MR Acoustic Radiation Force Imaging Research Articles

Design and Validation of a Patient-Specific Stereotactic Frame for Transcranial Ultrasound Therapy.

Transcranial-focused ultrasound (tFUS) procedures such as neuromodulation and blood-brain barrier (BBB) opening require precise focus placement within the brain. MRI is currently the most reliable tool for focus localization but can be prohibitive for procedures requiring recurrent therapies. We designed, fabricated, and characterized a patient-specific, 3-D-printed, stereotactic frame for repeated tFUS therapy. The frame is compact, with minimal footprint, can be removed and re-secured between treatments while maintaining sub-mm accuracy, and will allow for precise and repeatable transcranial FUS treatment without the need for MR-guidance following the initial calibration scan. Focus localization and repeatability were assessed via MR-thermometry and MR-acoustic radiation force imaging (ARFI) on an ex vivo skull phantom and in vivo nonhuman primates (NHPs), respectively. Focal localization, registration, steering, and re-steering were accomplished during the initial MRI calibration scan session. Keeping steering coordinates fixed in subsequent therapy and imaging sessions, we found good agreement between steered foci and the intended target, with target registration error (TRE) of 1.2 ± 0.3 ( n = 4 , ex vivo) and 1.0 ± 0.5 ( n = 3 , in vivo) mm. Focus position (steered and non-steered) was consistent, with sub-mm variation in each dimension between studies. Our 3-D-printed, patient-specific stereotactic frame can reliably position and orient the ultrasound transducer for repeated targeting of brain regions using a single MR-based calibration. The compact frame allows for high-precision tFUS to be carried out outside the magnet and could help reduce the cost of tFUS treatments where repeated application of an ultrasound focus is required with high precision.

Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement.Methods: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histological methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging.Results: Comparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) for the monitoring of High Intensity Focused Ultrasound (HIFU) ablation in anisotropic tissue.

We introduce a non-invasive MR-Acoustic Radiation Force Imaging (ARFI)-based elastography method that provides both the local shear modulus and temperature maps for the monitoring of High Intensity Focused Ultrasound (HIFU) therapy. To take tissue anisotropy into account, the local shear modulus μ is determined in selected radial directions around the focal spot by fitting the phase profiles to a linear viscoelastic model, including tissue-specific mechanical relaxation time τ. MR-ARFI was evaluated on a calibrated phantom, then applied to the monitoring of HIFU in a gel phantom, ex vivo and in vivo porcine muscle tissue, in parallel with MR-thermometry. As expected, the shear modulus polar maps reflected the isotropy of phantoms and the anisotropy of muscle. In the HIFU monitoring experiments, both the shear modulus polar map and the thermometry map were updated with every pair of MR-ARFI phase images acquired with opposite MR-ARFI-encoding. The shear modulus was found to decrease (phantom and ex vivo) or increase (in vivo) during heating, before remaining steady during the cooling phase. The mechanical relaxation time, estimated pre- and post-HIFU, was found to vary in muscle tissue. MR-ARFI allowed for monitoring of viscoelasticity changes around the HIFU focal spot even in anisotropic muscle tissue.

Generating Patient-Specific Acoustic Simulations for Transcranial Focused Ultrasound Procedures Based on Optical Tracking Information.

Optical tracking is a real-time transducer positioning method for transcranial focused ultrasound (tFUS) procedures, but the predicted focus from optical tracking typically does not incorporate subject-specific skull information. Acoustic simulations can estimate the pressure field when propagating through the cranium but rely on accurately replicating the positioning of the transducer and skull in a simulated space. Here, we develop and characterize the accuracy of a workflow that creates simulation grids based on optical tracking information in a neuronavigated phantom with and without transmission through an ex vivo skull cap. The software pipeline could replicate the geometry of the tFUS procedure within the limits of the optical tracking system (transcranial target registration error (TRE): 3.9 ± 0.7 mm). The simulated focus and the free-field focus predicted by optical tracking had low Euclidean distance errors of 0.5±0.1 and 1.2±0.4 mm for phantom and skull cap, respectively, and some skull-specific effects were captured by the simulation. However, the TRE of simulation informed by optical tracking was 4.6±0.2, which is as large or greater than the focal spot size used by many tFUS systems. By updating the position of the transducer using the original TRE offset, we reduced the simulated TRE to 1.1 ± 0.4 mm. Our study describes a software pipeline for treatment planning, evaluates its accuracy, and demonstrates an approach using MR-acoustic radiation force imaging as a method to improve dosimetry. Overall, our software pipeline helps estimate acoustic exposure, and our study highlights the need for image feedback to increase the accuracy of tFUS dosimetry.

