M. de Greef

Improving locoregional hyperthermia delivery using the 3-D controlled AMC-8 phased array hyperthermia system: A preclinical study

Background: The aim of this study is preclinical evaluation of our newly developed regional hyperthermia system providing 3-D SAR control: the AMC-8 phased array consisting of two rings, each with four 70 MHz waveguides. It was designed to achieve higher tumour temperatures and improve the clinical effectiveness of locoregional hyperthermia. Methods: The performance of the AMC-8 system was evaluated with simulations and measurements aiming at heating a centrally located target region in rectangular (30 × 30 × 110 cm) and elliptical (36 × 24 × 80 cm) homogeneous tissue equivalent phantoms. Three properties were evaluated and compared to its predecessor, the 2-D AMC-4 single ring four waveguide array: (1) spatial control and (2) size of the SAR focus, (3) the ratio between maximum SAR outside the target region and SAR in the focus. Distance and phase difference between the two rings were varied. Results: (1) Phase steering provides 3-D SAR control for the AMC-8 system. (2) The SAR focus is more elongated compared to the AMC-4 system, yielding a lower SAR level in the focus when using the same total power. This is counter-balanced by (3) a superficial SAR deposition which is half of that in the AMC-4 system, yielding a more favourable ratio between normal tissue and target SAR and allowing higher total power and up to 30% more SAR in the focus for 3 cm ring distance. Conclusion: The AMC-8 system is capable of 3-D SAR control and its SAR distribution is more favourable than for the 2-D AMC-4 system. This result promises improvement in clinical tumour temperatures.

Accelerated ray tracing for radiotherapy dose calculations on a GPU

PURPOSE The graphical processing unit (GPU) on modern graphics cards offers the possibility of accelerating arithmetically intensive tasks. By splitting the work into a large number of independent jobs, order-of-magnitude speedups are reported. In this article, the possible speedup of PLATOs ray tracing algorithm for dose calculations using a GPU is investigated. METHODS A GPU version of the ray tracing algorithm was implemented using NVIDIAs CUDA, which extends the standard C language with functionality to program graphics cards. The developed algorithm was compared based on the accuracy and speed to a multithreaded version of the PLATO ray tracing algorithm. This comparison was performed for three test geometries, a phantom and two radiotherapy planning CT datasets (a pelvic and a head-and-neck case). For each geometry, four different source positions were evaluated. In addition to this, for the head-and-neck case also a vertex field was evaluated. RESULTS The GPU algorithm was proven to be more accurate than the PLATO algorithm by elimination of the look-up table for z indices that introduces discretization errors in the reference algorithm. Speedups for ray tracing were found to be in the range of 2.1-10.1, relative to the multithreaded PLATO algorithm running four threads. For dose calculations the speedup measured was in the range of 1.5-6.2. For the speedup of both the ray tracing and the dose calculation, a strong dependency on the tested geometry was found. This dependency is related to the fraction of air within the patients bounding box resulting in idle threads. CONCLUSIONS With the use of a GPU, ray tracing for dose calculations can be performed accurately in considerably less time. Ray tracing was accelerated, on average, with a factor of 6 for the evaluated cases. Dose calculation for a single beam can typically be carried out in 0.6-0.9 s for clinically realistic datasets. These findings can be used in conventional planning to enable (nearly) real-time dose calculations. Also the importance for treatment optimization techniques is evident.

Optimization in hyperthermia treatment planning: The impact of tissue perfusion uncertainty

PURPOSE Hyperthermia treatment planning (HTP) potentially provides a valuable tool for monitoring and optimization of treatment. However, one of the major problems in HTP is that different sources of uncertainty degrade its reliability. Perfusion uncertainty is one of the largest uncertainties and hence there is an ongoing debate whether optimization should be limited to power-based strategies. In this study a systematic analysis is carried out addressing this question. METHODS The influence of perfusion uncertainty on optimization was analyzed for five patients with cervix uteri carcinoma heated with the AMC-8 70 MHz phased-array waveguide system. The effect of variations (up to +/- 50%) in both the muscle and tumor perfusion level was investigated. For every patient, reference solutions were calculated using constrained temperature-based optimization for 25 different and known perfusion distributions. Reference solutions were compared to those found by temperature-based optimization using standard perfusion values and four SAR-based optimization methods. The effect of heterogeneity was investigated by creating 5 x 100 perfusion distributions for different levels of local variation (+/- 25% and +/- 50%) and scale (1 and 2 cm). Here the performance of the temperature-based optimization method was compared to a SAR-based method that showed good performance in the previous analysis. RESULTS Solutions found with temperature-based optimization using a deviating perfusion distribution during optimization were found within 1.0 degrees C from the true optimum. For the SAR-based methods, deviations up to 2.9 degrees C were found. The spread found in these deviations was comparable, typically 0.5-1.0 degrees C. When applying intramuscle variation to the perfusion, temperature-based optimization proved to be the best strategy in 95% of the evaluated cases applying +/- 50% local variation. CONCLUSIONS Temperature-based optimization proves to be superior to SAR-based optimization both under variation of perfusion level as well as under the application of intratissue variation. The spread in achieved temperatures is comparable. These results are valid under the assumption of constant perfusion at hyperthermic levels. Although similar results are expected from models including thermoregulation, additional analysis is required to confirm this. In view of uncertainty in tissue perfusion and other modeling uncertainties, the authors propose feedback guided temperature-based optimization as the best candidate to improve thermal dose delivery during hyperthermia treatment.

