Proton Resonance Frequency Research Articles

Effect of the Dispersion Medium on NMR Relaxation Properties of Superparamagnetic Iron Oxide Nanoparticles between 0.24 mT and 14.1 T.

Due to weak exchange interactions, magnetite particles at a critical diameter of about 20 nm are considered monodomain. At this size, they exhibit a phenomenological magnetic property called superparamagnetism, making them useful as magnetic resonance imaging contrast agents, or MRI CAs. However, questions persist regarding the impact of using different physiological solvents and varying the environment in which these particles are dispersed on their performance, determined by their relaxivity. A colloidal suspension of superparamagnetic iron oxide nanoparticles (SPIONs) electrostatically stabilized by citrate ligand was synthesized using a fast, reliable, and reproducible developed microwave approach, ensuring high stability over time at pH 7. We studied the effects of three physiological media on these MRI CAs. Ultrapure water was used for the synthesis, while phosphate-buffered saline and physiological liquid were used to disperse the nanoparticles, as these media contain essential electrolytes for the functioning of the human body. The SPIONs underwent systematic characterizations to determine their physicochemical and magnetic properties. This study reports the longitudinal relaxivities of SPIONs at medically relevant magnetic field strengths. Field dependence of their relaxivity (efficacy) was evaluated using a nuclear magnetic resonance dispersion (NMRD) profile measured over a wide range of proton resonance frequencies between 5 kHz and 600 MHz. The Roch et al. model (Roch, A.; et al. J. Chem. Phys., 1999, 110, 5403-5411) was used to analyze the NMRD profile and evaluate the impact of SPIONs on water proton relaxation in the different redispersion media. It was observed in this study that the dynamics of water protons are not influenced by the redispersion media of these citrate-coated SPIONs. However, the presence of salt ions notably reduces their relaxivities by lowering the saturation magnetization of SPIONs.

Measurement and advanced data post-processing of proton resonance frequency shift in 7 T MRI to obtain local temperature in a tissue-mimicking phantom

Abstract The radio-frequency (RF) transmit power deposition in tissue during magnetic resonance imaging (MRI) at ultra-high fields, i.e. B 0 ≥ 7 T, is a major challenge for pulse sequences requesting large flip angles. The absorbed RF energy can pose safety risk to patients as it is rising temperature in the tissue. The temperature can be accessed using MRI itself via the proton-resonance frequency (PRF) shift technique, which at low B 0 has been shown a valid MR thermometry method. In this paper, we explore the applicability of the PRF method to the assessment of local temperature in 7 T MRI procedures. To this end, we built a phantom filled with a material presenting electrical conductivity and permittivity close to muscle tissue. Tubes filled with oil were placed nearby the phantom to observe the time dependent B 0 drift. MRI phase images were acquired by gradient-echo (GRE) sequences at time points between spin-echo sequences with large flip angle allowing for a continuous assessment of the temperature during a 114 min RF-heating experiment. All acquired phase images were post-processed with attention to the time dependent instability of B 0, and, in addition, to potential spatial and temporal phase discontinuities, known as wraps. In this paper, we present a strategy to analyze and to unfold these phase wraps for large measurement fields and long acquisition times. It is shown that the PRF shift method is beneficial for the assessment of temperature at 7 T MRI. The temperature maps for axial and coronal planes display a temperature increase of approximately 3.5 °C during the time of the RF-heating experiment. Overall it is shown that B 0-drift correction and, importantly, the spatio-temporal unwrapping are an indispensable part of post-processing.

Estimation of the Proton Resonance Frequency Coefficient in Agar-based Phantoms.