MRI-guided focused ultrasound neuromodulation of deep brain regions and circuits with real time feedback

Abstract Transcranial focused ultrasound (tFUS) is an emerging technology and has been regarded as the next generation of neuromodulation tools. tFUS is noninvasive and offers high precision targeting and stimulation of any brain region, including deep brain structures. Combined tFUS with MRI, such as MR-acoustic radiation force imaging (MR-ARFI) and functional MRI (fMRI), adds capabilities of real-time feedback on the FUS beam location and functional monitoring of FUS in action. In addition, advanced MRI contrasts provide tFUS safety assessment. In this presentation, I will review our progress on developing these methods for human applications and discuss how they are applied to modulate brain function in nonhuman primates. I will show data acquired at 7T and 3T MRI scanners and present results showing that tFUS exerts bidirectional (excitatory and inhibitory) modulation of brain BOLD fMRI signals at both somatosensory cortex and thalamus nucleus and their functional networks in a state-dependent manner. We are currently testing the hypothesis that varying intensities of tFUS selectively activate different types of neurons, resulting in bidirectional modulatory effects. Research Category and Technology and Methods Translational Research: 13. Other Brain Stimulation Technology Keywords: Transcranial focused ultrasound, MRI guidance, BOLD, Somatosensory and pain system

Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose-response relationship with MR-ARFI

Neuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. The purpose of this study was to confirm that MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) in the intact large animal; and to study the impact on cortical brain oscillations. The LGN on one side was identified with T2-weighted MRI in sheep (all male, n = 9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm localization of the targeted area in the brain. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time–frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics. The VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input. Sonication-associated microscopic displacements, as measured by MR-ARFI, correlated with the TUS-mediated suppression of visual evoked activity. TUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.

Image guidance and beam localization for transcranial focused ultrasound therapy

Therapeutic uses of transcranial focused ultrasound (tFUS) in the brain are being widely explored in both clinical and research settings from tissue destruction to blood brain barrier opening (BBBO) to neuromodulation. The appeal of tFUS is the ability to target structures throughout the brain with a millimeter scale focus. In order to understand the outcome of the treatment or experiment it is important to ensure the tFUS beam is targeted to and located at the region of interest. Image guidance allows for targeting of anatomical or functional structures within the brain. Here we present a targeting and localization scheme where optical tracking of the transducer is used to target the tFUS focus to a brain region within a previously acquired image and MR acoustic radiation force imaging is used to localize the beam in the brain to ensure the focus is at the target. By combining this targeting and localization scheme with a phased array transducer we are able to then steer the focus to ensure accurate sonications of specific brain regions using tFUS. This talk will discuss the application of this method to two different phased array transducers used for neuromodulation and BBBO in nonhuman primates.

Reduced-field of view three-dimensional MR acoustic radiation force imaging with a low-rank reconstruction fortargeting transcranial focused ultrasound.

To rapidly image and localize the focus in MR-guided focused ultrasound (FUS) while maintaining a low ultrasound duty cycle to minimize tissue effects. MR-acoustic radiation force imaging (ARFI) is key to targeting FUS procedures such as neuromodulation, and works by encoding ultrasound-induced displacements into the phase of MR images. However, it can require long scan times to cover a volume of tissue, especially when minimizing the FUS dose during targeting is paramount. To simultaneously minimize scan time and the FUS duty cycle, a 2-min three-dimensional (3D) reduced-FOV spin echo ARFI scan with two-dimensional undersampling was implemented at 3T with a FUS duty cycle of 0.85%. The 3D k-space sampling scheme incorporated uniform undersampling in one phase-encoded axis and partial Fourier (PF) sampling in the other. The scan interleaved FUS-on and FUS-off data collection to improve displacement map quality via a joint low-rank image reconstruction. Experiments in agarose and graphite phantoms and living macaque brains for neuromodulation and blood-brain barrier opening studied the effects of the sampling and reconstruction strategy on the acquisition, and evaluated its repeatability and accuracy. In the phantom, the distances between displacement centroids of 10 prospective reconstructions and a fully sampled reference were below 1 mm. In in vivo brain, the distances between centroids ranged from 1.3 to 2.1 mm. Results in phantom and in vivo brain both showed that the proposed method can recover the FUS focus compared to slower fully sampled scans. The proposed 3D MR-ARFI reduced-FOV method enables rapid imaging of the FUS focus while maintaining a low FUS duty cycle.