Uncertainty in hyperthermia treatment planning: the need for robust system design

Hyperthermia treatment planning (HTP) is an important tool to improve the quality of hyperthermia treatment. It is a practical way of designing new hyperthermia systems and can be used to optimize the phase and amplitude settings to achieve optimal heating. One of the main challenges to be dealt with however is the uncertainty in the modeling parameters. The role of dielectric and combined dielectric and perfusion uncertainty on optimization was investigated by means of HTP for six different systems: the 70 MHz AMC-4 (AMC: Academic Medical Center) and AMC-8 system, a 130 MHz version of the AMC-8 system, a three-ring AMC-12 system operating at 130 MHz, the BSD SigmaEye applicator and a dipole applicator with three rings each containing six dipole pairs operated at 150 MHz. For five patients with cervix uteri carcinoma, a patient model was created based on a hyperthermia planning CT. Variation of tissue parameters resulted in 16 dielectric models for every patient. In addition, four thermal models were created to study the combined effect of perfusion and dielectric uncertainty. The impact of dielectric uncertainty on optimization is found to be clearly dependent on the number of channels and increased from 0.5 °C for four channels to 1.5 °C for the 18-channel system. As a result, the potential gain relative to the AMC-4 system for the 70 MHz AMC-8 system was found to be largely compromised, while for the remaining systems a robust improvement in T(90) was observed. The dipole applicator showed the best target heating for two out of five patients, while for three others heating efficacy was comparable to the 130 MHz AMC-12 system or the 130 MHz AMC-8 system (one patient). Considering the increase in complexity when the number of channels is increased from 12 to 18, the AMC-12 system is considered as a good compromise between heating efficacy and robustness while still being a manageable heating system in clinical practice.

Body Conformal Antennas for Superficial Hyperthermia: The Impact of Bending Contact Flexible Microstrip Applicators on Their Electromagnetic Behavior

Hyperthermia is a powerful radiosensitizer for treatment of superficial tumors. This requires body conformal antennas with a power distribution as homogeneous as possible over the skin area. The contact flexible microstrip applicators (CFMA) operating at 434 MHz exist in several sizes, including the large size 3H and 5H. This paper investigates the behavior of the electromagnetic fields for the 3H and 5H CFMA in both flat and curved configurations, and the impact on performance parameters like the penetration depth (PD) and the effective heating depth (EHD). The underlying theory behind the electromagnetic behavior in curved situations is presented as well as numerical simulations of both flat and curved configurations. The results are compared to measurements of the electromagnetic field distributions in a cylindrical patient model. Due to their large size multimode solutions may exist, and our results confirm their existence. These multimode solutions affect both the power distribution and PD/EHD, with a dependence on applicator curvature. Therefore, the performance parameters like PD and EHD need to be carefully assessed when bending large size CFMA applicators to conform to the patient body. This conclusion also holds for other types of large size surface current applicators.

3D versus 2D steering in patient anatomies: A comparison using hyperthermia treatment planning

Purpose: In this study hyperthermia treatment planning is used to investigate whether the target temperature during hyperthermia treatment can be increased using the 3D AMC-8 instead of the 2D AMC-4 system (AMC: Academic Medical Center). Methods and materials: The heating ability of the AMC-4 and AMC-8 system was analysed for five patients with cervix uteri carcinoma. Dielectric and thermal models were generated, based on a hyperthermia planning computerised tomography (CT), at a resolution of 2.5 × 2.5 × 5.0 mm3. Calculation of the electric fields with the finite-difference time-domain method was followed by SAR- and temperature-based optimisation. The ability to correct for axial shifts of the patient by phase/amplitude steering was investigated for both systems. Finally, it was investigated whether adjusting the ring-to-ring distance of the AMC-8 system can be used for further optimisation. Results: An average increase in T90 of ∼0.5°C (0.2°–0.8°C) was found for the AMC-8 system compared to the AMC-4 system. The gain in T50 and T10 was also 0.5°C on average. The additional power required to achieve this gain was 36% to 71% of the power required for the AMC-4 system. The AMC-8 system has the capability of correcting changes in axial position (−8 cm, +8 cm), contrary to the AMC-4 system. For both systems the axial position should be known within 1–2 cm. Conclusions: Hyperthermia treatment with the AMC-8 system can lead to a clinically relevant increase of the target temperature compared to treatment with the AMC-4 system. The AMC-8 system provides large freedom in the axial positioning of the patient.

