Resonance Acoustic Radiation Force Imaging Research Articles

Practical targeting errors during optically tracked transcranial focused ultrasound using MR-ARFI and array-based steering.

Transcranial focused ultrasound (tFUS) is being explored for neuroscience research and clinical applications due to its ability to affect precise brain regions noninvasively. The ability to target specific brain regions and localize the beam during these procedures is important for these applications to avoid damage and minimize off-target effects. Here, we present a method to combine optical tracking with magnetic resonance (MR) acoustic radiation force imaging to achieve targeting and localizing of the tFUS beam. This combined method provides steering coordinates to target brain regions within a clinically practical time frame. Using an optically tracked hydrophone and bias correction with MR imaging we transformed the FUS focus coordinates into the MR space for targeting and error correction. We validated this method in vivo in 18 macaque FUS studies. Across these in vivo studies a single localization scan allowed for the average targeting error to be reduced from 4.8 mm to 1.4 mm and for multiple brain regions to be targeted with one transducer position. By reducing targeting error and providing the means to target multiple brain regions within a single session with high accuracy this method will allow further study of the effects of tFUS neuromodulation with more advanced approaches such as simultaneous dual or multi-site brain stimulation.

Poster Session I: Noninvasive neuromodulation of subcortical visual pathways with transcranial focused ultrasound.

Transcranial ultrasound stimulation (TUS) is an emerging tool to noninvasively modulate neural activity in deep brain areas. In preparation for our first in-human TUS studies, we targeted TUS to the lateral geniculate nucleus (visual thalamus) in a large mammal (sheep). Full-field light flash stimuli were presented with or without concomitant TUS in randomly interleaved trials. Similar to what has previously observed by Fry et al (Nature 1959) in cats, EEG visual-evoked potentials (VEPs) were reversibly suppressed by TUS to the LGN. No changes in VEPs were observed in sheep who received sham-TUS to a control site in the basal ganglia, ruling out potential transducer auditory-somatosensory confounds. Magnetic resonance acoustic radiation force imaging (MR-ARFI), a technique to measure the ultrasound focus in situ, showed a focal volume of microscopic displacement at the expected target. Excitingly, MR-ARFI predicted the suppressive effect on VEPs in individual subjects, suggesting that MR-ARFI can be used to confirm TUS targeting and estimate neurophysiological impact. We are now translating this paradigm into human, targeting TUS to the LGN while participants perform a contrast detection task with EEG recording of steady-state VEPs. MR-ARFI will be measured to evaluate targeting and estimate TUS dosage in each participant. This work provides the foundation for a dissection of the roles of different subcortical nuclei in different aspects of human vision.

SPatiotemporal-ENcoded acoustic radiation force imaging of focused ultrasound.

Neuromodulation technology has provided novel therapeutic approaches for diseases caused by neural circuit dysfunction. Transcranial focused ultrasound (FU) is an emerging neuromodulation approach that combines noninvasiveness with relatively sharp focus, even in deep brain regions. It has numerous advantages such as high precision and good safety in neuromodulation, allowing for modulation of both peripheral and central nervous systems. To ensure accurate treatment targeting in FU neuromodulation, a magnetic resonance acoustic radiation force imaging (MR-ARFI) sequence is crucial for the visualization of the focal point. Currently, the commonly used 2D Spin Echo ARFI (2D SE-ARFI) sequence suffers from the long acquisition time, while the echo planar imaging ARFI (EPI-ARFI) sequence with a shorter acquisition time is vulnerable to the magnetic field inhomogeneities. To address these problems, we proposed a spatiotemporal-encoded acoustic radiation force imaging sequence (i.e., SE-SPEN-ARFI, shortened to SPEN-ARFI) in this study. The displacement at the focal spot obtained was highly consistent with that of the SE-ARFI sequence. Our research shows that SPEN-ARFI allows for rapid image acquisition and has less image distortions even under great field inhomogeneities. Therefore, a SPEN-ARFI sequence is a practical alternative for the treatment planning in ultrasound neuromodulation.

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.

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.

A reduced aperture allows for transcranial focus localization at lower pressure.