Improving in situ acoustic intensity estimates using MR acoustic radiation force imaging in combination with multifrequency MR elastography.

Magnetic resonance acoustic radiation force imaging (MR-ARFI) enables focal spot localization during nonablative transcranial ultrasound therapies. As the acoustic radiation force is proportional to the applied acoustic intensity, measured MR-ARFI displacements could potentially be used to estimate the acoustic intensity at the target. However, variable brain stiffness is an obstacle. The goal of this study was to develop and assess a method to accurately estimate the acoustic intensity at the focus using MR-ARFI displacements in combination with viscoelastic properties obtained with multifrequency MR elastography (MRE). Phantoms with a range of viscoelastic properties were fabricated, and MR-ARFI displacements were acquired within each phantom using multiple acoustic intensities. Voigt model parameters were estimated for each phantom based on storage and loss moduli measured using multifrequency MRE, and these were used to predict the relationship between acoustic intensity and measured displacement. Using assumed viscoelastic properties, MR-ARFI displacements alone could not accurately estimate acoustic intensity across phantoms. For example, acoustic intensities were underestimated in phantoms stiffer than the assumed stiffness and overestimated in phantoms softer than the assumed stiffness. This error was greatly reduced using individualized viscoelasticity measurements obtained from MRE. We demonstrated that viscoelasticity information from MRE could be used in combination with MR-ARFI displacements to obtain more accurate estimates of acoustic intensity. Additionally, Voigt model viscosity parameters were found to be predictive of the relaxation rate of each phantom's time-varying displacement response, which could be used to optimize patient-specific MR-ARFI pulse sequences.

MARFit: An Integrated Software for Real-Time MR Guided Focused Ultrasound Neuromodulation System

MR guided focused ultrasound (MRgFUS) therapy has been a promising treatment modality for many neurological disorders. However, the lack of real-time image processing software platform sets barriers for relevant pre-clinical researches. This work intends to develop an integrated software for MRgFUS therapy. The software contains three functional modules: a communication module, an image post-processing module, and a visualization module. The communication module provides a data interface with an open-source MR image reconstruction platform (Gadgetron) to receive the reconstructed MR images in real-time. The post-processing module contains the algorithms of image coordinate registration, focus localization by MR acoustic radiation force imaging (MR-ARFI), temperature and thermal dose calculations, motion correction, and temperature feedback control. The visualization module displays monitoring information and provides a user-machine interface. The software was tested to be compatible with systems from two different vendors and validated in multiple scenarios for MRgFUS. The software was tested in many ex vivo and in vivo experiments to validate its functions. The in vivo transcranial focus localization experiments were carried out for targeting the focused ultrasound in neuromodulation.

A Breast-Specific MR Guided Focused Ultrasound Platform and Treatment Protocol: First-in-Human Technical Evaluation.

This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). Successful technical treatments were achieved in 80 % of the patients. All patients underwent the treatment with no sedation and 60 % of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 ±1.8mm while 6.2 ±1.9mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 % and 70 % of patients, respectively. The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts.

Considerations for ultrasound exposure during transcranial MR acoustic radiation force imaging

The aim of this study was to improve the sensitivity of magnetic resonance-acoustic radiation force imaging (MR-ARFI) to minimize pressures required to localize focused ultrasound (FUS) beams, and to establish safe FUS localization parameters for ongoing ultrasound neuromodulation experiments in living non-human primates. We developed an optical tracking method to ensure that the MR-ARFI motion-encoding gradients (MEGs) were aligned with a single-element FUS transducer and that the imaged slice was prescribed at the optically tracked location of the acoustic focus. This method was validated in phantoms, which showed that MR-ARFI-derived displacement sensitivity is maximized when the MR-ARFI MEGs were maximally aligned with the FUS propagation direction. The method was then applied in vivo to acquire displacement images in two healthy macaque monkeys (M fascicularis) which showed the FUS beam within the brain. Temperature images were acquired using MR thermometry to provide an estimate of in vivo brain temperature changes during MR-ARFI, and pressure and thermal simulations of the acoustic pulses were performed using the k-Wave package which showed no significant heating at the focus of the FUS beam. The methods presented here will benefit the multitude of transcranial FUS applications as well as future human applications.

