Therapeutic Ultrasound Device Research Articles

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study: Erratum.

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study: Erratum.

An Ultrasound Array of Emitter-Receiver Stacks for Microbubble-Based Therapy.

Most therapeutic ultrasound devices place emitters and receivers in separate locations, so that the long therapeutic pulses (>1 ms) can be emitted while receivers monitor the procedure. However, with such placement, emitters and receivers are competing for the same space, producing a trade-off between emission efficiency and reception sensitivity. Taking advantage of recent studies demonstrating that short-pulse ultrasound can be used therapeutically, we aimed to develop a device that overcomes such trade-offs. The array was composed of emitter-receiver stacks, which enabled both emission and reception from the same location. Each element was made of a lead zirconate titanate (PZT)-polyvinylidene fluoride (PVDF) stack. The PZT (frequency: 500 kHz, diameter: 16 mm) was used for emission and the PVDF (thickness: 28 μm, diameter: 16 mm) for broadband reception. 32 elements were assembled in a 3D-printed dome-shaped frame (focal length: 150 mm; [Formula: see text]-number: 1) and was tested in free-field and through an ex-vivo human skull. In free-field, the array had a 4.5 × 4.5 × 32 mm focus and produced a peak-negative pressure (PNP) of 2.12 MPa at its geometric center. The electronic steering range was ±15 mm laterally and larger than ±15 mm axially. Through the skull, the array produced a PNP of 0.63 MPa. The PVDF elements were able to localize broadband microbubble emissions across the skull. We built the first multi-element array for short-pulse and microbubble-based therapeutic applications. Stacked arrays overcome traditional trade-offs between the transmission and reception quality and have the potential to create a step change in treatment safety and efficacy.

How reliable are the ultrasonic output power values emitted by therapeutic ultrasound devices in physiotherapy?

Therapeutic ultrasound is one of the most used electrophysical agents in physiotherapy. Despite this important and widespread application, therapeutic ultrasound devices (TUSD) may operate outside the range recommended by the International Standard IEC 61689:2013, and, thus, may not contribute to the treatment (if the ultrasonic output power, UOP, used in clinical practice are lower than the nominal power, NP) or even aggravate the pre-existing injury (if the UOP used is higher than the NP). The aim of this study was to verify whether the UOP values emitted by three TUSD from the Physiotherapy Section of the Esquadrão de Saúde de Pirassununga (named as TUSD1, TUSD2 and TUSD3) were in accordance with the IEC 61689:2013. Additionally, statistical tests were employed to assess the repeatability of UOP measurements made with the TUSD on three different days. An acoustic radiation force balance was used to measure the UOP values emitted by TUSD in three days of testing by each equipment, which were configured to operate in continuous mode. In addition, 10 UOP measurements were performed for each NP value with all available frequencies and effective radiation area. TUSD, even with up-to-date maintenance, presented several values of UOP with relative error greater than that preconized by IEC 61689:2013 (81.39% of 1800 UOP measurements with TUSD1, 68.61% of 1800 UOP measurements with TUSD2 and 75.33% of 1200 UOP measurements with TUSD3). So, It is important that the professional responsible for monitoring the maintenance/calibration of this equipment is trained to interpret the reports prepared by companies that provide maintenance/calibration services.

(012) Vulvovaginal Atrophy (VVA) Treatment Compliance Correlates with Improved Outcome

