MRI compatibility testing of commercial high intensity focused ultrasound transducers.

PURPOSE: The study aimed to compare the performance of eight commercially available single-element High Intensity Focused Ultrasound (HIFU) transducers in terms of Magnetic Resonance Imaging (MRI) compatibility. METHODS: Imaging of an agar-based MRI phantom was performed in a 3 T MRI scanner utilizing T2-Weighted Fast Spin Echo (FSE) and Fast low angle shot (FLASH) sequences, which are typically employed for high resolution anatomical imaging and thermometry, respectively. Reference magnitude and phase images of the phantom were compared with images acquired in the presence of each transducer in terms of the signal to noise ratio (SNR), introduced artifacts, and overall image quality. RESULTS: The degree of observed artifacts highly differed among the various transducers. The transducer whose backing material included magnetic impurities showed poor performance in the MRI, introducing significant susceptibility artifacts such as geometric distortions and signal void bands. Additionally, it caused the most significant SNR drop. Other transducers were shown to exhibit high level of MRI compatibility as the resulting images closely resembled the reference images with minimal to no apparent artifacts and comparable SNR values. CONCLUSIONS: The study findings may facilitate researchers to select the most suitable transducer for their research, simultaneously avoiding unnecessary testing. The study further provides useful design considerations for MRI compatible transducers.

Advanced software for MRgFUS treatment planning.

BACKGROUND AND OBJECTIVES: Herein, a user-friendly software platform for 3-dimensional Focused Ultrasound treatment planning based on Magnetic Resonance Imaging (MRI) images is presented. METHODS: The software directly retrieves and loads MRI images. Various design tools can be used on the MRI images to define the treatment area and the sonication parameters. Based on the treatment plan, the software controls the robotic motion and motion pattern of Magnetic Resonance guided Focused Ultrasound (MRgFUS) robotic systems to execute the treatment procedure. Real-time treatment monitoring is achieved through MRI images and thermometry. The software's functionality and performance were evaluated in both laboratory and MRI environments. Different treatment plans were designed on MRI images and sonications were executed on agar-based phantoms and polymer films. RESULTS: Magnetic Resonance (MR) thermometry maps were acquired in the agar-based phantoms. An exceptional agreement was observed between the software-planned treatment area and the lesions produced on the polymer films. CONCLUSIONS: The developed software was successfully integrated with the MRI and robotic system controls for performing accurate treatment planning and real-time monitoring during sonications. The software provides an extremely user-friendly interface, while in the future it could be enhanced by providing dynamic modulation of the ultrasonic parameters during the treatment process.

FUS-mediated blood-brain barrier disruption for delivering anti-Aß antibodies in 5XFAD Alzheimer's disease mice.

PURPOSE: Amyloid-ß (Aß) peptides, the main component of amyloid plaques found in the Alzheimer's disease (AD) brain, are implicated in its pathogenesis, and are considered a key target in AD therapeutics. We herein propose a reliable strategy for non-invasively delivering a specific anti-Aß antibody in a mouse model of AD by microbubbles-enhanced Focused Ultrasound (FUS)-mediated Blood-brain barrier disruption (BBBD), using a simple single stage MR-compatible positioning device. METHODS: The initial experimental work involved wild-type mice and was devoted to selecting the sonication protocol for efficient and safe BBBD. Pulsed FUS was applied using a single-element FUS transducer of 1 MHz (80 mm radius of curvature and 50 mm diameter). The success and extent of BBBD were assessed by Evans Blue extravasation and brain damage by hematoxylin and eosin staining. 5XFAD mice were divided into different subgroups; control (n = 1), FUS + MBs alone (n = 5), antibody alone (n = 5), and FUS + antibody combined (n = 10). The changes in antibody deposition among groups were determined by immunohistochemistry. RESULTS: It was confirmed that the antibody could not normally enter the brain parenchyma. A single treatment with MBs-enhanced pulsed FUS using the optimized protocol (1 MHz, 0.5 MPa in-situ pressure, 10 ms bursts, 1% duty factor, 100 s duration) transiently disrupted the BBB allowing for non-invasive antibody delivery to amyloid plaques within the sonicated brain regions. This was consistently reproduced in ten mice. CONCLUSION: These preliminary findings should be confirmed by longer-term studies examining the antibody effects on plaque clearance and cognitive benefit to hold promise for developing disease-modifying anti-Aß therapeutics for clinical use.

Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer.

