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Purpose: To validate single reference variable flip angle (SR‐VFA) dynamic T1 mapping with and without T2* correction against inversion recovery (IR) T1 measurements. Methods: A custom cylindrical phantom with three concentric compartments was filled with variably doped agar to produce a smooth spatial gradient of the T1 relaxation rate as a function of angle across each compartment. IR T1, VFA T1, and B1+ measurements were made on the phantom before rotation, and multi‐echo stack‐of‐radial dynamic images were acquired during rotation via an MRI‐compatible motor. B1+‐corrected SR‐VFA and SR‐VFA‐T2* T1 maps were computed from the sliding window reconstructed images and compared against rotationally registered IR and VFA T1 maps to determine the percentage error. Results: Both VFA and SR‐VFA‐T2* T1 maps fell within 10% of IR T1 measurements for a low rotational speed, with a mean accuracy of 2.3% ± 2.6% and 2.8% ± 2.6%, respectively. Increasing rotational speed was found to decrease the accuracy due to increasing temporal smoothing over ranges where the T1 change had a nonconstant slope. SR‐VFA T1 mapping was found to have similar accuracy as the SR‐VFA‐T2* and VFA methods at low TEs (˜<2 ms), whereas accuracy degraded strongly with later TEs. T2* correction of the SR‐VFA T1 maps was found to consistently improve accuracy and precision, especially at later TEs. Conclusion: SR‐VFA‐T2* dynamic T1 mapping was found to be accurate against reference IR T1 measurements within 10% in an agar phantom. Further validation is needed in mixed fat–water phantoms and in vivo. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate numerical simulations of focused ultrasound (FUS) with a rabbit model, comparing simulated heating characteristics with magnetic resonance temperature imaging (MRTI) data collected during in vivo treatment. Methods: A rabbit model was treated with FUS sonications in the biceps femoris with 3D MRTI collected. Acoustic and thermal properties of the rabbit muscle were determined experimentally. Numerical models of the rabbits were created, and tissue-type-specific properties were assigned. FUS simulations were performed using both the hybrid angular spectrum (HAS) method and k-Wave. Simulated power deposition patterns were converted to temperature maps using a Pennes' bioheat equation-based thermal solver. Agreement of pressure between the simulation techniques and temperature between the simulation and experimental heating was evaluated. Contributions of scattering and absorption attenuation were considered. Results: Simulated peak pressures derived using the HAS method exceeded the simulated peak pressures from k-Wave by 1.6 ± 2.7%. The location and FWHM of the peak pressure calculated from HAS and k-Wave showed good agreement. When muscle acoustic absorption value in the simulations was adjusted to approximately 54% of the measured attenuation, the average root-mean-squared error between simulated and experimental spatial-average temperature profiles was 0.046 ± 0.019 °C/W. Mean distance between simulated and experimental COTMs was 3.25 ± 1.37 mm. Transverse FWHMs of simulated sonications were smaller than in in vivo sonications. Longitudinal FWHMs were similar. Conclusions: Presented results demonstrate agreement between HAS and k-Wave simulations and that FUS simulations can accurately predict focal position and heating for in vivo applications in soft tissue. [ABSTRACT FROM AUTHOR]

In this study, we investigated the impact of various simulated skull bone geometries on the determination of skull speed of sound and acoustic attenuation values via optimization using transmitted pressure amplitudes beyond the bone. Using the hybrid angular spectrum method (HAS), we simulated ultrasound transmission through four model sets of different geometries involving sandwiched layers of diploë and cortical bone in addition to three models generated from CT images of ex‐vivo human skull‐bones. We characterized cost‐function solution spaces for each model and, using optimization, found that when a model possessed appreciable variations in resolvable layer thickness, the predefined attenuation coefficients could be found with low error (RMSE < 0.01 Np/cm). However, we identified a spatial frequency cutoff in the models' geometry beyond which the accuracy of the property determination begins to fail, depending on the frequency of the ultrasound source. There was a large increase in error of the attenuation coefficients determined by the optimization when the variations in layer thickness were above the identified spatial frequency cutoffs, or when the lateral variations across the model were relatively low in amplitude. For our limited sample of three CT‐image derived bone models, the attenuation coefficients were determined successfully. The speed of sound values were determined with low error for all models (including the CT‐image derived models) that were tested (RMSE < 0.4 m/s). These results illustrate that it is possible to determine the acoustic properties of two‐component models when the internal bone structure is taken into account and the structure satisfies the spatial frequency constraints discussed. [ABSTRACT FROM AUTHOR]

