In situ theranostic platform combining highly localized magnetic fluid hyperthermia, magnetic particle imaging, and thermometry in 3D.

Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.

An augmented hybrid multibaseline and referenceless MR thermometry motion compensation algorithm for MRgHIFU hyperthermia.

PURPOSE: A hybrid principal component analysis and projection onto dipole fields (PCA-PDF) MR thermometry motion compensation algorithm was optimized with atlas image augmentation and validated. METHODS: Experiments were conducted on a 3T Philips MRI and Profound V1 Sonalleve high intensity focused ultrasound (high intensity focused ultrasound system. An MR-compatible robot was configured to induce motion on custom gelatin phantoms. Trials with periodic and sporadic motion were introduced on phantoms while hyperthermia was administered. The PCA-PDF algorithm was augmented with a predictive atlas to better compensate for larger sporadic motion. RESULTS: During periodic motion, the temperature SD in the thermometry was improved from 1 . 1 ± 0 . 1 $$ 1.1\pm 0.1 $$ to 0 . 5 ± 0 . 1 ∘ $$ 0.5\pm 0.{1}^{\circ } $$ C with both the original and augmented PCA-PDF application. For large sporadic motion, the augmented atlas improved the motion compensation from the original PCA-PDF correction from 8 . 8 ± 0 . 5 $$ 8.8\pm 0.5 $$ to 0 . 7 ± 0 . 1 ∘ $$ 0.7\pm 0.{1}^{\circ } $$ C. CONCLUSION: The PCA-PDF algorithm improved temperature accuracy to <1°C during periodic motion, but was not able to adequately address sporadic motion. By augmenting the PCA-PDF algorithm, temperature SD during large sporadic motion was also reduced to <1°C, greatly improving the original PCA-PDF algorithm.

Dense speed-of-sound shift imaging for ultrasonic thermometry.

Objective. Develop a dense algorithm for calculating the speed-of-sound shift between consecutive acoustic acquisitions as a noninvasive means to evaluating temperature change during thermal ablation.Methods. An algorithm for dense speed-of-sound shift imaging (DSI) was developed to simultaneously incorporate information from the entire field of view using a combination of dense optical flow and inverse problem regularization, thus speeding up the calculation and introducing spatial agreement between pixels natively. Thermal ablation monitoring consisted of two main steps: pixel shift tracking using Farneback optical flow, and mathematical modeling of the relationship between the pixel displacement and temperature change as an inverse problem to find the speed-of-sound shift. A calibration constant translates from speed-of-sound shift to temperature change. The method performance was tested inex vivosamples and compared to standard thermal strain imaging (TSI) methods.Main results. Thermal ablation at a frequency of 2 MHz was applied to an agarose phantom that created a speed-of-sound shift measured by an L12-5 imaging transducer. A focal spot was reconstructed by solving the inverse problem. Next, a thermocouple measured the temperature rise during thermal ablation ofex vivochicken breast to calibrate the setup. Temperature changes between 3 °C and 15 °C was measured with high thermometry precision of less than 2 °C error for temperature changes as low as 8 °C. The DSI method outperformed standard TSI in both spatial coherence and runtime in high-intensity focused ultrasound-induced hyperthermia.Significance. Dense ultrasonic speed-of-sound shift imaging can successfully monitor the speed-of-sound shift introduced by thermal ablation. This technique is faster and more robust than current methods, and therefore can be used as a noninvasive, real time and cost-effective thermometry method, with high clinical applicability.

Exploring the intra-4f and the bright white light upconversion emissions of Gd2O3:Yb3+,Er3+-based materials for thermometry.

