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Purpose MR thermometry is critical for safe and effective transcranial focused ultrasound. The current single-slice MR thermometry sequence cannot achieve all desired treatment monitoring requirements. We propose an approach in which the imaging requirements of different aspects of treatment monitoring are met by optimizing multiple sequences. Methods Imaging requirements were determined for three stages of MR-guided focused ultrasound brain treatment: 1) focal spot localization, 2) focal spot monitoring, and 3) background monitoring. Multiple-echo spiral thermometry sequences were optimized for each set of requirements and then validated with in vivo signal-to-noise ratio measurements and with phantom heating experiments. Results Each of the proposed sequences obtained better precision than the current two-dimensional Fourier transform (2DFT) thermometry sequence. Five-slice focal spot localization achieved two-fold better resolution with 1.9-fold better precision but two-fold longer acquisition compared to 2DFT. Five-slice focal monitoring achieved 2.1-fold better precision with similar speed but 12% larger voxels than 2DFT. Full-brain background monitoring was demonstrated in both axial (7.1 s) and sagittal (11.4 s) orientations. Phantom heating time curves were consistent across all sequences after correcting for resolution. Conclusion Multiple-echo spiral imaging significantly improves MR thermometry efficiency, enabling multiple-slice monitoring. Optimizing multiple specialized sequences provides better performance than can be achieved by any single sequence. Magn Reson Med 78:508-517, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

Purpose Low-bandwidth PRF shift thermometry is used to guide HIFU ablation treatments. Low sampling bandwidth is needed for high signal-to-noise ratio with short acquisition times, but can lead to off-resonance artifacts. In this work, improved multiple-echo thermometry is presented that allows for high bandwidth and reduced artifacts. It is also demonstrated with spiral sampling, to improve the trade-off between resolution, speed, and measurement precision. Methods Four multiple-echo thermometry sequences were tested in vivo, one using two-dimensional Fourier transform (2DFT) sampling and three using spirals. The spiral sequences were individually optimized for resolution, for speed, and for precision. Multifrequency reconstruction was used to correct for off-resonance spiral artifacts. Additionally, two different multiecho temperature reconstructions were compared. Results Weighted combination of per-echo phase differences gave significantly better precision than least squares off-resonance estimation. Multiple-echo 2DFT sequence obtained precision similar to single-echo 2DFT, while greatly increasing sampling bandwidth. The multiecho spiral acquisitions achieved 2× better resolution, 2.9× better uncertainty, or 3.4× faster acquisition time, without negatively impacting the other two design parameters as compared to single-echo 2DFT. Conclusion Multiecho spiral thermometry greatly improves the capabilities of temperature monitoring, and could improve transcranial treatment monitoring capabilities. Magn Reson Med 76:747-756, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Temperature estimation in proton resonance frequency (PRF) shift MR thermometry requires a reference, or pretreatment, phase image that is subtracted from image phase during thermal treatment to yield a phase difference image proportional to temperature change. Referenceless thermometry methods derive a reference phase image from the treatment image itself by assuming that in the absence of a hot spot, the image phase can be accurately represented in a smooth (usually low order polynomial) basis. By masking the hot spot out of a least squares (ℓ2) regression, the reference phase image's coefficients on the polynomial basis are estimated and a reference image is derived by evaluating the polynomial inside the hot spot area. Referenceless methods are therefore insensitive to motion and bulk main field shifts, however, currently these methods require user interaction or sophisticated tracking to ensure that the hot spot is masked out of the polynomial regression. This article introduces an approach to reference PRF shift thermometry that uses reweighted ℓ1 regression, a form of robust regression, to obtain background phase coefficients without hot spot tracking and masking. The method is compared to conventional referenceless thermometry, and demonstrated experimentally in monitoring HIFU heating in a phantom and canine prostate, as well as in a healthy human liver. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A single-voxel Carr-Purcell-Meibloom-Gill sequence was developed to measure localized T2 relaxation times of 13C-labeled metabolites in vivo for the first time. Following hyperpolarized [1-13C]pyruvate injections, pyruvate and its metabolic products, alanine and lactate, were observed in the liver of five rats with hepatocellular carcinoma and five healthy control rats. The T2 relaxation times of alanine and lactate were both significantly longer in HCC tumors than in normal livers ( p < 0.002). The HCC tumors also showed significantly higher alanine signal relative to the total 13C signal than normal livers ( p < 0.006). The intra- and inter-subject variations of the alanine T2 relaxation time were 11% and 13%, respectively. The intra- and inter-subject variations of the lactate T2 relaxation time were 6% and 7%, respectively. The intra-subject variability of alanine to total carbon ratio was 16% and the inter-subject variability 28%. The intra-subject variability of lactate to total carbon ratio was 14% and the inter-subject variability 20%. The study results show that the signal level and relaxivity of [1-13C]alanine may be promising biomarkers for HCC tumors. Its diagnostic values in HCC staging and treatment monitoring are yet to be explored. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Therapeutic ultrasound guided by MRI is a noninvasive treatment that potentially reduces mortality, lowers medical costs, and widens accessibility of treatments for patients. Recent developments in the design and fabrication of capacitive micro- machined ultrasonic transducers (CMUTs) have made them competitive with piezoelectric transducers for use in therapeutic ultrasound applications. In this paper, we present the first designs and prototypes of an eight-element, concentric-ring, CMUT array to treat upper abdominal cancers. This array was simulated and designed to focus 30-50 mm into tissue, and ablate a 2- to 3-cm-diameter tumor within 1 h. Assuming a surface acoustic output pressure of! MPa peak-to-peak (8.5 W/cm2) at 2.5 MHz, we simulated an array that produced a focal intensity of 680 W/cm2 when focusing to 35 mm. CMUT cells were then designed to meet these frequency and surface acoustic intensity specifications. These cell designs were fabricated as 2.5 mm x 2.5 mm test transducers and used to verify our models. The test transducers were shown to op- erate at 2.5 MHz with an output pressure of 1.4 MPa peak-to-peak (16.3 W/cm2). With this CMUT cell design, we fabricated a full eight-element array. Due to yield issues, we only developed electronics to focus the four center elements of the array. The beam profile of the measured array deviated from the simulated one be- cause of the crosstalk effects; the beamwidth matched within 10% and sidelobes increased by two times, which caused the measured gain to be 16.6 compared to 27.4. [ABSTRACT FROM AUTHOR]