Background: Ultrasound beam aberration correction is vital when focusing ultrasound through the skull bone in transcranial magnetic resonance‐guided focused ultrasound (tcMRgFUS) applications. Current methods make transducer element phase adjustments to compensate for the variation in skull properties (shape, thickness, and acoustic properties), but do not account for variations in the internal brain anatomy. Purpose: Our objective is to investigate the effect of cerebrospinal fluid (CSF) and brain anatomy on beam focusing in tcMRgFUS treatments. Methods: Simulations were conducted with imaging data from 20 patients previously treated with focused ultrasound for disabling tremor. The Hybrid Angular Spectrum (HAS) method was used to test the effect of including cerebral spinal fluid (CSF) and brain anatomy in determining the element phases used for aberration correction and beam focusing. Computer tomography (CT) and magnetic resonance imaging (MRI) images from patient treatments were used to construct a segmented model of each patient's head. The segmented model for treatment simulation consisted of water, skin, fat, brain, CSF, diploë, and cortical bone. Transducer element phases used for treatment simulation were determined using time reversal from the desired focus, generating a set of phases assuming a homogeneous brain in the intracranial volume, and a second set of phases assigning CSF acoustic properties to regions of CSF. In addition, for three patients, the relative effect of separately including CSF speed of sound values compared to CSF attenuation values was found. Results: We found that including CSF acoustic properties (speed of sound and attenuation) during phase planning compared to phase correction without considering CSF increased the absorbed ultrasound power density ratios at the focus over a range of 1.06 to 1.29 (mean of 17% ± 6%) for 20 patients. Separately considering the CSF speed of sound and CSF attenuation showed that the increase was due almost entirely to including the CSF speed of sound; considering only the CSF attenuation had a negligible effect. Conclusions: Based on HAS simulations, treatment planning phase determination using morphologically realistic CSF and brain anatomy yielded an increase of up to 29% in the ultrasound focal absorbed power density. Future work will be required to validate the CSF simulations. [ABSTRACT FROM AUTHOR]

Purpose: To develop an efficient MRI pulse sequence to simultaneously measure multiple parameters that have been shown to correlate with tissue nonviability following thermal therapies. Methods: A 3D segmented EPI pulse sequence was used to simultaneously measure proton resonance frequency shift (PRFS) MR thermometry (MRT), T1 relaxation time, and shear wave velocity induced by focused ultrasound (FUS) push pulses. Experiments were performed in tissue mimicking gelatin phantoms and ex vivo bovine liver. Using a carefully designed FUS triggering scheme, a heating duty cycle of approximately 65% was achieved by interleaving FUS ablation pulses with FUS push pulses to induce shear waves in the tissue. Results: In phantom studies, temperature increases measured with PRFS MRT and increases in T1 correlated with decreased shear wave velocity, consistent with material softening with increasing temperature. During ablation in ex vivo liver, temperature increase measured with PRFS MRT initially correlated with increasing T1 and decreasing shear wave velocity, and after tissue coagulation with decreasing T1 and increasing shear wave velocity. This is consistent with a previously described hysteresis in T1 versus PRFS curves and increased tissue stiffness with tissue coagulation. Conclusion: An efficient approach for simultaneous and dynamic measurements of PRSF, T1, and shear wave velocity during treatment is presented. This approach holds promise for providing co‐registered dynamic measures of multiple parameters, which correlates to tissue nonviability during and following thermal therapies, such as FUS. [ABSTRACT FROM AUTHOR]

Purpose: Present a method to use change in phase in repeated Cartesian k‐space measurements to monitor the change in magnetic field for dynamic MR temperature imaging. Methods: The method is applied to focused ultrasound heating experiments in a gelatin phantom and an ex vivo salt pork sample, without and with simulated respiratory motion. Results: In each experiment, phase variations due to B0 field drift and respiration were readily apparent in the measured phase difference. With correction, the SD of the temperature over time was reduced from 0.18°C to 0.14°C (no breathing) and from 0.81°C to 0.22°C (with breathing) for the gelatin phantom, and from 0.68°C to 0.13°C (no breathing) and from 1.06°C to 0.17°C (with breathing) for the pork sample. The accuracy in nonheated regions, assessed as the RMS error deviation from 0°C, improved from 1.70°C to 1.11°C (no breathing) and from 4.73°C to 1.47°C (with breathing) for the gelatin phantom, and from 5.95°C to 0.88°C (no breathing) and from 13.40°C to 1.73°C (with breathing) for the pork sample. The correction did not affect the temperature measurement accuracy in the heated regions. Conclusion: This work demonstrates that phase changes resulting from variations in B0 due to drift and respiration, commonly seen in MR thermometry applications, can be measured directly from 3D Cartesian acquisition methods. The correction of temporal field variations using the presented technique improved temperature accuracy, reduced variability in nonheated regions, and did not reduce accuracy in heated regions. [ABSTRACT FROM AUTHOR]