Abstract Introduction To effectively manage chronic conditions such as VVA, daily or semi-daily patient compliance to a treatment regimen is essential. Despite the fact that risk of cancer or cancer recurrence prevents many women from treating their VVA with hormone therapy, patient compliance to over-the-counter moisturizers and lubricants is relatively low: 40% of women find them completely unsatisfactory due to difficulty of use and lack of desired treatment outcome. As an alternative to current therapies, an at-home, easy-use therapeutic ultrasound device was developed with the potential to increase treatment compliance and help women successfully manage their VVA. This study aimed to optimize patient compliance by increasing ease of device use, minimizing therapy side effects, and tracking self-reported patient data electronically. Objectives To assess the correlation between patient-reported and objectively tracked actual compliance to therapy, as well as the association between treatment compliance and improvement in patient condition. Methods This randomized (1:1), double-blind, sham-controlled trial assessed the effectiveness of a daily, at-home ultrasound therapy, applied to the vaginal introitus for 8 min/day over the course of 12 weeks, on menopausal vaginal dryness in an ambulatory setting (Clinicaltrials.gov NCT00583-1). In 30 post- menopausal women (ages 48-70), device use compliance was collected via a self-reported electronic diary completed daily on a mobile phone. Objective compliance data were obtained from a logger installed in all devices, which recorded the duration and time the device was used every day. Participants self- assessed change (from baseline to 12 weeks) in VVA symptoms (vaginal dryness, soreness, irritation, dyspareunia) measured by the Vaginal Assessment Scale (VAS) with a 4-level response score ranging from none, mild, moderate, to severe. Healthcare providers evaluated change in vaginal tissue response (tissue elasticity, vaginal fluid, pH, mucosa, and vaginal moisture) assessed by the Vaginal Health Index (VHI) giving a numerical score (1-5) for each of the 5 parameters. Results After week-12 follow-up, participants in the operating group self-reported compliance (mean ± SE%) of 85.4 ± 5.4% and the device log objectively tracked compliance of 80.7 ± 7.2% (paired t-test, P=0.17). The sham group had self-reported compliance of 89.5 ± 2.1% and the device log compliance of 82.5 ± 5.2% (P=0.14). There was no significant difference (ANOVA) between operating and sham groups compliance for self-reported (P =0.46) or objective log data (P =0.83). With both operating and sham groups combined, there was a significant strong correlation (r=0.76, P<0.0001) between self-reported and device log compliance. Linear regression showed a significant positive dose-response between treatment and change in VHI score from baseline to week 12 (r=0.51, P=0.04). A smaller positive correlation was observed between treatment compliance and participants’ self-assessed change in VAS score (r=0.40, P=0.28). Conclusions Objective device use compliance was high (80.7-82.5%) across both groups assessed, indicating general participant desire to receive the therapy. In addition, participants with higher treatment rates had better scores in VHI, which indicated decreased VVA severity. For post-menopausal women, high adherence to the daily at-home ultrasound therapy proved efficacious in improving their condition of VVA and could offer a new therapeutic option. Disclosure Yes - Madorra. Industry funding only - investigator initiated and executed study – Yes.

Effects of therapeutic ultrasound and moderate heat on stallion testes

Transplantation of stem cells into dysfunctional testes is currently being investigated as a therapeutic option for men and stallions with advanced testicular degeneration. This series of “proof of concept” studies aimed to identify a safe and efficient method of inducing severe testicular degeneration to create an optimal equine recipient model for intratesticular stem cell transplantation (SCT). Two ex vivo and two in vivo experiments were conducted. At first, forty testes obtained from castrations were used to identify an effective therapeutic ultrasound (TUS) device and the protocol for increasing intratesticular temperature in stallions. Six min of treatment using the Vetrison Clinic Portable TUS machine raised the intratesticular temperature by 8°C-12.5 °C. This protocol was applied to treat three scrotal testes in three Miniature horse stallions, three times, every other day. Contralateral testes served as controls. There were signs of slight tubular degeneration in treated testes two and three weeks after TUS treatment. The number of seminiferous tubules (STs) with exfoliated germ cells (GCs) was increased in one testis only, three weeks after treatment. The degree of apoptosis of GCs was higher in each treated testis in comparison to the contralateral control testis. Next, the ability of various heating devices to increase intratesticular temperatures to at least 43 °C in stallion testes was tested, using twenty testes obtained from castrations. ThermaCare® Lower Back & Hip Pain Therapy Heatwrap (TC heat wrap) reliably increased intratesticular temperatures and kept them continuously between 43 °C and 48 °C for seven to 8 h. In the follow-up in vivo study, the left testes of three Miniature horse stallions were treated with TUS, after which both testes of each stallion were treated with moderate heat provided by the TC heat wrap (three times, every other day, for 5 h each time). There were signs of moderate tubular degeneration in the samples from all treated testes obtained three weeks after treatments (Heat only or Heat/TUS): areas with hypospermatogenesis, spermatogenic arrest, vacuolized Sertoli cells, numerous STs with exfoliated GCs, increased degree of GCs apoptosis, and changes in three histomorphometric numeric attributes of STs. We concluded that TUS or TC wraps increase intratesticular temperature of the isolated stallion testes. Further, treatment with TUS or moderate heat may induce mild to moderate degenerative changes in stallion testes. However, to achieve more robust result – severe testicular degeneration, our treatment protocol has to be modified.

