Development and testing of a system for controlled ultrasound hyperthermia treatment with a phantom device.

Hyperthermia is the process of raising tissue temperatures in the range 40 - 45 °C for a prolonged time (up to hours). Unlike in ablation therapy, raising the temperature to such levels does not cause necrosis of the tissue but has been postulated to sensitize the tissue for radiotherapy. The ability to maintain a certain temperature in a target region is key to a hyperthermia delivery system. The aim of this work was to design and characterize a heat delivery system for ultrasound hyperthermia able to generate a uniform power deposition pattern in the target region with a closed-loop control which would maintain the defined temperature over a defined period. The hyperthermia delivery system presented herein is a flexible design with the ability to strictly control the induced temperature rise with a feedback loop. The system can be reproduced elsewhere with relative ease and is adaptable for various tumor sizes/locations and for other temperature elevation applications, such as ablation therapy. The system was fully characterized and tested on a newly-designed custom-built phantom with controlled acoustic and thermal properties and containing embedded thermocouples. Additionally, a layer of thermochromic material was fixed above the thermocouples and the recorded temperature increase was compared to the RGB (red, green, and blue) color-change in the material. The transducer characterization allowed for input voltage to output power curves to be generated, thus allowing for comparison of power deposition to temperature increase in the phantom. Additionally, the transducer characterization generated a field map of the symmetric field. The system was capable of increasing the temperature of the target area by 6 °C above body temperature and maintain the temperature to within ±0.5 °C over a defined period. The increase in temperature correlated with the RGB image analysis of the thermochromic material. The results of this work have the potential to contribute towards increasing confidence in the delivery of hyperthermia treatment to superficial tumors. The developed system could potentially be used for phantom or small animal proof-of-principle studies. The developed phantom test device may be used for testing other hyperthermia systems.

On the Importance of Consistent Insonation Conditions During Hydrophone Calibration and Use.

Hydrophones are generally calibrated in acoustic fields with temporally localized (short pulse) or long duration (tone burst) signals. Free-field conditions are achieved by time gating any reflections from the hydrophone body, mounting structures, and surrounding water tank boundaries arriving at the active sensing element. Consequently, the sensitivity response of the hydrophone is a result of direct waves incident on its active element, free from any contaminating effects of reflections. However, when using tone bursts below 400 kHz to calibrate hydrophones, it may not be possible to isolate the direct wave from reflection artifacts. This means that the sensitivity responses derived at these frequencies using short pulse and tone burst signals might not be comparable as they can be characteristic of the acoustic field interaction with either/both the hydrophone active element alone or the hydrophone active element and body. Therefore, there is a need to consider an appropriate calibration method for a given hydrophone type, depending on whether the eventual application employs short pulse or tone burst acoustic fields. This article presents the findings from a short study comprising four needle-type hydrophones of active element diameters in the range of 1-4 mm. These hydrophones were calibrated from 30 kHz to 1.6 MHz using established calibration methodologies within the underwater acoustics (UWA) and ultrasound (US) areas employed at the National Physical Laboratory (NPL), Teddington, U.K. In UWA tone, burst acoustic fields are used, while in US, it is short pulses. The 2- and 4-mm-diameter needle hydrophones showed the largest variation at the overlapping frequencies, in which the maximum disagreement of UWA calibration was 30% relative to US calibration. For the 4-mm hydrophone, UWA calibration exhibited resonant sensitivity structure between 100 and 450 kHz, but which was absent in US calibration. This observed behavior was further investigated theoretically by using a validated acoustic wave solver to confirm the resonant sensitivity structure seen in the case of UWA calibration. The work contained within illustrates the need to ensure that the method of calibration is carefully considered in the context of the duration of the acoustic signals for which the hydrophone is intended.

Dissemination of the Acoustic Pascal: The Role and Experiences of a National Metrology Institute.