Purpose: To study in simulation and in theory the accuracy and precision of dynamic T1 measurements obtained using the previously published single‐reference variable flip angle (SR‐VFA) technique, with a focus on the effects of dynamic changes in T2* on the calculation. Methods: Monte Carlo simulations were performed over 1000 noisy iterations for the VFA method, the SR‐VFA method, and a proposed method, SR‐VFA with a T2* correction (SR‐VFA‐T2*). Dynamic T1 estimates were calculated analytically for each method, with signals modeled by the steady‐state spoiled gradient echo equation. The mean and standard deviation of these estimates were calculated and compared to truth, while varying repetition time (TR), baseline and dynamic T1, echo time (TE), baseline and dynamic T2*, flip angles, and the number of averages on baseline scans. Additionally, the variance of T1 in the SR‐VFA and SR‐VFA‐T2* methods was derived analytically based on the theory of propagation of errors. This equation was used to produce an inverse‐variance weighted linear combination to improve T1 mapping precision in the SR‐VFA‐T2* method. Flip angle sensitivity of dynamic T1 precision in the SR‐VFA and SR‐VFA‐T2* methods was also performed. Results: Substantial bias can be produced by the SR‐VFA method when the ratio of the T2* decay of the dynamic signal versus that of the baseline signals deviates from 1, with a 0.01 deviation leading to approximately a 1% bias in cases of high SNR and TR ≫ T1. This bias can be corrected by estimating the baseline and dynamic T2* values in this ratio via multiecho measurements. The bias and precision of the SR‐VFA‐T2* method, when normalized to scan time, is found to rival and sometimes improve upon the two flip angle VFA method when an inverse variance weighted linear combination is applied across its multiecho T1 maps. The analytic variance equation presented is found to be accurate within 1% relative to the Monte Carlo simulations over a broad parameter space. Flip angle ranges that maximize SR‐VFA and SR‐VFA‐T2*T1 precision over a broad parameter space are given, and each is defined relative to TR and T1. Conclusions: Multiecho SR‐VFA‐T2* T1 mapping is found in simulation and theory to be a promising alternative to the VFA method that maintains speed of the SR‐VFA method with accuracy and precision similar to the VFA method. [ABSTRACT FROM AUTHOR]

Purpose: Develop and evaluate the effectiveness of a T1‐based correction method for errors in proton resonant frequency shift thermometry due to non‐local field effects caused by heating in fatty breast tissues. Methods: Computational models of human breast tissue were created by segmenting MRI data from a healthy human volunteer. MR‐guided focused ultrasound (MRgFUS) heating and MR thermometry measurements were simulated in several locations in the heterogeneous segmented breast models. A T1‐based correction method for PRF thermometry errors was applied and the maximum positive and negative errors and the root mean squared error (RMSE) in a region around each heating location was evaluated with and without correction. The method uses T1 measurements to estimate the temperature change in fatty tissues and correct for their influence. Experimental data from a heating study in cadaver breast tissue were analyzed, and the expected PRFS error computed. Results: The simulated MR thermometry had maximum single voxel errors ranging between 10% and 18% when no correction was applied. Applying the correction led to a considerable improvement, lowering the maximum error range to 2%–5%. The 5th to 95th percentile interval of the temperature error distribution was also lowered with correction, from approximately 3.5 to 1°C. This correction worked even when T1 times were uniformly raised or lowered by 5%–10%. The experimental data showed predicted errors of 15%. Conclusions: This simulation study demonstrates that the T1‐based correction method reduces MR thermometry errors due to non‐local effects from heating in fatty tissues, potentially improving the accuracy of thermometry measurements during MRgFUS treatments. The presented correction method is reliant on having a patient‐specific 3D model of the breast, and may be limited by the accuracy of the fat temperatures which in turn may be limited by noise or bias present in the T1 measurements. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate that magnetic resonance‐guided focused ultrasound (MRgFUS) facilitates blood‐spinal cord barrier (BSCB) permeability and develop observer‐independent MRI quantification of BSCB permeability after MRgFUS for spinal cord injury (SCI). Methods: Noninjured Sprague‐Dawley rats (n = 3) underwent MRgFUS and were administered Evans blue post‐MRgFUS to confirm BSCB opening. Absorbance was measured by spectrophotometry and correlated with its corresponding image intensity. Rats (n = 21) underwent T8–T10 laminectomy and extradural compression of the spinal cord (23g weighted aneurysm‐type clip, 1 min). The intervention group (n = 11) was placed on a preclinical MRgFUS system, administered microbubbles (Optison, 0.2 mL/kg), and received 3 MRgFUS sonications (25 ms bursts, 1 Hz pulses for 3 min, 3 acoustic W, approximately 1.0–2.1 MPa peak pressure as measured via hydrophone). The sham group (n = 10) received equivalent procedures with no sonications. T1w MRI was obtained both pre‐ and post‐MRgFUS BSCB opening. Spinal cords were segmented manually or semiautomatically and a Pearson correlation with P ≤ 0.001 was used to correlate the two segmentation methods. MRgFUS sonication and control regions intensity values were evaluated with a paired t‐test with a P ≤ 0.01. Results: Semiautomatic segmentation reduced computational time by 95% and was correlated with manual segmentation (Pearson = 0.92, P < 0.001, n = 71 regions). In the noninjured rat group, Evans blue absorbance correlated with image intensity in the MRgFUS and control regions (Pearson = 0.82, P = 0.02, n = 6). In rats that underwent the SCI procedure, an increase in signal intensity in the MRgFUS targeted region relative to control was seen in all SCI rats (10.65 ± 12.4%, range: 0.96–43.9%, n = 11, P = 0.002). SCI sham MRgFUS revealed no change (0.63 ± 0.52%, 95% CI 0.320.95, n = 10). This result was significant between both groups (P = 0.003). Conclusion: The implemented semiautomatic segmentation procedure improved data analysis efficiency. Quantitative methods using contrast‐enhanced MRI with histological validation are sensitive for detection of blood‐spinal cord barrier opening induced by magnetic resonance‐guided focused ultrasound. [ABSTRACT FROM AUTHOR]

