Mirko Weihrauch

Adaptation of antenna profiles for control of MR guided hyperthermia (HT) in a hybrid MR‐HT system

A combined numerical-experimental iterative procedure, based on the Gauss-Newton algorithm, has been developed for control of magnetic resonance (MR)-guided hyperthermia (HT) applications in a hybrid MR-HT system BSD 2000 3D-MRI. In this MR-HT system, composed of a 3-D HT applicator Sigma-Eye placed inside a tunnel-type MR tomograph Siemens MAGNETOM Symphony (1.5 T), the temperature rise due to the HT radiation can be measured on-line in three dimensions by use of the proton resonance frequency shift (PRFS) method. The basic idea of our iterative procedure is the improvement of the systems characterization by a step-by-step modification of the theoretical HT antenna profiles (electric fields radiated by single antennas). The adaptation of antenna profiles is efficient if the initial estimates are radiation fields calculated from a good a priori electromagnetic model. Throughout the iterative procedure, the calculated antenna fields (FDTD) are step-by-step modified by comparing the calculated and experimental data, the latter obtained using the PRFS method. The procedure has been experimentally tested on homogeneous and inhomogeneous phantoms. It is shown that only few comparison steps are necessary for obtaining a dramatic improvement of the general predictability and quality of the specific absorption rate (SAR) inside the MR-HT hybrid system.

Non-invasive magnetic resonance thermography during regional hyperthermia

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43–45°C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application. Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Δφ corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per °C at 1.5 Tesla), diffusion coefficient D (ΔD/D = 2–3 % per °C), longitudinal relaxation time T1 ( per °C), and equilibrium magnetisation M0 ( per °C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes. The PRFS method is the most sensitive proton imaging technique. A sensitivity of ±0.5°C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T1 method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA− appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3°C.

Simulation of different applicator positions for treatment of a presacral tumour

Introduction: Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat due to the complex anatomy of the pelvis, which reflect, shield and diffract the power. This study is to clarify whether a change of position of the Sigma-Eye applicator in this region can improve the heating. Material and methods: Finite element (FE) planning calculations were made for a phantom model with a proximal presacral tumour using a fixed 100 MHz radiofrequency radiation. Shifts of the applicator were simulated in 1 cm steps in x-(lateral), y-(posterior) and z-(longitudinal) direction. Computations also considered the network effects of the Sigma-Eye applicator. Optimisation of the phases and amplitudes for all positions were performed after solving the bioheat-transfer-equation. The parameters T90, T50, sensitivity, hot spot volume and total deposited power have been sampled for every applicator position with optimised plans and a standard plan. Results: The ability to heat a presacral tumour clearly depends on the applicator position, for standard antenna adjustment and also for optimised steering of the Sigma-Eye applicator. The y-direction (anterior-posterior) is very sensitive. Using optimised steering for each position, in z-direction (longitudinal), we found an unexpected additional optimum at 8 cm cranial from the middle position of the phantom. The x-direction (lateral) is in a clinical setting less important and shows only smaller changes of T90 with an expected optimum in the central position. A positioning of the applicator in the axial and anterior position of the mid-pubic symphysis should be avoided for treatment of the presacral region, regardless of the used adjustment. Use of amplitude and phase optimisation yields better T90 values than plans optimised only by phases, but they are much more sensitive for small variations of phases and amplitudes during a treatment, and the total power of the Sigma-Eye applicator can be restricted by the treatment software. Conclusions: Complex geometry of the human pelvis seems to be the reason for the difficulties to warm up the proximal presacral region. The assumption that every position can be balanced by a proper phase adaption, is true only in a small range. A centring of the applicator on the mid-pubic symphysis to heat this region should be avoided. From the practical point of view improved warming should be performed by optimisation of phases only.