Hydrophones are pivotal measurement devices ensuring medical ultrasound acoustic exposures comply with the relevant national and international safety criteria. These devices have enabled the spatial and temporal distribution of key safety parameters to be determined in an objective and standardized way. Generally based on piezoelectric principles of operation, to convert generated voltage waveforms to acoustic pressure, they require calibration in terms of receive sensitivity, expressed in units of [Formula: see text]Pa-1. Reliable hydrophone calibration with associated uncertainties plays a key role in underpinning a measurement framework that ensures exposure measurements are comparable and traceable to internationally agreed units, irrespective of where they are carried out globally. For well over three decades, the U.K. National Physical Laboratory (NPL) has provided calibrations to the user community covering the frequency range 0.1-60 MHz, traceable to a primary realization of the acoustic pascal through optical interferometry. Typical uncertainties for sensitivity are 6%-22% (for a coverage factor k = 2), degrading with frequency. The article specifically focuses on the dissemination of the acoustic pascal through NPL's calibration services that are based on a comparison with secondary standard hydrophones previously calibrated using the NPL primary standard. The work demonstrates the stability of the employed dissemination protocols by presenting representative calibration histories on a selection of commercially available hydrophones. Results reaffirm the guidance provided within international standards for regular calibration of a hydrophone in order to underpin measurement confidence. The process by which internationally agreed realizations of the acoustic pascal are compared and validated through key comparisons (KCs) is also described.

Measurement of the ultrasound attenuation and dispersion in 3D-printed photopolymer materials from 1 to 3.5 MHz.

Over the past decade, the range of applications in biomedical ultrasound exploiting 3D printing has rapidly expanded. For wavefront shaping specifically, 3D printing has enabled a diverse range of new, low-cost approaches for controlling acoustic fields. These methods rely on accurate knowledge of the bulk acoustic properties of the materials; however, to date, robust knowledge of these parameters is lacking for many materials that are commonly used. In this work, the acoustic properties of eight 3D-printed photopolymer materials were characterised over a frequency range from 1 to 3.5 MHz. The properties measured were the frequency-dependent phase velocity and attenuation, group velocity, signal velocity, and mass density. The materials were fabricated using two separate techniques [PolyJet and stereolithograph (SLA)], and included Agilus30, FLXA9960, FLXA9995, Formlabs Clear, RGDA8625, RGDA8630, VeroClear, and VeroWhite. The range of measured density values across all eight materials was 1120-1180 kg · m-3, while the sound speed values were between 2020 to 2630 m · s-1, and attenuation values typically in the range 3-9 dB · MHz-1· cm-1.

Safety Aspects of Perinatal Ultrasound.

Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable. The perinatal period is probably less vulnerable than the first and second trimesters of pregnancy, and ultrasound is often a safer alternative to other diagnostic imaging modalities. Here we present step-by-step procedures for obtaining clinically relevant images while maintaining ultrasound safety. We briefly discuss the current status of the field of ultrasound safety, with special attention to the safety of novel modalities, safety considerations when ultrasound is employed for research and education, and ultrasound of particularly vulnerable tissues, such as the neonatal lung. This CME is prepared by ECMUS, the safety committee of EFSUMB, with contributions from OB/GYN clinicians with a special interest in ultrasound safety.

In vitro characterisation of ultrasound-induced heating effects in the mother and fetus: A clinical perspective.

INTRODUCTION: The quantification of heating effects during exposure to ultrasound is usually based on laboratory experiments in water and is assessed using extrapolated parameters such as the thermal index. In our study, we have measured the temperature increase directly in a simulator of the maternal-fetal environment, the 'ISUOG Phantom', using clinically relevant ultrasound scanners, transducers and exposure conditions. METHODS: The study was carried out using an instrumented phantom designed to represent the pregnant maternal abdomen and which enabled temperature recordings at positions in tissue mimics which represented the skin surface, sub-surface, amniotic fluid and fetal bone interface. We tested four different transducers on a commercial diagnostic scanner. The effects of scan duration, presence of a circulating fluid, pre-set and power were recorded. RESULTS: The highest temperature increase was always at the transducer-skin interface, where temperature increases between 1.4°C and 9.5°C were observed; lower temperature rises, between 0.1°C and 1.0°C, were observed deeper in tissue and at the bone interface. Doppler modes generated the highest temperature increases. Most of the heating occurred in the first 3 minutes of exposure, with the presence of a circulating fluid having a limited effect. The power setting affected the maximum temperature increase proportionally, with peak temperature increasing from 4.3°C to 6.7°C when power was increased from 63% to 100%. CONCLUSIONS: Although this phantom provides a crude mimic of the in vivo conditions, the overall results showed good repeatability and agreement with previously published experiments. All studies showed that the temperature rises observed fell within the recommendations of international regulatory bodies. However, it is important that the operator should be aware of factors affecting the temperature increase.