Upconversion broadband white light emission driven by low-power near-infrared (NIR) lasers has been reported for many materials, but the mechanisms and effects related to this phenomenon remain unclear. Herein, we investigate the origin of laser-induced continuous white light emission in synthesized nanoparticles (Gd0.89Yb0.10Er0.01)2O3 and a mechanical mixture of commercial oxides with the same composition 89% Gd2O3, 10% Yb2O3, and 1% Er2O3. We report their photophysical features with respect to sample compactness, laser irradiation (wavelength, power density, excitation cycles), pressure, temperature, and temporal dynamics. Despite the sensitizer (Yb3+) and activator (Er3+) being in different particles for the mechanical mixture, efficient discrete and continuous upconversion emissions were observed. Furthermore, the synthesized nanoparticles were developed as primary luminescent thermometers (upon excitation at NIR) in the 299-363 K range, using the Er3+ upconversion 2H11/2 → 4I15/2/4S3/2 → 4I15/2 intensity ratio. They were also operating as secondary ones in the 1949-3086 K, based on the blackbody distribution of the observed white light emission. Our findings provide important insights into the mechanisms and effects related to the transition from discrete to continuous upconversion emissions with potential applications in remote temperature sensing.

3D motion strategy for online volumetric thermometry using simultaneous multi-slice EPI at 1.5T: an evaluation study.

PURPOSE: In presence of respiratory motion, temperature mapping is altered by in-plane and through-plane displacements between successive acquisitions together with periodic phase variations. Fast 2D Echo Planar Imaging (EPI) sequence can accommodate intra-scan motion, but limited volume coverage and inter-scan motion remain a challenge during free-breathing acquisition since position offsets can arise between the different slices. METHOD: To address this limitation, we evaluated a 2D simultaneous multi-slice EPI sequence with multiband (MB) acceleration during radiofrequency ablation on a mobile gel and in the liver of a volunteer (no heating). The sequence was evaluated in terms of resulting inter-scan motion, temperature uncertainty and elevation, potential false-positive heating and repeatability. Lastly, to account for potential through-plane motion, a 3D motion compensation pipeline was implemented and evaluated. RESULTS: In-plane motion was compensated whatever the MB factor and temperature distribution was found in agreement during both the heating and cooling periods. No obvious false-positive temperature was observed under the conditions being investigated. Repeatability of measurements results in a 95% uncertainty below 2 °C for MB1 and MB2. Uncertainty up to 4.5 °C was reported with MB3 together with the presence of aliasing artifacts. Lastly, fast simultaneous multi-slice EPI combined with 3D motion compensation reduce residual out-of-plane motion. CONCLUSION: Volumetric temperature imaging (12 slices/700 ms) could be performed with 2 °C accuracy or less, and offer tradeoffs in acquisition time or volume coverage. Such a strategy is expected to increase procedure safety by monitoring large volumes more rapidly for MR-guided thermotherapy on mobile organs.

Multi-echo gradient echo pulse sequences: which is best for PRFS MR thermometry guided hyperthermia?

PURPOSE: MR thermometry (MRT) enables noninvasive temperature monitoring during hyperthermia treatments. MRT is already clinically applied for hyperthermia treatments in the abdomen and extremities, and devices for the head are under development. In order to optimally exploit MRT in all anatomical regions, the best sequence setup and post-processing must be selected, and the accuracy needs to be demonstrated. METHODS: MRT performance of the traditionally used double-echo gradient-echo sequence (DE-GRE, 2 echoes, 2D) was compared to multi-echo sequences: a 2D fast gradient-echo (ME-FGRE, 11 echoes) and a 3D fast gradient-echo sequence (3D-ME-FGRE, 11 echoes). The different methods were assessed on a 1.5 T MR scanner (GE Healthcare) using a phantom cooling down from 59 °C to 34 °C and unheated brains of 10 volunteers. In-plane motion of volunteers was compensated by rigid body image registration. For the ME sequences, the off-resonance frequency was calculated using a multi-peak fitting tool. To correct for B0 drift, the internal body fat was selected automatically using water/fat density maps. RESULTS: The accuracy of the best performing 3D-ME-FGRE sequence was 0.20 °C in phantom (in the clinical temperature range) and 0.75 °C in volunteers, compared to DE-GRE values of 0.37 °C and 1.96 °C, respectively. CONCLUSION: For hyperthermia applications, where accuracy is more important than resolution or scan-time, the 3D-ME-FGRE sequence is deemed the most promising candidate. Beyond its convincing MRT performance, the ME nature enables automatic selection of internal body fat for B0 drift correction, an important feature for clinical application.