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study.

Abstract A home-use, therapeutic ultrasound device was safe and effective for treating vaginal dryness after 12 weeks, and effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormone treatment option for postmenopausal women with vulvovaginal atrophy. Objective To evaluate safety and effectiveness of therapeutic ultrasound for treatment of postmenopausal vaginal dryness. Methods In a pilot study, postmenopausal women with self-reported vaginal dryness were randomized (1:1) to double-blind ultrasound treatment (n = 21) or sham (n = 21) for 12 weeks. Primary effectiveness endpoint was change from baseline to week 12 in Vaginal Assessment Scale symptoms (dryness, soreness, irritation, dyspareunia). Secondary effectiveness endpoint was scoring of clinician-reported Vaginal Health Index (elasticity, fluid, pH, mucosa, moisture). After 12 weeks, participants received open-label ultrasound treatment to 1 year. Safety endpoint was treatment-emergent adverse events. Results In the modified intent-to-treat population, women showed (mean ± standard error) reduction in Vaginal Assessment Scale with ultrasound treatment versus sham (n = 15, −0.5 ± 0.2 vs n = 15, −0.4 ± 0.3; P = 0.9) and improved Vaginal Health Index (n = 9, 2.7 ± 0.9 vs n = 9, 0.6 ± 1.4; P = 0.3). In the per-protocol analysis population, ultrasound treatment (n = 9) versus sham (n = 8) significantly reduced symptoms score (−0.6 ± 0.3 vs −0.0 ± 0.4; P = 0.05) and significantly improved Vaginal Health Index (2.7 ± 0.9 vs −0.4 ± 1.2; P = 0.03). Improvement in effectiveness endpoints were seen at 1 year compared with baseline. There were no differences in treatment-emergent adverse events between ultrasound treatment versus sham and no serious adverse events. Conclusions Home-use ultrasound was safe and effective for treating vaginal dryness after 12 weeks. Effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormonal treatment option for postmenopausal women with vulvovaginal atrophy.

Low-Cost Thermochromic Quality Assurance Phantom for Therapeutic Ultrasound Devices: A Proof of Concept.

High-intensity focused ultrasound (HIFU) transducer acoustic output can vary over time as a result of an inconsistent power supply, damage to the transducer or deterioration over time. Therefore, easy implementation of a daily quality assurance (DQA) method is of great importance for pre-clinical research and clinical applications. We present here a thermochromic material-based phantom validated by thermal simulations and found to provide repeatable visual power output assessments in fewer than 15 s that are accurate to within 10%. Whereas current available methods such as radiation force balance measurements provide an estimate of the total acoustic power, we explain here that the thermochromic phantom is sensitive to the shape of the acoustic field at focus by changing the aperture of a multi-element transducer with a fixed acoustic power. The proposed phantom allows the end user to visually assess the transducer's functionality without resorting to expensive, time-consuming hydrophone measurements or image analysis.

Harnessing Ultrasound for Targeting Drug Delivery to the Brain and Breaching the Blood-Brain Tumour Barrier.

Despite significant advances in developing drugs to treat brain tumours, achieving therapeutic concentrations of the drug at the tumour site remains a major challenge due to the presence of the blood–brain barrier (BBB). Several strategies have evolved to enhance brain delivery of chemotherapeutic agents to treat tumours; however, most approaches have several limitations which hinder their clinical utility. Promising studies indicate that ultrasound can penetrate the skull to target specific brain regions and transiently open the BBB, safely and reversibly, with a high degree of spatial and temporal specificity. In this review, we initially describe the basics of therapeutic ultrasound, then detail ultrasound-based drug delivery strategies to the brain and the mechanisms by which ultrasound can improve brain tumour therapy. We review pre-clinical and clinical findings from ultrasound-mediated BBB opening and drug delivery studies and outline current therapeutic ultrasound devices and technologies designed for this purpose.

