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The bioheat transfer models conventionally employed in etiology of human thermal infrared (TIR) emittance rely upon two assumptions: universal graybody emissivity and significant transmission of heat from subsurface tissue layers. In this study, a series of clinical and laboratory experiments were designed and carried out to conclusively evaluate the validity of the two assumptions. Results obtained from the objective analyses of TIR images of human facial and tibial regions demonstrated significant variations in spectral thermophysical properties at different anatomic locations on human body. The limited validity of the two assumptions signifies need for quantitative deconvolution of human TIR emittance in clinical, psychophysiological, and critical applications. A novel approach to joint inversion of the bioheat transfer model is also introduced, exploiting the deterministic temperature dependence of proton resonance frequency (PRF) in low-lipid human soft tissue for characterisation of the relationship between subsurface 3-D tissue temperature profiles and corresponding TIR emittance.

Denaturation of macromolecules within the tissues is believed to be the major factor contributing to the damage of tissues upon hyperthermia. As a result, the value of the spin-lattice relaxation time T1 of the tissue water, which is related to the translational and rotational rates of water, represents an intrinsic probe for investigating structural changes in tissues at high temperature. Therefore, the goal of this work is to investigate whether the simultaneous measurement of temperature and T1 using a hybrid proton resonance frequency (PRF)-T1 measurement technique can be used to detect irreversible changes in T1 that might be indicative of tissue damage. A new hybrid PRF-T1 sequence was implemented based on the variable flip angle driven-equilibrium single-pulse observation (DESPOT)1 method from a standard three dimensional segmented echo-planar imaging sequence by alternating two flip angles from measurement to measurement. The structural changes of the heated tissue volumes were analyzed based on the derived T1 values and the corresponding PRF temperatures. Using the hybrid PRF-T1 technique, we demonstrate that the change of spin lattice relaxation time T1 is reversible with temperature for low thermal dose (thermal dose ≤ 240 cumulative equivalent minutes [CEM] 43°C) and irreversible with temperature after significant accumulation of thermal dose in ex vivo chicken breast tissue. These results suggest that the hybrid PRF-T1 method may be a potentially powerful tool to investigate the extent and mechanism of heat damage of biological tissues.

Coupled cluster calculations of NMR shielding constants of alkali metal ions in water complexes are described. Adding to these benchmark values the relativistic corrections we obtain the final estimates of the shielding of solvated alkali metal ions. The results confirm with good accuracy the available absolute shielding scales of alkali metal ions. New values of magnetic dipole moments of alkali metal nuclei are derived by utilizing standardized alkali metal to proton resonance frequency ratios, and much better agreement with nuclear magnetic moments measured in atomic beam experiments is reached.

Thermal therapy procedures being carried out under MR guidance would be safer if temperature changes could be accurately monitored in both water-based and fat-based tissues. To this end we present a hybrid PRF/T1 approach for simultaneously measuring proton resonance frequency (PRF) shift temperatures in water-based tissues and T1 changes in fat-based tissues. The hybrid PRF/T1 sequence is a standard RF spoiled gradient echo sequence executed in a dynamic mode with two flip angles alternating every time frame. The PRF information is extracted every time frame using the image phase in the standard approach and the T1 information is extracted every two time frames using a variable flip angle (VFA) approach. Simulation studies, ex vivo high intensity focused ultrasound (HIFU) heating experiments, and in vivo stability experiments were performed to test the feasibility of the approach. The results indicate that the hybrid PRF/T1 approach provides PRF temperature maps of the same quality as those obtained by traditional PRF methods while simultaneously being able to track T1 changes in fat-based tissues. While several potential error sources exist for the T1 measurements, the approach is a promising start towards realizing quantitative temperature measurements in both water-based and fat-based tissues.

Determining the MR compatibility of medical implants and devices is becoming increasingly relevant. In most cases, the heating of conductive implants due to radiefrequency (RF) excitation pulses is measured by fluoroptic temperature sensors in relevant tests for approval. Another common method to determine these heating effects is MR thermometry using the proton resonance frequency. This method gives good results in homogeneous phantoms. However in many cases, technical shortcomings such as susceptibility artifacts prohibit exact proton resonance frequency thermometry near medical implants. Therefore, this work aimed at developing a fast T₁-based method which allows controlled MR-related heating of a medical implant while simultaneously quantifying the spatial and temporal temperature distribution. To this end, an inversion recovery snapshot Fast Low-Angle Shot (FLASH) sequence was modified with additional off-resonant heating pulses. With an accelerated imaging method and a sliding-window technique, every 7.6 s a new temperature map could be generated with a spatial in-plane resolution of 2 mm. The temperature deviation from calculated temperature values to reference fluoroptic probe was found to be smaller than 1 K.

The temperature dependence of the proton resonance frequency (PRF) is often used in MR thermometry. However, this method is prone to even very small changes in local magnetic field strength. Here, we report on the effects of susceptibility changes of surrounding air on the magnetic field inside an object and their inferred effect on the measured MR temperature. MR phase thermometry was performed on spherical agar phantoms enclosed in cylindrical containers at 7 T. The air susceptibility inside the cylindrical container was changed by both heating the air and changing the gas composition. Changing the temperature of surrounding air from 23 to 69°C caused an apparent MR temperature error of 2 K. When ambient air was displaced by 100% oxygen, the MR temperature error increased to 40 K. The magnetic field shift and therefore error in inferred MR temperature scales linearly with volume susceptibility change and has a strong and nontrivial dependence on the experimental configuration. Air susceptibility changes associated with oxygen concentration changes greatly affect PRF MR thermometry measurements. Air temperature changes can also affect these measurements, but to a smaller degree. For uncalibrated MR thermometry, air susceptibility changes may be a significant source of error.