Measurement of the temperature-dependent output of lead zirconate titanate transducers.

The effect of temperature and electrical drive conditions on the output of lead zirconate titanate (PZT) transducers is of particular interest in ultrasound metrology and medical ultrasound applications. In this work, the temperature-dependent output of two single-element PZT transducers was measured between 22 °C and 46 °C. Two independent measurement methods were used, namely radiation force balance measurements and laser vibrometry. When driven at constant voltage using a 50 Ω matched signal generator and amplifier using continuous wave (CW) or quasi-CW excitation, the output of the two transducers increased on average by 0.6 % per degree, largely due to an increase in transducer efficiency with temperature. The two measurement methods showed close agreement. Similar trends were observed when using single cycle excitation with the same signal chain. However, when driven using a pulser (which is not electrically matched), the two transducers exhibited different behaviour depending on their electrical impedance. Accounting for the temperature-dependent output of PZT transducers could have implications for many areas of ultrasound metrology, for example, in therapeutic ultrasound where a coupling fluid at an increased or decreased temperature is often used.

Tissue mimicking materials for imaging and therapy phantoms: a review.

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development.

Temperature Elevation in an Instrumented Phantom Insonated by B-Mode Imaging, Pulse Doppler and Shear Wave Elastography.

Diagnostic ultrasound is the gold standard for obstetric scanning and one of the most important imaging techniques for perinatal and neonatal monitoring and diagnosis. Ultrasound provides detailed real-time anatomic information, including blood flow measurements and tissue elasticity. The latter is provided through various techniques including shear wave elastography (SWE). SWE is increasingly used in many areas of medicine, especially in detection and diagnosis of breast, thyroid and prostate cancers and liver disease. More recently, SWE has found application in gynaecology and obstetrics. This method mimics manual palpation, revealing the elastic properties of soft biological tissues. Despite its rising potential and expanding clinical interest in its use in obstetrics and gynaecology (such as for assessment of cervical ripening or organ development and structure during pregnancy), its effects on and potential risks to the developing fetus remain unknown. Risks should be evaluated by regulatory bodies before recommendations are made on the use of SWE. Because ultrasound is known to produce thermal and mechanical effects, this study measured the temperature increase caused by B-mode, pulse Doppler (PD) and SWE, using an instrumented phantom with 11 embedded thermocouples. Experiments were performed with an Aixplorer diagnostic ultrasound system (Supersonic Imagine, Aix-en-Provence, France). As expected, the greatest heating was detected by the thermocouple closest to the surface in contact with the transducer (2.9°C for SWE, 1.2°C for PD, 0.7°C for B-mode after 380-s excitation). Both conduction from the transducer face and direct heating owing to ultrasound waves contribute to temperature increase in the phantom with SWE associated with a larger temperature increase than PD and B-mode. This article offers a methodological approach and reference data for future safety studies, as well as initial recommendations about SWE safety in obstetrics and gynaecology.

A Polyvinyl Alcohol-Based Thermochromic Material for Ultrasound Therapy Phantoms.

Temperature estimation is a fundamental step in assessment of the efficacy of thermal therapy. A thermochromic material sensitive within the temperature range 52.5°C-75°C has been developed. The material is based on polyvinyl alcohol cryogel with the addition of a commercial thermochromic ink. It is simple to manufacture, low cost, non-toxic and versatile. The thermal response of the material was evaluated using multiple methods, including immersion in a temperature-controlled water bath, a temperature-controlled heated needle and high-intensity focused ultrasound (HIFU) sonication. Changes in colour were evaluated using both RGB (red, green, blue) maps and pixel intensities. Acoustic and thermal properties of the material were measured. Thermo-acoustic simulations were run with an open-source software, and results were compared with the HIFU experiments, showing good agreement. The material has good potential for the development of ultrasound therapy phantoms.

A Radiation Force Balance Target Material for Applications below 0.5 MHz.