Localizing the focus during transcranial focused ultrasound procedures is important to ensure accurate targeting of specific brain regions and interpretation of results. Magnetic resonance acoustic radiation force imaging uses the displacement induced by the ultrasound focus in the brain to localize the beam, but the high pressure required to displace brain tissue may cause damage or confounds during subsequent neuromodulatory experiments. Here, reduced apertures were applied to a phased array transducer to generate comparable displacement to the full aperture but with 20% lower free field pressure.

Simultaneous acoustic radiation force imaging and MR thermometry based on a coherent echo-shifted sequence.

Simultaneous magnetic resonance (MR) acoustic radiation force imaging (ARFI) and MR thermometry (MRT) (STARFI) based on coherent echo-shifted (cES) sequence was proposed and comprehensively compared to radiofrequency (RF)-spoiled gradient echo (spGRE) STARFI. Through use of delicately designed gradients, a collection of echoes was delayed by one repetition time (TR) cycle. The crusher gradient after readout (RO) was used as the displacement encoding gradient (DEG). The sequence was intrinsically sensitive to temperature. High-intensity focused ultrasound (HIFU) pulses were interleaved ON/OFF in successive TRs to separate the phase changes induced by displacement due to acoustic radiation force (ARF) impulses and temperature. Bloch simulation was performed to study the phase sensitivity to displacement of the proposed cES STARFI and spGRE STARFI. The proposed cES sequence was evaluated and compared to spGRE STARFI in ex vivo porcine muscle and ex vivo porcine brain. The minimally achievable TR of cES STARFI was shorter than that of spGRE STARFI, indicating that the cES sequence was more time efficient. It was verified through Bloch simulation and ex vivo experiments that the phase sensitivity to displacement of cES STARFI was higher than that of spGRE STARFI. The optimal trigger delays of cES STARFI and spGRE STARFI in ex vivo porcine muscle were toffset =-2 and -1 ms, respectively. The displacement-induced phase change to acoustic pressure slopes of cES STARFI were 0.079, 0.079, and 0.047 rad/Mpa across the three muscle samples, while the slopes of spGRE STARFI were only 0.047, 0.052, and 0.027 rad/Mpa. The maximum temperature difference between cES STARFI and spGRE STARFI was 1.1 °C. In ex vivo porcine brain, both the displacement-induced phase-to-noise ratio (PNRd) and the temperature uncertainty of cES STARFI were better than those of spGRE STARFI (P<0.05). The temperature and displacement-induced phase change maps of cES STARFI and spGRE STARFI during HIFU treatment were in good accordance in time and spatial location. The cES STARFI sequence can provide simultaneous MR-ARFI and temperature measurements during pulsed HIFU applications. Though the exact displacement cannot be quantified directly, the sequence showed increased phase sensitivity compared with the spGRE sequence and provided efficient visualization of the focal spot. cES STARFI could therefore be a desirable alternative to spGRE STARFI in practical applications.

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep

BackgroundNeuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI). ObjectiveTo investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI. MethodsTwo rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS. ResultsNo FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS. ConclusionsThe absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

Acoustic radiation force imaging using a single-shot spiral readout

The purpose of this study is to develop and validate rapid magnetic resonance acoustic radiation force imaging (MR-ARFI) using a single shot spiral readout for focused ultrasound (FUS) guidance and for local tissue displacement measurements. A magnetic resonance guided FUS system was used to focus a 3 MHz ultrasound beam to a predetermined position. MR-ARFI was performed with a Bruker 7 T MRI using a modified single-shot spiral readout, with additional motion encoding gradients that convert local displacement into the phase image. Post processing was then used to analyze the resulting displacement and to evaluate the method’s performance for the detection of tissue changes resulting from thermal ablation. The single-shot spiral readout acquires a single MR-ARFI image in one second, which is up to two orders of magnitude faster than conventional 2D spin-warp spin echo that acquires the k-space data line by line. The ARFI displacement in tissue mimicking phantoms was detected and localized with less than 5% geometric distortion. The ARFI displacement was also measured pre and post thermal ablation in an ex vivo chicken breast. For transmitted peak negative pressure of 8.6 MPa, the maximum displacement of the tissue that was ablated to 70 °C was 78% lower than the pre-ablated tissue. Since spiral readout is not prone to geometrical distortion, it is well-suited for FUS guidance, without generating undesired temperature elevation. Additionally, local displacement measurements of tissues can be performed rapidly during thermal ablation procedures and may help to assess the success of the treatment.