Expansion of thermometry in magnetic hyperthermia cancer therapy: antecedence and aftermath.

Magnetic hyperthermia cancer therapy (MHCT) is a promising antitumor therapy based on the generation of heat by magnetic nanoparticles under the influence of an alternating-current magnetic field. However, an often-overlooked factor hindering the translation of MHCT to clinics is the inability to accurately monitor temperature, thereby leading to erroneous thermal control. It is significant to address 'thermometry' during magnetic hyperthermia because numerous factors are affected by the magnetic fields employed, rendering traditional thermometry methods unsuitable for temperature estimation. Currently, there is a dearth of literature describing appropriate techniques for thermometry during MHCT. This review offers a general outline of the various modes of conventional thermometry as well as cutting-edge techniques operating at cellular/nanoscale levels (nanothermometry) as prospective thermometers for MHCT in the future.

Validating a simulation model for laser-induced thermotherapy using MR thermometry.

OBJECTIVES: We want to investigate whether temperature measurements obtained from MR thermometry are accurate and reliable enough to aid the development and validation of simulation models for Laser-induced interstitial thermotherapy (LITT). METHODS: Laser-induced interstitial thermotherapy (LITT) is applied to ex-vivo porcine livers. An artificial blood vessel is used to study the cooling effect of large blood vessels in proximity to the ablation zone. The experimental setting is simulated using a model based on partial differential equations (PDEs) for temperature, radiation, and tissue damage. The simulated temperature distributions are compared to temperature data obtained from MR thermometry. RESULTS: The overall agreement between measurement and simulation is good for two of our four test cases, while for the remaining cases drift problems with the thermometry data have been an issue. At higher temperatures local deviations between simulation and measurement occur in close proximity to the laser applicator and the vessel. This suggests that certain aspects of the model may need some refinement. CONCLUSION: Thermometry data is well-suited for aiding the development of simulations models since it shows where refinements are necessary and enables the validation of such models.

Thermal Probing Techniques for a Single Live Cell.

Temperature is a significant factor in determining and characterizing cellular metabolism and other biochemical activities. In this study, we provide a brief overview of two important technologies used to monitor the local temperatures of individual living cells: fluorescence nano-thermometry and an array of micro-/nano-sized thin-film thermocouples. We explain some key technical issues that must be addressed and optimised for further practical applications, such as in cell biology, drug selection, and novel antitumor therapy. We also offer a method for combining them into a hybrid measuring system.

Integrated thermal and magnetic susceptibility modeling for air-motion artifact correction in proton resonance frequency shift thermometry.

PURPOSE: Hyperthermia treatments are successful adjuvants to conventional cancer therapies in which the tumor is sensitized by heating. To monitor and guide the hyperthermia treatment, measuring the tumor and healthy tissue temperature is important. The typical clinical practice heavily relies on intraluminal probe measurements that are uncomfortable for the patient and only provide spatially sparse temperature information. A solution may be offered through recent advances in magnetic resonance thermometry, which allows for three-dimensional internal temperature measurements. However, these measurements are not widely used in the pelvic region due to a low signal-to-noise ratio and presence of image artifacts. METHODS: To advance the clinical integration of magnetic resonance-guided cancer treatments, we consider the problem of removing air-motion-induced image artifacts. Thereto, we propose a new combined thermal and magnetic susceptibility model-based temperature estimation scheme that uses temperature estimates to improve the removal of air-motion-induced image artifacts. The method is experimentally validated using a dedicated phantom that enables the controlled injection of air-motion artifacts and with in vivo thermometry from a clinical hyperthermia treatment. RESULTS: We showed, using probe measurements in a heated phantom, that our method reduced the mean absolute error (MAE) by 58% compared to the state-of-the-art near a moving air volume. Moreover, with in vivo thermometry our method obtained a MAE reduction between 17% and 95% compared to the state-of-the-art. CONCLUSION: We expect that the combined thermal and magnetic susceptibility modeling used in model-based temperature estimation can significantly improve the monitoring in hyperthermia treatments and enable feedback strategies to further improve MR-guided hyperthermia cancer treatments.

POD-Kalman filtering for improving noninvasive 3D temperature monitoring in MR-guided hyperthermia.