Improved power steering with double and triple ring waveguide systems: The impact of the operating frequency

Introduction: Regional hyperthermia systems with 3D power steering have been introduced to improve tumour temperatures. The 3D 70-MHz AMC-8 system has two rings of four waveguides. The aim of this study is to evaluate whether T90 will improve by using a higher operating frequency and whether further improvement is possible by adding a third ring. Methods: Optimised specific absorption rate (SAR) distributions were evaluated for a centrally located target in tissue-equivalent phantoms, and temperature optimisation was performed for five cervical carcinoma patients with constraints to normal tissue temperatures. The resulting T90 and the thermal iso-effect dose (i.e. the number of equivalent min at 43°C) were evaluated and compared to the 2D 70-MHz AMC-4 system with a single ring of four waveguides. FDTD simulations were performed at 2.5 × 2.5 × 5 mm3 resolution. The applied frequencies were 70, 100, 120, 130, 140 and 150 MHz. Results: Optimised SAR distributions in phantoms showed an optimal SAR distribution at 140 MHz. For the patient simulations, an optimal increase in T90 was observed at 130 MHz. For a two-ring system at 70 MHz the gain in T90 was about 0.5°C compared to the AMC-4 system, averaged over the five patients. At 130 MHz the average gain in T90 was ∼1.5°C and ∼2°C for a two and three-ring system, respectively. This implies an improvement of the thermal iso-effect dose with a factor ∼12 and ∼30, respectively. Conclusion: Simulations showed that a 130-MHz two-ring waveguide system yields significantly higher tumour temperatures compared to 70-MHz single-ring and double-ring waveguide systems. Temperatures were further improved with a 130-MHz triple-ring system.

The impact of the waveguide aperture size of the 3D 70 MHz AMC-8 locoregional hyperthermia system on tumour coverage

The 70 MHz AMC-4 system, with one ring of four waveguides, provides 2D power steering. The newly developed AMC-8 system enables 3D steering, using two rings of four 70 MHz waveguides. The current waveguide aperture size is 20.2 x 34.3 cm(2). Waveguides and water boluses cover a large area of the body, which is not ideal for short patients. The aim of this study is investigating the impact of smaller waveguides on tumour coverage, using treatment planning. Finite-difference time-domain simulations were performed at 2.5 x 2.5 x 5 mm(3) resolution. Virtual AMC-8 systems with waveguide aperture sizes of 20.5 x 34.25, 17.5 x 34.25, 14.5 x 34.25, 11.5 x 34.25, 8.5 x 34.25 cm(2) and the AMC-4 system were modelled. Simulations were performed for elliptical (36 x 24 x 100 cm(3)) tissue-equivalent phantoms and for five cervical cancer patients. For the phantoms S(ratio) (SAR(max_border)/SAR(target)) was evaluated for standard and optimized settings. For the patients, temperature distributions were evaluated after optimization of tumour temperature, while limiting normal tissue temperatures to 45 degrees C. Phantom simulations showed a favourable S(ratio) for all two-ring systems, compared to the AMC-4 system, for optimized phase-amplitude settings. Patient simulations demonstrated that the improvement in T(90) for the operational AMC-8 system was approximately 0.5 degrees C. This improvement was independent of the aperture size. The average number of imminent hot spots and their total volume was almost comparable for 8.5 and 20.5 cm wide apertures, but the locations were different. Two-ring waveguide systems with eight antennas and aperture sizes in the range from 20.5 x 34.25 cm(2) to 8.5 x 34.25 cm(2) showed a stable gain in tumour temperature compared to a single-ring four-antenna system with 20.5 x 34.25 cm(2) wide apertures.

Increasing the HIFU ablation rate through an MRI-guided sonication strategy using shock waves: feasibility in the in vivo porcine liver

This study investigated whether an MR-guided pulsed HIFU ablation strategy could be implemented under clinical conditions, using a transducer designed for uterine fibroid ablation, to obtain an ablation rate that is sufficiently high for clinical abdominal HIFU therapy in highly perfused organs. A pulsed HIFU ablation strategy, aimed at increasing the energy absorption in the HIFU focal area by local shock wave formation in the non-linear pressure regime, was compared to an energy-equivalent continuous wave sonication strategy in the linear pressure regime. Both ablation strategies were used for transcutaneous sonication of pre-defined treatment cells in the livers of 5 pigs in vivo. Temperature evolution in both the target area as well as the pre-focal muscle layer was monitored simultaneously using MR thermometry. Local energy absorption and thermal dose volumes were shown to be increased using the pulsed ablation strategy, while preserving healthy tissue in the near field of the acoustic beam. Respiratory motion compensation of both acoustic energy delivery and MR thermometry was applied through gating based on MR navigator echoes. Histopathology showed that confluent vacuolated thermal lesions were created when the pulsed ablation strategy was used. Additionally, it was shown that the heat sink effect caused by the presence of larger vessels could be overcome. The pulsed HIFU ablation strategy achieved an ablation rate of approximately 4 ml per hour in the in vivo porcine liver, without causing undesired damage to healthy tissues in the near field.