Minimally invasive thermal therapy using high-power diode lasers is an active area of clinical research. Gold nanoshells (AuNS) can be tuned to absorb light in the range used for laser ablation and may facilitate more conformal tumor heating and sparing of normal tissue via enhanced tumor specific heating. This concept was investigated in a xenograft model of prostate cancer (PC-3) using MR temperature imaging (MRTI) in a 1.5T scanner to characterize the spatiotemporal temperature distribution resulting from nanoparticle mediated heating. Tumors with and without intravenously injected AuNS were exposed to an external laser tuned to 808 nm for 180 sec at 4 W/cm(2) under real-time monitoring with proton resonance frequency shift based MRTI. Microscopy indicated that these nanoparticles (140-150 nm) accumulated passively in the tumor and remained close to the tumor microvasculature. MRTI measured a statistically significant (p 0.001) increase in maximum temperature in the tumor cortex (mean = 21 ± 7°C) in +AuNS tumors versus control tumors. Analysis of the temperature maps helped demonstrate that the overall distribution of temperature within +AuNS tumors was demonstrably higher versus control, and resulted in damage visible on histopathology. This research demonstrates that passive uptake of intravenously injected AuNS in PC-3 xenografts converts the tumor vasculature into a potent heating source for nanoparticle mediated ablation at power levels which do not generate significant damage in normal tissue. When used in conjunction with MRTI, this has implications for development and validation of more conformal delivery of therapy for interstitial laser ablations.

Online MR temperature monitoring during radiofrequency (RF) ablation of cardiac arrhythmias may improve the efficacy and safety of the treatment. MR thermometry at 1.5 T using the proton resonance frequency (PRF) method was assessed in 10 healthy volunteers under normal breathing conditions, using a multi-slice, ECG-gated, echo planar imaging (EPI) sequence in combination with slice tracking. Temperature images were post-processed to remove residual motion-related artifacts. Using an MR-compatible steerable catheter and electromagnetic noise filter, RF ablation was performed in the ventricles of two sheep in vivo. The standard deviation of the temperature evolution in time (TSD) was computed. Temperature mapping of the left ventricle was achieved at an update rate of approximately 1 Hz with a mean TSD of 3.6 ± 0.9 °C. TSD measurements at the septum showed a higher precision (2.8 ± 0.9 °C) than at the myocardial regions at the heart–lung and heart–liver interfaces (4.1 ± 0.9 °C). Temperature rose maximally by 9 °C and 16 °C during 5 W and 10 W RF applications, respectively, for 60 s each. Tissue temperature can be monitored at an update rate of approximately 1 Hz in five slices. Typical temperature changes observed during clinical RF application can be monitored with an acceptable level of precision. Copyright © 2011 John Wiley & Sons, Ltd.

Purpose: To assess the feasibility, precision, and accuracy of real-time temperature mapping (TMap) during laser-induced thermotherapy (LITT) for clinical practice in patients liver with a gradient echo (GRE) sequence using the proton resonance frequency (PRF) method. Materials and Methods: LITT was performed on 34 lesions in 18 patients with simultaneous real-time visualization of relative temperature changes. Correlative contrast-enhanced T1-weighted magnetic resonance (MR) images of the liver were acquired after treatment using the same slice positions and angulations as TMap images acquired during LITT. For each slice, TMap and follow-up images were registered for comparison. Afterwards, segmentation based on temperature (T) >52°C on TMap and based on necrosis seen on follow-up images was performed. These segmented structures were overlaid and divided into zones where the TMap was found to either over- or underestimate necrosis on the postcontrast images. Regions with T>52°C after 20 minutes were defined as necrotic tissue based on data received from two different thermal dose models. Results: The average intersecting region of TMap and necrotic zone was 87% ± 5%, the overestimated 13% ± 4%, and the underestimated 13% ± 5%. Conclusion: This study demonstrates that MR temperature mapping appears reasonably capable of predicting tissue necrosis on the basis of indicating regions having greater temperatures than 52°C and could be used to monitor and adjust the thermal therapy appropriately during treatment. J. Magn. Reson. Imaging 2011;33:704–712. © 2011 Wiley-Liss, Inc.

Ultrasound hyperthermia is one of the most important methods in tumor treatment and characterized by non-invasiveness. Magnetic resonance imaging (MRI)-based temperature mapping techniques are safe compared with invasive methods and have been applied to detect temperature changes for a variety of applications. Among these techniques, the proton resonance frequency (PRF) method is relatively advanced. With a temperature measuring experiment, the effectiveness of PRF method has been proved, because the outcome temperature curve and the real temperature curve fit well. After that, an experiment has been conducted on tumors inside rabbit legs and the result indicates that this system is able to performance hyperthermia at targets based on PRF method in temperature mapping.

Purpose To compare magnetic resonance (MR) thermometry based on the proton resonance frequency (PRF) method using a single shot echoplanar imaging (ss EPI) sequence to both of the standard sequences, gradient echo (GRE) and segmented echoplanar imaging (seg EPI) in the in vivo human brain, at 1.5T and 3T. Material and methods Repetitive MR thermometry was performed on the brain of six volunteers using GRE, seg EPI, and ss EPI sequences on whole-body 1.5T and 3T clinical systems using comparable acquisition parameters. Phase stability and temperature data precision in the human head were determined over 12 min for the three sequences at both field strengths. An ex-vivo swine skeletal muscle model was used to evaluate temperature accuracy of the ss EPI sequence during heating by high intensity focused ultrasound (HIFU). Results In-vivo examinations of brain revealed an average temperature precision of 0.37 °C/0.39 °C/0.16 °C at 3T for the GRE/seg EPI/ss EPI sequences. At 1.5T, a precision of 0.58 °C/0.63 °C/0.21 °C was achieved. In the ex-vivo swine model, a strong correlation of temperature data derived using ss EPI and GRE sequences was found with a temperature deviation Conclusion The ss EPI sequence was the fastest and the most precise sequence for MR thermometry, with significantly higher accuracy compared to GRE.