BACKGROUND: During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39-44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model-based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage. PURPOSE: This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements. METHODS: The performance of POD-Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD-Kalman filtering could compensate for missing and unreliable MR thermometry measurements. RESULTS: First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that the combined method improved the match between temperature prediction and temperature acquired by intraluminal thermometry for patients treated for locally advanced cervical cancer. Considering all patients, the POD-Kalman filter improved MAE by 43% (filtered MR thermometry = 1.29°C, POD-Kalman filtered temperature = 0.74°C). Moreover, the SDE was improved by 47% (filtered MR thermometry = 1.16°C, POD-Kalman filtered temperature = 0.61°C). Specifically, the POD-Kalman filter reduced the MAE by approximately 60% in patients whose MR thermometry was unreliable because of the great amount of susceptibilities caused by the high level of intestinal gas motion. CONCLUSIONS: We showed that the POD-Kalman filter significantly improved the accuracy of temperature monitoring compared to MR thermometry in heating experiments and hyperthermia treatments. The results demonstrated that POD-Kalman filtering can improve thermal dosimetry during RF hyperthermia treatment, especially when MR thermometry is inaccurate.

Susceptibility artifact correction in MR thermometry for monitoring of mild radiofrequency hyperthermia using total field inversion.

PURPOSE: MR temperature monitoring of mild radiofrequency hyperthermia (RF-HT) of cancer exploits the linear resonance frequency shift of water with temperature. Motion-induced susceptibility distribution changes cause artifacts that we correct here using the total field inversion (TFI) approach. METHODS: The performance of TFI was compared to two background field removal (BFR) methods: Laplacian boundary value (LBV) and projection onto dipole fields (PDF). Data sets with spatial susceptibility change and B0 -drift were simulated, phantom heating experiments were performed, four volunteer data sets at thermoneutral conditions as well as data from one cervical cancer, two sarcoma, and one seroma patients undergoing mild RF-HT were corrected using the proposed methods. RESULTS: Simulations and phantom heating experiments revealed that using BFR or TFI preserves temperature-induced phase change, while removing susceptibility artifacts and B0 -drift. TFI resulted in the least cumulative error for all four volunteers. Temperature probe information from four patient data sets were best depicted by TFI-corrected data in terms of accuracy and precision. TFI also performed best in case of the sarcoma treatment without temperature probe. CONCLUSION: TFI outperforms previously suggested BFR methods in terms of accuracy and robustness. While PDF consistently overestimates susceptibility contribution, and LBV removes valuable pixel information, TFI is more robust and leads to more accurate temperature estimations.

Non-Invasive Microwave Hyperthermia and Simultaneous Temperature Monitoring with a Single Theranostic Applicator.

Cancer therapies are constantly evolving. Currently, heating tumor tissue is becoming more accessible as a stand-alone method or in combination with other therapies. Due to its multiple advantages over other heating mechanisms, microwave hyperthermia has recently gained a lot of traction. In this work, we present a complementary split-ring resonator that is simultaneously excited in two independent frequency bands. With a high-power signal, the applicator is excited and heats the tissue-under-test up to 50°C with an average heating rate of 0.72°C per second. Furthermore, we present a dielectric temperature control system using the same applicator for microwave hyperthermia applications, which currently still requires an additional thermometry system. By exciting the applicator with a low-power signal, we can constantly monitor its resonant frequency. This resonant frequency depends on the tissue properties, which in turn are temperature-dependent. In the temperature range from 20-50°C, a positive correlation between the temperature and resonant frequency was established.Clinical relevance - Exploiting the dual-band behavior of the complementary split-ring resonator to heat the tissue-under-test while dielectrically monitoring its temperature, creates new possibilities towards a theranostic, non-invasive microwave hyperthermia applicator.

Reaching Deeper: Absolute In Vivo Thermal Reading of Liver by Combining Superbright Ag2S Nanothermometers and In Silico Simulations.