A magnetic resonance (MR) shear wave elastography technique that uses transient acoustic radiation force impulses from a focused ultrasound (FUS) transducer and a sinusoidal-shaped MR displacement encoding strategy is presented. Using this encoding strategy, an analytic expression for calculating the shear wave speed in a heterogeneous medium was derived. Green's function-based simulations were used to evaluate the feasibility of calculating shear wave speed maps using the analytic expression. Accuracy of simulation technique was confirmed experimentally in a homogeneous gelatin phantom. The elastography measurement was compared to harmonic MR elastography in a homogeneous phantom experiment and the measured shear wave speed values differed by less than 14%. This new transient elastography approach was able to map the position and shape of inclusions sized from 8.5 to 14 mm in an inclusion phantom experiment. These preliminary results demonstrate the feasibility of using a straightforward analytic expression to generate shear wave speed maps from MR images where sinusoidal-shaped motion encoding gradients are used to encode the displacement-time history of a transiently propagating wave-packet. This new measurement technique may be particularly well suited for performing elastography before, during, and after MR-guided FUS therapies since the same device used for therapy is also used as an excitation source for elastography. [ABSTRACT FROM AUTHOR]

Magnetic resonance guided focused ultrasound (MRgFUS) treatment of tumors uses inter-sonication delays to allow heat to dissipate from the skin and other near-field tissues. Despite inter-sonication delays, treatment of tumors close to the skin risks skin burns. This work has designed and evaluated an open-source, conformable, skin-cooling system for body MRgFUS treatments to reduce skin burns and enable ablation closer to the skin. A MR-compatible skin cooling system is described that features a conformable skin-cooling pad assembly with feedback control allowing continuous flow and pressure maintenance during the procedure. System performance was evaluated with hydrophone, phantom and in vivo porcine studies. Sonications were performed 10 and 5 mm from the skin surface under both control and forced convective skin-cooling conditions. 3D MR temperature imaging was acquired in real time and the accumulated thermal dose volume was measured. Gross analysis of the skin post-sonication was further performed. Device conformability was demonstrated at several body locations. Hydrophone studies demonstrated no beam aberration, but a 5–12% reduction of the peak pressure due to the presence of the skin-cooling pad assembly in the acoustic near field. Phantom evaluation demonstrated there is no MR temperature imaging precision reduction or any other artifacts present due to the coolant flow during MRgFUS sonication. The porcine studies demonstrated skin burns were reduced in size or eliminated when compared to the control condition. An open-source design of an MRgFUS active skin cooling system demonstrates device conformability with a reduction of skin burns while ablating superficial tissues. [ABSTRACT FROM AUTHOR]

To develop and characterize a tissue-mimicking phantom that enables the direct comparison of magnetic resonance (MR) and ultrasound (US) imaging techniques useful for monitoring high-intensity focused ultrasound (HIFU) treatments. With no additions, gelatin phantoms produce little if any scattering required for US imaging. This study characterizes the MR and US image characteristics as a function of psyllium husk concentration, which was added to increase US scattering. Gelatin phantoms were constructed with varying concentrations of psyllium husk. The effects of psyllium husk concentration on US B-mode and MR imaging were evaluated at nine different concentrations. T1, T2, and T2* MR maps were acquired. Acoustic properties (attenuation and speed of sound) were measured at frequencies of 0.6, 1.0, 1.8, and 3.0 MHz using a through-transmission technique. Phantom elastic properties were evaluated for both time and temperature dependence. Ultrasound image echogenicity increased with increasing psyllium husk concentration while quality of gradient-recalled echo MR images decreased with increasing concentration. For all phantoms, the measured speed of sound ranged between 1567–1569 m/s and the attenuation ranged between 0.42–0.44 dB/(cm·MHz). Measured T1 ranged from 974–1051 ms. The T2 and T2* values ranged from 97–108 ms and 48–88 ms, respectively, with both showing a decreasing trend with increased psyllium husk concentration. Phantom stiffness, measured using US shear-wave speed measurements, increased with age and decreased with increasing temperature. The presented dual-use tissue-mimicking phantom is easy to manufacture and can be used to compare and evaluate US-guided and MR-guided HIFU imaging protocols. [ABSTRACT FROM AUTHOR]

