Professor Uwe Oelfke

Deputy Head of Division: Radiotherapy Physics Modelling

OrcID: 0000-0003-2309-0814

Phone: +44 20 8915 6221

Email: [email protected]

Location: Sutton

Uwe Oelfke

OrcID: 0000-0003-2309-0814

Phone: +44 20 8915 6221

Email: [email protected]

Location: Sutton

Biography

Professor Oelfke is Deputy Head of the Division of Radiotherapy and Imaging, Head of the Joint Department of Physics (The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust), Head of the Centre for Cancer Imaging and Team Leader for the Radiotherapy Physics Modelling Team.

His career began in Theoretical Nuclear Physics, gaining his PhD at the University of Hanover in 1990. He then moved to TRIUMF, Canada's national laboratory for particle and nuclear physics where he worked as a Post Doctoral Fellow, initially with the Nuclear Theory Group. He then moved to the Batho Biomedical Facility as a Research Associate, looking at Proton & Pion Therapy. It was at this stage he transferred from Nuclear to Medical Physics.

In 1997 he returned to Germany to join the German Cancer Research Centre (DKFZ) in Heidelberg as a Research Associate, where he became a group leader in 2001 and received a Professorship of Medical Radiation Physics from Heidelberg University in 2004. During 15 years in Heidelberg, his research was focused on adaptive and image-guided radiation therapy, treatment planning and modelling and Hadron therapy.

He firmly believes that medical physics research on cancer imaging and therapy is an essential component to improve the clinical outcomes of radiation oncology. ICR and RMH, as a world leading comprehensive cancer centre, now initiates the next generation of radiotherapy treatments by combining the most recent developments in cancer biology, cancer therapeutics and medical physics in a truly interdisciplinary approach.

Outside of work Professor Oelfke enjoys hiking with his family and playing table tennis.

Professor Oelfke is a member of the Cancer Research UK Convergence Science Centre, which brings together leading researchers in engineering, physical sciences, life sciences and medicine to develop innovative ways to address challenges in cancer.

Convergence Science Centre

Qualifications

PhD in Theoretical Nuclear Physics, University of Hanover, Germany.

Awards, Prizes or Honours

Certified Member, Canadian College of Physicists in Medicine, 1998.

Canada Research Chair, McMaster University, Hamilton, Ontario, 2001.

Elected Fellow, Institute of Physics, London, UK, 2004.

Member, European Society of Therapeutic Radiology and Oncology, 2006.

Editorial Boards

Physics in Medicine & Biology, 2007-2012.

Physics in Medicine & Biology (International Advisory Board), 2012.

Radiation Oncology, 2006.

European Journal of Medical Physics, 2006.

External Committees

Multidisciplinary Expert Panel Review, Panel Member, Cancer Research UK, 2014.

CyberKnife Clinical Advisory Board, Member, Accuray, 2017.

MR Linac Scientific Advisory Board, Member, Zurich University, 2017.

KVI Cart Review Panel, Member, University of Groningen, 2017.

Life Sciences and Health Metrology Programme Steering Board, Member, National Physical Laboratory, 2016.

CCAP Management Board, Member, Centre for the Clinical Application of Particles, 2017.

Types of Publications

Journal articles

Kyas, I. Partridge, M. Hesse, B.-.M. Oelfke, U. Schlegel, W (2004) [Validation of a scatter correction method for IMRT verification using portal imaging].. Show Abstract full text

Complex dose-delivery techniques, as currently applied in intensity-modulated radiation therapy (IMRT), require a highly efficient treatment-verification process. The present paper deals with the problem of the scatter correction for therapy verification by use of portal images obtained by an electronic portal imaging device (EPID) based on amorphous silicon. It also presents an iterative method for the scatter correction of portal images based on Monte Carlo-generated scatter kernels. First applications of this iterative scatter-correction method for the verification of intensity-modulated treatments are discussed on the basis of MVCT- and dose reconstruction. Several experiments with homogeneous and anthropomorphic phantoms were performed in order to validate the scatter correction method and to investigate the precision and relevance in view of its clinical applicability. It is shown that the devised concept of scatter correction significantly improves the results of MVCT- and dose reconstruction models, which is in turn essential for an exact online IMRT verification.

