High-quality Agar and Polyacrylamide Tumor-mimicking Phantom Models for Magnetic Resonance-guided Focused Ultrasound Applications.

Background: Tissue-mimicking phantoms (TMPs) have been used extensively in clinical and nonclinical settings to simulate the thermal effects of focus ultrasound (FUS) technology in real tissue or organs. With recent technological developments in the FUS technology and its monitoring/guided techniques such as ultrasound-guided FUS and magnetic resonance-guided FUS (MRgFUS) the need for TMPs are more important than ever to ensure the safety of the patients before being treated with FUS for a variety of diseases (e.g., cancer or neurological). The purpose of this study was to prepare a tumor-mimicking phantom (TUMP) model that can simulate competently a tumor that is surrounded by healthy tissue. Methods: The TUMP models were prepared using polyacrylamide (PAA) and agar solutions enriched with MR contrast agents (silicon dioxide and glycerol), and the thermosensitive component bovine serum albumin (BSA) that can alter its physical properties once thermal change is detected, therefore offering real-time visualization of the applied FUS ablation in the TUMPs models. To establish if these TUMPs are good candidates to be used in thermoablation, their thermal properties were characterized with a custom-made FUS system in the laboratory and a magnetic resonance imaging (MRI) setup with MR-thermometry. The BSA protein's coagulation temperature was adjusted at 55°C by setting the pH of the PAA solution to 4.5, therefore simulating the necrosis temperature of the tissue. Results: The experiments carried out showed that the TUMP models prepared by PAA can change color from transparent to cream-white due to the BSA protein coagulation caused by the thermal stress applied. The TUMP models offered a good MRI contrast between the TMPs and the TUMPs including real-time visualization of the ablation area due to the BSA protein coagulation. Furthermore, the T2-weighted MR images obtained showed a significant change in T2 when the BSA protein is thermally coagulated. MR thermometry maps demonstrated that the suggested TUMP models may successfully imitate a tumor that is present in soft tissue. Conclusion: The TUMP models developed in this study have numerous uses in the testing and calibration of FUS equipment including the simulation and validation of thermal therapy treatment plans with FUS or MRgFUS in oncology applications.

Feasibility of Ultrasonic Heating through Skull Phantom Using Single-element Transducer.

Background: Noninvasive neurosurgery has become possible through the use of transcranial focused ultrasound (FUS). This study assessed the heating ability of single element spherically focused transducers operating at 0.4 and 1.1 MHz through three-dimensional (3D) printed thermoplastic skull phantoms. Methods: Phantoms with precise skull bone geometry of a male patient were 3D printed using common thermoplastic materials following segmentation on a computed tomography head scan image. The brain tissue was mimicked by an agar-based gel phantom developed in-house. The selection of phantom materials was mainly based on transmission-through attenuation measurements. Phantom sonications were performed through water, and then, with the skull phantoms intervening the beam path. In each case, thermometry was performed at the focal spot using thermocouples. Results: The focal temperature change in the presence of the skull phantoms was reduced to less than 20 % of that recorded in free field when using the 0.4 MHz transducer, whereas the 1.1 MHz trans-skull sonication produced minimal or no change in focal temperature. The 0.4 MHz transducer showed better performance in trans-skull transmission but still not efficient. Conclusion: The inability of both tested single element transducers to steer the beam through the high attenuating skull phantoms and raise the temperature at the focus was confirmed, underlying the necessity to use a correction technique to compensate for energy losses, such those provided by phased arrays. The proposed phantom could be used as a cost-effective and ergonomic tool for trans-skull FUS preclinical studies.

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.

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.

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.

Evaluating acoustic and thermal properties of a plaque phantom.

PURPOSE: The aim of this study is to evaluate the acoustic and thermal properties of a plaque phantom. This is very important for the effective implementation of ultrasound not only in diagnosis but especially in treatment for the future. MATERIAL AND METHODS: An evaluation of acoustic and thermal properties of plaque phantoms to test their suitability mainly for ultrasound imaging and therapy was presented. The evaluation included measurements of the acoustic propagation speed using pulse-echo technique, ultrasonic attenuation coefficient using through transmission immersion technique, and absorption coefficient. Moreover, thermal properties (thermal conductivity, volumetric specific heat capacity and thermal diffusivity) were measured with the transient method using a needle probe. RESULTS: It was shown that acoustic and thermal properties of atherosclerotic plaque phantoms fall well within the range of reported values for atherosclerotic plaque and slightly different for thermal diffusivity and volumetric specific heat capacity for soft tissues. The mean value of acoustic and thermal properties and their standard deviation of plaque phantoms were 1523 ± 23 m/s for acoustic speed, 0.50 ± 0.02 W/mK for thermal conductivity, 0.30 ± 0.21 db/cm-MHz for ultrasonic absorption coefficient and 1.63 ± 0.46 db/cm-MHz for ultrasonic attenuation coefficient. CONCLUSIONS: This study demonstrated that acoustic and thermal properties of atherosclerotic plaque phantoms were within the range of reported values. Future studies should be focused on the optimum recipe of the atherosclerotic plaque phantoms that mimics the human atherosclerotic plaque (agar 4% w/v, gypsum 10% w/v and butter 10% w/v) and can be used for HIFU therapy.