Purpose: To present a novel MR shear wave elastography (MR‐SWE) method that efficiently measures the speed of propagating wave packets generated using acoustic radiation force (ARF) impulses. Methods: ARF impulses from a focused ultrasound (FUS) transducer were applied sequentially to a preselected set of positions and motion encoded MRI was used to acquire volumetric images of the propagating shear wavefront emanating from each point. The wavefront position at multiple propagation times was encoded in the MR phase image using a train of motion encoding gradient lobes. Generating a transient propagating wavefront at multiple spatial positions and sampling each at multiple time‐points allowed for shear wave speed maps to be efficiently created. MR‐SWE was evaluated in tissue mimicking phantoms and ex vivo bovine liver tissue before and after ablation. Results: MR‐SWE maps, covering an in‐plane area of ~5 × 5 cm, were acquired in 12 s for a single slice and 144 s for a volumetric scan. MR‐SWE detected inclusions of differing stiffness in a phantom experiment. In bovine liver, mean shear wave speed significantly increased from 1.65 ± 0.18 m/s in normal to 2.52 ± 0.18 m/s in ablated region (n = 581 pixels; P‐value < 0.001). Conclusion: MR‐SWE is an elastography technique that enables precise targeting and excitation of the desired tissue of interest. MR‐SWE may be particularly well suited for treatment planning and endpoint assessment of MR‐guided FUS procedures because the same device used for therapy can be used as an excitation source for tissue stiffness quantification. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a numerical inverse Green's function method for deriving specific absorption rates (SARs) from high‐intensity focused ultrasound (HIFU) sonications using tissue parameters (thermal conductivity, specific heat capacity, and mass density) and three‐dimensional (3D) magnetic resonance imaging (MRI) temperature measurements. Methods: SAR estimates were evaluated using simulations and MR temperature measurements from HIFU sonications. For simulations, a “true” SAR was calculated using the hybrid angular spectrum method for ultrasound simulations. This “true” SAR was plugged into a Pennes bioheat transfer equation (PBTE) solver to provide simulated temperature maps, which were then used to calculate the SAR estimate using the presented method. Zero mean Gaussian noise, corresponding to temperature precisions between 0.1 and 2.0°C, was added to the temperature maps to simulate a variety of in vivo situations. Experimental MR temperature maps from HIFU sonications in a gelatin phantom monitored with a 3D segmented echo planar imaging MRI pulse sequence were also used. To determine the accuracy of the simulated and phantom data, we reconstructed temperature maps by plugging in the estimated SAR to the PBTE solver. In both simulations and phantom experiments, the presented method was compared to two previously published methods of determining SAR, a linear and an analytical method. The presented numerical method utilized the full 3D data simultaneously, while the two previously published methods work on a slice‐by‐slice basis. Results: In the absence of noise, SAR distribution estimates obtained from the simulated heating profiles match closely (within 10%) to the initial true SAR distribution. The resulting temperature distributions also match closely to the corresponding initial temperature distributions (<0.2°C RMSE). In the presence of temperature measurement noise, the SAR distributions have noise amplified by the inverse convolution process, while the resulting temperature distributions still match closely to the initial “true” temperature distributions. In general, temperature RMSE was observed to be approximately 20–30% higher than the level of the added noise. By contrast, the previously published linear method is less sensitive to noise, but significantly underpredicts the SAR. The analytic method is also less sensitive to noise and matches SAR in the central plane, but greatly underpredicts in the longitudinal direction. Similar observations are made from the phantom studies. The described numerical inverse Green's function method is very fast — at least two orders of magnitude faster than the compared methods. Conclusion: The presented numerical inverse Green's function method is computationally fast and generates temperature maps with high accuracy. This is true despite generally overestimating the true SAR and amplifying the input noise. [ABSTRACT FROM AUTHOR]

MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended toin vivoapplications, improving HIFU sonication temperature rise predictions and treatment assessment. [ABSTRACT FROM PUBLISHER]

Background: A major challenge in using magnetic resonance temperature imaging (MRTI) to monitor focused ultrasound (FUS) applications is achieving high spatio-temporal resolution over a large field of view (FOV). This is important to accurately monitor all ultrasound (US) power depositions. Magnetic resonance (MR) subsampling in conjunction with thermal model-based reconstruction of the MRTI utilizing Pennes bioheat transfer equation (PBTE) is one promising approach. The thermal properties used in the thermal model are often estimated from a pre-treatment, low-power sonication. Methods: In this proof-of-concept study we investigate the use of US simulations computed using the hybrid angular spectrum (HAS) method to estimate the US power deposition density Q, thereby avoiding the pre-treatment sonication and any potential tissue damage. MRTI reconstructions are performed using a thermal model-based reconstruction method called model predictive filtering (MPF). Experiments are performed in a homogeneous gelatin phantom and in a gelatin phantom with embedded plastic skull. MPF reconstructions are compared to separate sonications imaged with fully sampled data over a smaller FOV. Temperature root-mean-square errors (RMSE) and focal spot positions and shapes are evaluated. Results: HAS simulations accurately predict the location of the focal spot (to within 1 mm) in both phantoms. Accurate temperature maps (RMSE below 1 °C), where the location of the focal spot agrees well with fully sampled "truth" (to within 1 mm), are also achieved in both phantoms. Conclusions: HAS simulations can be used to accurately predict the focal spot location in homogeneous media and when focusing through an aberrating plastic skull. The HAS simulated power deposition (Q) patterns can be used in the MPF thermal model-based reconstruction to obtain accurate temperature maps with high spatio-temporal resolution over large FOVs. [ABSTRACT FROM AUTHOR]

