Methods and potentials of magnetic resonance imaging for monitoring radiofrequency hyperthermia in a hybrid system.

INTRODUCTION: Non-invasive thermometry (NIT) is a valuable and probably indispensable tool for further development of radiofrequency (RF) hyperthermia. A hybridization of an MRI scanner with a hyperthermia system is necessary for a real-time NIT. The selection of the best thermographic method is difficult, because many parameters and attributes have to be considered. METHODS: In the hybrid system (Siemens Symphony/BSD-2000-3D) the standard methods for NIT were tested such as T1, diffusion (ADC: apparent diffusion coefficient) and proton-resonance-frequency shift (PFS) method. A series of three-dimensional datasets was acquired with different gradient-echo sequences, diffusion-weighted EPI spin-echo sequences and calculated MR-temperatures in the software platform AMIRA-HyperPlan. In particular for the PFS-method, corrective methods were developed and tested with respect to drift and other disturbances. Experiments were performed in phantoms and the results compared with direct temperature measurements. Then the procedures were transferred to clinical applications in patients with larger tumours of the lower extremity or the pelvis. RESULTS: Heating experiments and MR-thermography in a homogeneous cylindrical phantom give an excellent survey over the potentials of the methods. Under clinical conditions all these methods have difficulties due to motion, physiological changes, inhomogeneous composition and susceptibility variations in human tissues. The PFS-method is most stable in patients yielding reasonable MR temperature distributions and time curves for pelvic and lower extremity tumours over realistic treatment times of 60-90 min. Pooled data exist for rectal tumour recurrencies and soft tissue sarcomas. The fat tissue can be used for drift correction in these patients. T1 and diffusion-dependent methods appear less suitable for these patients. The standard methods have different sensitivities with respect to the various error sources. The advantages and pitfalls of every method are discussed with respect to the literature and illustrated by the phantom and patient measurements. CONCLUSIONS: MR-controlled RF hyperthermia in a hybrid system is well established in phantoms and already feasible for patients in the pelvic and lower extremity region. Under optimal conditions the temperature accuracy might be in the range of 0.5 degrees C. However a variety of developments, especially sequences and post-processing modules, are still required for the clinical routine.

[Part-body hyperthermia with a radiofrequency multiantenna applicator under online control in a 1.5 T MR-tomograph]. / Teilkörperhyperthermie mit einem Radiofrequenz-Multiantennen-Applikator unter online Kontrolle in einem 1.5 T MR-Tomographen.

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.

Performance and use of current sheet antennae for RF-hyperthermia of a phantom monitored by 3 tesla MR-thermography.

Several MR-compatible current sheet antennae (CSA) of different height (h) (16 cm (l) x 8 cm (w) x 1-5 cm (h)) were built for simulated RF (96 MHz) hyperthermia of a medium-sized (12l) tissue-equivalent phantom inside a 3 tesla whole body tomograph. Prior to use, efficiencies of the CSA were determined by network analysis and by calorimetry. Depending on the height h of the CSA and on the thickness d(bolus) of the water bolus used for RF-coupling of the CSA to the lossy medium, their efficiency varied between 20-70% and the CSA with h = 3 cm was selected for simulated RF hyperthermia. During heating, spatial temperature distributions (20-42 degrees C) of five slices (voxel size 2 x 2 x 10mm(3)) were recorded intermittently within 4 s/slice by measuring the temperature dependent shift of the (1)H resonance frequency (125.32 MHz). A phased array consisting of two identical CSA produced distinctly different spatial temperature distributions at 0 and 180 degrees phase difference between both RF channels feeding the antennae. Within a one-dimensional heat diffusion model, the specific absorption rate (SAR) of the electromagnetic wave generated by a single antenna was deduced from the experimental data resulting in a penetration depth (1/e(2)) of approximately 4 cm.

Antenna arrays in the SIGMA-eye applicator: interactions and transforming networks.