Nioutsikou, E. Webb, S. Panakis, N. Bortfeld, T. Oelfke, U (2005) Reconsidering the definition of a dose-volume histogram. full text
Menten, M.J. Guckenberger, M. Herrmann, C. Krauß, A. Nill, S. Oelfke, U. Wilbert, J (2012) Comparison of a multileaf collimator tracking system and a robotic treatment couch tracking system for organ motion compensation during radiotherapy.. Show Abstract full text

PURPOSE: One limitation of accurate dose delivery in radiotherapy is intrafractional movement of the tumor or the entire patient which may lead to an underdosage of the target tissue or an overdosage of adjacent organs at risk. In order to compensate for this movement, different techniques have been developed. In this study the tracking performances of a multileaf collimator (MLC) tracking system and a robotic treatment couch tracking system were compared under equal conditions. METHODS: MLC tracking was performed using a tracking system based on the Siemens 160 MLC. A HexaPOD robotic treatment couch tracking system was also installed at the same linac. A programmable 4D motion stage was used to reproduce motion trajectories with different target phantoms. Motion localization of the target was provided by the 4D tracking system of Calypso Medical Inc. The gained positional data served as input signal for the control systems of the MLC and HexaPOD tracking systems attempting to compensate for the target motion. The geometric and dosimetric accuracy for the tracking of eight different respiratory motion trajectories was investigated for both systems. The dosimetric accuracy of both systems was also evaluated for the tracking of five prostate motion trajectories. RESULTS: For the respiratory motion the average root mean square error of all trajectories in y direction was reduced from 4.1 to 2.0 mm for MLC tracking and to 2.2 mm for HexaPOD tracking. In x direction it was reduced from 1.9 to 0.9 mm (MLC) and to 1.0 mm (HexaPOD). The average 2%/2 mm gamma pass rate for the respiratory motion trajectories was increased from 76.4% for no tracking to 89.8% and 95.3% for the MLC and the HexaPOD tracking systems, respectively. For the prostate motion trajectories the average 2%/2 mm gamma pass rate was 60.1% when no tracking was applied and was improved to 85.0% for MLC tracking and 95.3% for the HexaPOD tracking system. CONCLUSIONS: Both systems clearly increased the geometric and dosimetric accuracy during tracking of respiratory motion trajectories. Thereby, the geometric accuracy was increased almost equally by both systems, whereas the dosimetric accuracy of the HexaPOD tracking system was slightly better for all considered respiratory motion trajectories. Substantial improvement of the dosimetric accuracy was also observed during tracking of prostate motion trajectories during an intensity-modulated radiotherapy plan. Thereby, the HexaPOD tracking system showed better results than the MLC tracking.

Bangert, M. Ziegenhein, P. Oelfke, U (2013) Comparison of beam angle selection strategies for intracranial IMRT.. Show Abstract full text

PURPOSE: Various strategies to select beneficial beam ensembles for intensity-modulated radiation therapy (IMRT) have been suggested over the years. These beam angle selection (BAS) strategies are usually evaluated against reference configurations applying equispaced coplanar beams but they are not compared to one another. Here, the authors present a meta analysis of four BAS strategies that incorporates fluence optimization (FO) into BAS by combinatorial optimization (CO) and one BAS strategy that decouples FO from BAS, i.e., spherical cluster analysis (SCA). The underlying parameters of the BAS process are investigated and the dosimetric benefits of the BAS strategies are quantified. METHODS: For three intracranial lesions in proximity to organs at risk (OARs) the authors compare treatment plans applying equispaced coplanar beam ensembles with treatment plans using five different BAS strategies, i.e., four CO techniques and SCA, to establish coplanar and noncoplanar beam ensembles. Treatment plans applying 5, 7, 9, and 11 beams are investigated. For the CO strategies the authors perform BAS runs with a 5°, 10°, 15°, and 20° angular resolution, which corresponds to a minimum of 18 coplanar and a maximum of 1400 noncoplanar candidate beams. In total 272 treatment plans with different BAS settings are generated for every patient. The quality of the treatment plans is compared based on the protection of OARs yet integral dose, target homogeneity, and target conformity are also considered. RESULTS: It is possible to reduce the average mean and maximum doses in OARs by more than 4 Gy (1 Gy) with optimized noncoplanar (coplanar) beam ensembles found with BAS by CO or SCA. For BAS including FO by CO, the individual algorithm used and the angular resolution in the space of candidate beams does not have a crucial impact on the quality of the resulting treatment plans. All CO algorithms yield similar target conformity and slightly improved target homogeneity in comparison to equispaced coplanar setups. Furthermore, optimized coplanar (noncoplanar) beam ensembles enabled more than a 6% (5%) reduction of the integral dose. For SCA, however, integral dose was increased and target conformity was decreased in comparison to equispaced coplanar setups-especially for a small number of beams. CONCLUSION: Both BAS strategies incorporating FO by CO and independent BAS strategies excluding FO provide dose savings in OARs for optimized coplanar and especially noncoplanar beam ensembles; they should not be neglected in the clinic.