Purpose 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. Methods 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. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Background: A tissue-mimicking phantom that accurately represents human-tissue properties is important for safety testing and for validating new imaging techniques. To achieve a variety of desired human-tissue properties, we have fabricated and tested several variations of gelatin phantoms. These phantoms are simple to manufacture and have properties in the same order of magnitude as those of soft tissues. This is important for quality-assurance verification as well as validation of magnetic resonance-guided focused ultrasound (MRgFUS) treatment techniques. Methods: The phantoms presented in this work were constructed from gelatin powders with three different bloom values (125, 175, and 250), each one allowing for a different mechanical stiffness of the phantom. Evaporated milk was used to replace half of the water in the recipe for the gelatin phantoms in order to achieve attenuation and speed of sound values in soft tissue ranges. These acoustic properties, along with MR (T1 and T2*), mechanical (density and Young's modulus), and thermal properties (thermal diffusivity and specific heat capacity), were obtained through independent measurements for all three bloom types to characterize the gelatin phantoms. Thermal repeatability of the phantoms was also assessed using MRgFUS and MR thermometry. Results: All the measured values fell within the literature-reported ranges of soft tissues. In heating tests using low-power (6.6 W) sonications, interleaved with high-power (up to 22.0 W) sonications, each of the three different bloom phantoms demonstrated repeatable temperature increases (10.4 ± 0.3 °C for 125-bloom, 10.2 ± 0.3 °C for 175-bloom, and 10.8 ± 0.2 °C for 250-bloom for all 6.6-W sonications) for heating durations of 18.1 s. Conclusion: These evaporated milk-modified gelatin phantoms should serve as reliable, general soft tissue-mimicking MRgFUS phantoms. [ABSTRACT FROM AUTHOR]

Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled "truth." For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 x 144 x 135 mm3 FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled "truth" below 0.35 °C. Conclusions: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations [ABSTRACT FROM AUTHOR]

Purpose To present a three-dimensional (3D) segmented echoplanar imaging (EPI) pulse sequence implementation that provides simultaneously the proton resonance frequency shift temperature of aqueous tissue and the longitudinal relaxation time (T1) of fat during thermal ablation. Methods The hybrid sequence was implemented by combining a 3D segmented flyback EPI sequence, the extended two-point Dixon fat and water separation, and the double flip angle T1 mapping techniques. High-intensity focused ultrasound (HIFU) heating experiments were performed at three different acoustic powers on excised human breast fat embedded in ex vivo porcine muscle. Furthermore, T1 calibrations with temperature in four different excised breast fat samples were performed, yielding an estimate of the average and variation of dT1/dT across subjects. Results The water only images were used to mask the complex original data before computing the proton resonance frequency shift. T1 values were calculated from the fat-only images. The relative temperature coefficients were found in five fat tissue samples from different patients and ranged from 1.2% to 2.6%/°C. Conclusion The results demonstrate the capability of real-time simultaneous temperature mapping in aqueous tissue and T1 mapping in fat during HIFU ablation, providing a potential tool for treatment monitoring in organs with large fat content, such as the breast. Magn Reson Med 72:178-187, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Real-time temperature monitoring is critical to the success of thermally ablative therapies. This work validates a 3D thermometry sequence with k-space field drift correction designed for use in magnetic resonance-guided focused ultrasound treatments for breast cancer. Fiberoptic probes were embedded in tissue-mimicking phantoms, and temperature change measurements from the probes were compared with the magnetic resonance temperature imaging measurements following heating with focused ultrasound. Precision and accuracy of measurements were also evaluated in free-breathing healthy volunteers (N = 3) under a non-heating condition. MR temperature measurements agreed closely with those of fiberoptic probes, with a 95% confidence interval of measurement difference from −2.0 °C to 1.4 °C. Field drift-corrected measurements in vivo had a precision of 1.1 ± 0.7 °C and were accurate within 1.3 ± 0.9 °C across the three volunteers. The field drift correction method improved precision and accuracy by an average of 46 and 42%, respectively, when compared to the uncorrected data. This temperature imaging sequence can provide accurate measurements of temperature change in aqueous tissues in the breast and support the use of this sequence in clinical investigations of focused ultrasound treatments for breast cancer. • Magnetic resonance guided focused ultrasound for breast cancer treatment • Respiratory artifact correction without gating or acquisition of additional data • Accurate thermometry in the breast using a segmented echo planar imaging readout [ABSTRACT FROM AUTHOR]