Agar-based phantoms are popular in high intensity focused ultrasound (HIFU) studies, with magnetic resonance imaging (MRI) preferred for guidance since it provides temperature monitoring by proton resonance frequency (PRF) shift magnetic resonance (MR) thermometry. MR thermometry monitoring depends on several factors, thus, herein, the PRF coefficient of agar phantoms was estimated. Seven phantoms were developed with varied agar (2, 4, or 6% w/v) or constant agar (6% w/v) and varied silica concentrations (2, 4, 6, or 8% w/v) to assess the effect of the concentration on the PRF coefficient. Each phantom was sonicated using varied acoustical power for a 30 s duration in both a laboratory setting and inside a 3T MRI scanner. PRF coefficients were estimated through linear trends between phase shift acquired using gradient sequences and thermocouple-based temperatures changes. Linear regression (R 2 = 0.9707-0.9991) demonstrated a proportional dependency of phase shift with temperature change, resulting in PRF coefficients between -0.00336 ± 0.00029 and -0.00934 ± 0.00050 ppm/°C for the various phantom recipes. Weak negative linear correlations of the PRF coefficient were observed with increased agar. With silica concentrations, the negative linear correlation was strong. For all phantoms, calibrated PRF coefficients resulted in 1.01-3.01-fold higher temperature changes compared to the values calculated using a literature PRF coefficient. Phantoms developed with a 6% w/v agar concentration and doped with 0%-8% w/v silica best resemble tissue PRF coefficients and should be preferred in HIFU studies. The estimated PRF coefficients can result in enhanced MR thermometry monitoring and evaluation of HIFU protocols.

Technical advances in motion-robust MR thermometry.

Proton resonance frequency shift (PRFS) MR thermometry is the most common method used in clinical thermal treatments because of its fast acquisition and high sensitivity to temperature. However, motion is the biggest obstacle in PRFS MR thermometry for monitoring thermal treatment in moving organs. This challenge arises because of the introduction of phase errors into the PRFS calculation through multiple methods, such as image misregistration, susceptibility changes in the magnetic field, and intraframe motion during MRI acquisition. Various approaches for motion correction have been developed for real-time, motion-robust, and volumetric MR thermometry. However, current technologies have inherent trade-offs among volume coverage, processing time, and temperature accuracy. These tradeoffs should be considered and chosen according to the thermal treatment application. In hyperthermia treatment, precise temperature measurements are of increased importance rather than the requirement for exceedingly high temporal resolution. In contrast, ablation procedures require robust temporal resolution to accurately capture a rapid temperature rise. This paper presents a comprehensive review of current cutting-edge MRI techniques for motion-robust MR thermometry, and recommends which techniques are better suited for each thermal treatment. We expect that this study will help discern the selection of motion-robust MR thermometry strategies and inspire the development of motion-robust volumetric MR thermometry for practical use in clinics.

MR Thermometry during Transcranial MR Imaging-Guided Focused Ultrasound Procedures: A Review.

Interest in transcranial MR imaging-guided focused ultrasound procedures has recently grown. These incisionless procedures enable precise focal ablation of brain tissue using real-time monitoring by MR thermometry. This article will provide an updated review on clinically applicable technical underpinnings and considerations of proton resonance frequency MR thermometry, the most common clinically used MR thermometry sequence.

Estimate of fetal brain temperature using proton resonance frequency thermometry during 3 Tesla fetal magnetic resonance imaging.

T2-weighted Single Shot Fast Spin Echo (SSFSE) scans at 3 Tesla (3T) are increasingly used to image fetal pathology due to their excellent tissue contrast resolution and signal-to-noise ratio (SNR). Temperature changes that may occur in response to radio frequency (RF) pulses used for these sequences at 3T have not been studied in human fetal brains. To evaluate the safety of T2-weighted SSFSE for fetal brains at 3T, magnetic resonance (MR) thermometry was used to measure relative temperature changes in a typical clinical fetal brain MR exam. Relative temperature was estimated using sets of gradient recalled echo (GRE) images acquired before and after T2-weighted SSFSE images which lasted 27.47±8.19 minutes. Thirty-one fetuses with cardiac abnormalities, and 20 healthy controls were included in this study. Fetal brain temperature was estimated by proton resonance frequency (PRF) thermometry and compared to the estimated temperature in the gluteal muscle of the mother. Seven scans with excessive motion were excluded. Local outlier factor (LOF) was performed to remove 12 additional scans with spurious phase measurements due to motion degradation and potential field drift. Linear regression was performed to determine if temperature changes are dependent on the rate of energy deposition during the scan. For the 32 participants used in the analysis, 17 with cardiac abnormalities and 15 healthy controls, the average relative fetal temperate change was 0.19±0.73 ℃ higher than the mother, with no correlation between relative temperature change and the rate of images acquired during the scans (regression coefficient =-0.05, R-squared =0.05, P=0.22, F-statistic =1.60). The difference in the relative temperature changes between the fetal brain and mother's gluteal tissue in the healthy controls was on average 0.08 ℃ lower and found not to be statistically different (P=0.76) to the group with cardiac abnormalities. Our results indicate that the estimated relative temperature changes of the fetal brain compared to the mother's gluteal tissue from RF pulses during the course of the T2-weighted SSFSE fetal MR exam are minimal. The differences in acquired phase between these regions through the exam were found not to be statistically different. These findings support that fetal brain imaging at 3T is within FDA limits and safe.