Fast, M.F. Teymurazyan, A. Pang, G. Oelfke, U. Rowlands, J.A (2013) Finding an improved amorphous-silicon x-ray flat-panel detector configuration for the in-line geometry.. Show Abstract full text

We have previously investigated the use of a conventional amorphous-silicon flat-panel detector (FPD) for intrafractional image guidance in the in-line geometry. In this configuration, the FPD is mounted between the patient and the treatment head, with the front of the FPD facing towards the patient. By geometrically separating signals from the diagnostic (kV) and treatment (MV) beams, it is possible to monitor the patient and treatment beam at the same time. In this study, we propose an FPD design based on existing technology with a 70% reduced up-stream areal density that is more suited to this new application. We have investigated our FPD model by means of a validated Monte Carlo simulation. Experimentally, simple rectangular fields were used to irradiate through the detector and observe the impact of removing detector components such as the support structure or the phosphor screen on the measured signal. The proposed FPD performs better than the conventional FPD: (i) attenuation of the MV beam is decreased by 60%; (ii) the MV signal is reduced by 20% for the primary MV field region which can avoid saturation of the FPD; and (iii) long range scatter from the MV into the kV region of the detector is greatly reduced.

Ziegenhein, P. Kamerling, C.P. Bangert, M. Kunkel, J. Oelfke, U (2013) Performance-optimized clinical IMRT planning on modern CPUs.. Show Abstract full text

Intensity modulated treatment plan optimization is a computationally expensive task. The feasibility of advanced applications in intensity modulated radiation therapy as every day treatment planning, frequent re-planning for adaptive radiation therapy and large-scale planning research severely depends on the runtime of the plan optimization implementation. Modern computational systems are built as parallel architectures to yield high performance. The use of GPUs, as one class of parallel systems, has become very popular in the field of medical physics. In contrast we utilize the multi-core central processing unit (CPU), which is the heart of every modern computer and does not have to be purchased additionally. In this work we present an ultra-fast, high precision implementation of the inverse plan optimization problem using a quasi-Newton method on pre-calculated dose influence data sets. We redefined the classical optimization algorithm to achieve a minimal runtime and high scalability on CPUs. Using the proposed methods in this work, a total plan optimization process can be carried out in only a few seconds on a low-cost CPU-based desktop computer at clinical resolution and quality. We have shown that our implementation uses the CPU hardware resources efficiently with runtimes comparable to GPU implementations, at lower costs.

Kraus, K.M. Heath, E. Oelfke, U (2011) Dosimetric consequences of tumour motion due to respiration for a scanned proton beam.. Show Abstract full text

A method for simulating spot-scanned delivery to a moving tumour was developed which uses patient-specific image and plan data. The magnitude of interplay effects was investigated for two patient cases under different fractionation and respiratory motion variation scenarios. The use of volumetric rescanning for motion mitigation was also investigated. For different beam arrangements, interplay effects lead to severely distorted dose distributions for a single fraction delivery. Baseline shift variations for single fraction delivery reduced the dose to the clinical target volume (CTV) by up to 14.1 Gy. Fractionated delivery significantly reduced interplay effects; however, local overdosage of 12.3% compared to the statically delivered dose remained for breathing period variations. Variations of the tumour baseline position and respiratory period were found to have the largest influence on target inhomogeneity; these effects were reduced with fractionation. Volumetric rescanning improved the dose homogeneity. For the CTV, underdosage was improved by up to 34% in the CTV and overdosage to the lung was reduced by 6%. Our results confirm that rescanning potentially increases the dose homogeneity; however, it might not sufficiently compensate motion-induced dose distortions. Other motion mitigation techniques may be required to additionally treat lung tumours with scanned proton beams.