Luminescent nano-thermometry is a fast-developing technique with great potential for in vivo sensing, diagnosis, and therapy. Unfortunately, it presents serious limitations. The luminescence generated by nanothermometers, from which thermal readout is obtained, is strongly distorted by the attenuation induced by tissues. Such distortions lead to low signal levels and entangle absolute and reliable thermal monitoring of internal organs. Overcoming both limitations requires the use of high-brightness luminescent nanothermometers and adopting more complex approaches for temperature estimation. In this work, it is demonstrated how superbright Ag2S nanothermometers can provide in vivo, reliable, and absolute thermal reading of the liver during laser-induced hyperthermia. For that, a new procedure is designed in which thermal readout is obtained from the combination of in vivo transient thermometry measurements and in silico simulations. The synergy between in vivo and in silico measurements has made it possible to assess relevant numbers such as the efficiency of hyperthermia processes, the total heat energy deposited in the liver, and the relative contribution of Ag2S nanoparticles to liver heating. This work provides a new way for absolute thermal sensing of internal organs with potential application not only to hyperthermia processes but also to advanced diagnosis and therapy.

Dual-Function MR-Guided Hyperthermia: An Innovative Integrated Approach and Experimental Demonstration of Proof of Principle.

Temperature monitoring plays a central role in improving clinical effectiveness of adjuvant hyperthermia. The potential of magnetic resonance thermometry for treatment monitoring purposes led to several MR-guided hyperthermia approaches. However, the proposed solutions were sub-optimal due to technological and intrinsic limitations. These hamper achieving target conformal heating possibilities (applicator limitations) and accurate thermometry (inadequate signal-to-noise-ratio (SNR)). In this work, we studied proof of principle of a dual-function hyperthermia approach based on a coil array (64 MHz, 1.5 T) that is integrated in-between a phased array for heating (434 MHz) for maximum signal receive in order to improve thermometry accuracy. Hereto, we designed and fabricated a superficial hyperthermia mimicking planar array setup to study the most challenging interactions of generic phased-array setups in order to validate the integrated approach. Experiments demonstrated that the setup complies with the superficial hyperthermia guidelines for heating and is able to improve SNR at 2-4 cm depth by 17%, as compared to imaging using the body coil. Hence, the results showed the feasibility of our dual-function MR-guided hyperthermia approach as basis for the development of application specific setups.

Real-Time Control of Nanoparticle-Mediated Thermal Therapy Using Photoacoustic Imaging.

OBJECTIVE: This work aims to determine whether photoacoustic (PA) thermometry from a commercially available PA imaging system can be used to control the temperature in nanoparticle-mediated thermal therapies. METHODS: The PA imaging system was interfaced to obtain PA images while scanning ex-vivo tissue. These images were then used to obtain temperature maps in real-time during heating. Validation and calibration of the PA thermometry were done using a fluoroptic thermometer. This thermometer was also used to develop and tune a software-based proportional integral derivative (PID) controller. Finally, a PA-based PID closed-loop controller was used to control gold nanorod (GNR) mediated laser therapy. RESULTS: The use of GNRs substantially enhanced laser heating; the temperature rise increased 7-fold by injecting a GNR solution with a concentration of 0.029 mg/mL. The control experiments showed that the desired temperature could be achieved and maintained at a targeted location in the ex-vivo tissue. The steady-state mean absolute deviations (MAD) from the targeted temperature during control were between 0.16 [Formula: see text] and 0.5 [Formula: see text], depending on the experiment. CONCLUSION: It was possible to control hyperthermia treatments using a software-based PID controller and a commercial PA imaging system. SIGNIFICANCE: The monitoring and control of the temperature in thermal-based therapies are important for assuring a prescribed temperature to the target tissue while minimizing the temperature of the surrounding healthy tissue. This easily implemented non-invasive control system will facilitate the realization of a broad range of hyperthermia treatments.

Fiber Bragg Grating Sensors for Performance Evaluation of Fast Magnetic Resonance Thermometry on Synthetic Phantom.

