Clinical evaluation and verification of the hyperthermia treatment planning system hyperplan.

PURPOSE: A prototype of the hyperthermia treatment planning system (HTPS) HyperPlan for the SIGMA-60 applicator (BSD Medical Corp., Salt Lake City, Utah, USA) has been evaluated with respect to clinical practicability and correctness. MATERIALS AND METHODS: HyperPlan modules extract tissue boundaries from computed tomography (CT) images to generate regular and tetrahedral grids as patient models, to calculate electric field (E-field) distributions, and to visualize three-dimensional data sets. The finite difference time-domain (FDTD) method is applied to calculate the specific absorption rate (SAR) inside the patient. Temperature distributions are calculated by a finite-element code and can be optimized. HyperPlan was tested on 6 patients with pelvic tumors. For verification, measured SAR values were compared with calculated SAR values. Furthermore, intracorporeal E-field scans were performed and compared with calculated profiles. RESULTS: The HTPS can be applied under clinical conditions. Measured absolute SAR (in W/kg), as well as relative E-field scans, correlated well with calculated values (+/-20%) using the contour-based FDTD method. Values calculated by applying the FDTD method directly on the voxel (CT) grid, were less well correlated with measured data. CONCLUSION: The HyperPlan system proved to be clinically feasible, and the results were quantitatively and qualitatively verified for the contour-based FDTD method.

Optimization of temperature distributions for regional hyperthermia based on a nonlinear heat transfer model.

We describe an optimization process specially designed for regional hyperthermia of deep seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat-transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Optimal heating is obtained by minimizing an integral object function which measures the distance between desired and model predicted temperatures. Sequential minima are calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. Numerical results for a Sigma 60 applicator are presented.

Electric field distributions in a phased-array applicator with 12 channels: measurements and numerical simulations.

In this paper we examine the SIGMA-Eye hyperthermia applicator (BSD Medical Corp., Salt Lake City, Utah 84119) with respect to the control of electric field distributions. This applicator is equipped with 12 pairs of antennas fed by 12 amplifiers, allowing the individual adjustment of phase and power for each of them. Measurements were conducted using phantoms with well-defined electrical properties. Specific electro-optical sensors, capable of measuring both electric field amplitudes and phases, have been developed, and a system for data acquisition and analysis has been set up. In its initial state the applicator appeared not to be satisfactorily matched at 100 MHz for the phantom used, with return losses up to 20% in power. By tuner readjustments we achieved values below 5%. For various settings of the amplifiers' control parameters we measured field distributions, both in the phantom and in the surrounding water bolus. The experimental results were compared with numerical simulations based on finite difference and finite element methods. Measured and calculated electric fields exhibit deviations of 10% on average, allowing, in principle, a satisfactory prediction of fields by numerical simulations or as well by on-line measurements at selected locations of the applicator at antenna proximity. However, to obtain this satisfactory agreement a modification of the control parameters in the calculations (phases and amplitudes in the feed points of the antennas) was necessary. The origin of these problems is mainly attributed to cross-talk phenomena and other characteristics of the transforming network, which need to be scrutinized further for a full understanding.

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.

A fast algorithm to find optimal controls of multiantenna applicators in regional hyperthermia.

The goal of regional hyperthermia is to heat up deeply located tumours to temperatures above 42 C while keeping the temperatures in normal tissues below tissue-dependent critical values. The aim of this paper is to describe and analyse functions which can be used for computing hyperthermia treatment plans in line with these criteria. All the functionals considered here can be optimized by efficient numerical methods. We started with the working hypothesis that maximizing the quotient of integral absorbed power inside the tumour and a weighted energy norm outside the tumour leads to clinically useful power distributions which also yield favourable temperature distributions. The presented methods have been implemented and tested with real patient data from the Charité Berlin. Campus Virchow-Klinikum. The results obtained by these fast routines are comparable with those obtained by relatively expensive global optimization techniques. Thus the described methods are very promising for online optimization in a hybrid system for regional hyperthermia where a fast response to MR-based information is important.

Impact of nonlinear heat transfer on temperature control in regional hyperthermia.

