Proton Resonance Frequency Shift Research Articles

Heat Modulation of Intrinsic MR Contrasts for Tumor Characterization.

Simple SummaryMulti-parametric magnetic resonance imaging (MRI) is a paradigm that combines several MR imaging contrast types to provide added layers of information for the characterization of tissue types, including benign and malignant tumors. The approach detailed in this manuscript evaluates heat-induced changes in intrinsic MRI contrast types in vivo for tumor characterization. Specifically, the quantitative longitudinal relaxation time (T1), transverse relaxation time (T2), water proton chemical shift (CS), and apparent diffusion coefficient (ADC) were measured at various temperatures for benign and malignant tumors in rats. Results indicate that heat-induced changes in these intrinsic contrast types can potentially improve MR imaging visualization and characterization of tumor tissue. The approach detailed here may have a strong impact on real-time interventional procedures where tumor boundaries need to be accurately delineated to maximize positive therapeutic response for MRI-guided focal therapy.(1) Background: The longitudinal relaxation time (T1), transverse relaxation time (T2), water proton chemical shift (CS), and apparent diffusion coefficient (ADC) are MR quantities that change with temperature. In this work, we investigate heat-induced intrinsic MR contrast types to add salient information to conventional MR imaging to improve tumor characterization. (2) Methods: Imaging tests were performed in vivo using different rat tumor models. The rats were cooled/heated to steady-state temperatures from 26–36 °C and quantitative measurements of T1, T2, and ADC were obtained. Temperature maps were measured using the proton resonance frequency shift (PRFS) method during the heating and cooling cycles. (3) Results: All tissue samples show repeatable relaxation parameter measurement over a range of 26–36 °C. Most notably, we observed a more than 3.3% change in T1/°C in breast adenocarcinoma tumors compared to a 1% change in benign breast fibroadenoma lesions. In addition, we note distinct values of T2/°C change for rat prostate carcinoma cells compared to benign tissue. (4) Conclusion: These findings suggest the possibility of improving MR imaging visualization and characterization of tissue with heat-induced contrast types. Specifically, these results suggest that the temporal thermal responses of heat-sensitive MR imaging contrast mechanisms in different tissue types contain information for improved (i) characterization of tumor/tissue boundaries for diagnostic and therapy purposes, and (ii) characterization of salient behavior of tissues, e.g., malignant versus benign tumors.

Phase-independent thermometry by Z-spectrum MR imaging.

Z-spectrum imaging, defined as the consecutive collection of images after saturating over a range of frequency offsets, has been recently proposed as a method to measure the fat-water fraction by the simultaneous detection of fat and water resonances. By incorporating a binomial pulse irradiated at each offset before the readout, the spectral selectivity of the sequence can be further amplified, making it possible to monitor the subtle proton resonance frequency shift that follows a change in temperature. We tested the hypothesis in aqueous and cream phantoms and in healthy mice, all under thermal challenge. The binomial module consisted of 2 sinc-shaped pulses of opposite phase separated by a delay. Such a delay served to spread out off-resonance spins, with the resulting excitation profile being a periodic function of the delay and the chemical shift. During heating experiments, the water resonance shifted downfield, and by fitting the curve to a sine function it was possible to quantify the change in temperature. Results from Z-spectrum imaging correlated linearly with data from conventional MRI techniques like T1 mapping and phase differences from spoiled GRE. Because the measurement is performed solely on magnitude images, the technique is independent of phase artifacts and is therefore applicable in mixed tissues (e.g., fat). We showed that Z-spectrum imaging can deliver reliable temperature change measurement in both muscular and fatty tissues.

Measurement of sub-zero temperatures in MRI using T1 temperature sensitive soft silicone materials: Applications for MRI-guided cryosurgery.