Straightforward Magnetic Resonance Temperature Measurements Combined with High Frame Rate and Magnetic Susceptibility Correction.

Proton resonance frequency shift (PRFS) is an MRI-based simple temperature mapping method that exhibits higher spatial and temporal resolution than temperature mapping methods based on T1 relaxation time and diffusion. PRFS temperature measurements are validated against fiber-optic thermal sensors (FOSs). However, the use of FOSs may introduce temperature errors, leading to both underestimation and overestimation of PRFS measurements, primarily due to material susceptibility changes caused by the thermal sensors. In this study, we demonstrated susceptibility-corrected PRFS (scPRFS) with a high frame rate and accuracy for suitably distributed temperatures. A single-echo-based background removal technique was employed for phase variation correction, primarily owing to magnetic susceptibility, which enabled fast temperature mapping. The scPRFS was used to validate the temperature fidelity by comparing the temperatures of fiber-optic sensors and conventional PRFS through phantom-mimicked human and ex vivo experiments. This study demonstrates that scPRFS measurements in agar-gel are in good agreement with the thermal sensor readings, with a root mean square error (RMSE) of 0.33-0.36 °C in the phantom model and 0.12-0.16 °C in the ex vivo experiment. These results highlight the potential of scPRFS for precise thermal monitoring and ablation in both low- and high-temperature non-invasive therapies.

Optimization of Gradient-Echo Echo-Planar Imaging for T2* Contrast in the Brain at 0.5 T.

Gradient-recalled echo (GRE) echo-planar imaging (EPI) is an efficient MRI pulse sequence that is commonly used for several enticing applications, including functional MRI (fMRI), susceptibility-weighted imaging (SWI), and proton resonance frequency (PRF) thermometry. These applications are typically not performed in the mid-field (<1 T) as longer T2* and lower polarization present significant challenges. However, recent developments of mid-field scanners equipped with high-performance gradient sets offer the possibility to re-evaluate the feasibility of these applications. The paper introduces a metric "T2* contrast efficiency" for this evaluation, which minimizes dead time in the EPI sequence while maximizing T2* contrast so that the temporal and pseudo signal-to-noise ratios (SNRs) can be attained, which could be used to quantify experimental parameters for future fMRI experiments in the mid-field. To guide the optimization, T2* measurements of the cortical gray matter are conducted, focusing on specific regions of interest (ROIs). Temporal and pseudo SNR are calculated with the measured time-series EPI data to observe the echo times at which the maximum T2* contrast efficiency is achieved. T2* for a specific cortical ROI is reported at 0.5 T. The results suggest the optimized echo time for the EPI protocols is shorter than the effective T2* of that region. The effective reduction of dead time prior to the echo train is feasible with an optimized EPI protocol, which will increase the overall scan efficiency for several EPI-based applications at 0.5 T.

Feasibility of cardiac MR thermometry at 0.55 T.