PURPOSE: The study aims to provide insights on the practicality of using single-element transducers for transcranial Focused Ultrasound (tFUS) thermal applications. METHODS: FUS sonications were performed through skull phantoms embedding agar-based tissue mimicking gels using a 1 MHz single-element spherically focused transducer. The skull phantoms were 3D printed with Acrylonitrile Butadiene Styrene (ABS) and Resin thermoplastics having the exact skull bone geometry of a healthy volunteer. The temperature field distribution during and after heating was monitored in a 3 T Magnetic Resonance Imaging (MRI) scanner using MR thermometry. The effect of the skull's thickness on intracranial heating was investigated. RESULTS: A single FUS sonication at focal acoustic intensities close to 1580 W/cm2 for 60 s in free field heated up the agar phantom to ablative temperatures reaching about 90 °C (baseline of 37 °C). The ABS skull strongly blocked the ultrasonic waves, resulting in zero temperature increase within the phantom. Considerable heating was achieved through the Resin skull, but it remained at hyperthermia levels. Conversely, tFUS through a 1 mm Resin skull showed enhanced ultrasonic penetration and heating, with the focal temperature reaching 70 °C. CONCLUSIONS: The ABS skull demonstrated poorer performance in terms of tFUS compared to the Resin skull owing to its higher ultrasonic attenuation and porosity. The thin Resin phantom of 1 mm thickness provided an efficient acoustic window for delivering tFUS and heating up deep phantom areas. The results of such studies could be particularly useful for accelerating the establishment of a wider range of tFUS applications.

Tumor phantom model for MRI-guided focused ultrasound ablation studies.

BACKGROUND: The persistent development of focused ultrasound (FUS) thermal therapy in the context of oncology creates the need for tissue-mimicking tumor phantom models for early-stage experimentation and evaluation of relevant systems and protocols. PURPOSE: This study presents the development and evaluation of a tumor-bearing tissue phantom model for testing magnetic resonance imaging (MRI)-guided FUS (MRgFUS) ablation protocols and equipment based on MR thermometry. METHODS: Normal tissue was mimicked by a pure agar gel, while the tumor simulator was differentiated from the surrounding material by including silicon dioxide. The phantom was characterized in terms of acoustic, thermal, and MRI properties. US, MRI, and computed tomography (CT) images of the phantom were acquired to assess the contrast between the two compartments. The phantom's response to thermal heating was investigated by performing high power sonications with a 2.4 MHz single element spherically focused ultrasonic transducer in a 3T MRI scanner. RESULTS: The estimated phantom properties fall within the range of literature-reported values of soft tissues. The inclusion of silicon dioxide in the tumor material offered excellent tumor visualization in US, MRI, and CT. MR thermometry revealed temperature elevations in the phantom to ablation levels and clear evidence of larger heat accumulation within the tumor owing to the inclusion of silicon dioxide. CONCLUSION: Overall, the study findings suggest that the proposed tumor phantom model constitutes a simple and inexpensive tool for preclinical MRgFUS ablation studies, and potentially other image-guided thermal ablation applications upon minimal modifications.

Phantom-based assessment of motion and needle targeting accuracy of robotic devices for magnetic resonance imaging-guided needle biopsy.

BACKGROUND: The current study proposes simple methods for assessing the performance of robotic devices intended for Magnetic Resonance Imaging (MRI)-guided needle biopsy. METHODS: In-house made agar-based breast phantoms containing biopsy targets served as the main tool in the evaluation process of an MRI compatible positioning device comprising a needle navigator. The motion accuracy of mechanical stages was assessed by calliper measurements. Laboratory evaluation of needle targeting included a repeatability phantom test and a laser-based method. The accuracy and repeatability of needle targeting was also assessed by MRI. RESULTS: The maximum error of linear motion for steps up to 10 mm was 0.1 mm. Needle navigation relative to the phantom and alignment with the various biopsy targets were performed successfully in both the laboratory and MRI settings. The proposed biopsy phantoms offered tissue-like signal in MRI and good haptic feedback during needle insertion. CONCLUSIONS: The proposed methods could be valuable in the process of validating the accuracy of MRI-guided biopsy robotic devices in both laboratory and real environments.

Robotic system for magnetic resonance imaging-guided focused ultrasound treatment of thyroid nodules.

BACKGROUND: Herein, a robotic system offering Magnetic Resonance-guided Focused Ultrasound (MRgFUS) therapy of thyroid nodules was developed. METHODS: The robotic system offers linear motion in 2 PC-controlled axes that navigate a 3 MHz single-element focused transducer. The system, through a C-arm structure attaches to the table of Magnetic Resonance Imaging (MRI) scanners and couples to the neck of patients lying in the supine position. The MRI compatibility of the developed system was assessed inside a 3 T scanner. Benchtop and MRI feasibility studies evaluating the heating performance of the system were executed on excised pork tissue and on homogeneous and thyroid model agar-based phantoms. RESULTS: The MRI compatibility of the system was successfully established. Grid sonications executed using robotic motion inflicted discrete and overlapping lesions on the excised tissue, while magnetic resonance (MR) thermometry successfully monitored thermal heating in agar-based phantoms. CONCLUSIONS: The developed system was found to be efficient with ex-vivo evaluation. The system can perform clinical MRgFUS therapy of thyroid nodules and other shallow targets after further in-vivo evaluation.