One standard method, proton resonance frequency shift, for measuring temperature using magnetic resonance imaging (MRI), in MRI-guided surgeries, fails completely below the freezing point of water. Because of this, we have developed a new methodology for monitoring temperature with MRI below freezing. The purpose of this paper is to show that a strong temperature dependence of the nuclear relaxation time T1 in soft silicone polymers can lead to temperature-dependent changes of MRI intensity acquired with T1 weighting. We propose the use of silicone filaments inserted in tissue for measuring temperature during MRI-guided cryoablations. The temperature dependence of T1 in bio-compatible soft silicone polymers was measured using nuclear magnetic resonance spectroscopy and MRI. Phantoms, made of bulk silicone materials and put in an MRI-compatible thermal container with dry ice, allowed temperature measurements ranging from -60°C to + 20°C. T1 -weighted gradient echo images of the phantoms were acquired at spatially uniform temperatures and with a gradient in temperature to determine the efficacy of using these materials as temperature indicators in MRI. Ex vivo experiments on silicone rods, 4mm in diameter, inserted in animal tissue were conducted to assess the practical feasibility of the method. Measurements of nuclear relaxation times of protons in soft silicone polymers show a monotonic, nearly linear, change with temperature (R2 >0.98) and have a significant correlation with temperature (Pearson's r>0.99, p<0.01). Similarly, the intensity of the MR images in these materials, taken with a gradient echo sequence, are also temperature dependent. There is again a monotonic change in MRI intensity that correlates well with the measured temperature (Pearson's r<-0.98 and p<0.01). The MRI experiments show that a temperature change of 3°C can be resolved in a distance of about 2.5mm. Based on MRI images and external sensor calibrations for a sample with a gradient in temperature, temperature maps with 3°C isotherms are created for a bulk phantom. Experiments demonstrate that these changes in MRI intensity with temperature can also be seen in 4mm silicone rods embedded in ex vivo animal tissue. We have developed a new method for measuring temperature in MRI that potentially could be used during MRI-guided cryoablation operations, reducing both procedure time and cost, and making these surgeries safer.

Assessment of Proton Resonance Frequency Shift Magnetic Resonance Thermography Imaging Quality for Head and Neck Tumors.

Assessment of Proton Resonance Frequency Shift Magnetic Resonance Thermography Imaging Quality for Head and Neck Tumors.

A T1-based correction method for proton resonance frequency shift thermometry in breast tissue.

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. 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 T1measurements 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. 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%. 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 T1measurements.

A Computational Study on Temperature Variations in MRgFUS Treatments Using PRF Thermometry Techniques and Optical Probes.

Structural and metabolic imaging are fundamental for diagnosis, treatment and follow-up in oncology. Beyond the well-established diagnostic imaging applications, ultrasounds are currently emerging in the clinical practice as a noninvasive technology for therapy. Indeed, the sound waves can be used to increase the temperature inside the target solid tumors, leading to apoptosis or necrosis of neoplastic tissues. The Magnetic resonance-guided focused ultrasound surgery (MRgFUS) technology represents a valid application of this ultrasound property, mainly used in oncology and neurology. In this paper; patient safety during MRgFUS treatments was investigated by a series of experiments in a tissue-mimicking phantom and performing ex vivo skin samples, to promptly identify unwanted temperature rises. The acquired MR images, used to evaluate the temperature in the treated areas, were analyzed to compare classical proton resonance frequency (PRF) shift techniques and referenceless thermometry methods to accurately assess the temperature variations. We exploited radial basis function (RBF) neural networks for referenceless thermometry and compared the results against interferometric optical fiber measurements. The experimental measurements were obtained using a set of interferometric optical fibers aimed at quantifying temperature variations directly in the sonication areas. The temperature increases during the treatment were not accurately detected by MRI-based referenceless thermometry methods, and more sensitive measurement systems, such as optical fibers, would be required. In-depth studies about these aspects are needed to monitor temperature and improve safety during MRgFUS treatments.

Experimental Observation of Temperature Change Induced by Echo Train Length of Fast-Spin Echo at 3T MRI

This study aims to observe and estimate the temperature changes caused by the echo train lengths (ETLs) of fast-spin echo to ensure radiofrequency (RF)-related safety. RF-induced heating on ETL-stepped changes is evaluated using the proton resonance frequency shift (PRF) method and optic-fiber thermography (OFT). The increase in temperature caused by a clinical sequence was compared to that accumulated by the corresponding ETLs. The temperatures are similarly increased in ETLs from 10 to 30 (PRF: 0.109 ± 0.025 ℃, OFT: 0.079 ± 0.009 ℃), suggesting that a large number of ETLs could be utilized at practical sites. The RF-induced heating in the clinical setting (PRF: 0.775 ± 0.069 ℃, OFT: 0.510 ± 0.015 ℃) is comparable to the estimated temperature on the ETL-stepped changes (PRF: 0.780 ℃, OFT: 0.553 ℃). These enable accelerated acquisition with a large number of ETLs to be practically used and RF-induced safety to be thoroughly guaranteed.