OBJECTIVES: In multiantenna applicators such as the SIGMA-60 or SIGMA-Eye, which consist of 4 or 12 pairs of antennas shunt to 4 or 12 amplifiers ("antenna couplets"), phases and amplitudes in the feed points of these antennas under certain conditions can significantly differ from the values selected at the multichannel amplifier (forward parameters), mainly due to coupling. In the SIGMA-Eye, this interaction is particularly affected by the transforming networks between the generators and the feed points, thus hampering the control of the feed point parameters. In this work, we perform measurements at existing applicators, present a formalism to describe the facts numerically, and investigate modifications of the transforming networks to improve the performance. METHODS AND MATERIALS: We prepared an experimental setup for the SIGMA-Eye applicator that is fed by forward waves of a 12-channel amplifier system. In this setup, we made the water bolus, the interior of the tissue-equivalent phantom, and the entire transforming network accessible for measuring probes. Then, we constructed various alternative transforming networks such as Pawsey loops, LC matching networks, and power dividers and compared them with the original matching network of the SIGMA-Eye applicator. In particular, we utilized a high-resistive probe to determine the disturbances and influences caused by some channels with respect to some selected feed points of the SIGMA-Eye dipoles. RESULTS: In the original SIGMA-Eye applicator, the influences of coupling channels on the phases and voltages in the feed point of a particular antenna are largest for adjacent longitudinal channels. Here, the +/- 10 degrees phase shift and +/- 30% voltage change were observed if the reference channel (i.e., the disturbed channel) and disturbing channel are equally powered. The changes eminently increased to -30 degrees to + 100 degrees phase shift and -80% to +50% voltage change if the reference channel is fed with much lower power (four to eight-fold) than the disturbing channel. The disturbance from distant channels is less but still significant, reaching shifts of -10 degrees to +50 degrees and -50% to +20%, respectively. Using Pawsey loops instead of the original ferrite rings in the SIGMA-Eye network, the efficacy of the baluns was improved by a more than a factor of 4. Using an LC matching network, dependencies on frequency and external arrangements can be reduced significantly. Applying a power divider circuit, the coupling between antennas combined to one channel is considerably diminished (down to <-25 dB). CONCLUSION: Coupling between resonators (pairs of antennas including the matching network) reduces the control of the SIGMA-Eye applicator, i.e., it causes deviations between the selection of forward parameters at the amplifier and the total actual parameters in the feed points of the antennas. Modified transformation networks can improve the control, in particular by reducing sheath currents and asymmetries. There is a linear but variable relationship between selected (amplifiers) and actually given (feed points) parameters. This linear mapping (described by a matrix) and its characteristics need further investigation.

Histopathological correlation to MRI findings during and after laser-induced thermotherapy in a pig pancreas model.

RATIONALE AND OBJECTIVES: To investigate whether percutaneous laser-induced thermotherapy (LITT) with continuous magnetic resonance (MR) monitoring of thermal effects within the pancreas is feasible in a porcine model. METHODS: Laser applicators were placed in the pancreas of 15 female pigs. A temperature-sensitive (thermo--fast low-angle shot) sequence was used for continuous monitoring of thermal effects during LITT at 1.5 T. Follow-up MR images were acquired, the pigs were observed for 7 days, and then a pathological examination was performed after sacrifice. RESULTS: Continuous MR monitoring visualized thermal effects in pancreatic tissue and thermal damage of the spleen (n = 1), the left kidney (n = 1), and peripancreatic fat (n = 4) but missed the thermal damage of the duodenum (n = 2). Thermal-induced lesions (10--32-mm diameter) were clearly visualized on contrast-enhanced T1-weighted images. CONCLUSIONS: Laser-induced thermotherapy of pancreatic tissue was feasible in this porcine model, and online monitoring was practicable. Further studies are necessary to increase the accuracy of online MR imaging of thermal effects.

Comparison of four magnetic resonance methods for mapping small temperature changes.

