Greg T. Clement

Transcranial magnetic resonance imaging- guided focused ultrasound surgery of brain tumors: initial findings in 3 patients.

OBJECTIVEThis work evaluated the clinical feasibility of transcranial magnetic resonance imaging–guided focused ultrasound surgery. METHODSTranscranial magnetic resonance imaging–guided focused ultrasound surgery offers a potential noninvasive alternative to surgical resection. The method combines a hemispherical phased-array transducer and patient-specific treatment planning based on acoustic models with feedback control based on magnetic resonance temperature imaging to overcome the effects of the cranium and allow for controlled and precise thermal ablation in the brain. In initial trials in 3 glioblastoma patients, multiple focused ultrasound exposures were applied up to the maximum acoustic power available. Offline analysis of the magnetic resonance temperature images evaluated the temperature changes at the focus and brain surface. RESULTSWe found that it was possible to focus an ultrasound beam transcranially into the brain and to visualize the heating with magnetic resonance temperature imaging. Although we were limited by the device power available at the time and thus seemed to not achieve thermal coagulation, extrapolation of the temperature measurements at the focus and on the brain surface suggests that thermal ablation will be possible with this device without overheating the brain surface, with some possible limitation on the treatment envelope. CONCLUSIONAlthough significant hurdles remain, these findings are a major step forward in producing a completely noninvasive alternative to surgical resection for brain disorders.

A non-invasive method for focusing ultrasound through the human skull

A technique for focusing ultrasound through the human skull is described and verified. The approach is based on a layered wavevector-frequency domain model, which propagates ultrasound from a hemisphere-shaped transducer through the skull using input from CT scans of the head. The algorithm calculates the driving phase of each transducer element in order to maximize the signal at the intended focus. This approach is tested on ten ex vivo human skulls using a 0.74 MHz, 320-element array. A stereotaxic reference frame is affixed to the skulls in order to provide accurate registration between the CT images and the transducer. The focal quality is assessed with a hydrophone placed inside the skull. In each trial the phase correction algorithm successfully restored the focus inside the skull at a location within 1 mm from the intended focal point. The results demonstrate the feasibility of using the method for completely non-invasive ultrasound brain surgery and therapy.

A hemisphere array for non-invasive ultrasound brain therapy and surgery

Ultrasound phased arrays may offer a method for non-invasive deep brain surgery through the skull. In this study a hemispherical phased array system is developed to test the feasibility of trans-skull surgery. The hemispherical shape is incorporated to maximize the penetration area on the skull surface, thus minimizing unwanted heating. Simulations of a 15 cm radius hemisphere divided into 11, 64, 228 and 512 elements are presented. It is determined that 64 elements are sufficient for correcting scattering and reflection caused by trans-skull propagation. An optimal operating frequency near 0.7 MHz is chosen for the array from numerical and experimental thermal gain measurements comparing the power between the transducer focus and the skull surface. A 0.665 MHz air-backed PZT array is constructed and evaluated. The array is used to focus ultrasound through an ex vivo human skull and the resulting fields are measured before and after phase correction of the transducer elements. Finally, to demonstrate the feasibility of trans-skull therapy, thermally induced lesions are produced through a human skull in fresh tissue placed at the ultrasound focus inside the skull.

Investigation of a large-area phased array for focused ultrasound surgery through the skull

Non-invasive treatment of brain disorders using ultrasound would require a transducer array that can propagate ultrasound through the skull and still produce sufficient acoustic pressure at a specific location within the brain. Additionally, the array must not cause excessive heating near the skull or in other regions of the brain. A hemisphere-shaped transducer is proposed which disperses the ultrasound over a large region of the skull. The large surface area covered allows maximum ultrasound gain while minimizing undesired heating. To test the feasibility of the transducer two virtual arrays are simulated by superposition of multiple measurements from an 11-element and a 40-element spherically concave test array. Each array is focused through an ex vivo human skull at four separate locations around the skull surface. The resultant ultrasound field is calculated by combining measurements taken with a polyvinylidene difluoride needle hydrophone providing the fields from a 44-element and a 160-element virtual array covering 88% and 33% of a hemisphere respectively. Measurements are repeated after the phase of each array element is adjusted to maximize the constructive interference at the transducers geometric focus. An investigation of mechanical and electronic beam steering through the skull is also performed with the 160-element virtual array, phasing it such that the focus of the transducer is located 14 mm from the geometric centre. Results indicate the feasibility of focusing and beam steering through the skull using an array spread over a large surface area. Further, it is demonstrated that beam steering through the skull is plausible.

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.

Correlation of ultrasound phase with physical skull properties.

Noninvasive treatment of brain disorders using focused ultrasound (US) requires a reliable model for predicting the distortion of the field due to the skull using physical parameters obtained in vivo. Previous studies indicate that control of US phase alone is sufficient for producing a focus through the skull using a phased US array. The present study concentrates on identifying methods to estimate phase distortion. This will be critical for the future clinical use of noninvasive brain therapy. Ten ex vivo human calvaria were examined. Each sample was imaged in water using computerized tomography (CT). The information was used to determine the inner and outer skull surfaces, thickness as a function of position, and internal structure. Phase measurement over a series of points was obtained by placing a skull fragment between a transducer and a receiver with the skull normal to the transducer. Correlation was found between the skull thickness and the US phase shift. A linear fit of the data follows that predicted by a homogeneous skull when average speed of sound 2650 m/s was used. Large variance (SD = 60 degrees, mean = 50 degrees ) indicates the additional role of internal bone speed and density fluctuations. In an attempt to reduce the variance, the skull was first studied as a three-layer structure. Next, density-dependent bone speed fluctuation was introduced to both the single-layer and three-layer models. It was determined that adjustment of the mean propagation speeds using density improves the overall phase prediction. Results demonstrate that it is possible to use thickness and density information from CT images to predict the US phase distortion induced by the skull accurately enough for therapeutic aberration correction. In addition, the measurements provide coefficients for phase dependence on skull thickness and density that can be used in clinical treatments.