Siggel, M. Ziegenhein, P. Nill, S. Oelfke, U (2012) Boosting runtime-performance of photon pencil beam algorithms for radiotherapy treatment planning.. Show Abstract full text

Pencil beam algorithms are still considered as standard photon dose calculation methods in Radiotherapy treatment planning for many clinical applications. Despite their established role in radiotherapy planning their performance and clinical applicability has to be continuously adapted to evolving complex treatment techniques such as adaptive radiation therapy (ART). We herewith report on a new highly efficient version of a well-established pencil beam convolution algorithm which relies purely on measured input data. A method was developed that improves raytracing efficiency by exploiting the capability of modern CPU architecture for a runtime reduction. Since most of the current desktop computers provide more than one calculation unit we used symmetric multiprocessing extensively to parallelize the workload and thus decreasing the algorithmic runtime. To maximize the advantage of code parallelization, we present two implementation strategies - one for the dose calculation in inverse planning software, and one for traditional forward planning. As a result, we could achieve on a 16-core personal computer with AMD processors a superlinear speedup factor of approx. 18 for calculating the dose distribution of typical forward IMRT treatment plans.

Zabel-du Bois, A. Nill, S. Ulrich, S. Oelfke, U. Rhein, B. Haering, P. Milker-Zabel, S. Schwahofer, A (2012) Dosimetric integration of daily mega-voltage cone-beam CT for image-guided intensity-modulated radiotherapy.. Show Abstract full text

PURPOSE: The goal of this work was to compare different methods of incorporating the additional dose of mega-voltage cone-beam CT (MV-CBCT) for image-guided intensity modulated radiotherapy (IMRT) of different tumor entities. MATERIAL AND METHODS: The absolute dose delivered by the MV-CBCT was calculated and considered by creating a scaled IMRT plan (scIMRT) by renormalizing the clinically approved plan (orgIMRT) so that the sum with the MV-CBCT dose yields the same prescribed dose. In the other case, a newly optimized plan (optIMRT) was generated by including the dose distribution of the MV-CBCT as pre-irradiation. Both plans were compared with the orgIMRT plan and a plan where the last fraction was skipped. RESULTS: No significant changes were observed regarding the 95% conformity index of the target volume. The mean dose of the organs at risk (OAR) increased by approx. 7% for the scIMRT plan and 5% for the optIMRT plan. A significant increase of the mean dose to the outline contour was observed, ranging from 3.1 ± 1.3% (optIMRT) to 13.0 ± 6.1% (scIMRT) for both methods over all entities. If the dose of daily MV-CBCT would have been ignored, the additional dose accumulated to nearly a whole treatment fraction with a general increase of approx. 10% to the OARs and approx. 4% to the target volume. CONCLUSION: Both methods of incorporating the additional MV-CBCT dose into the treatment plan are suitable for clinical practice. The dose distribution of the target volume could be achieved as conformal as with the orgIMRT plan, while only a moderate increase of mean dose to OAR was observed.

Fast, M.F. Krauss, A. Oelfke, U. Nill, S (2012) Position detection accuracy of a novel linac-mounted intrafractional x-ray imaging system.. Show Abstract full text