We describe an optimization process specially designed for regional hyperthermia of deep-seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Using linearly implicit methods in time and adaptive multilevel finite elements in space, we are able to integrate efficiently the instationary nonlinear heat equation with high accuracy. Optimal heating is obtained by minimizing an integral objective function which measures the distance between desired and model predicted temperatures. A sequence of minima is calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. We compare temperature distributions for two individual patients calculated on coarse and fine spatial grids and present numerical results of optimizations for a Sigma 60 Applicator of the BSD 2000 Hyperthermia System.

3-D computation of E fields by the volume-surface integral equation (VSIE) method in comparison with the finite-integration theory (FIT) method.

An algorithm has been developed for calculation of 3-dimensional E fields by the volume-surface integral equation (VSIE) method. Integration over surface elements is performed by elementary analytical formulas, assuming a linear interpolation of surface charges. Grid points at electrical interfaces are split off, well considering the E field behavior at these contours, specifically at sharp bends and multimedia junctions. Averaging procedures are utilized in order to avoid undefined or infinite values at critical points. The VSIE is solved by iteration using GMRES ("general minimum residuum") solver on a SUN workstation SPARC-IPX or Cray XMP, whereby convergence speed decreases considerably as the heterogeneity of the problem increases. Computation time (e.g., 20 min on a supercomputer for approximately 30,000 cells) needs to be reduced by further code development. Results for 3-D test cases (plane wave illuminating a layered cylinder) generally agree well with the finite-integration-theory (FIT) method if high E field gradients occur perpendicular to electrical boundaries. The VSIE method predicts slightly higher E fields only in critical regions. On the other hand, the FIT method at present is more efficient with respect to computation time for large domains with high cell numbers (> 100,000 cells).

[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.

Registration of different phases of contrast-enhanced CT/MRI data for computer-assisted liver surgery planning: evaluation of state-of-the-art methods.

The exact localization of intrahepatic vessels in relation to a tumour is an important issue in oncological liver surgery. For computer-assisted preoperative planning of surgical procedures high quality vessel models are required. In this work we show how to generate such models on the basis of registered CT or MRI data at different phases of contrast agent propagation. We combine well-established intensity-based rigid and non-rigid registration approaches using Mutual Information as distance measure with different masking strategies as well as intensity inhomogeneity correction for MRI data. Non-rigid deformations are modelled by multilevel cubic B-splines. Quantitative evaluations of 5 MRI and 5 CT image pairs show that the liver moves rigidly 7.2 (+/- 4.2) mm on average, while the remaining non-rigid deformations range from 1.4-3 mm. As a result we find that masked rigid registration is necessary and in many cases also sufficient on clinical data. After non-rigid registration the matching shows no deviations in most cases.

Development and testing of SAR-visualizing phantoms for quality control in RF hyperthermia.

A new prototype of an elliptical standard phantom with fat-equivalent walls and a lamp matrix for SAR (specific absorption rate) visualization has been developed. This paper outlines the manufacture of solid components based upon either polyester resin or epoxy resin, as well as the adjustment of their electrical conditions (epsilon r, sigma) by admixtures of carbon and/or aluminium powder. Visualizing sensors (LED = light-emitting diodes, miniature lamps) are evaluated with respect to their transformation of electric field strength into light. Standard SAR patterns of the hyperthermia system BSD-2000 have been semiquantitatively assessed by the visualizing technique (power stepping method) and quantitatively by E field sensor scans. Extracted iso-SAR distributions are in good agreement with E field sensor scans performed with a lamp sensor coupled to a fibre or using a dipole probe with high resistive leads. The requirement for periodic quality control of SAR patterns of RF (radio frequency) hyperthermia systems is demonstrated. Comparisons between techniques are given, specifically with respect to the LED phantom of Schneider and van Dijk.

Simulation studies promote technological development of radiofrequency phased array hyperthermia.

A treatment planning program package for radiofrequency hyperthermia has been developed. It consists of software modules for processing three-dimensional computerized tomography (CT) data sets, manual segmentation, generation of tetrahedral grids, numerical calculation and optimisation of three-dimensional E field distributions using a volume surface integral equation algorithm as well as temperature distributions using an adaptive multilevel finite-elements code, and graphical tools for simultaneous representation of CT data and simulation results. Heat treatments are limited by hot spots in healthy tissues caused by E field maxima at electrical interfaces (bone/muscle). In order to reduce or avoid hot spots suitable objective functions are derived from power deposition patterns and temperature distributions, and are utilised to optimise antenna parameters (phases, amplitudes). The simulation and optimisation tools have been applied to estimate the improvements that could be reached by upgrades of the clinically used SIGMA-60 applicator (consisting of a single ring of four antenna pairs). The investigated upgrades are increased number of antennas and channels (triple-ring of 3 x 8 antennas and variation of antenna inclination. Significant improvement of index temperatures (1-2 degrees C) is achieved by upgrading the single ring to a triple ring with free phase selection for every antenna or antenna pair. Antenna amplitudes and inclinations proved as less important parameters.