My contributions to ultrasound metrology

My work in ultrasound metrology has centered around developing pre-clinical testing methods for therapeutic ultrasound devices. These test methods include radiation force balance systems and methods specifically for high-intensity therapeutic ultrasound, time-delay spectrometry methods for measuring hydrophone sensitivity, acoustic characterization of tissue-mimicking material that has been approved as a medical device development tool and a comparison protocol of computational and experimental acoustic characterization for therapeutic ultrasound devices. The purpose of this work at the FDA is to develop bench testing methods to ensure proper review of medical ultrasound devices to evaluate device safety and performance. The test instruments and methods developed have helped promote the development and recognition of voluntary consensus standards, as well as FDA industry guidance, that can provide the basis for least-burdensome data collection requirements by manufacturers and allow the FDA to assess device safety and effectiveness in a more consistent, methodical and scientifically rigorous manner.

Development and characterization of polyurethane-based tissue and blood mimicking materials for high intensity therapeutic ultrasound.

A polyurethane-based tissue mimicking material (TMM) and blood mimicking material (BMM) for the acoustic and thermal characterization of high intensity therapeutic ultrasound (HITU) devices has been developed. Urethane powder and other chemicals were dispersed into either a high temperature hydrogel matrix (gellan gum) or degassed water to form the TMM and BMM, respectively. The ultrasonic properties of both TMM and BMM, including attenuation coefficient, speed of sound, acoustical impedance, and backscatter coefficient, were characterized at room temperature. The thermal conductivity and diffusivity, BMM viscosity, and TMM Young's modulus were also measured. Importantly, the attenuation coefficient has a nearly linear frequency dependence, as is the case for most soft tissues and blood at 37 °C. Their mean values are 0.61f1.2 dB cm-1 (TMM) and 0.2f1.1 dB cm-1 (BMM) based on measurements from 1 to 8 MHz using a time delay spectrometry (TDS) system. Most of the other relevant physical parameters are also close to the reported values of soft tissues and blood. These polyurethane-based TMM and BMM are appropriate for developing standardized dosimetry techniques, validating numerical models, and determining the safety and efficacy of HITU devices.

Inhibition of Walker‐256 Tumor Growth by Combining Microbubble‐Enhanced Ultrasound and Endostar

This research is to investigate the anti-tumor effects by combining anti-vascular effect of microbubble enhanced ultrasound (MEUS) mechanical destruction and anti-angiogenic effect of Endostar. Rats bearing Walker-256 tumor were randomly divided into 4 groups treated by Endostar + MEUS combination, Endostar, MEUS or Sham ultrasound (US), respectively. MEUS was induced by Sonazoid microbubble and a focused therapeutic US device. Contrast-enhanced ultrasound (CEUS) was used to assess tumor perfusion before and after treatment. Microvessel density (MVD) was evaluated with immunohistochemical staining of CD31, CD34, and VEGFA. TUNEL assay was used to determine the apoptosis rate of tumor cells. Endostar + MEUS combined group induced the most reduced blood perfusion and most retarded tumor growth compared with other 3 groups. Decreased MVD was shown in Endostar + MEUS, Endostar and MEUS group, but the lowest MVD value was presented in the combined treatment group. Significant increase was observed in the combined therapy group and MEUS group. This study showed an improved anti-vascular and anti-angiogenic effect achieved by combining Endostar and MEUS, and may provide a new method potential for anti-tumor therapy.

Acoustic holograms for thalamic focusing through the temporal-bone window

In this work, we numerically investigate the performance of acoustic holograms created using k-space simulations and a phase-conjugation method at 650 kHz to simultaneously target both thalami through the temporal bone window compared to a curved transducer. Furthermore, we calculate how a misalignment of the acoustic hologram and the skull could affect the resulting acoustic image in terms of focus pressure and treated volume. Our results show that transtemporal acoustic holograms are a robust method to improve focus quality and to enhance sonicated volumes on target deep-brain even under small misallocations of the therapeutic ultrasound device that can be used for highly selective and low-cost blood-brain barrier opening and neuromodulation applications.