On the accuracy of optically tracked transducers for image-guided transcranial ultrasound.

Transcranial focused ultrasound (FUS) is increasingly being explored to modulate neuronal activity. To target neuromodulation, researchers often localize the FUS beam onto the brain region(s) of interest using spatially tracked tools overlaid on pre-acquired images. Here, we quantify the accuracy of optically tracked image-guided FUS with magnetic resonance imaging (MRI) thermometry, evaluate sources of error and demonstrate feasibility of these procedures to target the macaque somatosensory region. We developed an optically tracked FUS system capable of projecting the transducer focus onto a pre-acquired MRI volume. To measure the target registration error (TRE), we aimed the transducer focus at a desired target in a phantom under image guidance, heated the target while imaging with MR thermometry and then calculated the TRE as the difference between the targeted and heated locations. Multiple targets were measured using either an unbiased or bias-corrected calibration. We then targeted the macaque S1 brain region, where displacement induced by the acoustic radiation force was measured using MR acoustic radiation force imaging (MR-ARFI). All calibration methods enabled registration with TRE on the order of 3mm. Unbiased calibration resulted in an average TRE of 3.26mm (min-max: 2.80-4.53mm), which was not significantly changed by prospective bias correction (TRE of 3.05mm; 2.06-3.81mm, p = 0.55). Restricting motion between the transducer and target and increasing the distance between tracked markers reduced the TRE to 2.43mm (min-max: 0.79-3.88mm). MR-ARFI images showed qualitatively similar shape and extent as projected beam profiles in a living non-human primate. Our study describes methods for image guidance of FUS neuromodulation and quantifies errors associated with this method in a large animal. The workflow is efficient enough for in vivo use, and we demonstrate transcranial MR-ARFI in vivo in macaques for the first time.

Multiple-point magnetic resonance acoustic radiation force imaging.

Purpose:To implement and evaluate an efficient multiple-point MR acoustic radiation force imaging pulse sequence that can volumetrically measure tissue displacement and evaluate tissue stiffness using focused ultrasound (FUS) radiation force.Methods:Bipolar motion-encoding gradients were added to a gradient-recalled echo segmented EPI pulse sequence with both 2D and 3D acquisition modes. Multiple FUS-ON images (FUS power > 0 W) were interleaved with a single FUS-OFF image (FUS power = 0 W) on the TR level, enabling simultaneous measurements of volumetric tissue displacement (by complex subtraction of the FUS-OFF image from the FUS-ON images) and proton resonance frequency shift MR thermometry (from the OFF image). Efficiency improvements included partial Fourier acquisition, parallel imaging, and encoding up to 4 different displacement positions into a single image. Experiments were performed in homogenous and dual-stiffness phantoms, and in ex vivo porcine brain.Results:In phantoms, 16-point multiple-point magnetic resonance acoustic radiation force imaging maps could be acquired in 5 s to 10 s for a 2D slice, and 60 s for a 3D volume, using parallel imaging and encoding 2 displacement positions/image. In ex vivo porcine brain, 16-point multiple-point magnetic resonance acoustic radiation force imaging maps could be acquired in 20 s for a 3D volume, using partial Fourier and parallel imaging and encoding 4 displacement positions/image. In 1 experiment it was observed that tissue displacement in ex vivo brain decreased by approximately 22% following FUS ablation.Conclusion:With the described efficiency improvements it is possible to acquire volumetric multiple-point magnetic resonance acoustic radiation force imaging maps, with simultaneous proton resonance frequency shift MR thermometry maps, in clinically acceptable times.