Comparison of MR-thermography and planning calculations in phantoms

A systematic comparison of three-dimensional MR (magnetic resonance) thermography and planning calculations in phantoms for the hyperthermia (HT) SIGMA-Eye applicator. We performed 2 x 6 experiments in a homogeneous cylindrical and a heterogeneous elliptical phantom by adjusting 82 different patterns with different phase control inside an MR tomograph (Siemens Magnetom Symphony, 1.5 Tesla). For MR thermography, we employed the proton resonance frequency shift method with a drift correction based on silicon tubes. For the planning calculations, we used the finite-difference time-domain (FDTD) method and, in addition, modeled the antennas and the transforming network. We generated regions according to a segmentation of bones and tissue, and used an interpolation technique with a subgrid of 0.5 cm size at the interfaces. A Gauss-Newton solver has been developed to adapt phases and amplitudes. A qualitative agreement between the planning program and measurements was obtained, including a correct prediction of hot spot locations. The final deviation between planning and measurement is in the range of 2-3 W/kg, i.e., below 10%. Additional HT phase and amplitude adaptation, as well as position correction of the phantom in the SIGMA-Eye, further improve the results. HT phase corrections in the range of 30-40 degrees and HT amplitude corrections of +/- 20-30% are required for the best agreement. The deviation /MR-FDTD/, and the HT phase/amplitude corrections depend on the type of phantom, certain channel groups, pattern steering, and the positioning error. Appropriate agreement between three-dimensional specific absorption rate distributions measured by MR-thermography and planning calculations is achieved, if the correct position and adapted feed point parameters are considered. As long as feed-point parameters are uncertain (i.e., cannot be directly measured during therapy), a prospective planning will remain difficult. However, we can use the information of MR thermography to better predict the patterns in the future even without the knowledge of feed-point parameters.

Which technique for radiation is most beneficial for patients with locally advanced cervical cancer? Intensity modulated proton therapy versus intensity modulated photon treatment, helical tomotherapy and volumetric arc therapy for primary radiation – an intraindividual comparison

BackgroundTo compare highly sophisticated intensity-modulated radiotherapy (IMRT) delivered by either helical tomotherapy (HT), RapidArc (RA), IMRT with protons (IMPT) in patients with locally advanced cervical cancer.Methods and materialsTwenty cervical cancer patients were irradiated using either conventional IMRT, VMAT or HT; ten received pelvic (PEL) and ten extended field irradiation (EFRT). The dose to the planning-target volume A (PTV_A: cervix, uterus, pelvic ± para-aortic lymph nodes) was 1.8/50.4 Gy. The SIB dose for the parametrium (PTV_B), was 2.12/59.36 Gy. MRI-guided brachytherapy was administered with 5 fractions up to 25 Gy. For EBRT, the lower target constraints were 95% of the prescribed dose in 95% of the target volume. The irradiated small bowel (SB) volumes were kept as low as possible. For every patient, target parameters as well as doses to the organs at risk (SB, bladder, rectum) were evaluated intra-individually for IMRT, HT, VMAT and IMPT.ResultsAll techniques provided excellent target volume coverage, homogeneity, conformity. With IMPT, there was a significant reduction of the mean dose (Dmean) of the SB from 30.2 ± 4.0 Gy (IMRT); 27.6 ± 5.6 Gy (HT); 34.1 ± 7.0 (RA) to 18.6 ± 5.9 Gy (IMPT) for pelvic radiation and 26.3 ± 3.2 Gy (IMRT); 24.0 ± 4.1 (HT); 25.3 ± 3.7 (RA) to 13.8 ± 2.8 Gy (IMPT) for patients with EFRT, which corresponds to a reduction of 38-52% for the Dmean (SB). Futhermore, the low dose bath (V10Gy) to the small bowel was reduced by 50% with IMPT in comparison to all photon techniques. Furthermore, Dmean to the bladder and rectum was decresed by 7-9 Gy with IMPT in patents with pelvic radiation and EFRT.ConclusionAll modern techniques (were proved to be dosimetrically adequate regarding coverage, conformity and homogeneity of the target. Protons offered the best sparing of small bowel and rectum and therefore could contribute to a significant reduction of acute and late toxicity in cervical cancer treatment.

Regularized antenna profile adaptation in online hyperthermia treatment

PURPOSE Online optimization of annular-phased-array hyperthermia (HT) is based on planning tools and magnetic resonance (MR) thermometry. Until now, the method has been validated in phantoms. Further developments and extensions are required for clinical purposes. In particular, the problem of deducing the electric field distribution inside the patient from MR thermometry is ill-posed, which leads to an amplification of measurement errors. A method to overcome this difficulty is proposed. METHODS The authors utilized a regularized Gauss-Newton algorithm with a fast bioheat transfer equation (BHTE) approximation to identify the field parameters. To evaluate the method, simulations with patient models are conducted and a treatment data set obtained from a heat treatment performed in the hybrid HT-MR system at the Charité Medical School is used to visualize the error amplification. RESULTS The regularization leads to a significantly improved accuracy of the predicted electric fields and temperatures compared to an unregularized approach. The BHTE approximation enables highly accurate temperature predictions in real-time. CONCLUSIONS Regularization proves to be necessary to identify electromagnetic field parameters. The proposed method is able to reproduce measurements without overfitting to the noise in the MR measurements and results in an improved treatment planning.

