P. Wust

Inductive heating of ferrimagnetic particles and magnetic fluids: Physical evaluation of their potential for hyperthermia

The potential of colloidal subdomain ferrite particle suspensions (SDP) (‘magnetic fluids’), exposed to an alternating magnetic field, is evaluated for hyperthermia. Power absorption measurements of different magnetic fluids are presented in comparison to multidomain ferrite particles (MDP). Variations with frequency as well as magnetic field strength have been investigated. The experimental results clearly indicate a definite superiority of even non-optimized magnetic fluids over MDP ferrites regarding their specific absorption rate (SAR). Based on the work of [Shliomis, Pshenichnikov, Morozov, Shurubor. Magnetic properties of ferrocolloids. J Magn Magn Mater 1990;85:40–46 and [Hanson The frequency dependence of the complex susceptibility of magnetic fluids. J Magn Magn Mater, 1991;96 (In press).], a solid-state physical model is applied to explain the specific properties of magnetic fluids with respect to a possible use in hyperthermia. The experimentally determined SAR data on magnetic fluids are used to estimate the heating capabilities of a magnetic induction heating technique assuming typical human dimensions and tissue parameters. It is considered that for a moderate concentration of 5 mg ferrite per gram tumour (i.e. 0.5% w/w) and clinically acceptable magnetic fields, intratumoral power absorption is comparable to RF heating with local applicators and superior to regional RF heating (by comparison with clinical SAR measurements from regional and local hyperthermia treatments). Owing to the high particle density per volume, inductive heating by magnetic fluids can improve temperature distributions in critical regions. Furthermore, localized application of magnetic fluids in a tumour might be easier and less traumatic than interstitial implantation techniques.

Endocytosis of dextran and silan-coated magnetite nanoparticles and the effect of intracellular hyperthermia on human mammary carcinoma cells in vitro

Abstract To obtain more evidence for intracellular magnetic fluid hyperthermia (MFH), endocytosis and hyperthermia efficacy of silan and dextran magnetite was investigated. Differential endocytosis was observed in dependence of nanoparticle and cell type. Clonogenic survival was 3-fold lower after MFH versus waterbath hyperthermia. The selective “remote inactivation” of cancer cells by an AC magnetic field has been demonstrated in vitro.

Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters

PURPOSE Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints. METHODS AND MATERIALS A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T(max), T(90)) averaged over time, cumulative minutes (cum min) (here for T(90) > reference temperature 40.5 degrees C), and equivalent minutes (equ min) (with respect to 43 degrees C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was performed, not only of the variance of thermal parameters with respect to clinical criteria such as toxicity, response, and survival but also its dependency on tumor characteristics. RESULTS The rate of resectability (89%) and response (59%) were high for the PRC group, and a clear positive correlation existed between index temperatures (T(90)) and thermal doses (cum min T(90) >/= 40.5 degrees C). Even though the overall 5-year survival was encouraging (60%) and significantly associated with response, there was no statistically significant relationship between temperature parameters and long-term survival for this limited number of patients. However, nonresectable tumors with higher thermal parameters (especially cum min T(90) >/= 40.5 degrees C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T(90) = 40.7 degrees C versus T(90) = 40.2 degrees C). However, these conditions for easier heating did not involve a favorable clinical outcome, since surgical resectability (22%) and response rate (28%) for the RRC group were low. We did not notice any other dependency of thermal parameters to a specific tumor or patient characteristics. Finally, neither acute toxicity (hot spots) induced by hyperthermia or RCT nor perioperative morbidity were correlated with temperature-derived parameters. Only a higher probability for the occurrence of hot spots was found during treatment with elevated power levels. CONCLUSION In this study with two subgroups, i.e., patients with PRC (n = 37) and RRC (n = 18), there exists a positive interrelationship between thermal parameters (such as T(90), cum min T(90) >/= 40,5 degrees C) and clinical parameters concerning effectiveness. Additional hyperthermia treatment does not seem to enhance toxicity or subacute morbidity. Procedures to measure temperatures and to derive thermal parameters, as well as the hyperthermia technique itself appear adequate enough to classify heat treatments in

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.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.

