Therapeutic Ultrasound Fields Research Articles

Comparison between experimental and computational methods for the acoustic and thermal characterization of therapeutic ultrasound fields

For high intensity therapeutic ultrasound (HITU) devices, pre-clinical testing can include measurement of power, pressure/intensity and temperature distribution, acoustic and thermal simulations, and assessment of targeting accuracy and treatment monitoring. Though relevant standards are available, technical challenges remain because of the often focused, large amplitude pressure fields encountered. Measurement and modeling issues include using hydrophones and radiation force balances at HITU power levels, validation of simulation models, and a suitable tissue-mimicking material (TMM) for temperature measurements. To better understand these issues, a comparison study was undertaken between simulations and measurements of the HITU acoustic field distribution in water and TMM, and temperature rise in TMM. For the specific conditions of this study, the following results were obtained. In water, the simulated values for p + and p- were 3% lower and 10% higher, respectively, than those measured by hydrophone. In TMM, the simulated values for p + and p- were 2% and 10% higher than those measured by hydrophone, respectively. The simulated spatial-peak temporal-average intensity values in water and TMM were greater than those obtained by hydrophone by 3%. Simulated and measured end-of-sonication temperatures agreed to within their respective uncertainties (coefficients of variation of approximately 20% and 10%, respectively).

Measurement and modelling of nonlinear ultrasound fields using Fabry-Perot sensors and k-wave

Measurement and modelling of nonlinear ultrasound fields underpins many aspects of clinical ultrasound therapies from transducer design, to treatment planning and computational dosimetry, and quality assurance during the manufacture and use of devices. Measurement of high amplitude nonlinear ultrasound fields presents a significant challenge due to the extreme pressures, temperature rises, and mechanical effects that are generated. Additionally, understanding the properties of suitable sensors and their effect on the measurement is critical to ensure that accurate measurements are obtained. Modelling the propagation of ultrasound under these conditions is similarly challenging, as simulations can become large and computationally expensive when highly nonlinear fields are simulated over clinically relevant domains, and experimental validation becomes more difficult. Here we discuss our approach to overcoming these challenges to perform accurate measurement and modelling of high intensity therapeutic ultrasound fields using the open-source k-Wave toolbox, and devices based on Fabry-Perot interferometers developed for measurement of high acoustic pressures.

Acoustic holography for calibration of ultrasound sources and in situ fields in therapeutic ultrasound

Therapeutic ultrasound sources, which are typically piezoelectric transducers, are intended to deliver known acoustic pressures to targeted tissue sites. Each transducer vibrates in a unique way and radiates a corresponding 3D ultrasound field. Accordingly, transducer vibrations should be known accurately in order to characterize the pressures delivered to the patient. Acoustic holography is a technique that relies on hydrophone measurements to reconstruct a source hologram that characterizes transducer vibrations [Sapozhnikov et al., JASA, 138(3), 1515–1532 (2015)]. In this way, a hologram is a signature of each transducer that can be monitored over time for quality assurance. Using holography-defined source boundary conditions, numerical forward projection of the ultrasound field based on the nonlinear wave equation can be used to accurately predict in situ temperatures and pressures in heterogeneous media for treatment planning. As such, acoustic holography goes beyond simple hydrophone scans and is uniquely suited to meet clinical needs for quantifying therapeutic ultrasound fields. In this paper, several examples of acoustic holography implementation are presented, including the characterization of single-element and multi-element flat and spherically curved sources working in linear and nonlinear regimes and in continuous and pulsed modes. [Work supported by NIH 1R01EB025187, R01EB007643, and R21CA219793; RFBR 17-02-00261 and 17-54-33034.]