Transcranial ultrasonic stimulation (TUS) is rapidly gaining traction for non-invasive human neuromodulation, with a pressing need to establish protocols that maximise neuromodulatory efficacy. In this review, we aggregate and examine empirical evidence for the relationship between tunable TUS parameters and in vitro and in vivo outcomes. Based on this multiscale approach, TUS researchers can make better informed decisions about optimal parameter settings. Importantly, we also discuss the challenges involved in extrapolating results from prior empirical work to future interventions, including the translation of protocols between models and the complex interaction between TUS protocols and the brain. A synthesis of the empirical evidence suggests that larger effects will be observed at lower frequencies within the sub-MHz range, higher intensities and pressures than commonly administered thus far, and longer pulses and pulse train durations. Nevertheless, we emphasise the need for cautious interpretation of empirical data from different experimental paradigms when basing protocols on prior work as we advance towards refined TUS parameters for human neuromodulation., Competing Interests: Declarations of interest: KBP has no competing interests related to the reported work. Unrelated to the reported work, KBP has a relationship with MR Instruments, having received equipment on loan, and with Attune Neurosciences as a consultant. LV has no competing interests related to the reported work. Unrelated to the reported work, LV has a relationship with Brainbox Initiative as a member of the scientific committee, with Nudge LLC, having received consulting fees, with Sonic Concepts Ltd, having received equipment on loan, and with Image Guided Therapy, having received equipment on loan.

Objective: Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs., Methods: In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria., Results: Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups., Conclusions: MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