Strategies for optimized application of annular-phased-array systems in clinical hyperthermia

A theoretical framework is presented for optimized heating of deep-seated tumours by phase and amplitude steering. The optimization problem for a specific tumour and perfusion case results in a functional dependency between power-level and maximum obtainable therapeutic efficiency. Different optimization criteria and strategies are outlined, which cause an increase of power or thermal dose in the tumour. Three tumour models (central pelvic tumour, eccentric abdominal tumour with or without necrosis) are analysed in detail. The simulation studies predict that appreciable parts of these tumours (50-100%) can be heated efficiently (42.5-43 degrees C) within the range of available and clinically tolerated power levels (1-5 kW/m), if tumour perfusion is less than 20-25 ml/100 g min. Some improvements are obtained by increasing the number of independent channels (from four to eight) and by the application of time-dependent (complementary) power-deposition patterns.

Temperature data and specific absorption rates in pelvic tumours: predictive factors and correlations

The system BSD 2000 has been in clinical use for regional hyperthermia for more than 10 years. Several technical details of this hyperthermia system, as well as the results of clinical studies employing this system have been investigated. The intention of this paper is to investigate the correlation between technical efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power densities and temperatures depending upon parameters such as tumour histology, tumour location, patient age, patient sex, and patient cross section. The possible conclusions of predictive factors derived from the above correlations were closely scrutinized. Data acquired from 772 treatment sessions of 190 patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum, cervix, prostate and anus, have been evaluated. For every session, index temperatures T90 (temperature attained at 90% of tumour related measurement points), cumulative minutes for T90 > Tref, tumour related power density (SAR: specific absorption rate, in W/kg) and the effective perfusion Weff (in ml/100 g min) were calculated. Temperatures were measured either invasively or endoluminally. The statistics software SPSS was employed subsequently for univariate, as well as multivariate analyses. The results exhibit that index temperatures mainly depend on the power density SAR and the hyperthermia induced effective perfusion. The total power P (in 100 W) and, complementarily, the relative power density absolute value(SAR) (= SAR/P) seem to have lesser influence. Clear differences between the tumour entities were established regarding their index temperatures and temperature distributions. SAR, Weff and P were correlated with several anatomical, biological and clinical factors. Sessions rendering low index temperatures and SAR values also revealed decreased individual tolerance to the treatment. This clearly displays that power-induced side effects define the limits of the efficiency of regional hyperthermia. Equivalent relationships and correlations are derived from intratumoural and endoluminal thermometry. Individual limitations of regional hyperthermia caused by anatomical, biological and clinical factors are liable to be difficult to overcome with the rather restricted potentials of the BSD 2000 system to control the SAR distribution.The system BSD 2000 has been in clinical use for regional hyperthermia for more than 10 years. Several technical details of this hyperthermia system, as well as the results of clinical studies employing this system have been investigated. The intention of this paper is to investigate the correlation between technical efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power densities and temperatures depending upon parameters such as tumour histology, tumour location, patient age, patient sex, and patient cross section. The possible conclusions of predictive factors derived from the above correlations were closely scrutinized. Data acquired from 772 treatment sessions of 190 patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum, cervix, prostate and anus, have been evaluated. For every session, index temperatures T 90 (temperature attained at 90% of tumour related measurement points), cumulative minutes for T90 > Tref, tumour related power density (SAR: specific absorption rate, in W/kg) and the effective perfusion Weff (inml/100gmin) were calculated. Temperatures were measured either invasively or endoluminally. The statistics software SPSS was employed subsequently for univariate, as well as multivariate analyses. The results exhibit that index temperatures mainly depend on the power density SAR and the hyperthermia induced effective perfusion. The total power P (in 100W) and, complementarily, the relative power density ||SAR|| (= SAR/P) seem to have lesser influence. Clear differences between the tumour entities were established regarding their index temperatures and temperature distributions. SAR, Weff and P were correlated with several anatomical, biological and clinical factors. Sessions rendering low index temperatures and SAR values also revealed decreased individual tolerance to the treatment. This clearly displays that powerinduced side effects define the limits of the efficiency of regional hyperthermia. Equivalent relationships and correlations are derived from intratumoural and endoluminal thermometry. Individual limitations of regional hyperthermia caused by anatomical, biological and clinical factors are liable to be difficult to overcome with the rather restricted potentials of the BSD 2000 system to control the SAR distribution.