Regional hyperthermia of the abdomen, a pilot study towards the treatment of peritoneal carcinomatosis

BackgroundPeritoneal carcinomatosis occurs in different cancer subtypes and is associated with a dismal prognosis. Some doubts remain whether the whole abdomen can be treated by regional hyperthermia, therefore we analyzed feasibility conducting a pilot study.MethodsA simulation of the abdominopelvic heat distribution in 11 patients with peritoneal carcinomatosis was done using the HyperPlan software and the SIGMA-60 and SIGMA-Eye applicators. Tissue-specific region-related electrical and thermal parameters were used to solve the Maxwell’s equations and the bioheat-transfer equation. Three-dimensional specific absorption rate (SAR) distributions and, additionally, estimated region-related perfusion rates were used to solve the bioheat-transfer equation. The predicted SAR and temperature distributions were compared with minimally invasive measurements in pelvic reference points.ResultsIn 11 patients (7 of them treated in the SIGMA-60 and 4 in the SIGMA-Eye applicator) the measured treatment variables (SAR, temperatures in the pelvic reference points) indicated that the heated volumes were higher for the SIGMA-Eye applicator. The mean computed abdominal SARs were less for the SIGMA-Eye (33 versus 44 W/kg). Nevertheless, the temperature distributions in the abdomen (peritoneal cavity) were more homogeneous in the SIGMA-Eye applicator as compared to the SIGMA-60 as indicated by higher values of T90 (mean 40.2 versus 38.2 °C) and T50 (mean 41.1 versus 40.2 °C), while the maximum temperatures were similar (in the range 41 to 43 °C). Even though the mean abdominal SAR was lower in the SIGMA-Eye, the heat distribution covered a larger volume of the abdomen (in particular the upper abdomen).For the SIGMA-60 applicator the achieved T90 appeared to be limited between 41 and 42 °C, for the SIGMA Eye applicator more effective T90 in the range 42 to 43 °C were obtained.ConclusionOur results suggest that an adequate heating of the abdomen and therefore abdominal regional hyperthermia in PC patients appears feasible. The SIGMA-Eye applicator appears to be superior compared to the SIGMA-60 applicator for abdominal hyperthermia.

Hyperthermia classic commentary: ‘Simulation studies promote technological development of radiofrequency phased array hyperthermia’ by Peter Wust et al., International Journal of Hyperthermia 1996;12:477–494

Simulation studies can estimate the potentials of regional hyperthermia based on the multi-antenna principle. They postulate an optimal parameter setup (phases, amplitudes) that should increase temperatures in heat treatments by 1 °C or more. However in praxi, slight inaccuracies and uncertainties accumulate in a way that the optimal adjustment is typically missed during a real treatment. The reasons for these errors are electrical and geometrical. A way out is an on-line control, which adapts the plans to the actual distributions. Magnetic resonance thermography is employed for on-line control, and control software has been developed. However, there is still a long way to reach the technological endpoint of multi-antenna systems for clinical applications.

Radiofrequency applicator concepts for simultaneous MR imaging and hyperthermia treatment of glioblastoma multiforme

Abstract Glioblastoma multiforme is the most frequent and most aggressive malignant brain tumor with de facto no long term curation by the use of current multimodal therapeutic approaches. The efficacy of brachytherapy and enhancing interstitial hyperthermia has been demonstrated. RF heating at ultrahigh fields (B0=7.0T, f=298MHz) has the potential of delivering sufficiently large thermal dosage for hyperthermia of relatively large tumor areas. This work focuses on electromagnetic field (EMF) simulations and provides realistic applicator designs tailored for simultaneous RF heating and MRI. Our simulations took advantage of target volumes derived from patient data, and our preliminary results suggest that RF power can be focused to both a small tumor area and a large clinical target volume.

Optimization of Clinical Radiofrequency Hyperthermia by Use of MR-Thermography in a Hybrid System

The method to acquire MR-temperature datasets by the proton-resonance-shift method is outlined and verified in phantoms and patients. An online adaptation process has been developed to achieve agreement between planning calculations and MR-temperature measurements. This is used as a basis to optimize the pattern by a control loop. This procedure is successful after the second iteration step in phantoms. In patients an increase of SAR (specific absorption rate) in the tumor relative to the surroundings has been demonstrated for the MR-temperature increase as optimization variable. The optimization results are even improved under clinical conditions, if perfusion and thermal conduction are considered during the optimization procedure. The mathematical background is presented.