New international standards for high pressure therapeutic ultrasound fields

High pressure levels of strongly focused therapeutic transducers create new challenges for formulating international standards for measurement and simulation. Earlier efforts of Working Group 6, High Intensity Therapeutic Ultrasound and Focusing Transducers, Technical Committee 87 of the International Electrotechnical Commission, resulted in a standard for measuring high power (up to 500 W) and a specification for measuring ultrasound fields at lower amplitudes using existing linear methods and scaling up to higher therapeutic levels. Presently, work is underway on a new document to describe direct approaches for characterizing ultrasound pressure fields in water up to 100 MPa through the use of state of the art optical and robust hydrophones. Because the real goal of our efforts is to determine therapeutic pressure levels in tissue at a target site, we have initiated work on a second hybrid approach which combines characterization of the radiated field close to the transducer in water with nonlinear field simulation programs. In this way the characterization data which preserve the uniqueness of a particular transducer are used as input to a simulator program for realistic field prediction. Our group is addressing how to simulate nonlinear propagation in heterogeneous absorbing tissues accurately and to benchmark simulation software.

Comparison between computational and experimental methods for the characterization of therapeutic ultrasound fields

Analytical modeling of medical ultrasound fields has been developed by the FDA to aid in pre-clinical characterization of therapeutic ultrasound devices. In order to assess this publicly available software, called the HIFU Simulator, acoustic and thermal measurements of power, pressure/intensity and temperature distribution have been performed for comparison. Measurement and modeling issues include using hydrophones and radiation force balances at therapeutic power levels, validation of simulation models, and tissue-mimicking material (TMM) development for temperature measurements. To better understand these issues, a comparison study was undertaken between simulations and measurements of the HITU acoustic field distribution in water and TMM, and temperature rise in TMM. For the specific conditions of this study, the following results were obtained. In water, the simulated values for p + and p- were 3% lower and 10% higher, respectively, than those measured by hydrophone. In TMM, the simulated values for p + and p- were 2% and 10% higher, respectively, than those measured by hydrophone. The simulated spatial-peak temporal-average intensity values in both water and TMM were greater than those obtained by hydrophone by 3%. Simulated and measured end-of-sonication temperatures agreed to within their respective uncertainties (coefficients of variation of approximately 20% and 10%, respectively).

Comparison between experimental and computational methods for the acoustic and thermal characterization of therapeutic ultrasound fields.

For high intensity therapeutic ultrasound (HITU) devices, pre-clinical testing can include measurement of power, pressure/intensity and temperature distribution, acoustic and thermal simulations, and assessment of targeting accuracy and treatment monitoring. Relevant International Electrotechnical Commission documents recently have been published. However, technical challenges remain because of the often focused, large amplitude pressure fields encountered. Measurement and modeling issues include using hydrophones and radiation force balances at HITU power levels, validation of simulation models, and tissue-mimicking material (TMM) development for temperature measurements. To better understand these issues, a comparison study was undertaken between simulations and measurements of the HITU acoustic field distribution in water and TMM and temperature rise in TMM. For the specific conditions of this study, the following results were obtained. In water, the simulated values for p+ and p- were 3% lower and 10% higher, respectively, than those measured by hydrophone. In TMM, the simulated values for p+ and p- were 2% and 10% higher than those measured by hydrophone, respectively. The simulated spatial-peak temporal-average intensity values in water and TMM were greater than those obtained by hydrophone by 3%. Simulated and measured end-of-sonication temperatures agreed to within their respective uncertainties (coefficients of variation of approximately 20% and 10%, respectively).