Assessment of radio-frequency heating of a parallel transmit coil in a phantom using multi-echo proton resonance frequency shift thermometry

We propose a workflow for validating parallel transmission (pTx) radio-frequency (RF) magnetic field heating patterns using Proton-Resonance Frequency shift (PRF)-based MR thermometry. Electromagnetic (EM) and thermal simulations of a 7 T 8-channel dipole coil were done using commercially available software (Sim4Life) to assess RF heating. The fabrication method for a phantom with electrical properties matched to human tissue is also described, along with methods for its electrical and thermal characterisation. Energy was deposited to specific transmit channels, whilst acquiring 3D PRF data using a pair of interleaved RF shim transmit modes. A multi-echo readout and pre-scan stabilisation protocol were used for increased sensitivity and to correct for measurement-to-measurement instabilities. The electrical properties of the phantom were found to be within 10% of the intended values. Adoption of a 14-min stabilisation scan gave sufficient suppression of any evolving background spatial variation in the B0 field to achieve <0.001 °C/mm thermometry drift over 10 min of subsequent scanning. Using two RF shim transmit modes enabled full phantom coverage and combining multiple echo times enabled a 13–54% improvement in the RMSE sensitivity to temperature changes. Combining multiple echoes reduced the peak RMSE by 45% and visually reduced measurement-to-measurement instabilities. A reference fibre optic probe showed temperature deviations from the PRF-estimated temperature to be smaller than 0.5 °C. Given the importance of RF safety in pTx applications, this workflow enables accurate validation of RF heating simulations with minimal additional hardware requirements.

Proton Resonance Frequency Shift Thermometry: A Review of Modern Clinical Practices.

Magnetic resonance imaging (MRI) has become a popular modality in guiding minimally invasive thermal therapies, due to its advanced, nonionizing, imaging capabilities and its ability to record changes in temperature. A variety of MR thermometry techniques have been developed over the years, and proton resonance frequency (PRF) shift thermometry is the current clinical gold standard to treat a variety of cancers. It is used extensively to guide hyperthermic thermal ablation techniques such as high-intensity focused ultrasound (HIFU) and laser-induced thermal therapy (LITT). Essential attributes of PRF shift thermometry include excellent linearity with temperature, good sensitivity, and independence from tissue type. This noninvasive temperature mapping method gives accurate quantitative measures of the temperature evolution inside biological tissues. In this review, the current status and new developments in the fields of MR-guided HIFU and LITT are presented with an emphasis on breast, prostate, bone, uterine, and brain treatments. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Correction of motion-induced susceptibility artifacts and B0 drift during proton resonance frequency shift-based MR thermometry in the pelvis with background field removal methods.

PurposeThe linear change of the water proton resonance frequency shift (PRFS) with temperature is used to monitor temperature change based on the temporal difference of image phase. Here, the effect of motion‐induced susceptibility artifacts on the phase difference was studied in the context of mild radio frequency hyperthermia in the pelvis.MethodsFirst, the respiratory‐induced field variations were disentangled from digestive gas motion in the pelvis. The projection onto dipole fields (PDF) as well as the Laplacian boundary value (LBV) algorithm were applied on the phase difference data to eliminate motion‐induced susceptibility artifacts. Both background field removal (BFR) algorithms were studied using simulations of susceptibility artifacts, a phantom heating experiment, and volunteer and patient heating data.ResultsRespiratory‐induced field variations were negligible in the presence of the filled water bolus. Even though LBV and PDF showed comparable results for most data, LBV seemed more robust in our data sets. Some data sets suggested that PDF tends to overestimate the background field, thus removing phase attributed to temperature. The BFR methods even corrected for susceptibility variations induced by a subvoxel displacement of the phantom. The method yielded successful artifact correction in 2 out of 4 patient treatment data sets during the entire treatment duration of mild RF heating of cervical cancer. The heating pattern corresponded well with temperature probe data.ConclusionThe application of background field removal methods in PRFS‐based MR thermometry has great potential in various heating applications and body regions to reduce motion‐induced susceptibility artifacts that originate outside the region of interest, while conserving temperature‐induced PRFS. In addition, BFR automatically removes up to a first‐order spatial B0 drift.

Recent technological advancements in thermometry.