Application of low-intensity pulsed therapeutic ultrasound on mesenchymal precursors does not affect their cell properties.

Ultrasound is considered a safe and non-invasive tool in regenerative medicine and has been used in the clinic for more than twenty years for applications in bone healing after the approval of the Exogen device, also known as low-intensity pulsed ultrasound (LIPUS). Beyond its effects on bone health, LIPUS has also been investigated for wound healing of soft tissues, with positive results for various cell processes including cell proliferation, migration and angiogenesis. As LIPUS has the potential to treat chronic skin wounds, we sought to evaluate the effects produced by a conventional therapeutic ultrasound device at low intensities (also considered LIPUS) on the migration capacity of mouse and human skin mesenchymal precursors (s-MPs). Cells were stimulated for 3 days (20 minutes per day) using a traditional ultrasound device with the following parameters: 100 mW/cm2 with 20% duty cycle and frequency of 3 MHz. At the parameters used, ultrasound failed to affect s-MP proliferation, with no evident changes in morphology or cell groupings, and no changes at the cytoskeletal level. Further, the migration and invasion ability of s-MPs were unaffected by the ultrasound protocol, and no major changes were detected in the gene/protein expression of ROCK1, integrin β1, laminin β1, type I collagen and transforming growth factor β1. Finally, RNA-seq analysis revealed that only 10 genes were differentially expressed after ultrasound stimulation. Among them, 5 encode for small nuclear RNAs and 2 encode for proteins belonging to the nuclear pore complex. Considering the results overall, while the viability of s-MPs was not affected by ultrasound stimulation and no changes were detected in proliferation/migration, RNA-seq analysis would suggest that s-MPs do respond to ultrasound. The use of 100 mW/cm2 intensity or conventional therapeutic ultrasound devices might not be optimal for the stimulation the properties of cell populations. Future studies should investigate the potential application of ultrasound using variations of the tested parameters.

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).

Durability study of a gellan gum-based tissue-mimicking phantom for ultrasonic thermal therapy.

Stability and duration of ultrasonic phantoms are still subjects of research. This work presents a tissue-mimicking material (TMM) to evaluate high-intensity therapeutic ultrasound (HITU) devices, composed of gellan gum (matrix), microparticles (scatterers), and chemicals. The ultrasonic velocity and attenuation coefficient were characterized as a function of temperature (range 20 °C-85 °C). The nonlinear parameter B/A was determined by the finite amplitude insertion substitution (FAIS) method, and the shear modulus was determined by a transient elastography technique. The thermal conductivity and specific heat were determined by the line source method. The attenuation was stable for 60 days, and in an almost linear frequency dependence (0.51f0.96 dB cm-1), at 20 °C (1-10 MHz). All other evaluated physical parameters are also close to typical soft tissue values. Longitudinal ultrasonic velocities were between 1.49 and 1.75 mm μs-1, the B/A parameter was 7.8 at 30 °C, and Young's modulus was 23.4 kPa. The thermal conductivity and specific heat values were 0.7 W(m K)-1 and 4.7 kJ(kg K)-1, respectively. Consistent temperature increases and thermal doses occurred under identical HITU exposures. Low cost, longevity, thermal stability, and thermal repeatability make TMM an excellent material for ultrasonic thermal applications. The TMM developed has the potential to assess the efficacy of hyperthermia devices and could be used to adjust the ultrasonic emission of HITU devices.

Effect of Low-Frequency Therapeutic Ultrasound on Induction of Nitric Oxide in CKD: Potential to Prevent Acute Kidney Injury