MR-ARFI-based method for the quantitative measurement of tissue elasticity: application for monitoring HIFU therapy

Monitoring thermal therapies through medical imaging is essential in order to ensure that they are safe, efficient and reliable. In this paper, we propose a new approach, halfway between MR acoustic radiation force imaging (MR-ARFI) and MR elastography (MRE), allowing for the quantitative measurement of the elastic modulus of tissue in a highly localized manner. It relies on the simulation of the MR-ARFI profile, which depends on tissue biomechanical properties, and on the identification of tissue elasticity through the fitting of experimental displacement images measured using rapid MR-ARFI. This method was specifically developed to monitor MR-guided high intensity focused ultrasound (MRgHIFU) therapy. Elasticity changes were followed during HIFU ablations (N = 6) performed ex vivo in porcine muscle samples, and were compared to temperature changes measured by MR-thermometry. Shear modulus was found to increase consistently and steadily a few seconds after the heating started, and such changes were found to be irreversible. The shear modulus was found to increase from 1.49 ± 0.48 kPa (before ablation) to 3.69 ± 0.93 kPa (after ablation and cooling). Thanks to its ability to perform quantitative elasticity measurements in a highly localized manner around the focal spot, this method proved to be particularly attractive for monitoring HIFU ablations.

Simultaneous MR thermometry and acoustic radiation force imaging using interleaved acquisition.

A novel and practical method for simultaneously performing MR acoustic radiation force imaging (ARFI) and proton resonance frequency (PRF)-shift thermometry has been developed and tested. This could be an important tool for evaluating the success of MR-guided focused ultrasound procedures for which MR-thermometry measures temperature and thermal dose and MR-ARFI detects changes in tissue mechanical properties. MR imaging was performed using a gradient recalled echo segmented echo-planar imaging pulse sequence with bipolar motion encoding gradients (MEG). Images with ultrasound pulses (ON) and without ultrasound pulses (OFF) during the MEG were interleaved at the repetition time (TR) level. ARFI displacements were calculated by complex subtraction of ON-OFF images, and PRF temperature maps were calculated by baseline subtraction. Evaluations in tissue-mimicking phantoms and ex vivo porcine brain tissue were performed. Constrained reconstruction improved the temporal resolution of dynamic measurements. Simultaneous maps of displacement and temperature were acquired in 2D and 3D while keeping tissue heating < 1°C. Accuracy of the temperature maps was comparable to the standard PRF sequence. Using constrained reconstruction and subsampled k-space (R = 4.33), 3D simultaneous temperature and displacement maps can be acquired every 4.7 s. This new sequence acquires simultaneous temperature and displacement maps with minimal tissue heating, and can be applied dynamically for monitoring tissue mechanical properties during ablation procedures. Magn Reson Med 79:1515-1524, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High sensitivity MR acoustic radiation force imaging using transition band balanced steady-state free precession.

MR acoustic radiation force imaging (MR-ARFI) provides a method to visualize the focal spot of a focused ultrasound (FUS) beam without introducing a significant temperature rise. With conventional spoiled MR-ARFI pulse sequences, the ARFI phase always equals the motion-encoded phase. In this work, MR-ARFI using transition band balanced steady-state free precession (bSSFP) is presented, which improves the sensitivity of MR-ARFI with high acquisition speed. Motion-encoding gradients (MEG) are inserted into bSSFP sequences for MR-ARFI. By applying an ultrasound pulse during the MEG, motion-encoded phase is generated, which leads to an amplified change in the image phase when operating in the bSSFP transition band. MR-ARFI was performed on a homemade gel phantom using both the proposed technique and a spoiled gradient echo ARFI sequence with identical MEG and FUS, and ARFI images were compared. The bSSFP-ARFI sequence generated an ARFI image phase that is more than 5 times larger than the motion-encoded phase in a few seconds with 2DFT readout. By keeping FUS pulses as short as 1.45 ms, temperature rise was insignificant during the measurement. bSSFP-ARFI has enhanced sensitivity compared with conventional MR-ARFI pulse sequences and could provide an efficient way to visualize the focal spot. Magn Reson Med 79:1532-1537, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Open-source, small-animal magnetic resonance-guided focused ultrasound system.