Treatment of mammary cancer with focused ultrasound: A pilot study in canine and feline patients.

In recent years, veterinary medicine has expanded its practices beyond conventional methods, gradually integrating the Focused Ultrasound (FUS) technology in the care of companion animals like dogs and cats. The current study aimed to examine the feasibility and provide insights into the application of thermal FUS in canine and feline mammary cancer therapy. FUS was delivered by a 2-MHz single-element spherically focused ultrasonic transducer as integrated with an existing robotic positioning device. The functionality of the FUS system and sonication protocol in efficiently and safely ablating live tissue was initially validated in a rabbit thigh model in a laboratory environment. Nine (9) dogs and cats with superficial mammary cancer were recruited through a dedicated campaign according to specific safety criteria. The veterinary patients underwent FUS ablation followed by immediate surgical resection of the entire malignancy. Histopathology examination demonstrated well-defined regions of coagulative necrosis in all treated tumors with no off-target damage. Further study with a larger patient population is needed to confirm the current findings and demonstrate the safety and feasibility of complete FUS ablation of deep-seated tumors.

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.

Preclinical robotic device for magnetic resonance imaging guided focussed ultrasound.

BACKGROUND: A robotic device featuring three motion axes was manufactured for preclinical research on focussed ultrasound (FUS). The device comprises a 2.75 MHz single element ultrasonic transducer and is guided by Magnetic Resonance Imaging (MRI). METHODS: The compatibility of the device with the MRI was evaluated by estimating the influence on the signal-to-noise ratio (SNR). The efficacy of the transducer in generating ablative temperatures was evaluated in phantoms and excised porcine tissue. RESULTS: System's activation in the MRI scanner reduced the SNR to an acceptable level without compromising the image quality. The transducer demonstrated efficient heating ability as proved by MR thermometry. Discrete and overlapping thermal lesions were inflicted in excised tissue. CONCLUSIONS: The FUS system was proven effective for FUS thermal applications in the MRI setting. It can thus be used for multiple preclinical applications of the emerging MRI-guided FUS technology. The device can be scaled-up for human use with minor modifications.

Characterization of a fat tissue mimicking material for high intensity focused ultrasound applications.

PURPOSE: Tissue-mimicking materials (TMMs) have a prominent role in validating new high intensity focused ultrasound (HIFU) therapies. Agar-based TMMs are often developed mimicking the thermal properties of muscle tissue, while TMMs simulating fat tissue properties are rarely developed. Herein, twelve agar-based TMMs were iteratively developed with varied concentrations of agar, water, glycerol and propan-2-ol, and characterized for their suitability in emulating the thermal conductivity of human fat tissue. METHODS: Varied agar concentrations (2%, 4%, 6%, 8%, 12%, 16% and 20% w/v) were utilized for developing seven water-based TMMs, while a 20% w/v agar concentration was utilized for developing two water/alcohol-based TMMs (50% v/v water and 50% v/v either glycerol or propan-2-ol) and three alcohol-based TMMs (varied glycerol and propan-2-ol concentrations). Thermal conductivity was measured for all TMMs, and the tissue mimicking material (TMM) exhibiting thermal conductivity closest to human fat was considered the optimum fat TMM and was further characterized using ultrasound (US) and Magnetic Resonance Imaging (MRI). RESULTS: For the seven water-based TMMs an inverse linear trend was observed between thermal conductivity and increased agar concentration, being between 0.524 and 0.445 W/m K. Alcohol addition decreased thermal conductivity of the two water/alcohol-based TMMs to about 0.33 W/m K, while in the alcohol-based TMMs, increased concentrations of propan-2-ol emerged as a modifier of thermal conductivity. The optimum fat TMM (33.3% v/v glycerol and 66.7% v/v propan-2-ol) exhibited a 0.231 W/m K thermal conductivity, and appeared hypoechoic on US images and with increased brightness on T1-Weighted MRI images. CONCLUSION: The optimum fat TMM emulates the thermal conductivity of human fat tissue and exhibits a fat-like appearance on US and MRI images. The TMM is cost-effective and has a long lifespan and possesses great potential for use in HIFU applications as a fat TMM.

Simple, inexpensive, and ergonomic phantom for quality assurance control of MRI guided Focused Ultrasound systems.

