Randy L. King

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.

MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh

In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumour coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5 T) guidance with one of two eight-sector, spherically curved piezoelectric transducers. The transducer, either a 1.1 or 1.7 MHz array, was driven by a multi-channel RF driving system. The transducer was mounted in an MRI-compatible manual positioning system and the rabbit was situated on top of the system. An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. Focused ultrasound surgery exposures were delivered to the thighs of seven New Zealand while rabbits. The experimental, gas-bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W or 21 W continuous wave exposure for 19.5 s. The respective control sonications were 20 s exposures of 14 W, 21 W and 28 W. During the exposures, MR thermometry was obtained from the temperature dependency of the proton resonance frequency shift. MRT2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble-enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise within the first 4 s and higher overall temperatures than the sonications without bubble formation. The spatial temperature maps and the thermal dose maps derived from the MRI thermometry closely correlated with the resulting lesion as examined by T2-weighted imaging. The lesions created with the gas-bubble-enhanced heating exposures were 2-3 times larger by volume, consistently more spherical in shape and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo. MRI thermometry techniques were successfully used to monitor the thermal effects mediated by the bubble-enhanced exposures.

In vivo demonstration of noninvasive thermal surgery of the liver and kidney using an ultrasonic phased array

A 256-element, continuous-wave ultrasonic phased array has been used to thermally coagulate deep-seated liver and kidney tissue. The array elements were formed on a 1-3 piezocomposite bowl with a 10-cm radius of curvature and 12-cm diameter. The 0.65 x 0.65 cm2 projection elements were driven at 1.1 MHz by a custom-built amplifier system. A series of in vivo porcine experiments demonstrated the ability to coagulate liver and kidney tissue using the large-scale phased array. The temperature response of the treatment was guided and monitored using magnetic resonance (MR) images. Focal lesion volumes greater than 0.5 cm3 in kidney and 2 cm3 in liver were formed from a single 20-s sonication.

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.

MRI-guided focused ultrasound surgery in the brain: Tests in a primate model

MRI‐guided focused ultrasound was tested in the brains of rhesus monkeys. Locations up to 4.8 cm deep were targeted. Focal heating was observed in all cases with MRI‐derived temperature imaging. Subthreshold heating was observed at the focus when the ultrasound beam was targeted with low power sonications, and in the ultrasound beam path during high‐power exposures. Lethal temperature values and histologically confirmed tissue damage were confined to the focal zone (e.g., not in the ultrasound beam path), except when the focus was close to the bone. In that case, damage to the neighboring brain tissue was observed. Focal lesions were observed on histological examination and, in some cases, in MR images acquired immediately after the ultrasound exposures. The capabilities demonstrated in this study will be of benefit for clinical ultrasound therapies in the brain. Magn Reson Med 49:1188–1191, 2003.

MRI monitoring of heating produced by ultrasound absorption in the skull: in vivo study in pigs.

The purpose of this study was to test the utility of MR thermometry for monitoring the temperature rise on the brain surface and in the scalp induced by skull heating during ultrasound exposures. Eleven locations in three pigs were targeted with unfocused ultrasound exposures (frequency = 690 kHz; acoustic power = 8.2–16.5 W; duration = 20 s). MR thermometry (a chemical shift technique) showed an average temperature rise in vivo of 2.8°C ± 0.6°C and 4.4°C ± 1.4°C on the brain surface and scalp, respectively, at an acoustic power level of 10 W. The temperature rise on the scalp agreed with that measured with a thermocouple probe inserted adjacent to the skull (average temperature rise = 4.6°C ± 1.0°C). Characterization of the transducer showed that the average acoustic intensity was 1.3 W/cm2 at an acoustic power of 10 W. The ability to monitor the temperature rise next to the skull with MRI‐based thermometry, as shown here, will allow for safety monitoring during clinical trials of transcranial focused ultrasound. Magn Reson Med 51:1061–1065, 2004.

The use of quantitative temperature images to predict the optimal power for focused ultrasound surgery: in vivo verification in rabbit muscle and brain.