Development of an US, MRI, and CT imaging compatible realistic mouse phantom for thermal ablation and focused ultrasound evaluation.

Tissue mimicking phantoms (TMPs) play an essential role in modern biomedical research as cost-effective quality assurance and training tools, simultaneously contributing to the reduction of animal use. Herein, we present the development and evaluation of an anatomically accurate mouse phantom intended for image-guided thermal ablation and Focused Ultrasound (FUS) applications. The proposed mouse model consists of skeletal and soft tissue mimics, whose design was based on the Computed tomography (CT) scans data of a live mouse. Advantageously, it is compatible with US, CT, and Magnetic Resonance Imaging (MRI). The compatibility assessment was focused on the radiological behavior of the phantom due to the lack of relevant literature. The X-ray linear attenuation coefficient of candidate materials was estimated to assess the one that matches best the radiological behavior of living tissues. The bone part was manufactured by Fused Deposition Modeling (FDM) printing using Acrylonitrile styrene acrylate (ASA) material. For the soft-tissue mimic, a special mold was 3D printed having a cavity with the unique shape of the mouse body and filled with an agar-based silica-doped gel. The mouse phantom accurately matched the size and reproduced the body surface of the imaged mouse. Tissue-equivalency in terms of X-ray attenuation was demonstrated for the agar-based soft-tissue mimic. The phantom demonstrated excellent MRI visibility of the skeletal and soft-tissue mimics. Good radiological contrast between the skeletal and soft-tissue models was also observed in the CT scans. The model was also able to reproduce realistic behavior during trans-skull sonication as proved by thermocouple measurements. Overall, the proposed phantom is inexpensive, ergonomic, and realistic. It could constitute a powerful tool for image-guided thermal ablation and FUS studies in terms of testing and optimizing the performance of relevant equipment and protocols. It also possess great potential for use in transcranial FUS applications, including the emerging topic of FUS-mediated blood brain barrier (BBB) disruption.

Challenges regarding MR compatibility of an MRgFUS robotic system.

Numerous challenges are faced when employing Magnetic Resonance guided Focused Ultrasound (MRgFUS) hardware in the Magnetic Resonance Imaging (MRI) setting. The current study aimed to provide insights on this topic through a series of experiments performed in the framework of evaluating the MRI compatibility of an MRgFUS robotic device. All experiments were performed in a 1.5 T MRI scanner. The main metric for MRI compatibility assessment was the signal to noise ratio (SNR). Measurements were carried out in a tissue mimicking phantom and freshly excised pork tissue under various activation states of the system. In the effort to minimize magnetic interference and image distortion, various set-up parameters were examined. Significant SNR degradation and image distortion occurred when the FUS transducer was activated mainly owing to FUS-induced target and coil vibrations and was getting worse as the output power was increased. Proper design and stable positioning of the imaged phantom play a critical role in reducing these vibrations. Moreover, isolation of the phantom from the imaging coil was proven essential for avoiding FUS-induced vibrations from being transferred to the coil during sonication and resulted in a more than 3-fold increase in SNR. The use of a multi-channel coil increased the SNR by up to 50 % compared to a single-channel coil. Placement of the electronics outside the coil detection area increased the SNR by about 65 %. A similar SNR improvement was observed when the encoders' counting pulses were deactivated. Overall, this study raises awareness about major challenges regarding operation of an MRgFUS system in the MRI environment and proposes simple measures that could mitigate the impact of noise sources so that the monitoring value of MR imaging in FUS applications is not compromised.

Treatment of canine and feline sarcoma using MR-guided focused ultrasound system.

PURPOSE: In recent years, veterinary medicine has enhanced its applications beyond traditional approaches, progressively incorporating the Focused Ultrasound (FUS) technology. This study investigated the ability of FUS to precisely ablate naturally occurring canine and feline soft tissue sarcomas (STS). METHODS: Six dogs and four cats with superficial tumours were enrolled in the study. The tumours were treated with a Magnetic Resonance guided FUS (MRgFUS) robotic system featuring a single element spherically focused transducer of 2.6 MHz. The tumours were then removed by surgery and sent for hematoxylin and eosin (H&E) staining. RESULTS: The MRgFUS system was capable of inflicting well-defined overlapping lesions in the tumours. The anatomical sites of the treated tumours were the neck, leg, face, back and belly. Coagulative necrosis was evidenced by histopathology assessment in 80% of cases. CONCLUSION: Therefore, this technology can be a therapeutic solution for veterinary cancer and a model for advancing the knowledge on human STS.

Full coverage path planning algorithm for MRgFUS therapy.