Non-invasive detection of small temperature changes (< 1 degree C) is pivotal to the further advance of regional hyperthermia as a treatment modality for deep-seated tumours. Magnetic resonance (MR) thermography methods are considered to be a promising approach. Four methods exploiting temperature-dependent parameters were evaluated in phantom experiments. The investigated temperature indicators were spin-lattice relaxation time T1, diffusion coefficient D, shift of water proton resonance frequency (water PRF) and resonance frequency shift of the methoxy group of the praseodymium complex (Pr probe). The respective pulse sequences employed to detect temperature-dependent signal changes were the multiple readout single inversion recovery (T One by Multiple Read Out Pulses; TOMROP), the pulsed gradient spin echo (PGSE), the fast low-angle shot (FLASH) with phase difference reconstruction, and the classical chemical shift imaging (CSI). Applying these sequences, experiments were performed in two separate and consecutive steps. In the first step, calibration curves were recorded for all four methods. In the second step, applying these calibration data, maps of temperature changes were generated and verified. With the equal total acquisition time of approximately 4 min for all four methods, the uncertainties of temperature changes derived from the calibration curves were less than 1 degree C (Pr probe 0.11 degrees C, water PRF 0.22 degrees C, D 0.48 degrees C and T1 0.93 degrees C). The corresponding maps of temperature changes exhibited slightly higher errors but still in the range or less than 1 degree C (0.97 degrees C, 0.41 degrees C, 0.70 degrees C, 1.06 degrees C respectively). The calibration results indicate the Pr probe method to be most sensitive and accurate. However, this advantage could only be partially transferred to the thermographic maps because of the coarse 16 x 16 matrix of the classical CSI sequence. Therefore, at present the water PRF method appears to be most suitable for MR monitoring of small temperature changes during hyperthermia treatment.

Design and test of a new multi-amplifier system with phase and amplitude control.

The clinical relevance of the radiofrequency regional hyperthermia (RF-RHT) as an adjuvant cancer therapy grows continuously. Simulation studies for optimization of RF-RHT based on the annular phased array systems have shown a significant improvement of power deposition patterns with increasing number of channels. However, this probably requires higher phase accuracy and amplitude stability than are provided by presently used clinical systems, e.g. BSD-2000. Measurements performed on the BSD-200 electronic revealed phase inaccuracies up to +/- 20 degrees and errors in the power registration of +/- 20 W (up to +/- 50 W in the low power range). These errors are further enhanced by the mismatching of the external load (antenna applicator) and thermal instabilities. To achieve the required phase accuracy and long-term stability in the prototype of a new amplifier system, single-sideband (SSB) mixing in combination with direct digital synthesizers (DDS), in-phase and quadrature-phase (IQ) processing and phase-lock loop (PLL) were used. In the DDS's the actual phase of the output signal of each channel is calculated in real-time. No analogue control loop is involved that may cause thermal offset or drift problems. Each DDS operates at a low intermediate frequency (IF) of 1 MHz. To transform the phase information of this IF signal into the desired RF band, SSB mixing-up is performed. A second frequency source, operating as a local oscillator (LO) in the RF band, is required for this technique. Also, the frequency adjustment of the desired RF signal is performed in the LO. These phase and frequency adjustment units are followed by the high efficiency AB-class solid state amplifier unit. The phase and power level stability of the amplifier are controlled by means of digital PLL structures in conjunction with look-up tables. For this control test signals are coupled out by means of directional couplers. The phase control is based on very sensitive phase comparison. These digital control loops are programmable and allow the implementation of different control algorithms. The achieved long-term accuracy (95% confidence interval) is +/- 1-3 W for output power levels ranging from 10-100 W, and +/- 1 degree for phase differences between each channel and a reference signal at a constant power level, and +/- 1.5 degrees for phase difference values at variable power levels between 10-100 W. In conclusion, the new amplifier system is smaller and more efficient than presently available commercial systems.

Non-invasive MR thermometry by 2D spectroscopic imaging of the Pr[MOE-DO3A] complex.