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.

A rapid magnetic resonance acoustic radiation force imaging sequence for ultrasonic refocusing

Magnetic resonance guided acoustic radiation force imaging (MR-ARFI) is being used to correct for aberrations induced by tissue heterogeneities when using high intensity focusing ultrasound (HIFU). A compromise between published MR-ARFI adaptive solutions is proposed to achieve efficient refocusing of the ultrasound beam in under 10 min. In addition, an ARFI sequence based on an EPI gradient echo sequence was used to simultaneously monitor displacement and temperature with a large SNR and low distortion.This study was conducted inside an Achieva 3T clinical MRI using a Philips Sonalleve MR-HIFU system to emit a 1 ms pulsed sonication with duty cycle of 2.3% at 300 Wac inside a polymer phantom. Virtual elements defined by a Hadamard array with sonication patterns composed of 6 phase steps were used to characterize 64 groups of 4 elements to find the optimal phase of the 256 elements of the transducer. The 384 sonication patterns were acquired in 580 s to identify the set of phases that maximize the displacement at the focal point. Three aberrators (neonatal skull, 8 year old skull and a checkered pattern) were added to each sonication pattern to evaluate the performance of this refocusing algorithm (n = 4).These aberrators reduced the relative intensities to 95.3%, 69.6% and 25.5% for the neonatal skull, 8 year old skull, and checkered pattern virtual aberrators respectively. Using a 10 min refocusing algorithm, relative intensities of 101.6%, 91.3% and 93.3% were obtained. Better relative intensities of 103.9%, 94.3% and 101% were achieved using a 25 min refocusing algorithm. An average temperature increase of 4.2 °C per refocusing test was induced for the 10 min refocusing algorithm, resulting in a negligible thermal dose of 2 EM.A rapid refocusing of the beam can be achieved while keeping thermal effects to a minimum.

Variable ultrasound trigger delay for improved magnetic resonance acoustic radiation force imaging

Magnetic resonance acoustic radiation force imaging (MR-ARFI) allows the quantification of microscopic displacements induced by ultrasound pulses, which are proportional to the local acoustic intensity. This study describes a new method to acquire MR-ARFI maps, which reduces the measurement noise in the quantification of displacement as well as improving its robustness in the presence of motion.Two MR-ARFI sequences were compared in this study. The first sequence ‘variable MSG’ involves switching the polarity of the motion sensitive gradient (MSG) between odd and even image frames. The second sequence named ‘static MSG’ involves a variable ultrasound trigger delay to sonicate during the first or second MSG for odd and even image frames, respectively. As previously published, the data acquired with a variable MSG required the use of reference data acquired prior to any sonication to process displacement maps. In contrary, data acquired with a static MSG were converted to displacement maps without using reference data acquired prior to the sonication. Displacement maps acquired with both sequences were compared by performing sonications for three different conditions: in a polyacrylamide phantom, in the leg muscle of a freely breathing pig and in the leg muscle of pig under apnea.The comparison of images acquired at even image frames and odd image frames indicates that the sequence with a static MSG provides a significantly better steady state (p < 0.001 based on a Student’s t-test) than the images acquired with a variable MSG. In addition no reference data prior to sonication were required to process displacement maps for data acquired with a static MSG. The absence of reference data prior to sonication provided a 41% reduction of the spatial distribution of noise (p < 0.001 based on a Student’s t-test) and reduced the sensitivity to motion for displacements acquired with a static MSG. No significant differences were expected and observed for thermal maps acquired with a variable MSG and a static MSG.The use of a static MSG with a variable ultrasound trigger delay improves the ARFI displacement map quality without additional acquisition time and remains compatible with the simultaneous acquisition of MR thermal maps.