Introduction: Post-contrast acute kidney injury (PC-AKI) develops in a significant proportion of patients with CKD after invasive cardiology procedures and is strongly associated with adverse outcomes. Objective: We sought to determine whether increased intrarenal nitric oxide (NO) would prevent PC-AKI. Methods: To create a large animal model of CKD, we infused 250 micron particles into the renal arteries in 56 ± 8 kg pigs. We used a low-frequency therapeutic ultrasound device (LOTUS – 29 kHz, 0.4 W/cm²) to induce NO release. NO and laser Doppler probes were used to assess changes in NO content and blood flow. Glomerular filtration rate (GFR) was measured by technetium-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA) radionuclide imaging. PC-AKI was induced by intravenous infusion of 7 cm³/kg diatrizoate. In patients with CKD, we measured GFR at baseline and during LOTUS using Tc-99m--DTPA radionuclide imaging. Results: In the pig model, CKD developed over 4 weeks (serum creatinine [Cr], mg/dL, 1.0 ± 0.2–2.6 ± 0.9, p < 0.01, n = 12). NO and renal blood flow (RBF) increased in cortex and medulla during LOTUS. GFR increased 75 ± 24% (p = 0.016, n = 3). PC-AKI developed following diatrizoate i.v. infusion (Cr 2.6 ± 0.7 baseline to 3.4 ± 0.6 at 24 h, p < 0.01, n = 3). LOTUS (starting 15 min prior to contrast and lasting for 90 min) prevented PC-AKI in the same animals 1 week later (Cr 2.5 ± 0.4 baseline to 2.6 ± 0.7 at 24 h, p = ns, n = 3). In patients with CKD (n = 10), there was an overall 25% increase in GFR in response to LOTUS (p < 0.01). Conclusions: LOTUS increased intrarenal NO, RBF, and GFR and prevented PC-AKI in a large animal model of CKD, and significantly increased GFR in patients with CKD. This novel approach may provide a noninvasive nonpharmacological means to prevent PC-AKI in high-risk patients.

A closer look at ultrasonic attenuation in a tissue-mimicking material

A well-characterized ultrasound tissue-mimicking material (TMM) can be important in determining the acoustic output and temperature rise from high intensity therapeutic ultrasound (HITU) devices and also in validating computer simulation models. A HITU TMM previously developed and characterized in our laboratory has been used in our acoustic and temperature measurements as well as modeled in our HITU simulation program. A discrepancy between the thermal measurement and simulation, though, led us to further investigate the TMM properties. We found that the 2-parameter analytic fit commonly used to represent the attenuation of the TMM in the computer modeling was not adequate over the entire frequency range of interest, 1 MHz to 8 MHz in this study, indicating that we and others may have not been characterizing TMMs, and possibly tissue, optimally. By comparing measurements and simulations, we found that a 3-parameter analytic fit for attenuation gave a more accurate value for attenuation at 1 MHz and 2 MHz. When using a 3-parameter fit, the temperature rise measurements in the FDA TMM agreed more closely with the simulation results.A well-characterized ultrasound tissue-mimicking material (TMM) can be important in determining the acoustic output and temperature rise from high intensity therapeutic ultrasound (HITU) devices and also in validating computer simulation models. A HITU TMM previously developed and characterized in our laboratory has been used in our acoustic and temperature measurements as well as modeled in our HITU simulation program. A discrepancy between the thermal measurement and simulation, though, led us to further investigate the TMM properties. We found that the 2-parameter analytic fit commonly used to represent the attenuation of the TMM in the computer modeling was not adequate over the entire frequency range of interest, 1 MHz to 8 MHz in this study, indicating that we and others may have not been characterizing TMMs, and possibly tissue, optimally. By comparing measurements and simulations, we found that a 3-parameter analytic fit for attenuation gave a more accurate value for attenuation at 1 MHz and 2 MHz...

A closer look at ultrasonic attenuation and heating in a tissue-mimicking material

A well-characterized ultrasound tissue-mimicking material (TMM) can be important in determining the acoustic output and temperature rise from high intensity therapeutic ultrasound (HITU) devices and also in validating computer simulation models. A HITU TMM previously developed and characterized in our laboratory has been used in our acoustic and temperature measurements as well as modeled in our HITU simulation program. A discrepancy between thermal measurement and simulation, though, led us to further investigate the TMM properties. We found that the 2-parameter analytic fit commonly used to represent the attenuation of the TMM in the computer modeling was not adequate over the entire frequency range of interest, 1 MHz to 8 MHz in this study, indicating that we and others may have not been characterizing TMMs, and possibly tissue, optimally. By comparing measurements and simulations, we found that a 3-parameter analytic fit for attenuation gave a more accurate value for attenuation at 1 MHz and 2 MHz, and using that fit the temperature rise measurements in the TMM that agreed more closely with the simulation results.