Thermometry is the key factor for achieving successful thermal therapy. Although invasive thermometry with a probe has been used for more than four decades, this method can only detect the local temperature within the probing volume. Noninvasive temperature imaging using a tomographic technique is ideal for monitoring hot-spot formation in the human body. Among various techniques, such as X-ray computed tomography, microwave tomography, echo sonography, and magnetic resonance (MR) imaging, the proton resonance frequency shift method of MR thermometry is the only method currently available for clinical practice because its temperature sensitivity is consistent in most aqueous tissues and can be easily observed using common clinical scanners. New techniques are being proposed to improve the robustness of this method against tissue motion. MR techniques for fat thermometry were also developed based on relaxation times. One of the latest non-MR techniques to attract attention is photoacoustic imaging.

Simultaneous fat-referenced proton resonance frequency shift thermometry and MR elastography for the monitoring of thermal ablations.

Simultaneous fat-referenced proton resonance frequency shift (FRPRFS) thermometry combined with MR elastography (MRE) is proposed, to continuously monitor thermal ablations for all types of soft tissues, including fat-containing tissues. Fat-referenced proton resonance frequency shift thermometry makes it possible to measure temperature even in the water fraction of fat-containing tissues while enabling local field-drift correction. Magnetic resonance elastography allows measuring the mechanical properties of tissues that are related to tissue structural damage. A gradient-echo MR sequence framework was proposed that combines the need for multiple TE acquisitions for the water-fat separation of FRPRFS, and the need for multiple MRE phase offsets for elastogram reconstructions. Feasibility was first assessed in a fat-containing gelatin phantom undergoing moderate heating by a hot water circulation system. Subsequently, high intensity focused ultrasound heating was conducted in porcine muscle tissue ex vivo (N = 4; 2 samples, 2 locations/sample). Both FRPRFS temperature maps and elastograms were updated every 4.1 seconds. In the gelatin phantom, FRPRFS was in good agreement with optical fiber thermometry (average difference 1.2 ± 1°C). In ex vivo high-intensity focused ultrasound experiments on muscle tissue, the shear modulus was found to decrease significantly by 34.3% ± 7.7% (experiment 1, sample 1), 17.9% ± 10.0% (experiment 2, sample 1), 55.1% ± 8.7% (experiment 3, sample 2), and 34.7% ± 8.4% (experiment 4, sample 2) as a result of temperature increase (ΔT = 22.5°C ± 4.2°C, 14.0°C ± 2.8°C, 14.7°C ± 3.7°C, and 14.5°C ± 3.0°C, respectively). This study demonstrated the feasibility of monitoring thermal ablations with FRPRFS thermometry together with MRE, even in fat-containing tissues. The acquisition time is similar to non-FRPRFS thermometry combined with MRE.

Mild hyperthermia by MR-guided focused ultrasound in an ex vivo model of osteolytic bone tumour: optimization of the spatio-temporal control of the delivered temperature

BackgroundMagnetic resonance guided focused ultrasound was suggested for the induction of deep localized hyperthermia adjuvant to radiation- or chemotherapy. In this study we are aiming to validate an experimental model for the induction of uniform temperature elevation in osteolytic bone tumours, using the natural acoustic window provided by the cortical breakthrough.Materials and methodsExperiments were conducted on ex vivo lamb shank by mimicking osteolytic bone tumours. The cortical breakthrough was exploited to induce hyperthermia inside the medullar cavity by delivering acoustic energy from a phased array HIFU transducer. MR thermometry data was acquired intra-operatory using the proton resonance frequency shift (PRFS) method. Active temperature control was achieved via a closed-loop predictive controller set at 6 °C above the baseline. Several beam geometries with respect to the cortical breakthrough were investigated. Numerical simulations were used to further explain the observed phenomena. Thermal safety of bone heating was assessed by cross-correlating MR thermometry data with the measurements from a fluoroptic temperature sensor inserted in the cortical bone.ResultsNumerical simulations and MR thermometry confirmed the feasibility of spatio-temporal uniform hyperthermia (± 0.5 °C) inside the medullar cavity using a fixed focal point sonication. This result was obtained by the combination of several factors: an optimal positioning of the focal spot in the plane of the cortical breakthrough, the direct absorption of the HIFU beam at the focal spot, the “acoustic oven effect” yielded by the beam interaction with the bone, and a predictive temperature controller. The fluoroptical sensor data revealed no heating risks for the bone and adjacent tissues and were in good agreement with the PRFS thermometry from measurable voxels adjacent to the periosteum.ConclusionTo our knowledge, this is the first study demonstrating the feasibility of MR-guided focused ultrasound hyperthermia inside the medullar cavity of bones affected by osteolytic tumours. Our results are considered a promising step for combining adjuvant mild hyperthermia to external beam radiation therapy for sustained pain relief in patients with symptomatic bone metastases.