Future progress in regional hyperthermia requires a practical method for non-invasive thermometry. In magnetic resonance tomography, spin density, T1 relaxation time, diffusion coefficient and proton resonance frequency are candidates to measure temperature distributions. When used clinically in the pelvic region, all these methods are compromized by artifacts arising from different tissues, tissue alterations under hyperthermia, physiological and random movements, inhomogeneities, drift phenomena, and field instabilities. In this study a paramagnetic complex was evaluated, Pr[MOE-DO3A], with praseodymium as central atom, similar to common gadolinium containing MRI contrast media. The temperature dependence of its methoxy side group approximately -24 ppm downfield from the water resonance at 25 degrees C was employed to determine 2-D temperature distributions in a cylindrical agar phantom containing 9.5 mM of Pr[MOE-DO3A]. The phantom was heated externally through a water jacket creating a stationary temperature distribution throughout the phantom. At first, the correlation between temperature and the chemical shift of the methyl group of the lanthanide complex Pr[MOE-DO3A] was determined. Calibration curves obtained exhibited a linear relationship of 0.12 +/- 0.01 ppm/degree C, nearly independent from the surrounding medium. Local temperature distributions were determined employing the spatially resolved method of spectroscopic imaging (SI). 2-D spectroscopic images for three orthogonal slices were obtained by narrow-band excitation and 16 phase encoding steps in two dimensions. The FOV was 180 mm and the slice thickness in all cases was 20 mm for maximal spatial temperature resolution (11.2 x 11.2 mm2). The results indicate a measurement time of about 5s per acquisition under the following conditions: An estimated concentration of 1 mmol/l, a reduced matrix size of 8 x 8, and a reduced repetition time of 3 x T1 (TR approximately 85 ms). Those SI measurements produced a SNR of approximately 4 per acquisition, a measurements duration of 10-20 s, equivalent to two to four acquisitions per spectrum, seem sufficient for online temperature monitoring during hyperthermia. The in vitro data suggest the spectroscopic temperature measurement utilizing a temperature-sensitive Pr[MOE-DO3A] complex with a therapeutically realistic concentration of 1 mmol/l to be suitable for clinical use. Compared to the methods tested so far (rho, T1, diffusion, proton resonance), the method presented has the unique advantage of being less susceptible to artifacts. The competing methods of non-invasive thermometry employing magnetic resonance imaging are currently being investigated using the same experimental setup.

Three-dimensional monitoring of small temperature changes for therapeutic hyperthermia using MR.

Radiofrequency hyperthermia of deep-seated pelvic tumors requires noninvasive monitoring of temperature distributions in patients. Methods of MR thermography were reported to be a promising tool in solving this problem. However, to be truly useful for monitoring hyperthermia treatments, MR thermography should be able to cover the entire pelvis in acquisition times no longer than for a breath-hold (< or = 15 seconds) and to resolve small temperature differences (< 1 degrees C). Three methods exploiting the temperature dependence of spin-lattice relaxation time (T1), of self-diffusion coefficient (D), and of chemical shift of proton resonance frequency (PRF) were applied in phantom experiments; the pulse sequences were the T1-weighted gradient echo, the pulsed diffusion gradient spin echo made faster through the keyhole technique, and the gradient echo with the phase reconstruction, respectively. The high planar resolution was compromised, and instead, coarse and more isotropic voxels were used. Experiments were performed in two consecutive steps, thus imitating a possible scenario for monitoring hyperthermia. In the first step, calibration curves were recorded, which were then used in the second step to obtain maps of temperature changes. The results show a clear superiority of the PRF method, followed by the D and the T1 methods. The uncertainty of temperature changes predicted both from calibration curves and from maps was less than 1 degrees C only with the PRF and the D-based methods.

[Thermometry by measuring the chemical shift of lanthanide complex]. / Thermometrie durch Messung der chemischen Verschiebung eines Lanthanidenkomplexes.

BACKGROUND: In the long-term, non-invasive thermometry is vital for the continued clinical and technological development of regional hyperthermia. In magnetic resonance tomography. T1 relaxation time, diffusion and proton resonance frequency are used to measure temperature distributions. When used clinically in the pelvic region, all of these methods are plagued with errors and artefacts on account of the tissue relationships, tissue changes under hyperthermia, physiological and stochastic movements, inhomogeneities, drift phenomena and instabilities. MATERIAL AND METHOD: We tested the relationship between the temperature and the chemical shift of a methyl group of a lanthanide complex with central atom praseodymium (Pr-MOE-DO3A. Schering AG). To do this we used cylindrical phantoms containing a 5-mmol-solution of this temperature-sensitive substance. High resolution spectra and relaxation times were determined in a Bruker AMX at 11.5 T. A calibration curve was then recorded by a Siemens Magnetom SP63 at 1.5 T. Local temperature distributions were determined using the chemical shift imaging method, with a matrix size of 16 x 8 and a narrow-band excitation pulse. The temperature distribution was created using a Nd:YAG laser applicator. RESULTS: At a distance of -25.7 ppm from the water line, we found a singlet line with a temperature-dependent chemical shift of 0.13 ppm/C. In the phantom experiment we found that the chemical shift had a linear relationship with a gradient independent of the surroundings, and a temperature resolution of +/-0.6 degree C. With a concentration of 1 mmol/l, a matrix size of 8 x 8 and a measurement period of 5 s per acquisition, phantom measurements using the CSI method produced a signal to noise ratio of 3.5 per acquisition, i.e a measurement period of 10 to 20 s per spectrum. CONCLUSIONS: Our in vitro data show that spectroscopic temperature measurement using a temperature-sensitive praseodymium complex with a therapeutically practical concentration of 1 mmol/l already appears to be suitable for clinical use Compared with the methods tested so far (T1, diffusion, proton resonance), this method has the special advantage of not being very susceptible to artefacts. The competing methods of non-invasive thermometry using magnetic resonance tomography/spectroscopy will be investigated next.