The increasing recognition of minimally invasive thermal treatment of tumors motivate the development of accurate thermometry approaches for guaranteeing the therapeutic efficacy and safety. Magnetic Resonance Thermometry Imaging (MRTI) is nowadays considered the gold-standard in thermometry for tumor thermal therapy, and assessment of its performances is required for clinical applications. This study evaluates the accuracy of fast MRTI on a synthetic phantom, using dense ultra-short Fiber Bragg Grating (FBG) array, as a reference. Fast MRTI is achieved with a multi-slice gradient-echo echo-planar imaging (GRE-EPI) sequence, allowing monitoring the temperature increase induced with a 980 nm laser source. The temperature distributions measured with 1 mm-spatial resolution with both FBGs and MRTI were compared. The root mean squared error (RMSE) value obtained by comparing temperature profiles showed a maximum error of 1.2 °C. The Bland-Altman analysis revealed a mean of difference of 0.1 °C and limits of agreement 1.5/-1.3 °C. FBG sensors allowed to extensively assess the performances of the GRE-EPI sequence, in addition to the information on the MRTI precision estimated by considering the signal-to-noise ratio of the images (0.4 °C). Overall, the results obtained for the GRE-EPI fully satisfy the accuracy (~2 °C) required for proper temperature monitoring during thermal therapies.

Recent technological advancements in thermometry.

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

Temperature estimation for MR-guided microwave hyperthermia using block-based compressed sensing.

Mild hyperthermia has been clinically employed as an adjuvant for radiation/chemotherapy and is under investigation for precise thermally-mediated delivery of cancer therapeutic agents. Magnetic Resonance Imaging (MRI) facilitates non-invasive, real-time spatial thermometry for monitoring and guiding hyperthermia procedures. Long image acquisition time during MR-guided hyperthermia may fail to capture rapid changes in temperature. This may lead to unwanted heating of healthy tissue and/or temperature rise above hyperthermic range. We have developed a block-based compressed sensing approach to reconstruct volumetric MR-derived microwave hyperthermia temperature profiles using a subset of measured data. This algorithm exploits the sparsity of MR images due to the presence of inter- and intra-slice correlation of hyperthermic MR-derived temperature profiles. We have evaluated the performance of our developed algorithm on a phantom and in vivo in mice using previously implemented microwave applicators. This algorithm reconstructs 3D temperature profiles with PSNR of 33 dB - 49 dB in comparison to the original profiles. In summary, this study suggests that microwave hyperthermia induced temperature profiles can be reconstructed using subsamples to reduce MR image acquisition time.

Simulation-based design and characterization of a microwave applicator for MR-guided hyperthermia experimental studies in small animals.

Purpose: The objective of this study was to design and characterize a 2.45 GHz microwave hyperthermia applicator for delivering hyperthermia in experimental small animals to 2 - 4 mm diameter targets located 1 - 3 mm from the skin surface, with minimal heating of the surrounding tissue, under 14.1 T MRI real-time monitoring and feedback control. Materials and methods: An experimentally validated 3D computational model was employed to design and characterize a non-invasive directional water-cooled microwave hyperthermia applicator. We assessed the effects of: reflector geometry, monopole shape, cooling water temperature, and flow rate on spatial-temperature profiles. The system was integrated with real-time MR thermometry and feedback control to monitor and maintain temperature elevations in the range of 4 - 5 °C at 1 - 3 mm from the applicator surface. The quality of heating was quantified by determining the fraction of the target volume heated to the desired temperature, and the extent of heating in non-targeted regions. Results: Model-predicted hyperthermic profiles were in good agreement with experimental measurements (Dice Similarity Coefficient of 0.95 - 0.99). Among the four considered criteria, a reflector aperture angle of 120 °, S-shaped monopole antenna with 0.6 mm displacement, and coolant flow rate of 150 ml/min were selected as the end result of the applicator design. The temperature of circulating water and input power were identified as free variables, allowing considerable flexibility in heating target sizes within varying distances from the applicator surface. 2 - 4 mm diameter targets positioned 1 - 3 mm from the applicator surface were heated to hyperthermic temperatures, with target coverage ratio ranging between 76 - 93 % and 11 - 26 % of non-targeted tissue heated. Conclusion: We have designed an experimental platform for MR-guided hyperthermia, incorporating a microwave applicator integrated with temperature-based feedback control to heat deep-seated targets for experimental studies in small animals.