Radiofrequency catheter ablation is an established treatment strategy for ventricular tachycardia, but remains associated with a low success rate. MR guidance of ventricular tachycardia shows promises to improve the success rate of these procedures, especially due to its potential to provide real-time information on lesion formation using cardiac MR thermometry. Modern low field MRI scanners (<1 T) are of major interest for MR-guided ablations as the potential benefits include lower costs, increased patient access and device compatibility through reduced device-induced imaging artefacts and safety constraints. However, the feasibility of cardiac MR thermometry at low field remains unknown. In this study, we demonstrate the feasibility of cardiac MR thermometry at 0.55 T and characterized its in vivo stability (i.e., precision) using state-of-the-art techniques based on the proton resonance frequency shift method. Nine healthy volunteers were scanned using a cardiac MR thermometry protocol based on single-shot EPI imaging (3 slices in the left ventricle, 150 dynamics, TE = 41 ms). The reconstruction pipeline included image registration to align all the images, multi-baseline approach (look-up-table length = 30) to correct for respiration-induced phase variations, and temporal filtering to reduce noise in temperature maps. The stability of thermometry was defined as the pixel-wise standard deviation of temperature changes over time. Cardiac MR thermometry was successfully acquired in all subjects and the stability averaged across all subjects was 1.8 ± 1.0°C. Without multi-baseline correction, the overall stability was 2.8 ± 1.6°C. In conclusion, cardiac MR thermometry is feasible at 0.55 T and further studies on MR-guided catheter ablations at low field are warranted.

Thermal measurements of a muscle-mimicking phantom during ultra-high field magnetic resonance imaging

Abstract At ultra-high field MRI (Bo&gt;7T) it is crucial to predict and control the patient safety. Commonly patient safety is controlled by the power deposited in the tissue (specific absorption rate - SAR). However, temperature distributions do not always correlate directly with SAR distributions, which makes temperature control also a crucial parameter to guarantee patient safety. In this work, temperature changes were accessed by MR thermometry, specifically by the proton resonance frequency shift technique (PRF). A phantom mimicking muscle tissue was used to evaluate the temperature rise caused by the radiofrequency (RF) absorption during 7T MRI, applied through a commercial birdcage head coil. A pulse-sequence protocol was implemented for both, the generation of temperature increase and the MR thermometry. To control the temperature, a digital thermometer was used, and oil tubes were utilized to dismiss the drift effects for PRF. Measurements of the phantom’s dielectric characteristics, i.e. conductivity and permittivity, were in good agreement with the literature values for muscle. Spatio-temporal evaluations showed a temperature increase in time via RF exposure and the feasibility of measuring temperature maps using the PRF shift method. The accuracy of the PRF shift method increased when the drift effects were quantified and dismissed, indicating a PRF reading accuracy differing less than 0.5 °C from the thermometer. Results also validate our heating and temperature imaging protocol. This study is a valuable contribution to the evaluation of heating effects caused by RF absorption and demonstrates potential impact on future thermal investigations, which may use different heating sources, as well validate thermal simulations.

Magnetic resonance fingerprinting based thermometry (MRFT): application toex vivoimaging near DBS leads.

The purpose of this study is to demonstrate the first work ofT1-based magnetic resonance thermometry using magnetic resonance fingerprinting (dubbed MRFT). We compared temperature estimation of MRFT with proton resonance frequency shift (PRFS) thermometry onex vivobovine muscle. We demonstrated MRFT's feasibility in predicting temperature onex vivobovine muscles with deep brain stimulation (DBS) lead.B0maps generated from MRFT were compared with gold standardB0maps near the DBS lead. MRFT and PRFS estimated temperatures were compared in the presence of motion. All experiments were performed on a 3 Tesla whole-body GE Premier system with a 21-channel receive head coil (GE Healthcare, Milwaukee, WI). Four fluoroptic probes were used to measure the temperature at the center of a cold muscle (probe 1), the room temperature water bottle (probe 2), and the center and periphery of the heated muscle (probes 3 and 4). We selected regions of interest (ROIs) around the location of the probes and used simple linear regression to generate the temperature sensitivity calibration equations that convertT1maps and Δsmaps to temperature maps. We then repeated the same setup and compared MRFT and PRFS thermometry temperature estimation with gold standard probe measurements. For the MRFT experiment on DBS lead, we taped the probe to the tip of the DBS lead and used a turbo spin echo sequence to induce heating near the lead. We selected ROIs around the tip of the lead to compare MRFT temperature estimation with probe measurements and compared with PRFS temperature estimation. Vendor-suppliedB0mapping sequence was acquired to compare with MRFT-generatedB0maps. We found strong linear relationships (R2> 0.958) betweenT1and temperature and Δsand temperatures in our temperature sensitivity calibration experiment. MRFT and PRFS thermometry both accurately predict temperature (RMSE < 1.55 °C) compared to probe measurements. MRFT estimated temperature near DBS lead has a similar trend as the probe temperature. BothB0maps show inhomogeneities around the lead. MRFT estimated temperature is less sensitive to motion.