Effects of magnetic fluid hyperthermia (MFH) on C3H mammary carcinoma in vivo.

Magnetic fluids (MF) have a potential for hyperthermia due to their good power absorption capabilities. Recent in vitro experiments with the so-called 'Magnetic Fluid Hyperthermia (MFH)' have shown that human tumours cells are homogeneously inactivated after AC magnetic field excitation of extracellular MF. The aim of the present study was the evaluation of a high dose MFH on intramuscularly implanted mammary carcinoma of the mouse. The tumours originated from initial in vivo passages of a spontaneous parent tumour. Because of larger variations of tumour growth in this rather primary model, logistic regression of non-averaged volumes was performed for each treatment modality. All growing tumours were randomized 30 days after transplantation (day of treatment) with an overall size distribution between 120-400 mm3. An intratumoural steady state temperature of 47 +/- 1.0 degrees C was maintained for 30 minutes with whole-body AC magnetic fields of 6-12.5 kA/m at 520 kHz. The magnetic fluid was #P6, which is a high biocompatible dextran magnetite. #P6 was given intratumourally (1.5 x 10(-2) mg ferrite/mm3) 20-30 minutes before excitation and was combined with magnetic targeting (50 mT), which yielded a 2.5-fold enhancement of the intratumoural iron concentration. Histological examinations of tumour tissue after intralesional ferrofluid administration alone indicated deep infiltration of the fluid into the carcinoma tissue, but no evidence of tissue damage as compared with untreated controls. In contrast, widespread tumour necrosis was observed after MFH. After application of either dextran or ferrofluid alone (no difference, p = 0.665), tumour growth was slightly delayed in comparison with untreated controls (p < 0.001). In contrast to the good fit of the controls (R = 0.92-0.87), tumour growth after MFH was much more heterogeneous; some tumours showed no evidence for regrowth at 50 days whereas others had grown quite readily. This most probably reflected the critical problem of homogeneity of the intratumoural MF distribution, which was also confirmed qualitatively by Magnetic Resonance Imaging (MRI), heterogeneous pigmentation of MFH treated tumours, and up to 1 degree C differences between temperature probes in the same tumour during AC magnetic field application. However, a quantitative comparison between intratumoural MF-heterogeneity and tumour response could not be performed in this study. Despite these current limitations, the regression analysis of the MFH data yielded a smaller tumour volume of about 1000 mm3 at 50 days growth time in contrast to all three controls. In conclusion, encouraging results have been obtained, which show, that one single high dose MFH is already able to induce local tumour control in many cases within 30 days after treatment. To overcome the uncertainties of intratumoural MF heterogeneity, advanced intralesional application methods are currently under development.

Health services reform in Poland: issues in recent developments.

After ten years of debate and discussion, the political situation within Poland finally allows the possibility to implement basic reforms in the health care system. Parallel development of the political and technical aspects of the reform has now lead to a final proposal for fundamental reforms in health system responsibility, financing and management. This article describes the current conceptual developments and the political and social context for these final reform proposals at the time of their submission to the government. The primary changes suggested are aimed at increasing the awareness of local, regional and national administrations, health care professionals and the general public that health care has a cost, and that resources must be used carefully if they are to cover health needs. In addition, 'health care' as a term must be extended to include factors and activities besides direct medical services. Such factors as air and water quality, diet, smoking and alcohol consumptions are examples of matters which will also be included in the focus of health system planners. A key element of the organisational reforms is decentralisation of responsibility for health care planning and administration within the framework of nationally set standards and priorities. Based on local decisions, the current basic organisation unit of health care delivery, the ZOZ or integrated health care units, will be redefined and either decomposed into their component services or receive newly defined responsibilities more adapted to the local realities of available manpower and medical facilities. In addition, the development of a private health care sector complementing and even competing with the public services sector will be actively encouraged.