BACKGROUND: High-quality methods for Magnetic Resonance guided Focussed Ultrasound (MRgFUS) therapy planning are needed for safe and efficient clinical practices. Herein, an algorithm for full coverage path planning based on preoperative MR images is presented. METHODS: The software functionalities of an MRgFUS robotic system were enhanced by implementing the developed algorithm. The algorithm's performance in accurate path planning following a Zig-Zag pathway was assessed on MR images. The planned sonication paths were performed on acrylic films using the robotic system carrying a 2.75 MHz single element transducer. RESULTS: Ablation patterns were successfully planned on MR images and produced on acrylic films by overlapping lesions with excellent match between the planned and experimental lesion shapes. CONCLUSIONS: The advanced software was proven efficient in planning and executing full ablation of any segmented target. The reliability of the algorithm could be enhanced through the development of a fully automated segmentation procedure.

Robotic system for top to bottom MRgFUS therapy of multiple cancer types.

BACKGROUND: A robotic system for Magnetic Resonance guided Focussed Ultrasound (MRgFUS) therapy of tumours in the breast, bone, thyroid, and abdomen was developed. METHODS: A special C-shaped structure was designed to be attached to the table of conventional magnetic resonance imaging (MRI) systems carrying 4 computer-controlled motion stages dedicated to positioning a 2.75 MHz spherically focussed transducer relative to a patient placed in the supine position. The developed system was evaluated for its MRI compatibility and heating abilities in agar-based phantoms and freshly excised tissue. RESULTS: Compatibility of the system with a clinical high-field MRI scanner was demonstrated. FUS heating in the phantom was successfully monitored by magnetic resonance thermometry without any evidence of magnetically induced phenomena. Cigar-shaped discrete lesions and well-defined areas of overlapping lesions were inflicted in excised tissue by robotic movement along grid patterns. CONCLUSIONS: The developed MRgFUS robotic system was proven safe and efficient by ex-vivo feasibility studies.

Ultrasound-assisted dilute acid hydrolysis for production of essential oils, pectin and bacterial cellulose via a citrus processing waste biorefinery.

An orange peel waste biorefinery was developed employing a design of experiments approach to optimize the ultrasound-assisted dilute acid hydrolysis process applied for production of useful commodities. Central composite design-based response surface methodology was used to approximate the combined effects of process parameters in simultaneous production of essential oils, pectin and a sugar-rich hydrolyzate. Application of a desirability function determined the optimal conditions required for maximal production efficiency of essential oils, pectin and sugars as 5.75% solid loading, 1.21% acid concentration and 34.2 min duration. Maximum production yields of 0.12% w/w essential oils, 45% w/w pectin and 40% w/w sugars were achieved under optimized conditions in lab- and pilot-scale facilities. The hydrolyzate formed was applied in bacterial cellulose fermentations producing 5.82 g biopolymer per 100 g waste. Design of experiments was efficient for process analysis and optimization providing a systems platform for the study of biomass-based biorefineries.

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.

Robotic system for magnetic resonance guided focused ultrasound ablation of abdominal cancer.

BACKGROUND: A prototype robotic system that uses magnetic resonance guided focused ultrasound (MRgFUS) technology is presented. It features three degrees of freedom (DOF) and is intended for thermal ablation of abdominal cancer. METHODS: The device is equipped with three identical transducers being offset between them, thus focussing at different depths in tissue. The efficacy and safety of the system in ablating rabbit liver and kidney was assessed, both in laboratory and magnetic resonance imaging (MRI) conditions. RESULTS: Despite these organs' challenging location, in situ coagulative necrosis of a tissue area was achieved. Heating of abdominal organs in rabbit was successfully monitored with MR thermometry. CONCLUSIONS: The MRgFUS system was proven successful in creating lesions in the abdominal area of rabbits. The outcomes of the study are promising for future translation of the technology to the clinic.

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.

Acoustical properties of 3D printed thermoplastics.

With focused ultrasound (FUS) gaining popularity as a therapeutic modality for brain diseases, the need for skull phantoms that are suitable for evaluating FUS protocols is increasing. In the current study, the acoustical properties of several three-dimensional (3D) printed thermoplastic samples were evaluated to assess their suitability to mimic human skull and bone accurately. Samples were 3D printed using eight commercially available thermoplastic materials. The acoustic properties of the printed samples, including attenuation coefficient, speed of sound, and acoustic impedance, were investigated using transmission-through and pulse-echo techniques. The ultrasonic attenuation, estimated at a frequency of 1.1 MHz, varied from approximately 7 to 32 dB/cm. The frequency dependence of attenuation was described by a power law in the frequency range of 0.2-3.5 MHz, and the exponential index of frequency was found to vary from 1.30 to 2.24. The longitudinal velocity of 2.7 MHz sound waves was in the range of 1700-3050 m/s. The results demonstrate that thermoplastics could potentially be used for the 3D construction of high-quality skull phantoms.

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.

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.