Laser-Ablative Synthesis of Silicon-Iron Composite Nanoparticles for Theranostic Applications.

The combination of photothermal and magnetic functionalities in one biocompatible nanoformulation forms an attractive basis for developing multifunctional agents for biomedical theranostics. Here, we report the fabrication of silicon-iron (Si-Fe) composite nanoparticles (NPs) for theranostic applications by using a method of femtosecond laser ablation in acetone from a mixed target combining silicon and iron. The NPs were then transferred to water for subsequent biological use. From structural analyses, it was shown that the formed Si-Fe NPs have a spherical shape and sizes ranging from 5 to 150 nm, with the presence of two characteristic maxima around 20 nm and 90 nm in the size distribution. They are mostly composed of silicon with the presence of a significant iron silicide content and iron oxide inclusions. Our studies also show that the NPs exhibit magnetic properties due to the presence of iron ions in their composition, which makes the formation of contrast in magnetic resonance imaging (MRI) possible, as it is verified by magnetic resonance relaxometry at the proton resonance frequency. In addition, the Si-Fe NPs are characterized by strong optical absorption in the window of relative transparency of bio-tissue (650-950 nm). Benefiting from such absorption, the Si-Fe NPs provide strong photoheating in their aqueous suspensions under continuous wave laser excitation at 808 nm. The NP-induced photoheating is described by a photothermal conversion efficiency of 33-42%, which is approximately 3.0-3.3 times larger than that for pure laser-synthesized Si NPs, and it is explained by the presence of iron silicide in the NP composition. Combining the strong photothermal effect and MRI functionality, the synthesized Si-Fe NPs promise a major advancement of modalities for cancer theranostics, including MRI-guided photothermal therapy and surgery.

Improved MR temperature imaging at 0.5T using view-sharing accelerated multiecho thermometry for MR-guided laser interstitial thermal therapy.

The aim of the current study was to improve temperature-monitoring precision using multiecho proton resonance frequency shift-based thermometry with view-sharing acceleration for MR-guided laser interstitial thermal therapy (MRgLITT) on a 0.5-T low-field MR system. Both precision and speed of the temperature measurement for clinical MRgLITT treatments suffer at low field, due to reduced image signal-to-noise ratio (SNR), decreased temperature-induced phase changes, and limited RF receiver channels. In this work, a bipolar multiecho gradient-recalled echo sequence with a temperature-to-noise ratio optimal weighted echo combination is applied to improve the temperature precision. A view-sharing-based approach is utilized to accelerate signal acquisitions while preserving image SNRs. The method was evaluated using ex vivo (pork and pig brain) LITT heating experiments and in vivo (human brain) nonheating experiments on a high-performance 0.5-T scanner. In terms of results, (1) after echo combination, multiecho thermometry (i.e., ~7.5-40.5ms, 7 TEs) provides ~1.5-1.9 times higher temperature precision than the no echo combination case (i.e., TE7 = 40.5ms) within the same readout bandwidth. Additionally, echo registration is necessary for the bipolar multiecho sequence; (2) for a threefold acceleration, the view-sharing approach with variable-density subsampling shows around 1.8 times lower temperature errors than the GRAPPA method. Particularly for view-sharing, variable-density subsampling performs better than Interleave subsampling; and (3) ex vivo heating and in vivo nonheating experiments demonstrated that the temperature accuracy was less than 0.5 and that the temperature precision was less than 0.6 using the proposed 0.5-T thermometry. It was concluded that view-sharing accelerated multiecho thermometry is a practical temperature measurement approach for MRgLITT at 0.5T.