In this study, we investigated the use of MRI-derived thermal imaging for determining the exposure parameters for focused ultrasound (FUS) surgery. Since the temperature rise induced by a FUS beam scales linearly with power, the temperature maps acquired during subthreshold sonications can be used to determine the power necessary to produce thermal tissue damage with a desired size. Thermal images acquired during multiple sonications delivered at different locations in rabbit thigh muscle and brain tissue in vivo were analyzed to test this hypothesis. First, the linearity of the induced temperature rise with the acoustic power was tested. Next, the temperature maps acquired during preliminary low power sonications were scaled up until the estimated size of the tissue damage was equal to the tissue damage size of subsequent high power sonications. A threshold thermal dose was used to estimate the onset of thermal damage. The predicted power (based on amount of scaling required to reach the target size) was then compared to the true high power value. Overall, the temperature rise varied linearly with power (slope of deltaThigh/deltaTlow vs Power(high)/Power(low) = 0.97, 0.93 for pairs of sonications at each location in brain, muscle). The predicted power matched the true high power in the brain sonications (slope = 1.04). The predicted power underestimated the true high power in the muscle sonications (slope = 0.87). This under-prediction was due to a deviation from linearity in those cases where tissue damage was detected in subsequent MR images (slope of deltaThigh/deltaTlow vs Power(high)/Power(low) = 1.02, 0.84 for no tissue damage, tissue damage). The source of this deviation was not clear from these experiments. Even with this underestimation of the power, this method will be useful because it will allow an estimate of the proper power to use during FUS surgery without exact knowledge of the tissue parameters.

Preliminary results using ultrasound transmission for image-guided thermal therapy

The feasibility of using an acoustic camera as a real-time imaging device for thermal surgery was investigated. The study compares camera images of tissue samples taken before, during and after a volume of tissue was thermally coagulated using focused ultrasound (US). This apparatus has analogous acoustic counterparts to an optical charge couple device (CCD) camera. The setup was operated in transmission mode, with a tissue sample placed between the camera and a 10-MHz illuminating transducer. A high-intensity continuous-wave US signal from a therapeutic transducer was focused inside the sample tissue. A reversible, time-dependent variation in image intensity was observed in the region of the therapeutic sonications in all tissues tested: bovine fat and porcine and rabbit livers. Correlations between image intensities and temperatures were shown; rabbit liver resulted in a correlation coefficient (R(2)) of 0.6694 and bovine fat resulted in an R(2) of 0.9455. When temperatures high enough to coagulate tissue were reached, permanent changes in the images were observed. Lesion locations and dimensions from the images were found to be comparable to the sectioned tissue samples. An R(2) of 0.919 resulted when lesion size detected from the camera was compared to the actual lesion size. Preliminary results may indicate that the camera has an application for monitoring thermal surgery.

Evaluation of the combined concentric-ring sector-vortex phased array for MR-guided ultrasound surgery

Using the combined concentric-ring sector-vortex phased array concept, the present work explores the viability of the design to treat regions of various sizes and depths. Several large-scale phased arrays were constructed to verify the array design for treatment of large deep-seated tumors. MRI guided in-vivo and ex-vivo experiments were performed to verify the extent to which the arrays power absorption pattern could be tailored for treatment of deep tissue. It is shown that the array design is able to target volumes of tissue at various distances from the transducer surface by electronically phasing the annular concentric ring elements. Furthermore, it is demonstrated that it is possible to increase the heated area in the radial plane by applying radial-sector phase rotation. Results are presented for a 12 cm diameter f/1.3 phased-array for ex-vivo and in-vivo experiments guided by MRI.

Design and evaluation of linear intracavitary ultrasound phased array for MRI-guided prostate ablative therapies

In this study, a linear, transrectal, ultrasound phased array capable of ablating large tissue volumes was fabricated and evaluated in tissue. The device was designed to be MRI compatible for use with MRI thermometry and guidance. The intracavitary applicator increases the treatable tissue volume by utilizing an ultrasonic motor to provide up to a 100-degree mechanical rotation angle to a 62-element 1D aperiodic ultrasound array. MRI guided in vivo and ex vivo experiments were performed to verify the arrays large volume ablative capabilities. The array generated 3 cm/spl times/2 cm/spl times/2 cm lesions with 8-12 half-minute sonications equally spaced in the volume. The results indicate that transrectal ultrasound coagulation of the whole prostate is feasible with the method developed.