PURPOSE: The authors have developed a system that monitors intrafractional target motion perpendicular to the treatment beam with the aid of radioopaque markers by means of separating kV image and megavoltage (MV) treatment field on a single flat-panel detector. METHODS: They equipped a research Siemens Artiste linear accelerator (linac) with a 41 × 41 cm(2) a-Si flat-panel detector underneath the treatment head. The in-line geometry allows kV (imaging) and MV (treatment) beams to share closely aligned beam axes. The kV source, usually mounted directly across from the flat-panel imager, was retracted toward the gantry by 13 cm to intentionally misalign kV and MV beams, resulting in a geometric separation of MV treatment field and kV image on the detector. Two consecutive images acquired within 140 ms (the first with MV-only and the second with kV and MV signal) were subtracted to generate a kV-only image. The images were then analyzed "online" with an automated threshold-based marker detection algorithm. They employed a 3D and a 4D phantom equipped with either a single radioopaque marker or three Calypso beacons to mimic respiratory motion. Measured room positions were either cross-referenced with a phantom voltage signal (single marker) or the Calypso system. The accuracy of the back-projection (from detected marker positions into room coordinates) was verified by a simulation study. RESULTS: A phantom study has demonstrated that the imaging framework is capable of automatically detecting marker positions and sending this information to the tracking tool at an update rate of 7.14 Hz. The system latency is 86.9 ± 1.0 ms for single marker detection in the absence of MV radiation. In the presence of a circular MV field of 5 cm diameter, the latency is 87.1 ± 0.9 ms. The total RMS position detection accuracy is 0.20 mm (without MV radiation) and 0.23 mm (with MV). CONCLUSIONS: Based on the evaluated motion patterns and MV field size, the positional accuracy and system latency indicate that this system is suitable for real-time adaptive applications.

Fast, M.F. Koenig, T. Oelfke, U. Nill, S (2012) Performance characteristics of a novel megavoltage cone-beam-computed tomography device.. Show Abstract full text

In this work, the image quality of a novel megavoltage cone-beam-computed tomography (CBCT) scanner is compared to three other image-guided radiation therapy devices by analysing images of different-sized quality assurance phantoms. The following devices are compared in terms of image uniformity, signal-to-noise ratio, contrast-to-noise ratio (CNR), electron density to HU conversion, presampling modulation transfer function (MTF(pre)) and combined spatial resolution and noise (Q-factor): (i) the Siemens Artiste kilovoltage (kV) (121 kV) CBCT device, (ii) the Artiste treatment beam line (TBL), 6 MV, (iii) the Tomotherapy (3.5 MV) fan-beam CT and (iv) Siemens' novel approach using a carbon target for a dedicated imaging beam line (IBL), 4.2 MV. Machine settings were selected to produce the same imaging dose for all devices. For a head phantom, IBL scans display CNR values 2.6 ± 0.3 times higher than for the TBL at the same dose level (for a CT-number range of -200 to -60 HU). kV CBCT, on the other hand, displays CNR values 7.9 ± 0.3 times higher than the IBL. There was no significant deviation in spatial resolution between IBL, TBL and Tomotherapy in terms of 50% and 10% MTF(pre). For kV CBCT, the MTF(pre) was significantly higher than those for other devices. In our Q-factor analysis, the IBL (14.6) scores higher than the TBL (7.9) and Tomotherapy (9.7) due to its lower noise level. The linearity of electron density to HU conversion is demonstrated for different-sized phantoms. Employing the IBL instead of the TBL significantly reduces the imaging dose by up to a factor of 5 at a constant image quality level, providing an immediate benefit for the patient.

Krauss, A. Fast, M.F. Nill, S. Oelfke, U (2012) Multileaf collimator tracking integrated with a novel x-ray imaging system and external surrogate monitoring.. Show Abstract full text

We have previously developed a tumour tracking system, which adapts the aperture of a Siemens 160 MLC to electromagnetically monitored target motion. In this study, we exploit the use of a novel linac-mounted kilovoltage x-ray imaging system for MLC tracking. The unique in-line geometry of the imaging system allows the detection of target motion perpendicular to the treatment beam (i.e. the directions usually featuring steep dose gradients). We utilized the imaging system either alone or in combination with an external surrogate monitoring system. We equipped a Siemens ARTISTE linac with two flat panel detectors, one directly underneath the linac head for motion monitoring and the other underneath the patient couch for geometric tracking accuracy assessments. A programmable phantom with an embedded metal marker reproduced three patient breathing traces. For MLC tracking based on x-ray imaging alone, marker position was detected at a frame rate of 7.1 Hz. For the combined external and internal motion monitoring system, a total of only 85 x-ray images were acquired prior to or in between the delivery of ten segments of an IMRT beam. External motion was monitored with a potentiometer. A correlation model between external and internal motion was established. The real-time component of the MLC tracking procedure then relied solely on the correlation model estimations of internal motion based on the external signal. Geometric tracking accuracies were 0.6 mm (1.1 mm) and 1.8 mm (1.6 mm) in directions perpendicular and parallel to the leaf travel direction for the x-ray-only (the combined external and internal) motion monitoring system in spite of a total system latency of ~0.62 s (~0.51 s). Dosimetric accuracy for a highly modulated IMRT beam--assessed through radiographic film dosimetry--improved substantially when tracking was applied, but depended strongly on the respective geometric tracking accuracy. In conclusion, we have for the first time integrated MLC tracking with x-ray imaging in the in-line geometry and demonstrated highly accurate respiratory motion tracking.