A Fat-Tissue Mimic Phantom for Therapeutic Ultrasound

As the number of treatments in the therapeutic ultrasound field targeted at fat tissue increase, the performance of the equipment should be evaluated for safety using a fat phantom. In this study, a fat phantom was fabricated using olive oil and a tissue-mimicking material (TMM) phantom. To evaluate the acoustic properties of the TMM phantom according to the changes in the olive oil, the composition ratio of a liquid mixture of olive oil with a surfactant was adjusted from 5?20% in 5% steps. The acoustic properties of the phantom were evaluated using the sound velocity, attenuation coefficient, density, and acoustic impedance. The experimental results showed that the sound velocity decreased with increasing amount of olive oil but the other acoustic properties did not change. In addition, the phantom using an olive-oil mixture with a 15% composition ratio was most similar to the acoustic characteristics of fat tissue with a sound velocity of 1477.35 m/s, an attenuation coefficient of 0.514 dB/MHz-cm, a density of 1.07 g/cm3, and an acoustic impedance of 1.575 MRayl. These experimental results are expected contribute to the accuracy of the results using a TMM phantom and will be useful for the therapeutic ultrasound field targeted at subcutaneous fat tissue.

Development and application of spot-poled membrane hydrophones for measurements of high intensity therapeutic ultrasound fields

The reliable characterization of high intensity therapeutic ultrasound (HITU, HIFU) fields is important regarding the safe and effective clinical application of the modality. However, the required acoustic output measurements pose several metrological challenges. Extreme pressure amplitudes easily cause damage to the typical sensors, pressure waveforms comprise a large number of higher harmonics, and a small sensing element size is desirable due to the strong focusing. Membrane hydrophones are widely used as reference sensors due to their advantageous and predictable characteristics. However, they are usually considered to be rather fragile instruments possibly not well suited for HITU field characterization. A membrane hydrophone previously developed at PTB was tested by means of successive measurements at focus with increasing driving voltage, and the pressure range detectable without destruction of the hydrophone was determined. Second, a novel hydrophone design comprising additional protective layers and a backing was developed to increase the robustness against cavitation. After calibration, measurements were performed using an HITU transducer with working frequencies of 1.06 and 3.2 MHz. The examples show the favorable applicability for HITU field characterization. The maximum detectable rarefactional and compressional pressure amplitudes were 15 and 77 MPa, respectively, with a detection bandwidth of 50 MHz.

Passive acoustic mapping of magnetic microbubbles in an in vitro flow model

Magnetic microbubbles can be successfully retained near a vascular target and simultaneously imaged using conventional B-mode ultrasound. When further modified to carry a drug, they could enable significant enhancements in targeted drug delivery for applications such as sonothrombolysis, where stable cavitation has been shown to play a key role. However, the effect of the increased proximity of the microbubbles under the effect of the magnetic field on their acoustic response remains unknown. Passive acoustic mapping is a method that enables real-time spatiotemporal monitoring of cavitation dynamics in an arbitrary plane or volume within the field of view of the ultrasound probe, and classification of the type of cavitation activity on the basis of the spatial distribution of frequency-domain emissions. In the present work, PAM is used to investigate the effect of bubble proximity and flow rate on the type, sustainability, intensity, and spatial distribution of cavitation activity observed for both magnetic and non-magnetic microbubbles excited by 0.5 MHz therapeutic ultrasound in an in vitro flow model. It is hoped that this study will not only yield a new method for real-time monitoring of drug delivery using magnetically trapped microbubbles, but will also help elucidate complex bubble–bubble interactions in therapeutic ultrasound fields.

2A1-R09 超音波画像情報のロボットへのフィードバックによる治療用超音波音場の3次元位置制御に関する研究(医療ロボティクス・メカトロニクス(2))

Ultrasound is widely applied to clinical purpose as Echography and High-intensity focused ultrasound for ablation therapy. Also, we have studied micro bubble control in blood vessel using ultrasound for acoustic targeted drug delivery. These techniques require accurate position control of therapeutic ultrasound field based on ultrasound image information. Therefore, we proposed a robotic system to control a position of an ultrasound transducer for therapy based on ultrasound image information. The system consists of an ultrasound probe for image-capturing, an ultrasound transducer, a robot with the therapeutic transducer, positioning software and an optical tracking device to integrate the coordinates. The system enables the transducer follows to a US imaging probe based on a therapeutic plan. In this study, positioning and following control accuracy was evaluated. The results demonstrate the system has a potential for targeting the transducer based on intra-operative planning.