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.

Evaluation of segmentation algorithms for generation of patient models in radiofrequency hyperthermia.

Time-efficient and easy-to-use segmentation algorithms (contour generation) are a precondition for various applications in radiation oncology, especially for planning purposes in hyperthermia. We have developed the three following algorithms for contour generation and implemented them in an editor of the HyperPlan hyperthermia planning system. Firstly, a manual contour input with numerous correction and editing options. Secondly, a volume growing algorithm with adjustable threshold range and minimal region size. Thirdly, a watershed transformation in two and three dimensions. In addition, the region input function of the Helax commercial radiation therapy planning system was available for comparison. All four approaches were applied under routine conditions to two-dimensional computed tomographic slices of the superior thoracic aperture, mid-chest, upper abdomen, mid-abdomen, pelvis and thigh; they were also applied to a 3D CT sequence of 72 slices using the three-dimensional extension of the algorithms. Time to generate the contours and their quality with respect to a reference model were determined. Manual input for a complete patient model required approximately 5 to 6 h for 72 CT slices (4.5 min/slice). If slight irregularities at object boundaries are accepted, this time can be reduced to 3.5 min/slice using the volume growing algorithm. However, generating a tetrahedron mesh from such a contour sequence for hyperthermia planning (the basis for finite-element algorithms) requires a significant amount of postediting. With the watershed algorithm extended to three dimensions, processing time can be further reduced to 3 min/slice while achieving satisfactory contour quality. Therefore, this method is currently regarded as offering some potential for efficient automated model generation in hyperthermia. In summary, the 3D volume growing algorithm and watershed transformation are both suitable for segmentation of even low-contrast objects. However, they are not always superior to user-friendly manual programs for contour generation. When the volume growing algorithm is used, the contours have to be postprocessed with suitable filters. The watershed transformation has a large potential if appropriately developed to 3D sequences and 3D interaction features. After all, the practicality and feasibility of every segmentation method critically depend on various details of the user software as pointed out in this article.

MRI diagnosis and staging of rectal carcinoma

W. Pegios, Th. J. Vogl, M. G. Mack, M. Hünerbein, H. Hintze, J. O. Balzer, H. Lobeck, P. Wust, P. Schlag, R. Felix Department of Radiology, Humboldt University of Berlin, Virchow Hospital, Augustenburger Platz 1, 13353 Berlin, Germany Department of Internal Medicine, Humboldt University of Berlin, Virchow Hospital, Augustenburger Platz 1, 13353 Berlin, Germany Department of Surgery, Humboldt University of Berlin, Virchow Hospital, Augustenburger Platz 1, 13353 Berlin, Germany Department of Pathology, Humboldt University of Berlin, Virchow Hospital, Augustenburger Platz 1, 13353 Berlin, Germany

A volume-surface integral equation method for solving Maxwell's equations in electrically inhomogeneous media using tetrahedral grids

Starting with the solution of Maxwells equations based on the volume integral equation (VIE) method, the transition to a volume-surface integral equation (VSIE) formulation is described. For the VSIE method, a generalized calculation method is developed to help us directly determine E fields at any interface combination in three-dimensional (3-D) electrically inhomogeneous media. The VSIE implementation described is based on separating the domain of interest into discrete parts using nonuniform tetrahedral grids. Interfaces are described using curved or plane triangles. Applying linear nodal elements, a general 3-D formulation is developed for handling scatter field contributions in the immediate vicinity of grid nodes, and this formulation is applicable to all multiregion junctions. The special case of a smooth interface around a grid node is given naturally by this formulation. Grid nodes are split into pairs of points for E-field calculation, and node normals are assigned to these points. The pairs of points are assigned to the elements adjoining the grid node. For each pair of points, the correct field jumps on the interface are given by a surface integral over the polarization surface charge density.