Background During an MR procedure, most of the transmitted RF power is transformed into heat referred to as the specific energy absorption rate(SAR). EU directive(IEC60602-3-33) mandates all scanners must measure SAR and provide safeguards for tissue-limits. Accurate estimation of SAR is critical in safeguarding vulnerable patients. Modern MRI systems can easily exceed safe SAR levels and our aim is to develop a protocol to verify patient specific SAR using a MR phantom heated solely by the RF fields. Methods Our phantom is a non-perfused material simplifying pennes-bioheat equation. The SAR at discreet points in the observation plane is determined by SAR ≈ C_agar Δ T / Δ t[W⧹kg] Where C_agar is 4200 J/kg.K, Δ T is the change in temperature and Δ t is the change in time. Δ T was determined via Proton Resonance Frequency Shift (PRF) thermometry. Δ T = ( ϕ - ϕ _ 0 ) /( α γ B_0 TE) Where.

A model-based proton resonance frequency shift (PRFS) thermometry method was developed to significantly reduce the temperature quantification errors encountered in the conventional phase mapping method and the spatiotemporal limitations of the spectroscopic thermometry method. Spectral data acquired using multi-echo gradient echo (GRE) is fit into a two-component signal model containing temperature information and fat is used as the internal reference. The noniterative extended Prony algorithm is used for the signal fitting and frequency estimate. Monte Carlo simulations demonstrate the advantages of the method for optimal water-fat separation and temperature estimation accuracy. Phantom experiments demonstrate that the model-based method effectively reduces the interscan motion effects and frequency disturbances due to the main field drift. The thermometry result of ex vivo goose liver experiment with high intensity focused ultrasound (HIFU) heating was also presented in the paper to indicate the feasibility of the model-based method in real tissue.

Conventional spectral-spatial pulses used for water-selective excitation in proton resonance frequency-shift MR thermometry require increased sequence length compared to shorter wideband pulses. This is because spectral-spatial pulses are longer than wideband pulses, and the echo time period starts midway through them. Therefore, for a fixed echo time, one must increase sequence length to accommodate conventional spectral-spatial pulses in proton resonance frequency-shift thermometry. We introduce improved water-selective spectral-spatial pulses for which the echo time period starts near the beginning of excitation. Instead of requiring increased sequence length, these pulses extend into the long echo time periods common to PRF sequences. The new pulses therefore alleviate the traditional tradeoff between sequence length and fat suppression. We experimentally demonstrate an 11% improvement in frame rate in a proton resonance frequency imaging sequence compared to conventional spectral-spatial excitation. We also introduce a novel spectral-spatial pulse design technique that is a hybrid of previous model- and filter-based techniques and that inherits advantages from both. We experimentally validate the pulses' performance in suppressing lipid signal and in reducing sequence length compared to conventional spectral-spatial pulses.

The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient-echo echo planar imaging (GRE-EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE-EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR-compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland- Altman analysis. In a preliminary clinical feasibility study, the rapid GRE-EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland-Altman mean of differences between MR and optical probe temperature measurements was

The objective of this study was to evaluate breathing influence on precision in temperature determination by using the proton resonance frequency (PRF) shift method depending on the location in abdominal organs at 0.2 and 1.5 T.Phase images were acquired with gradient echo sequences in a total of 12 volunteers at 1.5 and 0.2 T. Different examination protocols were performed (each 8 measurements with (1) in-/expiration, (2) free breathing, (3) under breathhold, (4) with breathing belt triggering, and (5) with navigator triggering (integrated in MR signal acquisition). Regions of interest were placed on liver and kidneys, and the resulting phase differences between the measurements were transformed into corresponding temperature differences.Precision significantly varied depending on the liver segment or location in the kidney. Gating techniques were found better than breathhold techniques and clearly better than non-gated examinations. The most precise approach reached a standard deviation of 2.0 degrees C under continuous breathing when navigator gating was used at 1.5 T.PRF temperature measurement is feasible even for moving organs in the abdomen at 0.2 and 1.5 T. The location of the target region and the required precision of the measurements should direct the choice of examination mode.

Purpose To validate echo combination as a means to reduce errors caused by fat in temperature measurements with the proton resonance frequency (PRF) shift method. Materials and Methods Computer simulations were performed to study the behavior of temperature measurement errors introduced by fat as a function of echo time. Error reduction by combining temperature images acquired at different echo times was investigated. For experimental verification, three echoes were acquired in a refocused gradient echo acquisition. Temperature images were reconstructed with the PRF shift method for the three echoes and then combined in a weighted average. Temperature measurement errors in the combined image and the individual echoes were compared for pure water and different fractions of fat in a computer simulation and for a phantom containing a homogenous mixture with 20% fat in an MR experiment. Results In both simulation and MR measurement, the presence of fat caused severe temperature underestimation or overestimation in the individual echoes. The errors were substantially reduced after echo combination. Residual errors were about 0.3°C for 10% fat and 1°C for 20% fat. Conclusion Echo combination substantially reduces temperature measurement errors caused by small fractions of fat. This technique then eliminates the need for fat suppression in tissues such as the liver. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc.

Richard Ernst, Hans Primas’ second Ph.D. student, gives a brief overview of Primas’ early achievements in the field of nuclear magnetic resonance and of his role in the development of a young branch of science.

A magnetic resonance (MR)-compatible three-dimensional (3-D) hyperthermia applicator was developed and evaluated in the magnetic resonance (MR) tomograph Siemens MAGNETOM Symphony 1.5 T. Radiating elements of this applicator are 12 so-called water coated antenna (WACOA) modules, which are designed as specially shaped and adjustable dipole structures in hermetically closed cassettes that are filled by deionized water. The WACOA modules are arranged in the applicator frame in two transversal antenna subarrays, six antennas per subarray. As a standard load for the applicator an inhomogeneous phantom was fabricated. Details of applicator's realization are presented and a 3-D comparison of calculated and measured temperature data sets is made. A fair agreement is achieved that demonstrates the numerically supported applicator's ability of phase-defined 3-D pattern steering. Further refinement of numerical models and measuring methods is necessary. The applicator's design and the E-field calculations were performed using the finite-difference time-domain (FDTD) method. The calculation and optimization of temperature patterns was obtained using the finite element method (FEM). For MR temperature measurements the proton resonance frequency (PRF) method was used.

