a finite wavelength inversion, the sediment model must include some resolution constraints in order to yield a stable inversion. A common approach, for example, is to consider a stack of homogeneous layers where each layer is thicker than, say, a quarter of a wavelength. An alternative constraint method based on a structure function or, equivalently, an autocorrelation function, is presented. It is shown that with a structure function constraint, a stable inversion is obtained even if the layered structure approaches a continuous profile. Without the constraint, the inversion becomes meaningless...