Subha Maruvada

Development of a HIFU Phantom

The field of high intensity focused ultrasound (HIFU) is developing rapidly. For basic research, quality control, and regulatory assessment a reusable phantom that has both thermal and acoustic properties close to that of soft tissue is critical. A hydrogel‐based tissue mimicking material (TMM) has been developed that shows promise for such a phantom. The acoustic attenuation, speed of sound, B/A, thermal diffusivity and conductivity, as well as the cavitation threshold, were measured and found to mimic published values for soft tissue. The attenuation of 0.53f1.04 from 1 MHz to 8 MHz, as well as the sound speed of 1565 m/s and the tissue‐like image quality, indicate the usefulness of the TMM for ultrasound imaging applications. These properties along with the thermal conductivity of 0.58 W/m‐ °C, diffusivity of 0.15 (mm2)/s, and the ability to withstand temperatures above 95 °C make this material appropriate for HIFU applications. The TMM also allows for the embedding of thermocouples and the formation o...

Characterization of high intensity focused ultrasound transducers using acoustic streaming

A new approach for characterizing high intensity focused ultrasound (HIFU) transducers is presented. The technique is based upon the acoustic streaming field generated by absorption of the HIFU beam in a liquid medium. The streaming field is quantified using digital particle image velocimetry, and a numerical algorithm is employed to compute the acoustic intensity field giving rise to the observed streaming field. The method as presented here is applicable to moderate intensity regimes, above the intensities which may be damaging to conventional hydrophones, but below the levels where nonlinear propagation effects are appreciable. Intensity fields and acoustic powers predicted using the streaming method were found to agree within 10% with measurements obtained using hydrophones and radiation force balances. Besides acoustic intensity fields, the streaming technique may be used to determine other important HIFU parameters, such as beam tilt angle or absorption of the propagation medium.

Effect of ethanol injection on cavitation and heating of tissues exposed to high-intensity focused ultrasound

Cavitation activity and temperature rise have been investigated in a tissue-mimicking material and excised bovine liver treated with ethanol and insonated with a 0.825 MHz focused acoustic transducer. The acoustic power was varied from 1.3 to 26.8 W to find the threshold leading to the onset of inertial cavitation. Cavitation events were quantified by three independent techniques: B-mode ultrasound imaging, needle hydrophone measurements and passive cavitation detection. Temperature in or near the focal zone was measured by thermocouples embedded in the samples. The results of this study indicate that the treatment of tissue phantoms and bovine liver samples with ethanol reduces their threshold power for inertial cavitation. This in turn leads to a sudden rise in temperature in ethanol-treated samples at a lower acoustic power than that in untreated ones. The analysis of passive cavitation detection data shows that once the threshold acoustic power is reached, inertial cavitation becomes a major contributor to acoustic scattering in ethanol-treated phantoms and bovine liver samples as compared to control. This study opens up the possibility of improved tumor ablation therapy via a combination of percutaneous ethanol injection and high-intensity focused ultrasound.

Correction for frequency-dependent hydrophone response to nonlinear pressure waves using complex deconvolution and rarefactional filtering: application with fiber optic hydrophones

Nonlinear acoustic signals contain significant energy at many harmonic frequencies. For many applications, the sensitivity (frequency response) of a hydrophone will not be uniform over such a broad spectrum. In a continuation of a previous investigation involving deconvolution methodology, deconvolution (implemented in the frequency domain as an inverse filter computed from frequency-dependent hydrophone sensitivity) was investigated for improvement of accuracy and precision of nonlinear acoustic output measurements. Timedelay spectrometry was used to measure complex sensitivities for 6 fiber-optic hydrophones. The hydrophones were then used to measure a pressure wave with rich harmonic content. Spectral asymmetry between compressional and rarefactional segments was exploited to design filters used in conjunction with deconvolution. Complex deconvolution reduced mean bias (for 6 fiber-optic hydrophones) from 163% to 24% for peak compressional pressure (p+), from 113% to 15% for peak rarefactional pressure (p-), and from 126% to 29% for pulse intensity integral (PII). Complex deconvolution reduced mean coefficient of variation (COV) (for 6 fiber optic hydrophones) from 18% to 11% (p+), 53% to 11% (p-), and 20% to 16% (PII). Deconvolution based on sensitivity magnitude or the minimum phase model also resulted in significant reductions in mean bias and COV of acoustic output parameters but was less effective than direct complex deconvolution for p+ and p-. Therefore, deconvolution with appropriate filtering facilitates reliable nonlinear acoustic output measurements using hydrophones with frequency-dependent sensitivity.

Effects of ultrasound and ultrasound contrast agent on vascular tissue

BackgroundUltrasound (US) imaging can be enhanced using gas-filled microbubble contrast agents. Strong echo signals are induced at the tissue-gas interface following microbubble collapse. Applications include assessment of ventricular function and virtual histology.AimWhile ultrasound and US contrast agents are widely used, their impact on the physiological response of vascular tissue to vasoactive agents has not been investigated in detail.Methods and resultsIn the present study, rat dorsal aortas were treated with US via a clinical imaging transducer in the presence or absence of the US contrast agent, Optison. Aortas treated with both US and Optison were unable to contract in response to phenylephrine or to relax in the presence of acetylcholine. Histology of the arteries was unremarkable. When the treated aortas were stained for endothelial markers, a distinct loss of endothelium was observed. Importantly, terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL) staining of treated aortas demonstrated incipient apoptosis in the endothelium.ConclusionsTaken together, these ex vivo results suggest that the combination of US and Optison may alter arterial integrity and promote vascular injury; however, the in vivo interaction of Optison and ultrasound remains an open question.