PURPOSE To demonstrate the potential of quantitative MRI-assisted thermometry for the treatment of tumor patients with regional hyperthermia (RHT) and interstitial laser thermotherapy (ILTT). METHODS Two patients and seven tissue samples were investigated using the T1-relaxation time and the chemical shift of the proton resonance frequency (PRF) as temperature sensitive MRI-parameters at 0.2 and 1.5 T. Thermotherapy was applied using either a dedicated MRI-hyperthermia hybrid system or a temperature controlled laser with 830 nm. RESULTS Both patients were treated successfully showing clinical benefit. T1 and PRF are depending on the applied thermotherapy method and on the MR-system suitable for MRI-assisted thermometry. The clinical application based on phantom results is not necessarily adequate. CONCLUSION Clinical application and phantom experiments of RHT and ILTT show the potential of MRI-assisted thermometry for further improvement of both minimal invasive thermotherapy methods. Further investigations concerning optimization of the MRI-techniques, the influence of perfusion or the determination of threshold values are necessary.

Objective of this study is the integration of a multiantenna applicator for part-body hyperthermia (BSD 2000/3D) in a 1.5 T MR-tomograph (Siemens Magnetom Symphony) in order to perform noninvasive MR monitoring in real time to increase safety and effectiveness of heat treatments. The positioning unit is mechanically coupled to the MR gantry from the back side and the body coil is utilised for imaging. For that purpose, the hyperthermia antenna system (100 MHz, 1.500 W) and the MR receiver (63.9 MHs) have to be decoupled in terms of high frequency (filter) and electromagnetically (emc). The processing of MR data sets is performed in a hyperthermia planning system. A simultaneous operation of radiofrequency hyperthermia and MR system is possible at clinically relevant power levels. MR imaging is used for tumor-diagnostics (standard spin echo sequences), for hyperthermia planning (T1-weighted gradient echo sequences in equal- and opposed-phase techniques), and for temperature measurements according to the proton resonance frequency method (PRF method, phase evaluation registration using a gradient echo sequence with long echo time). In 33 patients with advanced pelvic and abdominal tumors we performed 150 heat sessions under MR monitoring. For 70% of these patients a visualisation of temperature sensitive data during treatment was possible. The evaluated difference images represent a superposition of real temperature -increase and a (temperature-induced) perfusion elevation. The -hybrid approach renders development of part body hyperthermia possible as an MR-controlled intervention in radiology.

Proton resonance frequency (PRF) shift MRI thermometry was incorporated into a fast low angle shot imaging sequence to acquire two-dimensional temperature maps of two model liquid–particulate mixtures undergoing ohmic heating process. The samples used consisted of two phases, namely whey gel and NaCl solution, and were enclosed in an in-house made ohmic heating device driven by an 143 V AC power supply. Salt was added to the gel and solution to alter their electrical conductivity. The PRF shift was used as a temperature indicator, which was linearly and reversibly proportional to the temperature change. The specific PRF shift for the whey gel was determined as −0.0098 and −0.0097 ppm/°C for the two samples. For the NaCl solution, the values were −0.0096 and −0.0102 ppm/°C, respectively. Detailed temperature maps with spatial resolution of 0.94 mm and temporal resolution of 0.64 s were obtained. The temperature uncertainties were about ±1 °C for the whey gel and ±2 °C for the solution. The ease to interpret, the speed, and the accuracy of this new technique justify its applications in dynamic food process. The temperature maps provided details for the investigation of uneven heating of a liquid–particulate mixture undergoing ohmic heating and this temperature mapping technique is a powerful tool for ohmic model development and validation.

The effect of perfusion on the temperature distribution during radio-frequency hyperthermia and laser-induced thermotherapy was investigated with the perfused porcine kidney model. The phase shift-based proton resonance frequency shift method was used to map the temperature distribution. In experiments with modulated perfusion rates it was demonstrated that perfusion dissipates a significant amount of the absorbed energy and, therefore, the resulting heat distribution is strongly dependent on the perfusion rate. The measured time course of the temperature distribution was used to estimate the thermal conductivity, local perfusivity and heat absorption rate of the tissue. These parameters were in a good agreement with literature data. This approach can also be extended to measure heat absorption and heat transfer parameters in vivo, which can significantly improve the accuracy of thermotherapy session planning.

In MRI-guided high-intensity focused ultrasound (MR-HIFU) therapy, temperature-dependent proton resonance frequency (PRF) shift is a key factor to quantify and visualize the spatial heating pattern in treated and surrounding tissue. However, during treatment, multiple scanner-related changes can impact the accuracy of the temperature measurements obtained with the PRF shift method and cause an over/under estimation of temperature, which can be a major safety issue for treatments involving real-time temperature control. Hence, it is necessary to apply corrections to ensure accurate temperature measurements during heating. Prior to image acquisition, the central MR frequency F0 can be measured to adjust the F0 of next image acquisition. After acquisition, corrections can be applied to the acquired images to remove scanner-related influences, most importantly phase drift. Different phase drift correction algorithms such as conventional and polynomial adaptive drift correction estimate the background phase by fitting a linear or polynomial to the image phase outside the treatment area and perform the correction accordingly. The goal of this study was to understand the performance of these algorithms for long heating durations as would be experienced during hyperthermia or transurethral HIFU (>20 minutes).