Koenig, T. Ziegenhein, P. Oelfke, U (2012) A survey of target materials and orientations suitable for the production of coherent bremsstrahlung in megavoltage imaging.. Show Abstract full text

Megavoltage imaging in image-guided radiotherapy usually suffers from the relatively small fraction of photons present in the energy range providing good soft tissue contrast, which corresponds to photon energies below 50 keV. As a consequence, comparatively high imaging doses are required to form low-noise images. Single-crystal targets can help to alleviate this problem through the emission of so-called coherent bremsstrahlung, amounting to a net increase in low-energy photons if the electron beam impinging on a target is carefully aligned with a major symmetry axis of the underlying crystal lattice. In this work, we present an overview of crystal materials and directions that appeared particularly promising during our studies of this phenomenon, based on theoretical considerations. We find that, while diamond targets perform best in absolute terms, those transition metals that exhibit a body-centred cubic lattice appear as interesting alternatives.

Altenstein, G. Nill, S. Heller, J. Heid, O. Oelfke, U (2012) A novel 2D binary collimator for IMRT dose delivery: dosimetric characterization using Monte Carlo simulations.. Show Abstract full text

We present a novel technical concept of a two-dimensional binary multileaf collimator (2D-bMLC) especially designed for fast dose delivery in rotational IMRT. The 2D-bMLC consists of individually controlled absorber channels, which are arranged side by side forming a 2D collimator aperture. In each channel three separate tungsten modules are arranged behind each other. To open and close an element, the central module is shifted between two positions. The purpose of this work is the presentation of the 2D-bMLC concept and its dosimetric evaluation. To determine the dosimetric properties, we designed a Monte Carlo model of an exemplary 2D-bMLC, consisting of 30 × 30 elements. A virtual source model of a flattening filter-free 7 MV linac was used to characterize the linac phase space. A primary radiation efficiency factor of 43% was calculated for the open 2D-bMLC by dividing the integral dose scored for a 2D-bMLC field by the integral dose scored for an open field with the same dimensions. The leakage calculated for the closed collimator was below 0.5%. Following the primary photon fluence distribution, the bixel intensity decreases with the distance of the element to the central axis of the treatment machine. From the collimator field's center toward its borders, the geometric bixel widths increase in a symmetric and predictable manner by up to 4%. The increase is explained by the specific design of the 2D-bMLC. Abutting element beams exhibit a slight tongue-and-groove effect if opened sequentially. This effect as well as the primary radiation efficiency is basically affected by the source size and the dimensions of the collimator elements. We successfully established and evaluated a dosimetric model of the 2D-bMLC. The results are promising, and we will therefore investigate on real patient plans, if the concept could be advantageous for fast rotational IMRT treatments.

Bangert, M. Ziegenhein, P. Oelfke, U (2012) Characterizing the combinatorial beam angle selection problem.. Show Abstract full text