A unified model for the speed of sound in cranial bone based on genetic algorithm optimization

The density and structure of bone is highly heterogeneous, causing wide variations in the reported speed of sound for ultrasound propagation. Current research on the propagation of high intensity focused ultrasound through an intact human skull for non-invasive therapeutic action on brain tissue requires a detailed model for the acoustic velocity in cranial bone. Such models have been difficult to derive empirically due to the aforementioned heterogeneity of bone itself. We propose a single unified model for the speed of sound in cranial bone based upon the apparent density of bone by CT scan. This model is based upon the coupling of empirical measurement, theoretical acoustic simulation and genetic algorithm optimization. The phase distortion caused by the presence of skull in an acoustic path is empirically measured. The ability of a theoretical acoustic simulation coupled with a particular speed-of-sound model to predict this phase distortion is compared against the empirical data, thus providing the fitness function needed to perform genetic algorithm optimization. By performing genetic algorithm optimization over an initial population of candidate speed-of-sound models, an ultimate single unified model for the speed of sound in both the cortical and trabecular regions of cranial bone is produced. The final model produced by genetic algorithm optimization has a nonlinear dependency of speed of sound upon local bone density. This model is shown by statistical significance to be a suitable model of the speed of sound in bone. Furthermore, using a skull that was not part of the optimization process, this model is also tested against a published homogeneous speed-of-sound model and shown to return an improved prediction of transcranial ultrasound propagation.

Field characterization of therapeutic ultrasound phased arrays through forward and backward planar projection

Spatial planar projection techniques propagate field measurements from a single plane in front of a transmitter to arbitrary new planes closer to or further away from the source. A linear wave vector frequency-domain projection algorithm is applied to the acoustic fields measured from several focused transducer arrays designed for ultrasound therapy. A polyvinylidene difluoride hydrophone is first scanned in a water tank over a plane using a three-dimensional positioning system to measure the complex pressure field as a function of position. The field is then projected to a series of new planes using the algorithm. Results of the projected fields are compared with direct measurements taken at corresponding distances. Excellent correlation is found between the projected and measured data. The method is shown to be accurate for use with phase-controlled field patterns, providing a rapid and accurate method for obtaining field information over a large spatial volume. This method can significantly simplify the characterization procedure required for phased-array application used for therapy. Most significantly, the wavefront propagated back to a phased array can be used to predict the field produced by different phase and amplitude settings of the array elements. A field back-projected to the source could be used as an improved source function in acoustic modeling.

Micro-receiver guided transcranial beam steering

A new method for focusing ultrasound energy in brain tissue through the skull is investigated. The procedure is designed for use with a therapeutic transducer array and a small catheter-inserted hydrophone receiver placed in the brain to guide the arrays focus. When performed at high-intensity, a focal intensity on the order of several hundred watts per centimeter-squared is achieved, and cells within a target volume are destroyed. The present study tests the feasibility and range of the method using an ex vivo human skull. Acoustic phase information is obtained from the stationary receiver and used to electrically shift the beam to new locations as well as correct for aberrations due to the skull. The method is applied to a 104-element 1.1 MHz array and a 120-element 0.81 MHz array. Using these array configurations, it is determined that the method can reconstruct and steer a focus over a distance of 50 mm. Application of this minimally invasive technique for ultrasound brain therapy and surgery also is investigated in vitro with a 64-element 0.664 MHz hemisphere array designed for transskull surgery. Tissue is placed inside of a skull and a catheter-inserted receiver is inserted into the tissue. A focus intense enough to coagulate the tissue is achieved at a predetermined location 10 mm from the receiver, the maximum distance that this large element array can electronically steer the focus.

Comparison of modelled and observed in vivo temperature elevations induced by focused ultrasound: implications for treatment planning.

Two numerical models for predicting the temperature elevations resulting from focused ultrasound heating of muscle tissue were tested against experimental data. Both models use the Rayleigh-Sommerfeld integral to calculate the pressure field from a source distribution. The first method assumes a source distribution derived from a uniformly radiating transducer whereas the second uses a source distribution obtained by numerically projecting pressure field measurements from an area near the focus backward toward the transducer surface. Both of these calculated ultrasound fields were used as heat sources in the bioheat equation to calculate the temperature elevation in vivo. Experimental results were obtained from in vivo rabbit experiments using eight-element sector-vortex transducers at 1.61 and 1.7 MHz and noninvasive temperature mapping with MRI. Results showed that the uniformly radiating transducer model over-predicted the peak temperature by a factor ranging from 1.4 to 2.8, depending on the operating mode. Simulations run using the back-projected sources were much closer to experimental values, ranging from 1.0 to 1.7 times the experimental results, again varying with mode. Thus, a significant improvement in the treatment planning can be obtained by using actual measured ultrasound field distributions in combination with backward projection.