MRgFUS (Magnetic Resonance guided Focused UltraSound) is a new and non-invasive technique to treat different diseases in the oncology field, that uses Focused Ultrasound (FUS) to induce necrosis in the lesion. Temperature change measurements during ultrasound thermo-therapies can be performed through magnetic resonance monitoring by using Proton Resonance Frequency (PRF) thermometry. It measures the phase variation resulting from the temperature-dependent changes in resonance frequency by subtracting one phase baseline image from actual phase. Referenceless thermometry aims to re-duce artefacts caused by tissue motion and frequency drift, fitting the back-ground phase outside the heated region. The aim of this contribution is to pro-pose a novel background phase reconstruction method using Radial Basis Func-tion (RBF) interpolation. The effectiveness of the method has been demonstrat-ed by comparing it against the classical PRF shift and polynomial referenceless approach. The comparison evaluates temperature rises in uterine fibroids during MRgFUS treatments on a set of 10 patients.

The clinical role of magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) is rapidly expanding due to its merit of non-invasiveness. MR thermometry based on a proton resonance frequency shift technique is able to accurately measure HIFU-induced temperature changes, which provides considerable advantages over ultrasonography-guided HIFU in terms of safety and therapeutic efficacy. Recent studies and the resulting technological advances in MR-HIFU such as MR thermometry for moving organs, MR-acoustic radiation force imaging, and a volumetric mild hyperthermia technique further will expand its clinical roles from mere ablation therapy to targeted drug delivery and chemo- or radio-sensitisation for cancer treatment. In this article, MR-HIFU therapy is comprehensively reviewed with an emphasis on the roles of MR imaging in HIFU therapy, techniques of MR monitoring, recent advances in clinical MR-HIFU systems, and potential future applications of MR-HIFU therapy. In addition, the pros and cons of MR-HIFU when compared with ultrasonography-guided HIFU are discussed.

The proton-resonance frequency (PRF) shift method of MR thermometry provides an easy and practical means of quantitatively monitoring in vivo temperatures for MR image-guided thermal-coagulation therapy. However, reported discrepancies in the numerical value of the PRF-thermal coefficient persist, when measured in a variety of experimental conditions and in different tissue types, both ex vivo and in vivo. In this report, a potential source of variation in the PRF-shift method of thermometry is identified that manifests as a constant incremental phase shift per unit change in temperature that is independent of the echo-time setting, when constructing temperature-sensitive phase images from a gradient-echo pulse sequence. It is proposed that this confounding phase-shift offset arises from thermally induced changes in the electrical conductivity of the material. To this end, it is demonstrated that the MR-derived temperature changes could be in error by as much as 28%, as measured from a simple calibration experiment on freshly excised cow liver. A simple method of overcoming this phase-shift offset is described.

The proton-resonance frequency (PRF) shift method of thermometry has become a promising tool for magnetic resonance image-guided thermal therapies. Although the PRF thermal coefficient has recently been shown to be independent of tissue type when measured ex vivo, significant discrepancy remains on its value for tissues measured in vivo under a variety of experimental conditions. The authors identify a potential source of variation in the PRF thermal coefficient that arises from temperature-induced changes in the volume magnetic susceptibility of tissue and is dependent on the orientation and geometry of the heat-delivery device and its associated heat pattern. This study demonstrates that spatial variations in the apparent PRF thermal coefficient could lead to errors of up to +/-30% in the magnetic resonance estimated temperature change if this effect is ignored.

In this work the temperature dependence of the proton resonance frequency was assessed in agarose gel with a high melting temperature (95 degrees C) and in porcine liver in vitro at temperatures relevant to thermotherapy (25-80 degrees C). Furthermore, an optically tissue-like agarose gel phantom was developed and evaluated for use in MRI. The phantom was used to visualize temperature distributions from a diffusing laser fibre by means of the proton resonance frequency shift method. An approximately linear relationship (0.0085 ppm degrees C(-1)) between proton resonance frequency shift and temperature change was found for agarose gel, whereas deviations from a linear relationship were observed for porcine liver. The optically tissue-like agarose gel allowed reliable MRI temperature monitoring, and the MR relaxation times (T1 and T2) and the optical properties were found to be independently alterable. Temperature distributions around a diffusing laser fibre, during irradiation and subsequent cooling, were assessed with high spatial resolution (voxel size = 4.3 mm3) and with random uncertainties ranging from 0.3 degrees C to 1.4 degrees C (1 SD) with a 40 s scan time.

The temperature sensitivity of the proton-resonance frequency (PRF) has proven valuable for the monitoring of MR image-guided thermal coagulation therapy. However, there is significant inconsistency in reported values of the PRF-thermal coefficient, as measured from experiments encompassing a range of in vivo and ex vivo tissue types and experimental conditions. A method of calibrating the temperature dependence of the PRF is described and results are presented that indicate a tissue-type independence. To this end, other possible mechanisms for variations in the PRF-thermal coefficient are suggested, including physiological perturbations and volume magnetic susceptibility effects from geometry and orientation.

1H MRS thermometry has been investigated for brain trauma and hypothermia monitoring applications but has not been explored in brain tumours. The proton resonance frequency (PRF) of water is dependent on temperature but is also influenced by microenvironment factors, such as fast proton exchange with macromolecules, ionic concentration and magnetic susceptibility. 1H MRS has been utilized for brain tumour diagnostic and prognostic purposes in children; however, the water PRF measure may provide complementary information to further improve characterization. Water PRF values were investigated from a repository of MRS data acquired from childhood brain tumours and children with apparently normal brains. The cohort consisted of histologically proven glioma (22), medulloblastoma (19) and control groups (28, MRS in both the basal ganglia and parietal white matter regions). All data were acquired at 1.5 T using a short TE (30 ms) single voxel spectroscopy (PRESS) protocol. Water PRF values were calculated using methyl creatine and total choline. Spectral peak amplitude weighted averaging was used to improve the accuracy of the measurements. Mean PRF values were significantly larger for medulloblastoma compared with glioma, with a difference in the means of 0.0147 ppm (p < 0.05), while the mean PRF for glioma was significantly lower than for the healthy cohort, with a difference in the means of 0.0061 ppm (p < 0.05). This would suggest the apparent temperature of the glioma group was ∼1.5 °C higher than the medulloblastomas and ∼0.7 °C higher than a healthy brain. However, the PRF shift may not reflect a change in temperature, given that alterations in protein content, microstructure and ionic concentration contribute to PRF shifts. Measurement of these effects could also be used as a supplementary biomarker, and further investigation is required. This study has shown that the water PRF value has the potential to be used for characterizing childhood brain tumours, which has not been reported previously. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