Characterization of susceptibility artifacts in magnetic resonance thermometry images during laser interstitial thermal therapy: dimension analysis and temperature error estimation

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

Appearance and modeling of bubble artifacts in intracranial magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) temperature images

PurposeTo understand if unexplained signal artifacts in MRg-LITT proton resonance frequency- (PRF-) shift thermometry images are caused by air bubbles or hemorrhages, and to characterize their effects on temperature measurements. MethodsRetrospective image data from an IRB-approved clinical trial of intracranial MRg-LITT were inspected for asymmetric distortions observed in phase data during ablations, which have been previously reported as likely hemorrhages. A total of eight patient cases were selected: seven with artifact occurrence and one without. Mathematical image models for air bubbles or hemorrhages were implemented to estimate the size of the air bubble or hemorrhage needed to explain the clinically observed phase artifacts. Correlations and Bland-Altman analyses were used to determine if an air bubble model or a hemorrhage model was better correlated to the clinical data. The model was used to inject bubbles into clean PRF phase data without artifacts to examine how temperature profile distortions change with slice orientation. The simulated air-bubble injected data were compared to clinical data containing artifacts to examine the bubbles' effects on temperature and thermal damage estimates. ResultsThe model demonstrated that air bubbles up to approximately 1 cm in diameter could explain the clinically observed phase artifacts. The bubble model predicts that a hemorrhage would have to be 2.2 times as large as an air bubble in order to explain the same extent of phase distortion observed in clinical data. Air bubbles had 16% percent higher correlations to the clinical PRF phase data than hemorrhages, even after rescaling the hemorrhage phases to better match the data. The air bubble model also explains how the phase artifacts lead to both large positive and large negative temperature errors, up to ±100 °C, which could cascade to damage estimate errors of several millimeters. ConclusionResults showed that the artifacts are likely caused by air bubbles rather than hemorrhages, which may be introduced before heating or appear during heating. Manufacturers and users of devices that rely upon PRF-shift thermometry should be aware these phase distortions from bubble artifacts can result in large temperature errors.

MR thermometry imaging for low intensity focused ultrasound modulation of spinal nervous tissue

ObjectivesPreviously in rodent and swine models, we have shown that external low intensity focused ultrasound (liFUS) can be used to modulate pain responses. To ensure no adverse heating events occur with liFUS modulation in a non-invasive manner, we perform initial work in swine to show that magnetic resonance thermometry imaging (MRTI) is capable of measuring <2.0 °C changes at the L5 DRG. Further, we show that our device can be constructed in an MR-compatible fashion to minimize artifact. MethodsThree MRTI techniques (referenceless, corrected proton resonance frequency shift (PRFS), and PRFS) were applied to assess accuracy of detecting thermal changes at the L5 DRG in unheated euthanized swine. A region of interest (ROI) that includes the L5 DRG was delineated, within which MRTI temperature changes were spatially averaged (ground truth 0 °C). In separate experiments with phantoms, B0 field-inhomogeneity, RF transmit (B1+) and fast gradient echo (fSPGR) magnitude images were acquired to downselect liFUS device materials that produce the least MRI artifacts. ResultsReferenceless, corrected PRFS, and PRFS MRTI resulted in temperature measurements of 0.8 ± 1.1 °C, 1.1 ± 1.3 °C and 5.2 ± 5 °C, respectively. Both materials caused B0 perturbation but minimal B1+ and MRTI artifacts. The presence of imaging artifacts did not preclude thermal imaging of the region. SignificanceWe provide preliminary data suggesting that referenceless MRTI can adequately detect small thermal changes at the DRG that may occur with neuromodulation, which is one of the first steps in creating a table of safe parameters for liFUS therapy in humans.

Real-time automatic temperature regulation during in vivo MRI-guided laser-induced thermotherapy (MR-LITT)

Precise control of tissue temperature during Laser-Induced Thermotherapy (LITT) procedures has the potential to improve the clinical efficiency and safety of such minimally invasive therapies. We present a method to automatically regulate in vivo the temperature increase during LITT using real-time rapid volumetric Magnetic Resonance thermometry (8 slices acquired every second, with an in-plane resolution of 1.4 mmx1.4 mm and a slice thickness of 3 mm) using the proton-resonance frequency (PRF) shift technique. The laser output power is adjusted every second using a feedback control algorithm (proportional-integral-derivative controller) to force maximal tissue temperature in the targeted region to follow a predefined temperature–time profile. The root-mean-square of the difference between the target temperature and the measured temperature ranged between 0.5 °C and 1.4 °C, for temperature increases between + 5 °C to + 30 °C above body temperature and a long heating duration (up to 15 min), showing excellent accuracy and stability of the method. These results were obtained on a 1.5 T clinical MRI scanner, showing a potential immediate clinical application of such a temperature controller during MR-guided LITT.