BackgroundMR-guided focused ultrasound or high-intensity focused ultrasound (MRgFUS/MRgHIFU) is a non-invasive therapeutic modality with many potential applications in areas such as cancer therapy, drug delivery, and blood-brain barrier opening. However, the large financial costs involved in developing preclinical MRgFUS systems represent a barrier to research groups interested in developing new techniques and applications. We aim to mitigate these challenges by detailing a validated, open-source preclinical MRgFUS system capable of delivering thermal and mechanical FUS in a quantifiable and repeatable manner under real-time MRI guidance.MethodsA hardware and software package was developed that includes closed-loop feedback controlled thermometry code and CAD drawings for a therapy table designed for a preclinical MRI scanner. For thermal treatments, the modular software uses a proportional integral derivative controller to maintain a precise focal temperature rise in the target given input from MR phase images obtained concurrently. The software computes the required voltage output and transmits it to a FUS transducer that is embedded in the delivery table within the magnet bore. The delivery table holds the FUS transducer, a small animal and its monitoring equipment, and a transmit/receive RF coil. The transducer is coupled to the animal via a water bath and is translatable in two dimensions from outside the magnet. The transducer is driven by a waveform generator and amplifier controlled by real-time software in Matlab. MR acoustic radiation force imaging is also implemented to confirm the position of the focus for mechanical and thermal treatments.ResultsThe system was validated in tissue-mimicking phantoms and in vivo during murine tumor hyperthermia treatments. Sonications were successfully controlled over a range of temperatures and thermal doses for up to 20 min with minimal temperature overshoot. MR thermometry was validated with an optical temperature probe, and focus visualization was achieved with acoustic radiation force imaging.ConclusionsWe developed an MRgFUS platform for small-animal treatments that robustly delivers accurate, precise, and controllable sonications over extended time periods. This system is an open source and could increase the availability of low-cost small-animal systems to interdisciplinary researchers seeking to develop new MRgFUS applications and technology.

Evaluation of a three‐dimensional MR acoustic radiation force imaging pulse sequence using a novel unbalanced bipolar motion encoding gradient

MR guided focused ultrasound procedures require accurate focal spot localization in three dimensions. This study presents a three-dimensional (3D) pulse sequence for acoustic radiation force imaging (ARFI) that efficiently localizes the focal spot by means of ultrasound induced tissue displacement over a large field-of-view. A novel unbalanced bipolar motion encoding gradient was implemented to maximize time available for motion encoding, reduce echo times, and allow for longer echo train lengths. Two advanced features, kz reduction factor (KZRF) and kz -level interleaving, were implemented to reduce tissue heating. Studies in gelatin phantoms compared the location of peak displacement and temperature measured by 3D MR thermometry. MR-ARFI induced tissue heating was evaluated through a parametric study of sequence parameters and MR thermometry measurements during repeated application of ARFI sonication patterns. Sequence performance was characterized in the presence of respiration and tissue inhomogeneity. The location of peak displacement and temperature rise agreed within 0.2 ± 0.1 mm and 0.5 ± 0.3 mm in the transverse and longitudinal direction, respectively. The 3D displacement maps were acquired safely, and the KZRF and kz -level interleaving features reduced tissue heating by 51%. High quality displacement maps were obtained despite respiration and tissue inhomogeneities. This sequence provides a safe, accurate, and simple approach to localizing the focal spot in three dimensions with a single scan. Magn Reson Med 76:803-813, 2016. © 2015 Wiley Periodicals, Inc.

Concurrent Visualization of Acoustic Radiation Force Displacement and Shear Wave Propagation with 7T MRI.

Manual palpation is a common and very informative diagnostic tool based on estimation of changes in the stiffness of tissues that result from pathology. In the case of a small lesion or a lesion that is located deep within the body, it is difficult for changes in mechanical properties of tissue to be detected or evaluated via palpation. Furthermore, palpation is non-quantitative and cannot be used to localize the lesion. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) can also be used to evaluate the properties of biological tissues non-invasively. In this study, an MRgFUS system combines high field (7T) MR and 3 MHz focused ultrasound to provide high resolution MR imaging and a small ultrasonic interrogation region (~0.5 x 0.5 x 2 mm), as compared with current clinical systems. MR-Acoustic Radiation Force Imaging (MR-ARFI) provides a reliable and efficient method for beam localization by detecting micron-scale displacements induced by ultrasound mechanical forces. The first aim of this study is to develop a sequence that can concurrently quantify acoustic radiation force displacements and image the resulting transient shear wave. Our motivation in combining these two measurements is to develop a technique that can rapidly provide both ARFI and shear wave velocity estimation data, making it suitable for use in interventional radiology. Secondly, we validate this sequence in vivo by estimating the displacement before and after high intensity focused ultrasound (HIFU) ablation, and we validate the shear wave velocity in vitro using tissue-mimicking gelatin and tofu phantoms. Such rapid acquisitions are especially useful in interventional radiology applications where minimizing scan time is highly desirable.