The purpose of this work was to determine the accuracy of Proton Resonance Frequency (PRF) thermometry during MR-guided Focused Ultrasound (MRgFUS) ablation on explanted Thiel embalmed human and animal liver, fresh animal liver, and compared to gel phantom.PRF thermometry during MRgFUS was conducted using a 1.5T MRI system. The phantom and the organs were sonicated with the following energies: 300J, 600J, 1000J and 1400J. The temperature increase which was measured using PRF thermometry during sonication was compared to actual temperature rise in the same conditions measured by fibre optic thermocouple.Sonication of fresh animal liver showed temperature differences varying between 0.27°C and 0.40°C, whereas the phantom results showed temperature differences from 0.23°C to 0.40°C. For the Thiel embalmed organs, the temperature difference varied from 1.17 °C to 3.13°C for the ovine liver, and from 1.3°C to 3.10°C for the human liver.The temperature differences measured in the fresh liver were small and similar to those found for the gel phantom. However, the temperature differences calculated for the Thiel embalmed organs were higher compared to the fresh organ. This indicates that the PRF-based temperature calibration of the Focused Ultrasound machine for Thiel embalmed tissue is necessary.

High energy management in nuclear system and refractory metals productions are equipped with challenging procedures in terms of precise and remote controlling. In order to predict occurrence of contamination and avoidance of huge damages, there are often difficulties to access the equipment during their operation. In addition, estimating the precise and remote nucleation critical temperature of decay and growth of radioactive materials in the nuclear system has also proven to be a great challenge. Other than that, the eutectic crystallization temperature of the refractory metals during production also need to provide a precise estimation. However, it has been understood that the conventional temperature sensors are yet to be applicable to work precisely in such harsh environments. On the other hand, proton resonance frequency thermometry phenomenon have not been utilized or developed to serve as temperature sensors; despite the fact that they are capable to measure temperature in quantum level. Therefore, this article provides a review of the prior art on proton resonance frequency thermometry with its application and reliability, and elaborates on the trajectory of ultra-precise temperature measurement as the latest development.

The purpose of this study was to evaluate magnetic resonance (MR) temperature imaging of the laser-induced thermotherapy (LITT) comparing the proton resonance frequency (PRF) and T 1 thermometry methods. LITT was applied to a liver-mimicking acrylamide gel phantom. Temperature rise up to 70 °C was measured using a MR-compatible fiber-optic thermometer. MR imaging was performed by a 1.5-T scanner utilizing fast gradient echo sequences including a segmented echo planar imaging (seg-EPI) sequence for PRF and the following sequences for T 1 method: fast low-angle shot (FLASH), inversion recovery turbo flash (IRTF), saturation recovery turbo flash (SRTF), and true fast imaging (TRUFI). Temperature-induced change of the pixel values in circular regions of interest, selected on images under the temperature probe tip, was recorded. For each sequence, a calibration constant could be determined to be -0.0088 ± 0.0002 ppm °C(-1) (EPI), -1.15 ± 0.03 °C(-1) (FLASH), -1.49 ± 0.03 °C(-1) (IRTF), -1.21 ± 0.03 °C(-1) (SRTF), and -2.52 ± 0.12 °C(-1) (TRUFI). These constants were evaluated in further LITT experiments in phantom comparing the calculated temperatures with the fiber optic-measured ones; temperature precisions of 0.60 °C (EPI), 0.81 °C (FLASH), 1.85 °C (IRTF), 1.95 °C (SRTF), and 3.36 °C (TRUFI) were obtained. Furthermore, performing the Bland-Altman analysis, temperature accuracy was determined to be 0.23 °C (EPI), 0.31 °C (FLASH), 1.66 °C (IRTF), 1.19 °C (SRTF), and 3.20 °C (TRUFI). In conclusion, the seg-EPI sequence was found to be more convenient for MR temperature imaging of LITT due to its relatively high precision and accuracy. Among the T 1 method sequences, FLASH showed the highest accuracy and robustness.

Selective photothermal interaction using dye-assisted non-invasive laser irradiation has limitations when treating deeper tumors or when the overlying skin is heavily pigmented. We developed an interstitial laser irradiation method to induce the desired photothermal effects. An 805-nm near-infrared laser with a cylindrical diffuser was used to treat rat mammary tumors by placing the active tip of the fiber inside the target tumors. Three different power settings (1.0 to 1.5 watts) were applied to treat animal tumors with an irradiation duration of 10 minutes. The temperature distributions of the treated tumors were measured by a 7.1-Tesla magnetic resonance imager using proton resonance frequency (PRF) method. Three-dimensional temperature profiles were reconstructed and assessed using PRF. This is the first time a 7.1-Tesla magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. This study provides a basic understanding of the photothermal interaction needed to control the thermal damage inside tumor using interstitial laser irradiation. It also shows that PRF can be used effectively in monitoring photothermal interaction. Our long-term goal is to develop a PRF-guided laser therapy for cancer treatment.

