An in vitro Model for Experimental Evaluation of Sonothrombolysis under Tissue-mimicking Material Conditions.

Background: The mechanical properties of therapeutic ultrasound (US) have attracted scientific interest for thrombolysis enhancement in combination with thrombolytic agents and microbubbles (MBs). The aim of the study was to develop an in vitro model to observe how the effects of sonothrombolysis change in the case where a tissue-mimicking material (TMM) is placed in the path of the US beam before the clot. Methods: Fully retracted blood clots were prepared and pulse sonicated for 1 h under various conditions. The system was in a state of real circulating flow with a branch of an open bypass and an occluded tube containing a blood clot, thus mimicking the case of ischemic stroke. The effectiveness of thrombolysis was quantified in milligrams of clots removed. An agar-based TMM was developed around the occluded tube. Results: The clot breakdown in a TMM was found to be more pronounced than in water, presumably due to the retention of the acoustic field. A higher level of acoustic power was required to initiate clot lysis (>76 W acoustic power) using only focused US (FUS). The greatest thrombolysis enhancement was observed with the largest chosen pulse duration (PD) and the use of MBs (150 mg clot mass lysis). The synergistic effect of FUS in combination with MBs on the enzymatic fibrinolysis enhanced thrombolysis efficacy by 260% compared to thrombolysis induced using only FUS. A reduction in the degree of clot lysis was detected due to the attenuation factor of the intervening material (30 mg at 1 and 4 ms PD). Conclusion: In vitro thrombolytic models including a TMM can provide a more realistic evaluation of new thrombolytic protocols. However, higher acoustic power should be considered to compensate for the attenuation factor. The rate of clot lysis is slow and the clinical use of this method will be challenging.

A High Intensity Focused Ultrasound System for Veterinary Oncology Applications.

BACKGROUND: Magnetic resonance-guided focused ultrasound surgery is an incisionless energy-based thermal method that is used for ablating tumors in the veterinary clinic. AIMS AND OBJECTIVES: In this article we describe a prototype of a veterinary system compatible with magnetic resonance imaging intended for small-to-medium-sized companion animals that was developed and tested in vivo in adult rabbits. METHODS: Real-time monitoring of the ablation during the experiment was possible with MR thermometry. Experiments involved thermal monitoring of sonications applied in the thigh of the rabbits. A 38-mm diameter transducer operating at 2.6 MHz was used with a 60-mm-focal length. The robotic system employed 3 linear axes and one angular axis. For this study, only X and Y axis were enabled. Due to the target size limitations, motion in Z and Θ was not needed. The functionality of the positioning device was evaluated by means of MR thermometry, demonstrating sufficient heating and accurate motion in both axes of operation. RESULTS: The postmortem findings confirm the ability of the system to induce thermal ablations in vivo in the absence of adverse effects. CONCLUSIONS: The device is a reliable and affordable solution for companion animal hospitals, offering and additional tool for the veterinary oncology society.

Experimental evaluation of the near-field and far-field heating of focused ultrasound using the thermal dose concept.

BACKGROUND: Conventional motion algorithms utilized during High Intensity Focused Ultrasound (HIFU) procedures usually sonicate successive tissue cells, thereby inducing excess deposition of thermal dose in the pre-focal region. Long delays (~60 s) are used to reduce the heating around the focal region. In the present study the experimental evaluation of six motion algorithms so as to examine the required delay and algorithm for which the pre-focal (near-field) and post-focal (far-field) heating can be reduced using thermal dose estimations is presented. MATERIALS AND METHODS: A single element spherically focused transducer operating at 1.1 MHz and focusing beam at 9 cm, was utilized for sonication on a 400 mm2 area of an agar-based phantom. Movement of the transducer was performed with each algorithm, using 0-60 s (10 s step) delays between sonications. Temperatures were recorded at both near and far-field regions and thermal dose calculations were implemented. RESULTS: With the algorithms used in the present study, a delay of 50-60 s was required to reduce heating in the near-field region. A 30 s delay induced a safe thermal dose in the far-field region using all algorithms except sequential which still required 60 s delay. CONCLUSIONS: The study verified the conservative need for 60 s delay for the sequential plan treatment. Nevertheless, present findings suggest that prolonged treatment times can be significantly reduced in homogeneous tissues by selection of the optimized nonlinear algorithm and delay.

Simple methods to test the accuracy of MRgFUS robotic systems.

BACKGROUND: Robotic-assisted diagnostic and therapeutic modalities require a highly accurate performance to be certified for clinical application. In this paper, three simple methods for assessing the accuracy of motion of magnetic resonance-guided focused ultrasound (MRgFUS) robotic systems are presented. METHODS: The accuracy of motion of a 4 degrees of freedom robotic system intended for preclinical use of MRgFUS was evaluated by calliper-based and magnetic resonance imaging (MRI) methods, as well as visually by performing multiple ablations on a plastic film. RESULTS: The benchtop results confirmed a highly accurate motion in all axes of operation. The spatial positioning errors estimated by MRI evaluation were defined by the size of the imaging pixels. Lesions arrangement in discrete and overlapping patterns confirmed satisfactory alignment of motion trajectories. CONCLUSIONS: We believe the methods presented here should serve as a standard for evaluating the accuracy of motion of MRgFUS robotic systems.