Acoustic output power is an important safety-related parameter whose standardised measurement method involves use of a radiation force balance in conjunction with a special target that is typically designed to be totally absorbing to ultrasound. International Standard International Electrotechnical Commission (IEC) 61161 specifies important performance criteria for such an absorber, such as transmission loss and reflection loss. Currently, there is a lack of acoustic absorbers meeting these requirements at low frequencies (<0.5 MHz). This is unsatisfactory given emerging clinical applications, particularly therapeutic. Described here is an acoustic absorber appropriate for application below 0.5 MHz. Through use of two National Physical Laboratory measurement facilities, the absorber transmission loss and reflection loss have been derived over the frequency range 50-500 kHz. Results are presented and compared with performance requirements specified in IEC 61161, revealing the efficacy of the new material as an absorbing radiation force balance target down to a frequency of approximately 120 kHz.

The Effect of Curing Temperature and Time on the Acoustic and Optical Properties of PVCP.

Polyvinyl chloride plastisol (PVCP) has been increasingly used as a phantom material for photoacoustic and ultrasound imaging. As one of the most useful polymeric materials for industrial applications, its mechanical properties and behavior are well-known. Although the acoustic and optical properties of several formulations have previously been investigated, it is still unknown how these are affected by varying the fabrication method. Here, an improved and straightforward fabrication method is presented, and the effect of curing temperature and curing time on the PVCP acoustic and optical properties, as well as their stability over time, is investigated. The speed of sound and attenuation were determined over a frequency range from 2 to 15 MHz, while the optical attenuation spectra of samples were measured over a wavelength range from 500 to 2200 nm. The results indicate that the optimum properties are achieved at curing temperatures between 160 °C and 180 °C, while the required curing time decreases with increasing temperature. The properties of the fabricated phantoms were highly repeatable, meaning that the phantoms are not sensitive to the manufacturing conditions provided that the curing temperature and time are within the range of complete gelation-fusion (samples are optically clear) and below the limit of thermal degradation (indicated by the yellowish appearance of the sample). The samples' long-term stability was assessed over 16 weeks, and no significant change was observed in the measured acoustic and optical properties.

Directivity and Frequency-Dependent Effective Sensitive Element Size of Membrane Hydrophones: Theory Versus Experiment.

It is important to know hydrophone frequency-dependent effective sensitive element size in order to account for spatial averaging artifacts in acoustic output measurements. Frequency-dependent effective sensitive element size may be obtained from hydrophone directivity measurements. Directivity was measured at 1, 2, 3, 4, 6, 8, and 10 MHz from ±60° in two orthogonal planes for eight membrane hydrophones with nominal geometrical sensitive element radii ( ag ) ranging from 100 to [Formula: see text]. The mean precision of directivity measurements (obtained from four repeated measurements at each frequency and angle) averaged over all frequencies, angles, and hydrophones was 5.8%. Frequency-dependent effective hydrophone sensitive element radii aeff(f) were estimated by fitting the theoretical directional response for a disk receiver to directivity measurements using the sensitive element radius ( a ) as an adjustable parameter. For the eight hydrophones in aggregate, the relative difference between effective and geometrical sensitive element radii, ( aeff - ag)/ag , was fit to C /( kag)n , where k = 2π/λ and λ = wavelength. The functional fit yielded C = 1.89 and n = 1.36 . The root mean square difference between the data and the model was 34%. It was shown that for a given value for ag , [Formula: see text] for membrane hydrophones far exceeds that for needle hydrophones at low frequencies (e.g., < 4 MHz when [Formula: see text]). This empirical model for [Formula: see text] provides information required for the compensation of spatial averaging artifacts in acoustic output measurements and is useful for choosing an appropriate sensitive element size for a given experiment.

Directivity and Frequency-Dependent Effective Sensitive Element Size of Needle Hydrophones: Predictions From Four Theoretical Forms Compared With Measurements.