The beam angle selection (BAS) problem in intensity-modulated radiation therapy is often interpreted as a combinatorial optimization problem, i.e. finding the best combination of η beams in a discrete set of candidate beams. It is well established that the combinatorial BAS problem may be solved efficiently with metaheuristics such as simulated annealing or genetic algorithms. However, the underlying parameters of the optimization process, such as the inclusion of non-coplanar candidate beams, the angular resolution in the space of candidate beams, and the number of evaluated beam ensembles as well as the relative performance of different metaheuristics have not yet been systematically investigated. We study these open questions in a meta-analysis of four strategies for combinatorial optimization in order to provide a reference for future research related to the BAS problem in intensity-modulated radiation therapy treatment planning. We introduce a high-performance inverse planning engine for BAS. It performs a full fluence optimization for ≈3600 treatment plans per hour while handling up to 50 GB of dose influence data (≈1400 candidate beams). For three head and neck patients, we compare the relative performance of a genetic, a cross-entropy, a simulated annealing and a naive iterative algorithm. The selection of ensembles with 5, 7, 9 and 11 beams considering either only coplanar or all feasible candidate beams is studied for an angular resolution of 5°, 10°, 15° and 20° in the space of candidate beams. The impact of different convergence criteria is investigated in comparison to a fixed termination after the evaluation of 10 000 beam ensembles. In total, our simulations comprise a full fluence optimization for about 3000 000 treatment plans. All four combinatorial BAS strategies yield significant improvements of the objective function value and of the corresponding dose distributions compared to standard beam configurations with equi-spaced coplanar beams. The genetic and the cross-entropy algorithms showed faster convergence in the very beginning of the optimization but the simulated annealing algorithm eventually arrived at almost the same objective function values. These three strategies typically yield clinically equivalent treatment plans. The iterative algorithm showed the worst convergence properties. The choice of the termination criterion had a stronger influence on the performance of the simulated annealing algorithm than on the performance of the genetic and the cross-entropy algorithms. We advocate to terminate the optimization process after the evaluation of 1000 beam combinations without objective function decrease. For our simulations, this resulted in an average deviation of the objective function from the reference value after 10 000 evaluated beam ensembles of 0.5% for all metaheuristics. On average, there was only a minor improvement when increasing the angular resolution in the space of candidate beam angles from 20° to 5°. However, we observed significant improvements when considering non-coplanar candidate beams for challenging head and neck cases.

Koenig, T. Schulze, J. Zuber, M. Rink, K. Butzer, J. Hamann, E. Cecilia, A. Zwerger, A. Fauler, A. Fiederle, M. Oelfke, U (2012) Imaging properties of small-pixel spectroscopic x-ray detectors based on cadmium telluride sensors.. Show Abstract full text

Spectroscopic x-ray imaging by means of photon counting detectors has received growing interest during the past years. Critical to the image quality of such devices is their pixel pitch and the sensor material employed. This paper describes the imaging properties of Medipix2 MXR multi-chip assemblies bump bonded to 1 mm thick CdTe sensors. Two systems were investigated with pixel pitches of 110 and 165 μm, which are in the order of the mean free path lengths of the characteristic x-rays produced in their sensors. Peak widths were found to be almost constant across the energy range of 10 to 60 keV, with values of 2.3 and 2.2 keV (FWHM) for the two pixel pitches. The average number of pixels responding to a single incoming photon are about 1.85 and 1.45 at 60 keV, amounting to detective quantum efficiencies of 0.77 and 0.84 at a spatial frequency of zero. Energy selective CT acquisitions are presented, and the two pixel pitches' abilities to discriminate between iodine and gadolinium contrast agents are examined. It is shown that the choice of the pixel pitch translates into a minimum contrast agent concentration for which material discrimination is still possible. We finally investigate saturation effects at high x-ray fluxes and conclude with the finding that higher maximum count rates come at the cost of a reduced energy resolution.

Ulrich, S. Sterzing, F. Nill, S. Schubert, K. Herfarth, K.K. Debus, J. Oelfke, U (2009) Comparison of arc-modulated cone beam therapy and helical tomotherapy for three different types of cancer.. Show Abstract full text

PURPOSE: Arc-modulated cone beam therapy (AMCBT) is a fast treatment technique deliverable in a single rotation with a conventional C-arm shaped linac. In this planning study, the authors assess the dosimetric properties of single-arc therapy in comparison to helical tomotherapy for three different tumor types. METHODS: Treatment plans for three patients with prostate carcinoma, three patients with anal cancer, and three patients with head and neck cancer were optimized for helical tomotherapy and AMCBT. The dosimetric comparison of the two techniques is based on physical quantities derived from dose-volume histograms. RESULTS: For prostate cancer, the quality of dose distributions calculated for AMCBT was of equal quality as that generated for tomotherapy with the additional benefits of a faster delivery and a lower integral dose. For highly complex geometries, the plan quality achievable with helical tomotherapy could not be achieved with arc-modulated cone beam therapy. CONCLUSIONS: Rotation therapy with a conventional linac in a single arc is capable to deliver a high and homogeneous dose to the target and spare organs at risk. Advantages of this technique are a fast treatment time and a lower integral dose in comparison to helical tomotherapy. For highly complex cases, e.g., with several target regions, the dose shaping capabilities of AMCBT are inferior to those of tomotherapy. However, treatment plans for AMCBT were also clinically acceptable.