Field drift correction of proton resonance frequency shift temperature mapping with multichannel fast alternating nonselective free induction decay readouts.

PurposeTo demonstrate that proton resonance frequency shift MR thermometry (PRFS‐MRT) acquisition with nonselective free induction decay (FID), combined with coil sensitivity profiles, allows spatially resolved B 0 drift‐corrected thermometry.MethodsPhantom experiments were performed at 1.5T and 3T. Acquisition of PRFS‐MRT and FID were performed during MR‐guided high‐intensity focused ultrasound heating. The phase of the FIDs was used to estimate the change in angular frequency δωdrift per coil element. Two correction methods were investigated: (1) using the average δωdrift over all coil elements (0th‐order) and (2) using coil sensitivity profiles for spatially resolved correction. Optical probes were used for independent temperature verification. In‐vivo feasibility of the methods was evaluated in the leg of 1 healthy volunteer at 1.5T.ResultsIn 30 minutes, B 0 drift led to an apparent temperature change of up to –18°C and –98°C at 1.5T and 3T, respectively. In the sonicated area, both corrections had a median error of 0.19°C at 1.5T and –0.54°C at 3T. At 1.5T, the measured median error with respect to the optical probe was –1.28°C with the 0th‐order correction and improved to 0.43°C with the spatially resolved correction. In vivo, without correction the spatiotemporal median of the apparent temperature was at –4.3°C and interquartile range (IQR) of 9.31°C. The 0th‐order correction had a median of 0.75°C and IQR of 0.96°C. The spatially resolved method had the lowest median at 0.33°C and IQR of 0.80°C.ConclusionFID phase information from individual receive coil elements allows spatially resolved B 0 drift correction in PRFS‐based MRT.

A variable flip angle golden-angle-ordered 3D stack-of-radial MRI technique for simultaneous proton resonant frequency shift and T1 -based thermometry.

To develop and evaluate a variable-flip-angle golden-angle-ordered 3D stack-of-radial MRI technique for simultaneous proton resonance frequency shift (PRF) and T1 -based thermometry in aqueous and adipose tissues, respectively. The proposed technique acquires multiecho radial k-space data in segments with alternating flip angles to measure 3D temperature maps dynamically on the basis of PRF and T1 . A sliding-window k-space weighted image contrast filter is used to increase temporal resolution. PRF is measured in aqueous tissues and T1 in adipose tissues using fat/water masks. The accuracy for T1 quantification was evaluated in a reference T1 /T2 phantom. In vivo nonheating experiments were conducted in healthy subjects to evaluate the stability of PRF and T1 in the brain, prostate, and breast. The proposed technique was used to monitor high-intensity focused ultrasound (HIFU) ablation in ex vivo porcine fat/muscle tissues and compared to temperature probe readings. The proposed technique achieved 3D coverage with 1.1-mm to 1.3-mm in-plane resolution and 2-s to 5-s temporal resolution. During 20 to 30 min of nonheating in vivo scans, the temporal coefficient of variation for T1 was <5% in the brain, prostate, and breast fatty tissues, while the standard deviation of relative PRF temperature change was within 3°C in aqueous tissues. During ex vivo HIFU ablation, the temperatures measured by PRF and T1 were consistent with temperature probe readings, with an absolute mean difference within 2°C. The proposed technique achieves simultaneous PRF and T1 -based dynamic 3D MR temperature mapping in aqueous and adipose tissues. It may be used to improve MRI-guided thermal procedures.

A rapid beam simulation framework for transcranial focused ultrasound

Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

Accumulated thermal dose in MRI-guided focused ultrasound for essential tremor: repeated sonications with low focal temperatures.

The object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C-54°C. Seventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors' institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = -0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance-induced spatial-shifting artifacts. Mean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C-54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor. In transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.

Prolonged heating in nontargeted tissue during MR-guided focused ultrasound of bone tumors.