Development of a freely available simulator with graphical interface for modeling nonlinear focused ultrasound fields with shocks

Measurement-based modeling is gaining acceptance as a standard tool for characterizing the nonlinear fields of existing therapeutic ultrasound devices and designing new ones. Here, a freely available simulation tool is presented for modeling axially symmetric, strongly nonlinear HIFU beams with shocks in a layered propagation medium such as water and different types of tissue. Two nonlinear wave equations are included in the simulator: the KZK equation generalized to include an equivalent source boundary condition for strongly focused beams and the Westervelt equation in a nonlinear wide-angle parabolic representation. Both equations are solved in the frequency domain and permit definition of the HIFU transducer as an annular array. The geometrical parameters and power output of the array, electronic focus steering along the beam axis, and acoustic properties of the layered propagation medium can be configured via graphical interface. Visualization and output of various acoustic field parameters such as peak positive and negative pressures, shock amplitude, intensity, heat deposition rate, and total power of a beam are also provided. The simulator can be used for transducers without ideal symmetry through definition of an equivalent radially symmetric source. Widespread availability of such simulation tools will help advance standardized utilization of measurement-based modeling and facilitate the adoption of such approaches for HIFU treatment planning. [Work supported by NIH R01EB7643, R01EB025187, and RSF №14-12-00974.]

Abstract P6-12-13: Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device

Abstract Objectives: Breast cancer survivors need a non-hormonal treatment for vaginal dryness, as estrogen replacement therapy is often contraindicated or undesired. Therapeutic ultrasound applied to the vaginal introitus is safe and was shown to increase vaginal temperature and blood flow in our phase I study. We now report results from a twelve-week trial of daily, self-applied therapeutic ultrasound to the vaginal introitus. Methods: Breast cancer survivors and post-menopausal women with symptomatic vaginal atrophy were enrolled. A gynecologic oncologist supervised participants in application of a gel-pad equipped ultrasound head (Intelect TranSport, Chattanooga Group) to the vaginal introitus at an enrollment visit, and instructed women on self-application. Daily, 8-minute treatment applications for 12 weeks were planned, and dose was titrated as needed for comfort. Vaginal Maturation Index (VMI) specimens were collected and Vaginal Health Index (VHI) was recorded at study visits. Patient-reported outcomes for vaginal dryness and personal lubrication were recorded on a Likert-type scale (0-3). Student's t-test was used to analyze ordinal and continuous variables in an intent-to-treat analysis. Results: From December 2015 to January 2017, 20 women were enrolled, including 7 breast cancer survivors. Mean VMI for the study population was 25.1 (median 25) at baseline, and 21.4 (median 6) after 12 weeks of treatment (p&amp;gt;0.05). Similarly, there were no significant changes seen in mean VHI, which was 12.8 (median 13) at baseline and 14.1 (median 14) at 12 weeks (p&amp;gt;0.05). Statistically significant improvements were seen in both vaginal dryness and lubrication as reported by patients' scores. The mean vaginal dryness score for the population was 1.9 (median 2) at baseline and 1 (median 1) at 12 weeks (p&amp;lt;0.05). The effect was more pronounced in a subset of women (n=6) who did not use ultrasound jelly with their device (mean baseline score of 2.3 reduced to 1 at 12 weeks). Baseline vaginal lubrication scores (mean 0.6, median 1) for the population also improved after 12 weeks (mean 1.4, median 1, p&amp;lt;0.05), though the scores remained in the “mild” range. The six women who used the ultrasound device without jelly reported essentially no lubrication at the start of the study (mean 0.17, median 0), and had notably improved symptoms, reporting moderate lubrication after 12 weeks (mean and median score 1.5). Of the 15 women who completed the treatment according to protocol, 93% reported an improvement in at least one of their symptoms. Conclusions: Self-application of therapeutic ultrasound to the vaginal introitus decreased symptoms of vaginal atrophy in the majority of users. While no detectable changes in tissue physiology were noted with the VMI or VHI tools, the notable improvement in patient-reported outcomes warrants further study. A phase III clinical trial with a customized device is planned. Citation Format: MacLaughlan David S, Rockweiler H, Krone R, Middelton S, Blayney D. Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-13.