A method is presented which allows precise temperature and longitudinal (T1) relaxation time measurements with high spatial and temporal resolution. This is achieved by combining dynamic variable flip angle based T1 relaxation mapping with proton resonance frequency shift based thermometry. Herein, dynamic T1 mapping is either used as a complementary measure of temperature or for the detection of T1 contrast agent release. For the first application, the temperature evolution during a high-intensity focused ultrasound tissue ablation experiment was measured in both, porcine fat and muscle, simultaneously. In this application, temperature accuracies of 2.5 K for T1-based thermometry in fat and 1.2 K for proton resonance frequency shift-based thermometry in muscle were observed. The second application relates to MR-guidance of high-intensity focused ultrasound-induced local drug delivery by means of thermo-sensitive liposomes labeled with a T1 contrast agent (Gd-HPDO3A). When the measured temperature exceeded the phase transition temperature of the liposomes, T1 was observed to decrease with a good temporal and spatial correlation due to the release of Gd-HPDO3A. The presented results demonstrate the feasibility of the proposed method for two important applications in MR-guided noninvasive therapy. It offers a high temporal resolution when compared with interleaved Look-Locker based T1 mapping techniques and thus represents an interesting candidate for simultaneous real-time monitoring of T1 and temperature changes. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

The conventional implementations of proton resonance frequency shift (PRFS) magnetic resonance thermometry (MRT) require the subtraction of single or multiple temporal references, a motion sensitive critical feature. A pilot study was conducted here to investigate the clinical feasibility of near-harmonic two-dimensional (2D) referenceless PRFS MRT, using patient data from MR-guided laser ablation of liver malignancies.PRFS MRT with respiratory-triggered multi-slice gradient-recalled (GRE) acquisition was performed under free breathing in six patients. The precision of the novel referenceless MRT was compared with the reference phase subtraction. Coupling the referenceless MRT with a model-based, real-time compatible regularisation algorithm was also investigated.The precision of MRT was improved by a factor of 3.3 when using the referenceless method as compared to the reference phase subtraction. The approach combining referenceless PRFS MRT and model-based regularisation yielded an estimated precision of 0.7° to 2.1°C, resulting in millimetre-range agreement between the calculated thermal dose and the 24 h post-treatment unperfused regions in liver.The application of the near-harmonic 2D referenceless MRT method was feasible in a clinical scenario of MR-guided laser-induced thermal therapy (LITT) ablation in liver and permitted accurate prediction of the thermal lesion under free breathing in conscious patients, obviating the need for a controlled breathing under general anaesthesia.

Purpose: To combine temperature-related information of phase images and magnitude images acquired from an MR spoiled gradient echo sequence using a postprocessing method referred to as PRF-shift-weighted imaging (PRFSWI). Materials and Methods: Phase images are capable of detecting shifts in proton resonance frequency (PRF) caused by local changes in temperature. Magnitude images provide anatomical information for treatment planning and positioning as well as temperature-related contrast. We used PRFSWI to produce a phase-mask and performed multiplication on the magnitude image to increase temperature-related contrast. Results: Through MRI-guided focused ultrasound (MRIgFUS) experiments (both ex vivo and in vivo), we determined that PRFSWI is capable of enhancing the contrast of a heated area even in the initial stages of transmitting high-intensity focused ultrasound energy. Conclusion: The PRFSWI images are sensitive to changes in temperature and display the heated spot directly in the magnitude images. Although the images do not provide quantitative data related to temperature, this method could be used as a complement to the phase temperature mapping method in the real-time monitoring of MRIgFUS experiments. J. Magn. Reson. Imaging 2011;33:1474–1481. © 2011 Wiley-Liss, Inc.

A new approach to MRI thermometry using encapsulated hyperpolarized xenon is demonstrated. The method is based on the temperature dependent chemical shift of hyperpolarized xenon in a cryptophane-A cage. This shift is linear with a slope of 0.29 ppm °C(-1) which is perceptibly higher than the shift of the proton resonance frequency of water (ca. 0.01 ppm °C(-1)) that is currently used for MRI thermometry. Using spectroscopic imaging techniques, we collected temperature maps of a phantom sample that could discriminate by direct NMR detection between temperature differences of 0.1 °C at a sensor concentration of 150 μM. Alternatively, the xenon-in-cage chemical shift was determined by indirect detection using saturation transfer techniques (Hyper-CEST) that allow detection of nanomolar agent concentrations. Thermometry based on hyperpolarized xenon sensors improves the accuracy of currently available MRI thermometry methods, potentially giving rise to biomedical applications of biosensors functionalized for binding to specific target molecules.

Proton resonance frequency shift (PRFS)‐based MR thermometry is hampered by temporal field changes. Temporal changes in the susceptibility distribution lead to field changes and are therefore a possible source of errors. The susceptibility of fat, χfat, is temperature dependent, in the same order of magnitude as the temperature dependence of the chemical shift of water (0.01 ppm/° C). PRFS‐based temperature measurements may therefore be corrupted by non‐local field effects due to temperature induced susceptibility changes in fatty tissue. We performed simulations to quantify the influence of dχfat/dT on PRFS‐based MR temperature maps during thermal interventions in the breast. Susceptibility distributions were calculated for a 3D breast model without and with a stationary Gaussian temperature distribution and a maximum temperature of 57° C. Subsequently, the magnetic field was calculated in Fourier‐domain from these susceptibility distributions. Changes in the magnetic field distribution were quantified b...

Conductive implants are in most cases a strict contraindication for MRI examinations, as RF pulses applied during the MRI measurement can lead to severe heating of the surrounding tissue. Understanding and mapping of these heating effects is therefore crucial for determining the circumstances under which patient examinations are safe. The use of fluoroptic probes is the standard procedure for monitoring these heating effects. However, the observed temperature increase is highly dependent on the positioning of such a probe, as it can only determine the temperature locally. Temperature mapping with MRI after RF heating can be used, but cooling effects during imaging lead to a significant underestimation of the heating effect. In this work, an MRI thermometry method was combined with an MRI heating sequence, allowing for temperature mapping during RF heating. This technique may provide new opportunities for implant safety investigations. Magn Reson Med 60:457– 461, 2008. © 2008 Wiley-Liss, Inc.

