Objective This work evaluated the clinical feasibility of transcranial MRI-guided focused ultrasound surgery (TcMRgFUS). Methods In initial trials in three glioblastoma patients, multiple focused ultrasound exposures were applied up to maximum acoustic power available. Offline analysis of the MR temperature images evaluated the temperature changes at the focus and brain surface. Instrumentation The method combines a hemispherical phased array transducer and patient-specific treatment planning based on acoustic models with feedback control based on MR temperature imaging to overcome the effects of the skull and allow for controlled and precise thermal ablation in the brain. Technical Development TcMRgFUS offers a potential noninvasive alternative to surgical resection. Results We found that it was possible to focus an ultrasound beam transcranially into the brain and to visualize the heating with MR temperature imaging. While we were limited by the device power available at the time and thus appeared 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. Conclusion While significant hurdles remain, these findings are a major step forward in producing a completely noninvasive alternative to surgical resection for brain disorders.

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.

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 T 2 and contrast-enhanced T 1 -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.

Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.

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A new transskull propagation technique, which deliberately induces a shear mode in the skull bone, is investigated. Incident waves beyond Snell's 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 skull's 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.

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.

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