Evaluation of a Developed MRI-Guided Focused Ultrasound System in 7 T Small Animal MRI and Proof-of-Concept in a Prostate Cancer Xenograft Model to Improve Radiation Therapy.

Focused ultrasound (FUS) can be used to physiologically change or destroy tissue in a non-invasive way. A few commercial systems have clinical approval for the thermal ablation of solid tumors for the treatment of neurological diseases and palliative pain management of bone metastases. However, the thermal effects of FUS are known to lead to various biological effects, such as inhibition of repair of DNA damage, reduction in tumor hypoxia, and induction of apoptosis. Here, we studied radiosensitization as a combination therapy of FUS and RT in a xenograft mouse model using newly developed MRI-compatible FUS equipment. Xenograft tumor-bearing mice were produced by subcutaneous injection of the human prostate cancer cell line PC-3. Animals were treated with FUS in 7 T MRI at 4.8 W/cm2 to reach ~45 °C and held for 30 min. The temperature was controlled via fiber optics and proton resonance frequency shift (PRF) MR thermometry in parallel. In the combination group, animals were treated with FUS followed by X-ray at a single dose of 10 Gy. The effects of FUS and RT were assessed via hematoxylin-eosin (H&E) staining. Tumor proliferation was detected by the immunohistochemistry of Ki67 and apoptosis was measured by a TUNEL assay. At 40 days follow-up, the impact of RT on cancer cells was significantly improved by FUS as demonstrated by a reduction in cell nucleoli from 189 to 237 compared to RT alone. Inhibition of tumor growth by 4.6 times was observed in vivo in the FUS + RT group (85.3%) in contrast to the tumor volume of 393% in the untreated control. Our results demonstrated the feasibility of combined MRI-guided FUS and RT for the treatment of prostate cancer in a xenograft mouse model and may provide a chance for less invasive cancer therapy through radiosensitization.

Monitoring MR-guided high intensity focused ultrasound therapy using transient supersonic shear wave MR-elastography

Objective. The aim of the paper is to propose an all-in-one method based on magnetic resonance-supersonic shear wave imaging (MR-SSI) and proton resonance frequency shift (PRFS) to monitor high intensity focused ultrasound (HIFU) thermal ablations. Approach. Mechanical properties have been shown to be related to tissue damage induced by thermal ablations. Monitoring elasticity in addition to temperature changes may help in ensuring the efficacy and the accuracy of HIFU therapies. For this purpose, an MR-SSI method has been developed where the ultrasonic transducer is used for both mechanical wave generation and thermal ablation. Transient quasi-planar shear waves are generated using the acoustic radiation force, and their propagation is monitored in motion-sensitized phase MR images. Using a single-shot gradient-echo echo-planar-imaging sequence, MR images can be acquired at a sufficiently high temporal resolution to provide an update of PRFS thermometry and MR-SSI elastography maps in real time. Main results. The proposed method was first validated on a calibrated elasticity phantom, in which both the possibility to detect inclusions with different stiffness and repeatability were demonstrated. The standard deviation between the 8 performed measurements was 2% on the background of the phantom and 11%, at most, on the inclusions. A second experiment consisted in performing a HIFU heating in a gelatin phantom. The temperature increase was estimated to be 9 °C and the shear modulus was found to decrease from 2.9 to 1.8 kPa, reflecting the gel softening around the HIFU focus, whereas it remained steady in non-heated areas. Significance. The proposed MR-SSI technique allows monitoring HIFU ablations using thermometry and elastography simultaneously, without the need for an additional external mechanical exciter such as those used in MR elastography.

Simultaneous proton resonance frequency T1 - MR shear wave elastography for MR-guided focused ultrasound multiparametric treatment monitoring.

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