Electromagnetic phased arrays for regional hyperthermia: optimal frequency and antenna arrangement.

This paper investigates the effects of the three-dimensional arrangement of antennae and frequency on temperature distributions that can be achieved in regional hyperthermia using an electromagnetic phased array. It compares the results of power-based and temperature-based optimization. Thus, one is able to explain the discrepancies between previous studies favouring more antenna rings on the one hand and more antennae per ring on the other hand. The sensitivity of the results is analysed with respect to changes in amplitudes and phases, as well as patient position. This analysis can be used for different purposes. First, it provides additional criteria for selecting the optimal frequency. Secondly, it can be used for specifying the required phase and amplitude accuracy for a real phased array system. Furthermore, it may serve as a basis for technological developments in order to reduce both types of sensitivities described above.

Clinical, physiological and anatomical determinants for radiofrequency hyperthermia.

Temperature/time curves and corresponding CT scans of > 200 regional heat treatments with the hyperthermia system BSD-2000 in 43 patients have been analysed. In vivo variables and treatment parameters such as local specific absorption rate SAR, local relative SAR parallel SAR parallel, total power P, local cooling coefficients wb, and local steady-state temperature elevations delta Tss (above systemic temperature) have been determined. For determination of wb the well-known and accepted steady-state approach has been used, which was slightly modified for the purposes of this study. Specifically, comparison of cooling coefficients at the beginning and end of heat treatments were performed in tumours and normal tissues. Other variables are anatomical descriptors from CT scans, score of side effects plim, and various clinical factors. A variance analysis of the dependent variables, specifically delta Tss and parallel SAR parallel, is performed with respect to factors which were estimated as predictive. The intratumoral steady-state temperature elevations are determined by the perfusion-related cooling coefficients and local SAR to almost the same extent. Increase of cooling coefficients in tumours during the heat treatment characterizing the thermoregulatory potential have a slight but less important influence with respect to the achieved temperature elevations. SAR is influenced by several anatomical factors which determine the relative SAR distribution and clinical factors which limit the total power P. However, options for controlling present RHT systems in order to optimize the relative SAR distribution or to avoid hot spot phenomena appear limited. Three-dimensional modelling calculations show that the spatial arrangement of electrical interfaces emerging from bone and fat structures limits SAR control in available RHT technology and is mainly responsible for local power-dependent discomfort (Wust et al. 1994b). Some conclusions are drawn, about how technological development of hyperthermia technology can contribute towards overcoming this problem.

Noninvasive prediction of SAR distributions with an electro-optical E field sensor.

An integrated electro-optical (eo) E field sensor is developed on the basis of a Ti:LiNbO3 Mach-Zehnder interferometer. A measuring device based on the lock-in principle is introduced to register the E field in phase and amplitude using this E field probe. Segmented electrodes are used to minimize influences from the dielectric surroundings on the base point capacitance of the receiving dipole. The operating point is stabilized against drift phenomena resulting from optical damage and pyroelectric effect. Sensitivity, dynamic range, harmonic distortions and mechanical properties of a prototype of this electro-optical E field sensor are evaluated. A phantom setup in the SIGMA-60 applicator was developed to test this electro-optical sensor for hyperthermia applications. Power deposition patterns of various standard adjustments of the SIGMA ring are visualized in an elliptical lamp phantom. Simultaneously, E field in phase and amplitude is determined on a closed curve in 10 degrees steps around the phantom in a substitute bolus. The numbers are stored and utilized as boundary conditions in a two-dimensional finite elements code which calculates the SAR distribution on an appropriate triangular grid inside the closed curve. An excellent qualitative agreement is obtained between visualized and calculated SAR patterns. This novel measurement method is therefore suitable for noninvasive monitoring of SAR patterns during clinical application of regional radiofrequency hyperthermia.

Influence of patient models and numerical methods on predicted power deposition patterns.