Directivity is a hydrophone specification that describes response as a function of angle of incidence. The goal of this study was to compare, in the context of needle hydrophones, the commonly used rigid baffle model for hydrophone directivity to three alternative models: soft baffle, unbaffled (UB), and rigid piston (RP). Directivity measurements were performed at 1, 2, 3, 4, 6, 8, and 10 MHz from ±7° in two orthogonal planes for two ceramic and two polymer needle hydrophones with nominal geometrical sensitive element diameters of 200, 400, 600, and 1000 . Effective hydrophone sensitive element radius was estimated by least-squares fitting the four models to directivity measurement data using the sensitive element radius (a) as an adjustable parameter. For > 4 (where and = wavelength), the RP model outperformed the other three models. For , the average error in estimated sensitive element radius was 7% [95% confidence interval (CI): 3%-12%] for the RP model while the lowest average error by the other three models was 46% (95% CI: 38%-54%) for the UB model.

Temperature elevation measured in a tissue-mimicking phantom for transvaginal ultrasound at clinical settings.

INTRODUCTION: This paper reports the results of an audit to assess the possible thermal hazard associated with the clinical use of ultrasound scanners in UK Hospitals for transvaginal ultrasound imaging. METHODS: An anatomically relevant phantom composed of a block of agar-based tissue mimicking material with embedded thermal sensors was developed. Seventeen hospitals around the UK were visited and a total of 64 configurations were tested. A representative typical scanning protocol was adopted, which primarily used B-mode with 30 s periods of colour-flow and pulsed Doppler modes for both gynaecology and obstetrics pre-sets. RESULTS: The results confirmed that the highest temperature increase is always at the surface. The greatest temperature rise measured across all the systems was 3.6℃, with an average of 2.0℃ and 2.16℃ for gynaecology and obstetrics pre-sets, respectively. For some systems, the temperature increased rapidly when selecting one of the Doppler modes, so using them for longer than 30 s will in many cases lead to greater heating. It is also shown that, in agreement with previous studies, the displayed thermal index greatly underestimates the temperature rise, particularly close to the transducer face but even to distances approaching 2 cm. CONCLUSIONS: Overall, the results of the audit for the temperature rise during transvaginal ultrasound at clinical settings fell within the limits indicated by the national and international standards, for the pre-sets tested and following a representative typical scanning protocol. Only selected pre-sets were tested and the scanner outputs were not maximised (for example by using zoom, greater depth or narrow sector angles). Consequently, higher temperatures than those measured can certainly be achieved.

The Feasibility of Thermal Imaging as a Future Portal Imaging Device for Therapeutic Ultrasound.

This technical note describes a prototype thermally based portal imaging device that allows mapping of energy deposition on the surface of a tissue mimicking material in a focused ultrasound surgery (FUS) beam by using an infrared camera to measure the temperature change on that surface. The aim of the work is to explore the feasibility of designing and building a system suitable for rapid quality assurance (QA) for use with both ultrasound- and magnetic resonance (MR) imaging-guided clinical therapy ultrasound systems. The prototype was tested using an MR-guided Sonalleve FUS system (with the treatment couch outside the magnet bore). The system's effective thermal noise was 0.02°C, and temperature changes as low as 0.1°C were easily quantifiable. The advantages and drawbacks of thermal imaging for QA are presented through analysis of the results of an experimental session.

Removing vascular obstructions: a challenge, yet an opportunity for interventional microdevices.

Cardiovascular diseases are the leading cause of death worldwide; they are mainly due to vascular obstructions which, in turn, are mainly caused by thrombi and atherosclerotic plaques. Although a variety of removal strategies has been developed for the considered obstructions, none of them is free from limitations and conclusive. The present paper analyzes the physical mechanisms underlying state-of-art removal strategies and classifies them into chemical, mechanical, laser and hybrid (namely chemo-mechanical and mechano-chemical) approaches, while also reviewing corresponding commercial/research tools/devices and procedures. Furthermore, challenges and opportunities for interventional micro/nanodevices are highlighted. In this spirit, the present review should support engineers, researchers active in the micro/nanotechnology field, as well as medical doctors in the development of innovative biomedical solutions for treating vascular obstructions. Data were collected by using the ISI Web of Knowledge portal, buyer's guides and FDA databases; devices not reported on scientific publications, as well as commercial devices no more for sale were discarded. Nearly 70% of the references were published since 2006, 55% since 2008; these percentages respectively raise to 85% and 65% as regards the section specifically reviewing state-of-art removal tools/devices and procedures.