PURPOSE: The popularity of Magnetic Resonance guided Focused Ultrasound (MRgFUS) as a beneficial therapeutic solution for many diseases is increasing rapidly, thus raising the need for reliable quality assurance (QA) phantoms for routine testing of MRgFUS systems. In this study, we propose a thin acrylic film as the cheapest and most easily accessible phantom for assessing the functionality of MRgFUS hardware and software. METHODS: Through the paper, specific QA tests are detailed in the framework of evaluating an MRgFUS preclinical robotic device comprising a single element spherically focused transducer with a nominal frequency of 2.75 MHz. These tests take advantage of the reflection of ultrasonic waves at a plastic-air interface, which results in almost immediate lesion formation on the film at a threshold of applied acoustic energy. RESULTS: The phantom offered qualitative information on the power field distribution of the FUS transducer and the ability to visualize different FUS protocols. It also enabled quick and reliable assessment of various navigation algorithms as they are used in real treatments, and also allowed for the assessment of the accuracy of robotic motion. CONCLUSION: Therefore, it could serve as a useful tool for detecting defects in system's performance over its lifetime after establishing a baseline while concurrently contributing to establish QA and calibration guidelines for clinical routine controls.

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.

Robotic device for transcranial focussed ultrasound applications in small animal models.

BACKGROUND: Focussed Ultrasound (FUS) combined with microbubbles (MBs) was proven a promising modality for non-invasive blood brain barrier disruption (BBBD). Herein, two devices for FUS-mediated BBBD in rodents are presented. METHODS: A two-axes robotic device was manufactured for navigating a single element FUS transducer of 1 MHz relative to the brain of rodents. A second more compact device featuring a single motorized vertical axis was also developed. Their performance was assessed in terms of motion accuracy, MRI compatibility and trans-skull BBBD in wild type mice using MBs in synergy with pulsed FUS. RESULTS: Successful BBBD was evidenced by the Evans Blue dye method, as well as by Fibronectin and Fibrinogen immunostaining. BBB permeability was enhanced when the applied acoustic intensity was increased. CONCLUSIONS: The proposed devices constitute a cost-effective and ergonomic solution for FUS-mediated BBBD in small animal models. Further experimentation is needed to examine the repeatability of results and optimise the therapeutic protocol.

Ultrasonic attenuation of canine mammary tumours.

BACKGROUND: Canine mammary tumours (CMTs) are the most common neoplasm appearing in female dogs and are considered the equivalent animal model of human breast cancer. However, in the literature, there is a gap for ultrasonic characterisation of these tumours. In this study, experimental measurements for acoustic attenuation and propagation speed of three surgically excised malignant CMTs were implemented. METHODS: The three tumours were fixed in formaldehyde for up to 72 h and a total of five sample pieces were sectioned from the three tumours to account for the varied morphology observed along the tumours. The through-transmission and pulse-echo techniques were employed for experimental measurements of the acoustic attenuation and propagation speed. RESULTS: Acoustic propagation speed of the five samples as measured at 2.7 MHz was in the range of 1568-1636 m/s. Correspondingly, acoustic attenuation was in the range of 1.95-3.45 dB/cm.MHz. Variations in both speed and attenuation were observed between samples acquired from the same tumour. CONCLUSIONS: Present findings suggest that both acoustic attenuation and propagation speed of CMTs are higher than normal canine tissues due to increased heterogeneity and varied morphology visually observed between the tumour specimens and evidenced by histological examination. Nevertheless, experimental results could aid in enhancing the use of ultrasound in the diagnosis and treatment of CMTs as well as provide essential data for comparative oncology.

MR relaxation times of agar-based tissue-mimicking phantoms.

Agar gels were previously proven capable of accurately replicating the acoustical and thermal properties of real tissue and widely used for the construction of tissue-mimicking phantoms (TMPs) for focused ultrasound (FUS) applications. Given the current popularity of magnetic resonance-guided FUS (MRgFUS), we have investigated the MR relaxation times T1 and T2 of different mixtures of agar-based phantoms. Nine TMPs were constructed containing agar as the gelling agent and various concentrations of silicon dioxide and evaporated milk. An agar-based phantom doped with wood powder was also evaluated. A series of MR images were acquired in a 1.5 T scanner for T1 and T2 mapping. T2 was predominantly affected by varying agar concentrations. A trend toward decreasing T1 with an increasing concentration of evaporated milk was observed. The addition of silicon dioxide decreased both relaxation times of pure agar gels. The proposed phantoms have great potential for use with the continuously emerging MRgFUS technology. The MR relaxation times of several body tissues can be mimicked by adjusting the concentration of ingredients, thus enabling more accurate and realistic MRgFUS studies.