Thermal dosimetry during MR-guided focused ultrasound (MRgFUS) of bone tumors underpredicts ablation zone. Intraprocedural understanding of heat accumulation near bone is needed to prevent undesired treatment of nontargeted tissue. Temperature decay rates predict prolonged, spatially varying heating during MRgFUS bone treatments. Prospective case series. Nine patients with localized painful bone tumors (five bone metastasis, four osteoid osteomas), were compared with five patients with uterine fibroid tumors treated using MRgFUS. Proton resonance frequency shift thermometry using 2D-GRE with echo-planar imaging at 3 T. Tissue response was derived by fitting data from extended thermometry acquisitions to a decay model. Decay rates and time to peak temperature (TTP) were analyzed in segmented zones between the bone target and skin. Decay rates were used to calculate intersonication cooling times required to return to body temperature; these were compared against conventional system-mandated cooling times. Kolmogorov-Smirnov tests for normality, and Student's t-test was used to compare decay rates. Spatial TTP delay and predicted cooling times used Wilcoxon signed rank tests. P < 0.05 was significant. Tissue decay rates in bone tumor patients were 3.5 times slower than those in patients with fibroids (τbone = 0.037 ± 0.012 vs. τfibroid = 0.131 ± 0.010, P < 0.05). Spatial analysis showed slow decay rates effecting baseline temperature as far as 12 mm away from the bone surface, τ4 = 0.015 ± 0.026 (median ± interquartile range [IQR]). Tissue within 9 mm of bone experienced delayed TTP (P < 0.01). In the majority of bone tumor treatments, system-predicted intersonication cooling times were insufficient for nearby tissue to return to body temperature (P = 0.03 in zone 4). MRgFUS near bone is susceptible to long tissue decay rates, and unwanted cumulative heating up to 1.2 cm from the surface of the bone. Knowledge of decay rates may be used to alter treatment planning and intraprocedural thermal monitoring protocols to account for prolonged heating by bone. 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1526-1533.

Low-rank plus sparse compressed sensing for accelerated proton resonance frequency shift MR temperature imaging.

To improve multichannel compressed sensing (CS) reconstruction for MR proton resonance frequency (PRF) shift thermography, with application to MRI-induced RF heating evaluation and MR guided high intensity focused ultrasound (MRgFUS) temperature monitoring. A new compressed sensing reconstruction is proposed that enforces joint low rank and sparsity of complex difference domain PRF data between post heating and baseline images. Validations were performed on 4 retrospectively undersampled dynamic data sets in PRF applications, by comparing the proposed method to a previously described L1 and total variation- (TV-) based CS approach that also operates on complex difference domain data, and to a conventional low rank plus sparse (L+S) separation-based CS reconstruction applied to the original domain data. In all 4 retrospective validations, the proposed reconstruction method outperformed the conventional L+S and L1 +TV CS reconstruction methods with a 3.6× acceleration ratio in terms of temperature accuracy with respect to fully sampled data. For RF heating evaluation, the proposed method achieved RMS error of 12%, compared to 19% for the L+S method and 17% for the L1 +TV method. For in vivo MRgFUS thalamotomy, the peak temperature reconstruction errors were 19%, 31%, and 35%, respectively. The complex difference-based low rank and sparse model enhances compressibility for dynamic PRF temperature imaging applications. The proposed multichannel CS reconstruction method enables high acceleration factors for PRF applications including RF heating evaluation and MRgFUS sonication.

Simultaneous proton resonance frequency shift thermometry and T1 measurements using a single reference variable flip angle T1 method.

Implement simultaneous proton resonance frequency (PRF) shift and T1 measurements with equivalent temporal resolution using a single reference variable flip angle method. This novel method allows for simultaneous thermometry in both aqueous and fatty tissue. This method acquires a single reference image at the lower flip angle and all dynamic images at the higher angle. T1 is calculated using a single reference variable flip angle method, which accounts for the reference image temperature remaining constant. Monte Carlo simulations determined the optimal dynamic flip angle for combined PRF and T1 measurements. This method was evaluated in MR-guided focused ultrasound heating experiments using a gelatin phantom and human cadaver breasts. In vivo measurement precision was demonstrated in healthy female volunteers under nonheating conditions. Temperature rise during MR-guided focused ultrasound heating was measured in aqueous tissue with both PRF and T1 . Both measures show good qualitative agreement in both space and time in aqueous tissue. The T1 change due to temperature increase was measured in fat, demonstrating the expected temporal response. The dynamic flip angle that produces optimal SNR for PRF measurements is lower than the optimal angle for T1 measurements, necessitating the selection of a compromise angle. The single reference variable flip angle method provides a reliable way to simultaneously measure PRF temperature and T1 change and overcomes PRF's inability to simultaneously monitor temperature in aqueous and adipose tissues. Future work will calibrate T1 change to temperature, enabling real-time temperature in fat and increasing patient safety and treatment efficacy during thermal interventional treatments.