Improved impulse response for hydrophone measurements in therapeutic ultrasound fields.

The accurate measurement of pressure waveforms in high intensity focused ultrasound (HIFU) fields is complicated by the fact that many devices operate at output levels where shock waves can form in the focal region. In tissue ablation applications, the accurate measurement of the shock amplitude is important for predicting tissue heating since the absorption at the shock is proportional to the shock amplitude cubed. To accurately measure shocked pressure waveforms, not only must a hydrophone with a broad bandwidth (>100 MHz) be used, but the frequency response of the hydrophone must be known and used to correct the measured waveform. In this work, shocked pressure waveforms were measured using a fiber optic hydrophone and a frequency response for the hydrophone was determined by comparing measurements with numerical modeling using a KZK‐type equation. The impulse response was separately determined by comparing a measured and an idealized shock pulse generated by an electromagnetic lithotripter. The frequency responses determined by the two methods were in good agreement. Calculations of heating using measured HIFU waveforms that had been deconvolved with the determined frequency response agreed well with measurements in tissue phantom. [Work supported by NIH DK43881, NSBRI SMST01601, NIH EB007643, and RFBR.]

Investigation of the viscous heating artefact arising from the use of thermocouples in a focused ultrasound field

Accurate temperature measurements in therapeutic ultrasound fields are necessary for understanding damage mechanisms, verification of thermal modelling and calibration of non-invasive clinical thermometry. However, artefactual heating, primarily due to viscous forces which result from motion relative to the surrounding tissue, occurs when metal thermocouples are used in an ultrasound field. The magnitude and time dependence of this artefact has been characterized by comparison with novel thin-film thermocouples (TFTs) at 1–2 cm focal depths in fresh degassed ex vivo bovine liver. High-intensity focused ultrasound exposures (1.7 MHz; free-field spatial-peak temporal-average intensities 40–600 W cm−2) were used. Subtraction of the TFT data from that obtained for other thermocouples yielded the time dependence of the viscous heating artefact. This was found to be intensity independent up to 600 W cm−2 (below the threshold for cavitation and lesion formation) and remained significant at radial distances out to the first side lobe in the focal plane. The contribution of viscous heating to cooling was also found to be significant for at least 5 s after the end of insonation. The ratio of viscous artefact to absorptive heating after 5 s was: 1.76 ± 0.07 for a fine-wire, 0.45 ± 0.07 and 1.93 ± 0.07 for two different sheathed-wires and 0.24 ± 0.07 for a needle thermocouple.

Cost-effective assembly of a basic fiber-optic hydrophone for measurement of high-amplitude therapeutic ultrasound fields

Design considerations, assembly details, and operating procedures of one version of a cost-effective basic fiber-optic probe hydrophone (FOPH) are described in order to convey practical information to groups interested in constructing a similar device. The use of fiber optic hydrophones can overcome some of the limitations associated with traditional polyvinylidene difluoride (PVDF) hydrophones for calibration of acoustic fields. Compared to standard PVDF hydrophones, FOPH systems generally have larger bandwidths, enhanced spatial resolution, reduced directionality, and greater immunity to electromagnetic interference, though they can be limited by significantly lower sensitivities. The FOPH system presently described employs a 100-microm multimode optical fiber as the sensing element and incorporates a 1-W laser diode module, 2 x 2 optical coupler, and general-purpose 50-MHz silicon p-i-n photodetector. Wave forms generated using the FOPH system and a reference PVDF hydrophone are compared, and intrinsic and substitution methods for calibrating the FOPH system are discussed. The voltage-to-pressure transfer factor is approximately 0.8 mV/MPa (-302 dB re 1 V/microPa), though straightforward modifications to the optical components in the FOPH system are discussed that can significantly increase this value. Recommendations are presented to guide the choice of optical components and to provide practical insight into the routine usage of the FOPH device.