Evaluation of Pseudorandom Sonications for Reducing Cavitation With a Clinical Neurosurgery HIFU Device.

Transcranial high-intensity focused ultrasound is used in clinics for treating essential tremor (ET) and proposed for many other brain disorders. This promising treatment modality requires high energy resulting eventually in undesired cavitation and potential side effects. The goals of the present work were: 1) to evaluate the potential increase of the cavitation threshold using pseudorandom gated sonications and 2) to assess the heating capabilities with such sonications. The experiments were performed with the transcranial magnetic resonance (MR)-compatible ExAblate Neuro system (InSightec, Haifa, Israel) operating at a frequency of 670 kHz, either in continuous wave (CW) or with pseudorandom gated sonications of 50% duty cycle. Cavitation activity with the two types of sonications was compared using chemical dosimetry of hydroxyl radical production at the focus of the transducer, after propagation in water or through a human skull. Heating trials were performed in a hydrogel tissue-mimicking material embedded in a human skull to mimic a clinical situation. The temperature was measured by MR-thermometry when focusing at the geometrical focus and steering off focus up to 15 mm. Compared with CW sonications, the use of gated sonication did not affect the efficiency (60%) nor the steering abilities of the transducer. After propagation through a human skull, gated sonication required a higher pressure level (10 MPa) to initiate cavitation as compared with CW (5.8 MPa). Moreover, at equivalent acoustic power above the cavitation threshold, the level of cavitation activity initiated with gated sonications was much lower with gated sonication than with continuous sonications, almost half after propagation through water and one-third after propagation through a skull. This lowered cavitation activity may be attributed to a breaking of the dynamic of the bubbles moving from monochromatic to more broadband sonications and to the removal of residual cavitation nuclei between pulses with gated sonications. The heating capability was not affected by the gated sonications, and similar temperature increases were reached at focus with both types of sonications when sonicating at equivalent acoustic power, both in water or after propagation through a human skull (+15 °C at 325 W for 10 s). These data, acquired with a clinical system, suggest that gated sonication could be an alternative to continuous sonications when cavitation onset is an issue.

Head phantoms for transcranial focused ultrasound.

PURPOSE: In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research. METHODS: Three different models of phantoms are developed and tested to be accurate, repeatable experimental options to provide means to further this research. The three models are a cadaver, a gel-filled skull, and a head mold containing a skull and filled with gel that mimics the brain and the skin. Each was positioned in a clinical tcMRgFUS system and sonicated at 1100 W (acoustic) for 12 s at different locations. Maximum temperature rise as measured by MR thermometry was recorded and compared against clinical data for a similar neurosurgical target. Results are presented as heating efficiency in units (°C/kW/s) for direct comparison to available clinical data. The procedure for casting thermal phantom material is presented. The utility of each phantom model is discussed in the context of various tcMRgFUS research areas. RESULTS: The cadaveric phantom model, gel-filled skull model, and full head phantom model had heating efficiencies of 5.3, 4.0, and 3.9 °C/(kW/s), respectively, compared to a sample clinical heating efficiency of 2.6 °C/(kW/s). In the seven research categories considered, the cadaveric phantom model was the most versatile, though less practical compared to the ex-vivo skull-based phantoms. CONCLUSIONS: Casting thermal phantom material was shown to be an effective way to prepare tissue-mimicking material for the phantoms presented. The phantom models presented are all useful in tcMRgFUS research, though some are better suited to a limited subset of applications depending on the researchers needs.

FEA modeling of CMUT with membrane stand-off structures to enable selectable frequency-mode operation.

A selectable, dual-frequency, capacitive micro- machined ultrasonic transducer (CMUT) designed for both high-frequency imaging and low-frequency therapeutic effect is presented. A validated finite element analysis (FEA) CMUT model was used to examine the performance of the proposed dual-frequency transducer. CMUT device simulations were used to design a hybrid device incorporating stand-off structures that divide a large, low-frequency membrane into smaller, high-frequency sub-membranes when the membrane is partially collapsed so that the stand-offs contact the substrate. In low-frequency operation, simulations indicated that the peak negative pressure achieved by the hybrid device, when biased by 30.0 VDC and excited by a 2-MHz signal with 30.0 V amplitude, exceeded 190 kPa, which is sufficient for microbubble rupture. Low-frequency mode bandwidth was 93% at a center frequency of 2.1 MHz. In the high-frequency mode of operation, the device was excited by 175 Vdc and 87.5 Vac, which generated a peak negative pressure of 247 kPa. Device center frequency was 44.1 MHz with a - 6-dB fractional bandwidth of 42%.

Filled and unfilled temperature-dependent epoxy resin blends for lossy transducer substrates.

In the context of our ongoing investigation of low-cost 2-dimensional (2-D) arrays, we studied the temperature- dependent acoustic properties of epoxy blends that could serve as an acoustically lossy backing material in compact 2-D array-based devices. This material should be capable of being machined during array manufacture, while also providing adequate signal attenuation to mitigate backing block reverberation artifacts. The acoustic impedance and attenuation of 5 unfilled epoxy blends and 2 filled epoxy blends - tungsten and fiberglass fillers - were analyzed across a 35 degrees C temperature range in 5 degrees C increments. Unfilled epoxy materials possessed an approximately linear variation of impedance and sigmoidal variation of attenuation properties over the range of temperatures of interest. An intermediate epoxy blend was fitted to a quadratic trend line with R(2) values of 0.94 and 0.99 for attenuation and impedance, respectively. It was observed that a fiberglass filler induces a strong quadratic trend in the impedance data with temperature, which results in increased error in the characterization of attenuation and impedance. The tungsten-filled epoxy was not susceptible to such problems because a different method of fabrication was required. At body temperature, the tungsten-filled epoxy could provide a 44 dB attenuation of the round-trip backing block echo in our application, in which the center frequency is 5 MHz and the backing material is 1.1 mm thick. This is an 11 dB increase in attenuation compared with the fiberglass-filled epoxy in the context of our application. This work provides motivation for exploring the use of custom-made tungsten-filled epoxy materials as a substitute PCB-based substrate to provide electrical signal interconnect.

Fabrication and evaluation of fully-sampled, two-dimensional transducer array for "Sonic Window" imaging system.

A low-cost, fully-sampled, 3600 element 2D transducer array operating at 5 MHz and designed for use in a hand-held ultrasound system is described here. Four array configurations are presented--(1) array with both matching and pedestal backing layers, (2) array with a matching layer but no backing pedestal, (3) array with a backing pedestal but no matching layer, and (4) array with neither matching layer nor backing pedestal. Each array was characterized in terms of impedance measurements, pulse-echo response, and experimental beamprofile. Comparative finite element analysis simulations are also presented. Average estimated active element yield for the four arrays was 94%. The array with pedestal layer proved the most promising, providing a 26% bandwidth and a 1.7 dB improvement in sensitivity with respect to the array with neither pedestal nor matching layer. Although this bandwidth is acceptable for our specific application (C-scan imaging), reverberations within the substrate material remain a potential challenge. We are currently working to fabricate a custom PCB material to address this concern, and may also consider using a pre-compensated transmit waveform or matched digital filter approach to further reduce the effects of such reverberations.