BACKGROUND: A hyperthermia planning system has been developed for generating patient and applicator models as well as calculating and visualizing E-field and temperature distributions. Significant dependencies on models and algorithms have been found. METHODS: Computerized tomography (CT) data sets are first transformed into so called 'labelled CT-volume'-data sets of equal resolution, which are used for segmentation. The first type of patient model obtained subsequently is based on regions with specified electrical properties representing tissues or organs (so called 'region-based model'). The second patient model renders a direct transformation of Hounsfield Units (HU) to electrical constants (so called 'HU-based model'). The FDTD-method (finite difference time domain) is then applied on a cubic lattice employing either an auxiliary 'sub-cubic lattice' (for HU-based segmentation) or a tetrahedron grid (for region-based segmentation) to assign the electrical properties, both representing the anatomy of the patient. E-field distributions are corrected by a post-processing procedure with respect to the geometry of interfaces defined by the tetrahedron grid. For comparison, the VSIE method (volume surface integral equation) is performed on the same tetrahedron grid. The applicator model assumes eight half-wavelength dipole antennas fed with constant voltages with water as background medium. RESULTS: For both numerical methods (FDTD, VSIE) the resulting antenna input impedances as well as the current distributions along the antennas were quite similar and almost insensitive to the particular geometry model (region-based, HU-based). In contrast to that, the power deposition patterns in the interior of the patient depended strongly on those models. Major differences can be related to different labels of the tissue type bone in the HU-based model in comparison to the definition via regions. Conversely, comparable results were obtained using the VSIE method and the FDTD method on the region-based patient model with a posteriori correction at the tetrahedron grid points. SAR (specific absorption rate) elevations up to a factor of 10 were predicted when employing region-based models. Those peaks might correspond to specific toxicity of electromagnetic radiation clinically known as hot spot phenomena or musculo-skeletal syndromes. Conversely, HU-based models generated quite homogeneous power deposition patterns with fluctuations of at most factor 2. CONCLUSION: The methods employing region-based geometry models such as the VSIE method and FDTD method in conjunction with a posteriori correction at tissue interfaces result in comparable E-field distributions for regional hyperthermia. Due to its shorter calculation time, the FDTD method is currently used in the clinic. Predictions derived from HU-based models without prior corrections of tissue specifications are not always supported by clinical experience.

[The use of an early postoperative interstitial-hyperthermia combination therapy in malignant gliomas]. / Einsatz einer früh postoperativen interstitiellen Hyperthermiekombinationstherapie bei malignen Gliomen.

BACKGROUND: The survival of people suffering from malignant gliomas (WHO level III and IV) is predominantly limited by local progress in the primary tumor region. Interstitial hyperthermia combined with radiotherapy or chemotherapy is one approach for the intensification of local therapy. It is possible to combine (partial) tumor resection with hyperthermia as well as with brachytherapy by implanting catheters intraoperatively. PATIENTS AND METHODS: A pilot study was performed to examine practicality, tolerability, effectiveness and scope for improvement in early postoperative hyperthermia treatment following catheter implantation as part of (partial) tumor resection. Each CT data set was transferred into a VAX 3100 workstation for retrospective analysis of the hyperthermia treatment. The implanted catheters were segmented and the distributions of power density and temperature were simulated. We sought to achieve the best possible temperature distributions by optimising the catheter arrangement in the planning calculations. The corresponding Ir-192-source brachytherapy treatments were simulated in a similar way using the implanted, as well as optimised catheter arrays. RESULTS: Intraoperative catheter implantation in 4 patients was problem-free. Postoperative complications were not observed, neither were infections. Interstitial microwave hyperthermia in combination with percutaneous irradiation or chemotherapy a few days after the operation was also tolerated well by all patients. Effective temperatures (of at least 42 degrees C) were regularly achieved at measurement points, but the temperature distributions were unsatisfactory, with T90 values (the temperature reached in at least 90% of the target volume) of under 38 degrees C. Measured temperature/position curves showed qualitative correlation with the simulated calculations. The catheter positions determined by optimisation varied significantly from the positions clinically used. CONCLUSIONS: Early postoperative combination therapy using hyperthermia for the treatment of malignant gliomas is a very practical approach. The optimisation strategies described should be used preoperatively to plan catheter arrays for interstitial hyperthermia and brachytherapy, and these arrays should be implanted using stereotaxic surgery.