Magnetic resonance image-guided focused ultrasound robotic system for transrectal prostate cancer therapy.

BACKGROUND: A magnetic resonance image (MRI) guided robotic device for focussed ultrasound therapy of prostate cancer (PC) was developed. The device offers movement in 5 degrees of freedom (DOF) and uses a single-element transducer that operates at 3.2 MHz, has a diameter of 25 mm and focuses at 45 mm. METHODS: The MRI compatibility of the system was evaluated in a 1.5 T scanner. The ability of the transducer to create lesions was evaluated in laboratory and MRI settings, on ex vivo pork tissue and in vivo rabbit thigh tissue. RESULTS: Cavitational and thermal lesions were created on the excised pork tissue. In vivo experiments proved the efficacy of the system in ablating muscle tissue without damaging intervening areas. CONCLUSIONS: The MRI compatible robotic system can be placed on the table of any commercial MRI scanner up to 7 T. The device has the ability of future use for transrectal focal therapy of PC with the patient in supine position.

Characterization of a soft tissue-mimicking agar/wood powder material for MRgFUS applications.

This study describes the development and characterization of an agar-based soft tissue-mimicking material (TMM) doped with wood powder destined for fabricating MRgFUS applications. The main objective of the following work was to investigate the suitability of wood powder as an inexpensive alternative in replacing other added materials that have been suggested in previous studies for controlling the ultrasonic properties of TMMs. The characterization procedure involved a series of experiments designed to estimate the acoustic (attenuation coefficient, absorption coefficient, propagation speed, and impedance), thermal (conductivity, diffusivity, specific heat capacity), and MR properties (T1 and T2 relaxation times) of the wood-powder doped material. The developed TMM (2% w/v agar and 4% w/v wood powder) as expected demonstrated compatibility with MRI scanner following images artifacts evaluation. The acoustic attenuation coefficient of the proposed material was measured over the frequency range of 1.1-3 MHz and found to be nearly proportional to frequency. The measured attenuation coefficient was 0.48 dB/cm at 1 MHz which was well within the range of soft tissue. Temperatures over 37 °C proved to increase marginally the attenuation coefficient. Following the transient thermoelectric method, the acoustic absorption coefficient was estimated at 0.34 dB/cm-MHz. The estimated propagation speed (1487 m/s) was within the range of soft tissue at room temperature, while it significantly increased with higher temperature. The material possessed an acoustic impedance of 1.58 MRayl which was found to be comparable to the corresponding value of muscle tissue. The thermal conductivity of the material was estimated at 0.51 W/m K. The measured relaxation times T1 (844 ms) and T2 (66 ms) were within the range of values found in the literature for soft tissue. The phantom was tested for its suitability for evaluating MRgFUS thermal protocols. High acoustic energy was applied, and temperature change was recorded using thermocouples and MR thermometry. MR thermal maps were acquired using single-shot Echo Planar Imaging (EPI) gradient echo sequence. The TMM matched adequately the acoustic and thermal properties of human tissues and through a series of experiments, it was proven that wood concentration enhances acoustic absorption. Experiments using MR thermometry demonstrated the usefulness of this phantom to evaluate ultrasonic thermal protocols by monitoring peak temperatures in real-time. Thermal lesions formed above a thermal dose were observed in high-resolution MR images and visually in dissections of the proposed TMM.

Ultrasonic Attenuation of an Agar, Silicon Dioxide, and Evaporated Milk Gel Phantom.

BACKGROUND: It has been demonstrated that agar-based gel phantoms can emulate the acoustic parameters of real tissues and are the most commonly used tissue-mimicking materials for high-intensity focused ultrasound applications. The following study presents ultrasonic attenuation measurements of agar-based phantoms with different concentrations of additives (percent of agar, silicon dioxide and evaporated milk) in an effort of matching the material's acoustic property as close as possible to human tissues. METHODS: Nine different agar-based phantoms with various amounts of agar, silicon dioxide, and evaporated milk were prepared. Attenuation measurements of the samples were conducted using the through-transmission immersion techniques. RESULTS: The ultrasonic attenuation coefficient of the agar-based phantoms varied in the range of 0.30-1.49 dB/cm-MHz. The attenuation was found to increase in proportion to the concentration of agar and evaporated milk. Silicon dioxide was found to significantly contribute to the attenuation coefficient up to 4% weight to volume (w/v) concentration. CONCLUSION: The acoustic attenuation coefficient of agar-based phantoms can be adjusted according to the tissue of interest in the range of animal and human tissues by the proper selection of agar, silicon dioxide, and evaporated milk.