Pulsed High–Intensity-focused US and Tissue Plasminogen Activator (TPA) Versus TPA Alone for Thrombolysis of Occluded Bypass Graft in Swine

PURPOSE Prosthetic arteriovenous or arterial-arterial bypass grafts can thrombose and be resistant to revascularization. A thrombosed bypass graft model was created to evaluate the potential therapeutic enhancement and safety profile of pulsed high-intensity-focused ultrasound (pHIFU) on pharmaceutical thrombolysis. MATERIALS AND METHODS In swine, a right carotid-carotid expanded polytetrafluoroethylene bypass graft was surgically constructed, containing a 40% stenosis at its distal end to induce graft thrombosis. The revascularization procedure was performed 7 days after surgery. After model development and dose response experiments (n = 11), two cohorts were studied: pHIFU with tissue plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The experiments were identical in both groups except no energy was delivered in the sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft opacified by contrast medium on angiograms was quantified with digital image processing software. A blinded reviewer calculated the change in the graft area opacified by contrast medium and expressed it as a percentage, representing percentage of thrombolysis. RESULTS Combining pHIFU with 0.5 mg of TPA resulted in a 52% ± 4% increase in thrombolysis on angiograms obtained at 30 minutes, compared with a 9% ± 14% increase with sham pHIFU and 0.5 mg TPA (P = .003). Histopathologic examination demonstrated no differences between the groups. CONCLUSIONS Thrombolysis of occluded bypass grafts was significantly increased when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest that application of pHIFU may augment thrombolysis with a reduced time and dose.

Temperature Measurements in Tissue‐Mimicking Material during HIFU Exposure

Cavitation in high intensity focused ultrasound (HIFU) procedures can yield unpredictable results, particularly when the same location is targeted for more than several seconds. To study this effect, temperature rise was measured in tissue mimicking material (TMM) during HIFU exposures. A 50 um thin wire thermocouple (TC) was embedded in the center of a hydrogel‐based TMM that was previously developed for HIFU applications. HIFU at 825 kHz was focused at the TC junction. Thirty second HIFU exposures of increasing pressure from 1–7 MPa were applied and the temperature rise and decay during and after sonication were recorded. B‐mode imaging was used to monitor any cavitation activity during sonication. If cavitation was noted during the sonication, the sonication was repeated at the same pressure level two more times at 20 minute intervals in order to characterize the repeatability given that cavitation had occurred. The cavitation threshold of the TMM was determined to be approximately 3 MPa at 825 kHz. Te...

Two efficient methods for measuring hydrophone frequency response in the 100 kHz to 2 MHz range

As new medical applications of ultrasound emerge with operating frequencies in the hundreds of kilohertz to low megahertz region, it becomes more important to have convenient calibration methods for hydrophones in this frequency range. Furthermore, short diagnostic ultrasound pulses affected by finite amplitude distortion require that the hydrophone frequency response be known well below the center frequency. National standards laboratories can provide accurate calibration data at these frequencies, but the two methods now employed, laser interferometry and three-transducer reciprocity, are both single-frequency techniques, and they can be time-consuming procedures. Therefore, two efficient methods for generating a wideband acoustic pressure spectrum have been implemented to cover this frequency range. In one method a high-voltage pulse generator was used to excite a thick piezoelectric ceramic disk, producing a plane-wave acoustic pressure transient <1 µs in duration with peak amplitude of about 40 kPa. In the other technique, time delay spectrometry (TDS), a purpose-built 1–3 piezoelectric composite source transducer weakly focused at 20 cm was swept over the 0–2 MHz range. Its transmitting voltage response at 1 MHz was 11 kPa/V. The broadband pulse technique has the advantage of being simpler to implement, but TDS has a much greater signal-to-noise ratio because of the frequency-swept narrowband filter employed.

Multiple Cavitation Detection Methods for Evaluating Tissue Mimicking Materials during HIFU Exposure

Temperature rise during HIFU procedures and the possibility of cavitation activity during heating are important to quantify in planning a safe and effective treatment. Therefore, in pre‐clinical testing it is essential to characterize clinical HIFU devices using tissue‐mimicking materials (TMMs) with well known characteristics, including cavitation properties. The purpose of this study was to monitor cavitation behavior and determine its effect on temperature rise in a HIFU TMM containing an embedded thermocouple. A 50 μm fine wire thermocouple was embedded in a hydrogel‐based TMM previously developed for HIFU. HIFU at 1.1 MHz was focused at the thermocouple junction. HIFU focal pressures from 1–5 MPa were applied and the temperature rise and decay were recorded. Three hydrophones were used to monitor cavitation activity during sonication. A hydrophone confocal with the HIFU transducer and a cylindrical hydrophone lateral to the HIFU beam were used as passive cavitation detectors for spectral analysis of ...

A Simplified Ultrasonic Time‐Delay Spectrometry (TDS) System Employing Digital Processing to Minimize Hardware Requirements

Time delay spectrometry (TDS) is a swept‐frequency technique that has proven useful in several ultrasonic applications. The research systems that have been used depended on features of commercial equipment no longer manufactured; commercial TDS ultrasonic systems are not available. The system described here is easy to replicate with readily available equipment and a digitizer and computer capable of handling audio frequency signals. Two applications are shown to demonstrate the capability of this design.