Purpose: MR thermometry is critical for safe and effective transcranial focused ultrasound. The current single-slice MR thermometry sequence cannot achieve all desired treatment monitoring requirements. We propose an approach in which the imaging requirements of different aspects of treatment monitoring are met by optimizing multiple sequences., Methods: Imaging requirements were determined for three stages of MR-guided focused ultrasound brain treatment: 1) focal spot localization, 2) focal spot monitoring, and 3) background monitoring. Multiple-echo spiral thermometry sequences were optimized for each set of requirements and then validated with in vivo signal-to-noise ratio measurements and with phantom heating experiments., Results: Each of the proposed sequences obtained better precision than the current two-dimensional Fourier transform (2DFT) thermometry sequence. Five-slice focal spot localization achieved two-fold better resolution with 1.9-fold better precision but two-fold longer acquisition compared to 2DFT. Five-slice focal monitoring achieved 2.1-fold better precision with similar speed but 12% larger voxels than 2DFT. Full-brain background monitoring was demonstrated in both axial (7.1 s) and sagittal (11.4 s) orientations. Phantom heating time curves were consistent across all sequences after correcting for resolution., Conclusion: Multiple-echo spiral imaging significantly improves MR thermometry efficiency, enabling multiple-slice monitoring. Optimizing multiple specialized sequences provides better performance than can be achieved by any single sequence. Magn Reson Med 78:508-517, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions., Theory and Methods: Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments., Results: Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization., Conclusion: Heat-induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR-guided focused ultrasound surgery ablations, but the distortions can be corrected using an online-compatible algorithm. Magn Reson Med 76:172-182, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

A single-voxel Carr-Purcell-Meibloom-Gill sequence was developed to measure localized T(2) relaxation times of (13)C-labeled metabolites in vivo for the first time. Following hyperpolarized [1-(13)C]pyruvate injections, pyruvate and its metabolic products, alanine and lactate, were observed in the liver of five rats with hepatocellular carcinoma and five healthy control rats. The T(2) relaxation times of alanine and lactate were both significantly longer in HCC tumors than in normal livers (p < 0.002). The HCC tumors also showed significantly higher alanine signal relative to the total (13)C signal than normal livers (p < 0.006). The intra- and inter-subject variations of the alanine T(2) relaxation time were 11% and 13%, respectively. The intra- and inter-subject variations of the lactate T(2) relaxation time were 6% and 7%, respectively. The intra-subject variability of alanine to total carbon ratio was 16% and the inter-subject variability 28%. The intra-subject variability of lactate to total carbon ratio was 14% and the inter-subject variability 20%. The study results show that the signal level and relaxivity of [1-(13)C]alanine may be promising biomarkers for HCC tumors. Its diagnostic values in HCC staging and treatment monitoring are yet to be explored., (Copyright © 2010 John Wiley & Sons, Ltd.)

Catheter-based ultrasound applicators have been developed for delivering hyperthermia or high-temperature thermal ablation of cancer and benign disease of the prostate. These devices allow for control of heating along the length and angular expanse during therapy delivery. Four types of transurethral applicators were devised for thermal treatment of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns and rotation; planar and curvilinear devices with narrow heating patterns and rotation; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate these devices and develop treatment delivery strategies. MR thermal imaging was used to monitor temperature and thermal dose in multiple slices through the target volume. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. The sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation under motor control and modulated dwell time can be used to tightly conform thermal ablation to selected regions. Interstitial implants with directional devices can be used to effectively ablate targeted regions of the gland while protecting the rectum. The MR derived 52 degrees C and lethal thermal dose contours (t43=240 min) effectively defined the extent of thermal damage and provided a means for real-time control of the applicators. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast (5-40 min) and precise thermal ablation of prostate.

Purpose: To demonstrate in vivo MR-guided temperature mapping during radiofrequency (RF) ablation of the liver with a commercially available RF generator modified to allow simultaneous RF treatment and MRI., Materials and Methods: A commercial RF generator was modified using passive filtering to allow the continuous application of the treatment current during MRI studies. A total of six ablations were performed with the device in vivo in three porcine livers, and imaging was concurrently performed using one of two different temperature mapping strategies., Results: MR images acquired during RF ablation demonstrated no noticeable interference from the RF ablation device, which was operated at clinically relevant power levels. Temperature maps showed areas of heating that were consistent with the dimensions of the RF ablation probe, with some asymmetry (likely depending on the orientation of the probe and heat propagation effects), and some differences in heating-spot area stability depending on the specific temperature mapping strategy used. Lesions were visualized on post-ablation imaging and sectioning., Conclusion: The feasibility of performing RF ablation with a modified commercial RF generator simultaneously with MRI was demonstrated. Interference-free MR temperature maps were produced with both variable respiratory motion and mechanical ventilation, and showed the extent of heating as the ablation progressed., (2006 Wiley-Liss, Inc.)