Systematic review of pre-clinical and clinical devices for magnetic resonance-guided radiofrequency hyperthermia

Clinical trials have demonstrated the therapeutic benefits of adding radiofrequency (RF) hyperthermia (HT) as an adjuvant to radio- and chemotherapy. However, maximum utilization of these benefits is hampered by the current inability to maintain the temperature within the desired range. RF HT treatment quality is usually monitored by invasive temperature sensors, which provide limited data sampling and are prone to infection risks. Magnetic resonance (MR) temperature imaging has been developed to overcome these hurdles by allowing noninvasive 3D temperature monitoring in the target and normal tissues. To exploit this feature, several approaches for inserting the RF heating devices into the MR scanner have been proposed over the years. In this review, we summarize the status quo in MR-guided RF HT devices and analyze trends in these hybrid hardware configurations. In addition, we discuss the various approaches, extract best practices and identify gaps regarding the experimental validation procedures for MR - RF HT, aimed at converging to a common standard in this process

Interaction between Purkinje Cells and Inhibitory Interneurons May Create Adjustable Output Waveforms to Generate Timed Cerebellar Output

We develop a new model that explains how the cerebellum may generate the timing in classical delay eyeblink conditioning. Recent studies show that both Purkinje cells (PCs) and inhibitory interneurons (INs) have parallel signal processing streams with two time scales: an AMPA receptor-mediated fast process and a metabotropic glutamate receptor (mGluR)-mediated slow process. Moreover, one consistent finding is an increased excitability of PC dendrites (in Larsell's lobule HVI) in animals when they acquire the classical delay eyeblink conditioning naturally, in contrast to in vitro studies, where learning involves long-term depression (LTD). Our model proposes that the delayed response comes from the slow dynamics of mGluR-mediated IP3 activation, and the ensuing calcium concentration change, and not from LTP/LTD. The conditioned stimulus (tone), arriving on the parallel fibers, triggers this slow activation in INs and PC spines. These excitatory (from PC spines) and inhibitory (from INs) signals then interact at the PC dendrites to generate variable waveforms of PC activation. When the unconditioned stimulus (puff), arriving on the climbing fibers, is coupled frequently with this slow activation the waveform is amplified (due to an increased excitability) and leads to a timed pause in the PC population. The disinhibition of deep cerebellar nuclei by this timed pause causes the delayed conditioned response. This suggested PC-IN interaction emphasizes a richer role of the INs in learning and also conforms to the recent evidence that mGluR in the cerebellar cortex may participate in slow motor execution. We show that the suggested mechanism can endow the cerebellar cortex with the versatility to learn almost any temporal pattern, in addition to those that arise in classical conditioning

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

The shape of kernel density estimates in higher dimensions

\u3cp\u3eClinical studies have established a strong benefit from adjuvant mild hyperthermia to radio- and chemotherapy for many tumor sites, including the head and neck. The recently developed HYPERcollar allows applying local radiofrequency hyperthermia to tumors in the entire head and neck. Treatment quality is optimized using a combination of electromagnetic and temperature simulators and assessed using invasively placed thermometers. To replace the current invasive thermometry, we are investigating if magnetic resonance (MR) measurements can be exploited for continuous and 3D thermal dose assessment during treatment. In this study, we designed an MR compatible laboratory prototype applicator. We showed that the laboratory prototype applicator, based on re-designed patch antennas, enables MR guided focused heating and allows effective mitigating of image distortion. Hence, we conclude that hybrid MR-hyperthermia treatment in the head and neck region is feasible. The novel hybrid laboratory prototype further allows thorough investigation of patient and systems induced imaging distortions in preparation of the design of a clinical applicator.\u3c/p\u3

Advances in magnetic resonance guided radiofrequency hyperthermia

\u3cp\u3eClinical studies have established that adjuvant mild hyperthermia significantly increases the efficacy of radio-and chemotherapy across many tumor sites. Radiofrequency hyperthermia treatment quality is usually monitored with invasive temperature sensors, which provides limited data sampling and causes infection risks. To mitigate these issues, magnetic resonance (MR) measurements can be exploited for 3D thermal dose assessment during treatment. To this end, a number of novel hardware approaches have been proposed to combine RF heating and imaging more effectively. In this work, we review the status of MR guided radiofrequency hyperthermia, including the electromagnetic inter-systems interactions. We review the various purposes of MR imaging in radiofrequency hyperthermia, and describe different hybrid hardware configurations before closing with suggested technology improvements that could accelerate clinical adoption of this technology.\u3c/p\u3

Systematic review of pre-clinical and clinical devices for magnetic resonance-guided radiofrequency hyperthermia

\u3cp\u3eClinical trials have demonstrated the therapeutic benefits of adding radiofrequency (RF) hyperthermia (HT) as an adjuvant to radio- and chemotherapy. However, maximum utilization of these benefits is hampered by the current inability to maintain the temperature within the desired range. RF HT treatment quality is usually monitored by invasive temperature sensors, which provide limited data sampling and are prone to infection risks. Magnetic resonance (MR) temperature imaging has been developed to overcome these hurdles by allowing noninvasive 3D temperature monitoring in the target and normal tissues. To exploit this feature, several approaches for inserting the RF heating devices into the MR scanner have been proposed over the years. In this review, we summarize the status quo in MR-guided RF HT devices and analyze trends in these hybrid hardware configurations. In addition, we discuss the various approaches, extract best practices and identify gaps regarding the experimental validation procedures for MR - RF HT, aimed at converging to a common standard in this process.\u3c/p\u3