Magnetic Resonance Imaging for the Exploitation of Bubble-Enhanced Heating by High-Intensity Focused Ultrasound: A Feasibility Study in ex Vivo Liver

Bubble-enhanced heating (BEH) may be exploited to improve the heating efficiency of high-intensity focused ultrasound in liver and to protect tissues located beyond the focal point. The objectives of this study, performed in ex vivo pig liver, were (i) to develop a method to determine the acoustic power threshold for induction of BEH from displacement images measured by magnetic resonance acoustic radiation force imaging (MR-ARFI), and (ii) to compare temperature distribution with MR thermometry for HIFU protocols with and without BEH. The acoustic threshold for generation of BEH was determined in ex vivo pig liver from MR-ARFI calibration curves of local tissue displacement resulting from sonication at different powers. Temperature distributions (MR thermometry) resulting from “conventional” sonications (20 W, 30 s) were compared with those from “composite” sonications performed at identical parameters, but after a HIFU burst pulse (0.5 s, acoustic power over the threshold for induction of BEH). Displacement images (MR-ARFI) were acquired between sonications to measure potential modifications of local tissue displacement associated with modifications of tissue acoustic characteristics induced by the burst HIFU pulse. The acoustic threshold for induction of BEH corresponded to a displacement amplitude of approximately 50 μm in ex vivo liver. The displacement and temperature images of the composite group exhibited a nearly spherical pattern, shifted approximately 4 mm toward the transducer, in contrast to elliptical shapes centered on the natural focal position for the conventional group. The gains in maximum temperature and displacement values were 1.5 and 2, and the full widths at half-maximum of the displacement data were 1.7 and 2.2 times larger than in the conventional group in directions perpendicular to ultrasound propagation axes. Combination of MR-ARFI and MR thermometry for calibration and exploitation of BEH appears to increase the efficiency and safety of HIFU treatment.

Noninvasive biomarkers in non-alcoholic fatty liver disease: current status and a glimpse of the future.

The development of non invasive biomarkers of disease has become a major focus of interest in nonalcoholic fatty liver disease (NAFLD). The large prevalence of the disease and the invasive nature of the investigation means that screening with liver biopsy is impractical. In addition to screening, the differentiation of those with simple steatosis vs steatohepatitis and fibrosis is clinically important as the prognosis of each differs. Serum biomarkers may be a combination of simple markers derived from large data sets or direct markers of disease activity. Serum markers of inflammation, apoptosis and oxidative stress in addition to fibrosis have been extensively studied in patients with NAFLD. Other techniques such as transient elastography, magnetic resonance elastography and acoustic radiation force imaging are becoming more established as noninvasive methods of detecting fibrosis in a variety of chronic liver conditions in addition to NAFLD. Newer high throughput methods such as proteomics and glycomics allow the nonhypothesis-driven identification of novel markers and may also potentially contribute to our understanding of the pathogenesis of the condition. This review addresses some of the methodological issues which need to be considered in the search for the ideal biomarker. It is likely that a combination of serum biomarkers and techniques such as transient elastography may provide the optimal diagnostic discrimination however this remains to be proven in large studies.

Keyhole acceleration for magnetic resonance acoustic radiation force imaging (MR ARFI)

MR ARFI measures the displacement induced by the ultrasonic radiation force and provides the location of the focal spot without significant heating effects. Displacements maps obtained with MR ARFI provide an indirect estimation of the acoustic beam intensity at the target. This measure is essential for dose estimation prior to focused ultrasound treatments (FUS) and adaptive focusing procedures of MR-guided transcranial and transribs FUS. In the latter case, the beam correction is achieved by maximizing the displacement at focus. A significant number of serial MR ARFI images are required and thus, a partial k-space updating method, such as keyhole appears as a method of choice. The purpose of this work is to demonstrate via simulations and experiments the efficiency of the keyhole technique combined with a two-dimensional spin-echo MR ARFI pulse sequence. The method was implemented in an ex vivo calf brain taking advantage of the a priori knowledge of the focal spot profile. The coincidence of the phase-encoding axis with the longest axis of the focal spot makes the best use of the technique. Our approach rapidly provides the focal spot localization with accuracy, and with a substantial increase to the signal-to-noise ratio, while reducing ultrasound energy needed during MR-guided adaptive focusing procedures.

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head

This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using magnetic resonance acoustic radiation force imaging (MR-ARFI) in the framework of non-invasive transcranial high intensity focused ultrasound (HIFU) therapy. Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. The authors evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical magnetic resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A noniterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation-based on X-ray computed tomography (CT) scans. The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications.