This review covers the theoretical background, pulse sequence considerations, practical implementations, and multitudes of applications of magnetic resonance acoustic radiation force imaging (MR-ARFI) described to date. MR-ARFI is an approach to encode tissue displacement caused by the acoustic radiation force of a focused ultrasound field into the phase of a MR image. The displacement encoding is done with motion encoding gradients (MEG) which have traditionally been added to spin echo-type and gradient recalled echo-type pulse sequences. Many different types of MEG (monopolar, bipolar, tripolar etc.) have been described and pros and cons are discussed. We further review studies investigating the safety of MR-ARFI, as well as approaches to simulate the MR-ARFI displacement. Lastly, MR-ARFI applications such as for focal spot localization, tissue stiffness interrogation following thermal ablation, trans-skull aberration correction, and simultaneous MR-ARFI and MR thermometry are discussed. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1., (© 2025 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: The single reference variable flip angle sequence with a multi-echo stack of stars acquisition (SR-VFA-SoS) simultaneously measures temperature change using proton resonance frequency (PRF) shift and T 1 -based thermometry methods. This work evaluates SR-VFA-SoS thermometry in MR-guided focused ultrasound in an in vivo rabbit model., Methods: Simultaneous PRF shift thermometry and T 1 -based thermometry were obtained in a New Zealand white rabbit model (n = 7) during MR-guided focused ultrasound surgery using the SR-VFA-SoS sequence at 3 T. Distinct locations in muscle (n = 16), fat (n = 12), or the interface of both tissues (n = 23) were heated. The T 1 -temperature coefficient of fat was determined using least-squares fitting of inversion recovery-based T 1 maps of untreated fat harvested from the animal and was applied to the in vivo measured heat-induced T 1 changes to create temperature maps., Results: Using k-space weighted image contrast reconstruction, temporal resolution of 1.71 s was achieved for simultaneous thermometry at 1.5 × 1.5 × 2 mm voxel resolution. PRF shift thermometry was not sensitive to heating in fat. T 1 changes were observed in fat at the ultrasound focus. The mean T 1 -temperature coefficient for fat was determined to be 1.9%/°C ± 0.2%/°C. Precision was 0.76°C ± 0.18°C for PRF shift thermometry in muscle and 1.93°C ± 0.60°C for T 1 -based thermometry in fat. Sonications in muscle showed an increase in T 1 of 2.4%/°C ± 0.9%/°C., Conclusion: The SR-VFA-SoS sequence was shown to simultaneously measure temperature change using PRF shift and T 1 -based methods in an in vivo model, providing thermometry for both aqueous and fat tissues., (© 2025 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

This study introduces a comprehensive hardware-software framework designed to enhance the quality of block face image capture-an essential intermediary step for registering 2D histology images to ex vivo magnetic resonance (MR) images. A customized camera mounting and lighting system is employed to maintain consistent relative positioning and lighting conditions. Departing from traditional transparent paraffin, dyed paraffin is utilized to enhance contrast for subsequent automatic segmentation. Our software facilitates fully automated data collection and organization, complemented by a real-time Quality Assurance (QA) section to assess the captured image's quality during the sectioning process. The setup is evaluated and validated using rabbit muscle and rat brain which underwent MR-guided focused ultrasound ablations. The customized hardware system establishes a robust image capturing environment. The software with a real-time QA section, enables operators to promptly rectify low-quality captures, thereby preventing data loss. The execution of our proposed framework produces robust registration results for H&E images to ex vivo MR images.•The presented hardware-software framework ensures the uniformity and resilience of the block face image capture process, contributing to a more reliable and efficient registration of 2D histology images to ex vivo MR images., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

This work investigates the use of configuration state imaging together with deep neural networks to develop quantitative MRI techniques for deployment in an interventional setting. A physics modeling technique for inhomogeneous fields and heterogeneous tissues is presented and used to evaluate the theoretical capability of neural networks to estimate parameter maps from configuration state signal data. All tested normalization strategies achieved similar performance in estimating T 2 and T 2 * . Varying network architecture and data normalization had substantial impacts on estimated flip angle and T 1 , highlighting their importance in developing neural networks to solve these inverse problems. The developed signal modeling technique provides an environment that will enable the development and evaluation of physics-informed machine learning techniques for MR parameter mapping and facilitate the development of quantitative MRI techniques to inform clinical decisions during MR-guided treatments., Competing Interests: Disclosure of Interests. The authors have no competing interests to declare that are relevant to the content of this article.

Purpose: To validate single reference variable flip angle (SR-VFA) dynamic T 1 mapping with and without T 2 * correction against inversion recovery (IR) T 1 measurements., Methods: A custom cylindrical phantom with three concentric compartments was filled with variably doped agar to produce a smooth spatial gradient of the T 1 relaxation rate as a function of angle across each compartment. IR T 1 , VFA T 1 , and B 1 + measurements were made on the phantom before rotation, and multi-echo stack-of-radial dynamic images were acquired during rotation via an MRI-compatible motor. B 1 + -corrected SR-VFA and SR-VFA-T 2 * T 1 maps were computed from the sliding window reconstructed images and compared against rotationally registered IR and VFA T 1 maps to determine the percentage error., Results: Both VFA and SR-VFA-T 2 * T 1 maps fell within 10% of IR T 1 measurements for a low rotational speed, with a mean accuracy of 2.3% ± 2.6% and 2.8% ± 2.6%, respectively. Increasing rotational speed was found to decrease the accuracy due to increasing temporal smoothing over ranges where the T 1 change had a nonconstant slope. SR-VFA T 1 mapping was found to have similar accuracy as the SR-VFA-T 2 * and VFA methods at low TEs (˜<2 ms), whereas accuracy degraded strongly with later TEs. T 2 * correction of the SR-VFA T 1 maps was found to consistently improve accuracy and precision, especially at later TEs., Conclusion: SR-VFA-T 2 * dynamic T 1 mapping was found to be accurate against reference IR T 1 measurements within 10% in an agar phantom. Further validation is needed in mixed fat-water phantoms and in vivo., (© 2023 International Society for Magnetic Resonance in Medicine.)

Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound-remotely applied, depth-penetrating energy-may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects' visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MRI imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior.