MR temperature monitoring for MR-RF hyperthermia:a systems-level approach

\u3cp\u3eNon-invasive high-resolution 3D MR temperature maps can significantly improve dosimetry during thermal dose delivery in hyperthermic oncology. However, with long treatment times, system- and patient-induced drift in the B\u3csub\u3e0\u3c/sub\u3e main magnetic field of the MR scanner may adversely impact the accuracy of temperature measurements. In addition, the insertion of conventional RF hyperthermia apparatus into an MR scanner obstructs the use of commercial MR receive coil arrays in the scanner bore. If they had been available for use, such receive arrays could potentially increase imaging signal-to-noise ratio (SNR) and/or temporal resolution of MR thermometry. Here, we describe a systems-level perspective of improving temperature monitoring in MR-RF hyperthermia. This approach includes a previously developed fat-referenced MR thermometry technique, and a dual-function coil array design that addresses the limitations in imaging SNR and temporal resolution that are inherent in conventional MR-guided RF hyperthermia systems. We will also discuss system-level considerations that can adversely impact MRT measurements when integrating a RF hyperthermia sub-system with a MRI system.\u3c/p\u3

A printed Yagi–Uda antenna for application in magnetic resonance thermometry guided microwave hyperthermia applicators

Biological studies and clinical trials show that addition of hyperthermia stimulates conventional cancer treatment modalities and significantly improves treatment outcome. This supra-additive stimulation can be optimized by adaptive hyperthermia to counteract strong and dynamic thermoregulation. The only clinically proven method for the 3D non-invasive temperature monitoring required is by magnetic resonance (MR) temperature imaging, but the currently available set of MR compatible hyperthermia applicators lack the degree of heat control required. In this work, we present the design and validation of a high-frequency (433 MHz ISM band) printed circuit board antenna with a very low MR-footprint. This design is ideally suited for use in a range of hyperthermia applicator configurations. Experiments emulating the clinical situation show excellent matching properties of the antenna over a 7.2% bandwidth (S 11  &lt;  −15 dB). Its strongly directional radiation properties minimize inter-element coupling for typical array configurations (S 21  &lt;  −23 dB). MR imaging distortion by the antenna was found negligible and MR temperature imaging in a homogeneous muscle phantom was highly correlated with gold-standard probe measurements (root mean square error: RMSE  =  0.51 °C and R 2  =  0.99). This work paves the way for tailored MR imaging guided hyperthermia devices ranging from single antenna or incoherent antenna-arrays, to real-time adaptive hyperthermia with phased-arrays

Exploration of MR-guided head and neck hyperthermia by phantom testing of a modified prototype applicator for use with proton resonance frequency shift thermometry

\u3cp\u3eMagnetic resonance thermometry (MRT) offers non-invasive temperature imaging and can greatly contribute to the effectiveness of head and neck hyperthermia. We therefore wish to redesign the HYPERcollar head and neck hyperthermia applicator for simultaneous radio frequency (RF) heating and magnetic resonance thermometry. In this work we tested the feasibility of this goal through an exploratory experiment, in which we used a minimally modified applicator prototype to heat a neck model phantom and used an MR scanner to measure its temperature distribution. We identified several distorting factors of our current applicator design and experimental methods to be addressed during development of a fully MR compatible applicator. To allow MR imaging of the electromagnetically shielded inside of the applicator, only the lower half of the HYPERcollar prototype was used. Two of its antennas radiated a microwave signal (150 W, 434 MHz) for 11 min into the phantom, creating a high gradient temperature profile (ΔTmax = 5.35 °C). Thermal distributions were measured sequentially, using drift corrected proton resonance frequency shift-based MRT. Measurement accuracy was assessed using optical probe thermometry and found to be about 0.4 °C (0.1-0.7 °C). Thermal distribution size and shape were verified by thermal simulations and found to have a good correlation (r(2 )= 0.76).\u3c/p\u3

Laboratory prototype for experimental validation of MR-guided radiofrequency head and neck hyperthermia

\u3cp\u3eClinical studies have established a strong benefit from adjuvant mild hyperthermia (HT) to radio- and chemotherapy for many tumor sites, including the head and neck (H&amp;N). The recently developed HYPERcollar allows the application of local radiofrequency HT to tumors in the entire H&amp;N. Treatment quality is optimized using electromagnetic and thermal simulators and, whenever placement risk is tolerable, assessed using invasively placed thermometers. To replace the current invasive procedure, we are investigating whether magnetic resonance (MR) thermometry can be exploited for continuous and 3D thermal dose assessment. In this work, we used our simulation tools to design an MR compatible laboratory prototype applicator. By simulations and measurements, we showed that the redesigned patch antennas are well matched to 50 Ω (S11&lt;-10 dB). Simulations also show that, using 300 W input power, a maximum specific absorption rate (SAR) of 100 W kg(-1) and a temperature increase of 4.5 °C in 6 min is feasible at the center of a cylindrical fat/muscle phantom. Temperature measurements using the MR scanner confirmed the focused heating capabilities and MR compatibility of the setup. We conclude that the laboratory applicator provides the possibility for experimental assessment of the feasibility of hybrid MR-HT in the H&amp;N region. This versatile design allows rigorous analysis of MR thermometry accuracy in increasingly complex phantoms that mimic patients' anatomies and thermodynamic characteristics. \u3c/p\u3