The ultrafast echo-planar magnetic resonance imaging technology, developed and built in Nottingham, has been used to produce the first snapshot images of the human fetus in utero. The imager, operating at a proton resonance frequency of 22 MHz, produces transaxial views in 64 or 128 milliseconds. These images comprise either 64 x 128 or 128 x 128 pixels with an in-plane resolution of 3 x 3 mm2. The slice thickness is 10 mm. Fetal scans of up to 32 contiguous slices are produced in a few minutes. These have been used to study the internal structure of the uterus and the fetus in a range of cases with gestations ranging from 26 weeks to term. Echo-planar imaging seems particularly suitable as an imaging modality since its high speed obviates image blurring arising from fetal motion.

Purpose To improve the immunity of the proton resonance frequency shift (PRFS) method of MRI temperature mapping against magnetic field disturbances. Since PRFS is a phase-sensitive method, it misinterprets magnetic field disturbances as artifact temperature changes. If not corrected, the resulting temperature artifacts can completely obscure the true temperature estimation, especially if the temperature elevations are small. Materials and Methods Since the fat protons experience the same magnetic field disturbances as the water protons, but no temperature-related frequency shift, the fat signal has been used for correcting PRFS temperature maps for the disturbances. A simple correction method is proposed that has either better compensation capability than the phase correction methods previously reported or higher spatial and temporal resolution than the spectroscopic correction methods previously reported. The evaluated method is based on the utilization of several gradient and spin echoes acquired within one repetition interval with water- and fat-selective scans. Results In a series of phantom experiments, the improved method is shown to enable the reconstruction of accurate temperature maps in spite of interscan motion, suboptimal fat–water separation, and a wide range of magnetic field disturbances. Conclusion Our approach can be used for the guidance of thermal therapies involving tissues containing fat or surrounded by fat. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc.

A new rapid application development platform has been used to develop a system for MRI guided HIFU therapies with real‐time automatic feedback control and visualizations to monitor treatment progression. As the treatment dose is being administered to the patient, the MRI system calculates the Proton Resonance Frequency (PRF) based temperature measurements and sends them to our application over a TCP/IP network. The current thermal dose distribution and the next desired SAR pattern are immediately calculated. As the next dose is administered to the patient, the application applies a 1D color map to visualize thermal dose and a 2D color map to visualize temperature and SAR. The user is able to move 3D planes through the visualizations during the treatment in order to monitor treatment progression.

Successful HIFU surgery demands accurate and reliable temperature monitoring. Heating affects acoustic properties of biological tissues changing the acoustic field and consequent heat deposition. As a result, HIFU thermal lesions grow asymmetrically from the focus toward the transducer and perpendicularly to the beam axis. If the growth process is not monitored, the healthy tissues located on the beam path can be damaged. We propose an improved approach to MRI temperature mapping designed for the real‐time guidance of HIFU surgery, which is based on the acquisition of images along the HIFU beam and allows monitoring and analyzing heat deposition and distribution patterns. Our method visualizes the heat deposition site and shows its evolution during the surgery. In‐vitro HIFU experiments have been performed under real‐time MRI temperature monitoring using the Proton Resonance Frequency Shift method. A set of mathematical operations has been applied to MRI temperature maps, which revealed the HIFU thermal focus (which not always coincides with the geometrical focus) as well as the focus’ shape, size and displacements during sonications. The operations also visualized the HIFU beam waist as well as the hot area borders and main heat transfer directions. Our approach provides information for on‐line prevention of undesirable heat deposition resulting from intra‐operative changes of tissue acoustic properties. Since making small sharp HIFU lesions demands the usage of short high‐power sonications, predicting the thermal lesion growth resulting from the next sonication becomes highly desirable. Our method has a potential to supply the information necessary for such predictions, which can increase the safety and improving the clinical outcome of the HIFU surgery.

MR-guided high-intensity focused ultrasound (HIFU) ablation is a promising, noninvasive method for treatment of bone tumors and palliation of pain. During thermal therapy, temperature mapping is necessary to ensure proper heat deposition in targeted tumors as well as to prevent undesired heating in healthy tissues. However, conventional proton resonance frequency-based MR thermometry cannot be applied in cortical bone due to its short T2* relaxation time. Recently, it was shown that ultrashort echo-time MRI can be used to assess T1 change in cortical bone due to temperature change (Han M, ISMRM 2014, P262). This work focused on characterization of temperature dependence of T1 in cortical bone by performing a calibration experiment.

Respiratory induced resonance offset (RIRO) is a periodic disturbance of a magnetic field due to breathing. Such disturbance handicaps the accuracy of the proton resonance frequency shift (PRFS) method of MRI temperature mapping in anatomies situated nearby the lungs and chest wall. In this work, we propose a method capable of minimizing errors caused by RIRO in PRFS temperature maps. In this method, a set of baseline images characterizing RIRO at a variety of respiratory cycle instants is acquired before the thermal treatment starts. During the treatment, the temperature evolution is found from two successive images. Then, the calculated temperature changes are corrected for the additional contribution caused by RIRO using the pre-treatment baseline images acquired at the identical instances of the respiratory cycle. Our method is shown to improve the accuracy and stability of PRFS temperature maps in the presence of RIRO and inter-scan motion in phantom and volunteers' breathing experiments. Our method is also shown to be applicable to anatomies moving during breathing if a proper registration procedure is applied.

MRI is a unique tool for minimally invasive thermal ablation in that it can provide both targeting, monitoring and control during the procedure. Monitoring is achieved by using MRI temperature mapping. In this review the relevant physics is explained as a background to the state-of-the-art methods for computing temperature maps as well as the more cutting edge methods. The review covers both methods to monitor heating and cooling of tissue and explains temperature mapping using Proton Resonance Frequency shift, T1 mapping, diffusion mapping, R2* mapping and thermal models.