Ultrasound focusing using magnetic resonance acoustic radiation force imaging: Application to ultrasound transcranial therapy

Magnetic resonance guided ultrasonic therapy is a promising minimally invasive technology for constantly growing variety of clinical applications. Delivery of focused ultrasound (FUS) energy to the targeted point with optimal intensity is highly desired; however, due to tissue aberrations, optimal focal intensity is not always achieved. Especially in transcranial applications, the acoustic waves are shifted and distorted mainly by the skull. In order to verify that magnetic resonance acoustic radiation force imaging (MR-ARFI) can be used as a focusing tool in transcranial treatments, such an imaging was applied in vivo on a porcine brain via ex vivo human skull. Then, by the use of MR-ARFI technique, an improved ultrasound focusing algorithm is proposed and demonstrated for both transcranial and none brain applications. MR-ARFI images were acquired on a GE 1.5 T scanner equipped with InSightec FUS systems ExAblate 2000 and ExAblate 4000. Imaging was performed with MR-ARFI sequences of line-scan spin-echo and single-shot gradient-echo echo-planar. The in-plane resolution of both acquisitions was 0.9 x 0.9 mm2. The total acquisition time of MR-ARFI image was 31 s by the line-scan sequence and 1 s by the echo-planar sequence. An in vivo experiment was performed using FUS transducer, which is built out of 1024 ultrasound transmitting piezoelectric elements at 220 kHz frequency. The transducer was focused into the brain of a pig, which was wrapped in a human skull, in degassed water environment to resemble human treatments. The pig underwent a wide bilateral craniectomy to prevent a bone heating from the ultrasound beams. Two focusing experiments were performed in phantoms using 1 MHz and 710 kHz FUS transducers working with 208 and 225 elements, respectively. In the first experiment, aberration was added virtually to the apparatus by adding random phases to the phase map of the transducer. A simple focusing correction scheme was used, in which the corrected phase of a group of elements was chosen such that it maximizes the radiation force at the focal point. In the second experiment, aberrations made by a human skull were corrected using geometrical and phase based adjustments on segments of the transducer. A maximum displacement of 10 microm was obtained using 1.4 kW acoustic power on a live pig's head that its skull was removed and replaced by ex vivo human skull. Aberration correction using MR-ARFI resulted in near optimal focus, as the radiation force was similar to the nonaberration case. Transcranial, MR-ARFI based aberration correction performed better than CT based aberration correction, a technique that is currently used in brain FUS treatments. In the present work, the authors show for the first time a result of MR-ARFI in a live brain through ex vivo human skull. They have demonstrated that aberration correction could be done using MR-ARFI by measuring the radiation force at the focal point. Aberration correction using MR-ARFI is a promising noninvasive technique for transcranial focusing, which may result in near optimal focus and more reliable and safer brain FUS treatments.

Magnetic resonance acoustic radiation force imaging

Acoustic radiation force impulse imaging is an elastography method developed for ultrasound imaging that maps displacements produced by focused ultrasound pulses systematically applied to different locations. The resulting images are "stiffness weighted" and yield information about local mechanical tissue properties. Here, the feasibility of magnetic resonance acoustic radiation force imaging (MR-ARFI) was tested. Quasistatic MR elastography was used to measure focal displacements using a one-dimensional MRI pulse sequence. A 1.63 or 1.5 MHz transducer supplied ultrasound pulses which were triggered by the magnetic resonance imaging hardware to occur before a displacement-encoding gradient. Displacements in and around the focus were mapped in a tissue-mimicking phantom and in an ex vivo bovine kidney. They were readily observed and increased linearly with acoustic power in the phantom (R2=0.99). At higher acoustic power levels, the displacement substantially increased and was associated with irreversible changes in the phantom. At these levels, transverse displacement components could also be detected. Displacements in the kidney were also observed and increased after thermal ablation. While the measurements need validation, the authors have demonstrated the feasibility of detecting small displacements induced by low-power ultrasound pulses using an efficient magnetic resonance imaging pulse sequence that is compatible with tracking of a dynamically steered ultrasound focal spot, and that the displacement increases with acoustic power. MR-ARFI has potential for elastography or to guide ultrasound therapies that use low-power pulsed ultrasound exposures, such as drug delivery.