We report on a 75-year-old woman with a history of right MCA aneurysm clipping and medically refractive right-hand tremor. We successfully performed focused ultrasound thalamotomy of the left ventral intermediate nucleus under MR imaging-guidance at 3T. A thorough pretreatment evaluation of MR thermometry was critical to ensure that adequate precision could be achieved at the intended target. The tremor showed a 75% decrease at 24 hours postprocedure and a 50% decrease at a 3-month follow-up. There were no immediate adverse events., (© 2024 by American Journal of Neuroradiology.)

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 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.

Purpose: To develop an efficient MRI pulse sequence to simultaneously measure multiple parameters that have been shown to correlate with tissue nonviability following thermal therapies., Methods: A 3D segmented EPI pulse sequence was used to simultaneously measure proton resonance frequency shift (PRFS) MR thermometry (MRT), T 1 relaxation time, and shear wave velocity induced by focused ultrasound (FUS) push pulses. Experiments were performed in tissue mimicking gelatin phantoms and ex vivo bovine liver. Using a carefully designed FUS triggering scheme, a heating duty cycle of approximately 65% was achieved by interleaving FUS ablation pulses with FUS push pulses to induce shear waves in the tissue., Results: In phantom studies, temperature increases measured with PRFS MRT and increases in T 1 correlated with decreased shear wave velocity, consistent with material softening with increasing temperature. During ablation in ex vivo liver, temperature increase measured with PRFS MRT initially correlated with increasing T 1 and decreasing shear wave velocity, and after tissue coagulation with decreasing T 1 and increasing shear wave velocity. This is consistent with a previously described hysteresis in T 1 versus PRFS curves and increased tissue stiffness with tissue coagulation., Conclusion: An efficient approach for simultaneous and dynamic measurements of PRSF, T 1 , and shear wave velocity during treatment is presented. This approach holds promise for providing co-registered dynamic measures of multiple parameters, which correlates to tissue nonviability during and following thermal therapies, such as FUS., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective. Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a lesion through light irradiation and consequent temperature increase. Magnetic resonance thermometry imaging (MRTI) provides a multidimensional measurement of the temperature inside the target, thus enabling accurate monitoring of the damaged zone during the procedure. In proton resonance frequency shift-based thermometry, artifacts in the images may strongly interfere with the estimated temperature maps. In our work, after noticing the formation of the dipolar-behavior artifact linkable to magnetic susceptibility changes during in vivo LITT, an investigation of susceptibility artifacts in tissue-mimicking phantoms was implemented. Approach. The artifact was characterized: (i) by measuring the area and total volume of error regions and their evolution during the treatment; and (ii) by comparison with temperature reference provided by three temperature sensing needles. Lastly, a strategy to avoid artifacts formation was devised by using the temperature-sensing needles to implement a temperature-controlled LITT. Main results. The artifact appearance was associated with gas bubble formation and with unwanted treatment effects producing magnetic susceptibility changes when 2 W laser power was set. The analysis of the artifact's dimension demonstrated that in the sagittal plane the dipolar-shape artifact may consistently spread following the temperature trend until reaching a volume 8 times bigger than the ablated one. Also, the artifact shape is quite symmetric with respect to the laser tip. An absolute temperature error showing a negative Gaussian profile in the area of susceptibility artifact with values up to 64.4 °C was estimated. Conversely, a maximum error of 2.8 °C is measured in the area not-affected by artifacts and far from the applicator tip. Finally, by regulating laser power, susceptibility artifacts formation was avoided, and appreciable thermal damage was induced. Significance. These findings may help in improving the MRTI-based guidance of thermal therapies., (Creative Commons Attribution license.)

Purpose: Present a method to use change in phase in repeated Cartesian k-space measurements to monitor the change in magnetic field for dynamic MR temperature imaging., Methods: The method is applied to focused ultrasound heating experiments in a gelatin phantom and an ex vivo salt pork sample, without and with simulated respiratory motion., Results: In each experiment, phase variations due to B 0 field drift and respiration were readily apparent in the measured phase difference. With correction, the SD of the temperature over time was reduced from 0.18°C to 0.14°C (no breathing) and from 0.81°C to 0.22°C (with breathing) for the gelatin phantom, and from 0.68°C to 0.13°C (no breathing) and from 1.06°C to 0.17°C (with breathing) for the pork sample. The accuracy in nonheated regions, assessed as the RMS error deviation from 0°C, improved from 1.70°C to 1.11°C (no breathing) and from 4.73°C to 1.47°C (with breathing) for the gelatin phantom, and from 5.95°C to 0.88°C (no breathing) and from 13.40°C to 1.73°C (with breathing) for the pork sample. The correction did not affect the temperature measurement accuracy in the heated regions., Conclusion: This work demonstrates that phase changes resulting from variations in B 0 due to drift and respiration, commonly seen in MR thermometry applications, can be measured directly from 3D Cartesian acquisition methods. The correction of temporal field variations using the presented technique improved temperature accuracy, reduced variability in nonheated regions, and did not reduce accuracy in heated regions., (© 2022 International Society for Magnetic Resonance in Medicine.)