Pfaffenberger, A. Schneider, U. Poppe, B. Oelfke, U (2009) Phenomenological modelling of second cancer incidence for radiation treatment planning.. Show Abstract full text

It is still an unanswered question whether a relatively low dose of radiation to a large volume or a higher dose to a small volume produces the higher cancer incidence. This is of interest in view of modalities like IMRT or rotation therapy where high conformity to the target volume is achieved at the cost of a large volume of normal tissue exposed to radiation. Knowledge of the shape of the dose response for radiation-induced cancer is essential to answer the question of what risk of second cancer incidence is implied by which treatment modality. This study therefore models the dose response for radiation-induced second cancer after radiation therapy of which the exact mechanisms are still unknown. A second cancer risk estimation tool for treatment planning is presented which has the potential to be used for comparison of different treatment modalities, and risk is estimated on a voxel basis for different organs in two case studies. The presented phenomenological model summarises the impact of microscopic biological processes into effective parameters of mutation and cell sterilisation. In contrast to other models, the effective radiosensitivities of mutated and non-mutated cells are allowed to differ. Based on the number of mutated cells present after irradiation, the model is then linked to macroscopic incidence by summarising model parameters and modifying factors into natural cancer incidence and the dose response in the lower-dose region. It was found that all principal dose-response functions discussed in the literature can be derived from the model. However, from the investigation and due to scarcity of adequate data, rather vague statements about likelihood of dose-response functions can be made than a definite decision for one response. Based on the predicted model parameters, the linear response can probably be rejected using the dynamics described, but both a flattening response and a decrease appear likely, depending strongly on the effective cell sterilisation of the mutated cells. Thus insights could be gained into the impact of parameters describing the effective mutation or cell sterilisation of non-mutated as well as of mutated cells, which constitute precursors of cancer. The biggest drawbacks in the estimation of second cancer incidence remain the low statistical power of clinical studies on radiation induction of cancer and the inability to isolate the effect due to radiation alone - if the latter is possible at all. We conclude that at the present stage of knowledge, further investigations have to be carried out in order to really compare treatment modalities with respect to the second cancer risk they imply.

Koenig, T. Oelfke, U (2010) Single crystal targets may improve soft-tissue contrast in megavoltage imaging by means of coherent bremsstrahlung.. Show Abstract full text

Coherent bremsstrahlung denotes the process of bremsstrahlung emission by electrons traversing a single crystal, causing prominent peaks in the resulting photon spectra at low energies. While this phenomenon has been known for decades, little attempt has been made to exploit its potential for megavoltage imaging, where the quality of images is affected by low contrast due to the lack of sufficient photons at the energy range suited for diagnostic purposes. We provide a theoretical foundation of coherent bremsstrahlung in the first-order Born approximation without confinement to high energies. Based on this theory, first evidence is given that diamond crystals are capable of boosting the amount of diagnostic photons by about 10-20%. It is shown that this behaviour is largely conserved for polychromatic electrons hitting thick targets, where multiple scattering dominates the energy distribution of the emitted photons.

Tacke, M.B. Nill, S. Krauss, A. Oelfke, U (2010) Real-time tumor tracking: automatic compensation of target motion using the Siemens 160 MLC.. Show Abstract full text

PURPOSE: Advanced high quality radiation therapy techniques such as IMRT require an accurate delivery of precisely modulated radiation fields to the target volume. Interfractional and intrafractional motion of the patient's anatomy, however, may considerably deteriorate the accuracy of the delivered dose to the planned dose distributions. In order to compensate for these potential errors, a dynamic real-time capable MLC control system was designed. METHODS: The newly developed adaptive MLC control system contains specialized algorithms which are capable of continuous optimization and correction of the aperture of the MLC according to the motion of the target volume during the dose delivery. The algorithms calculate the new leaf positions based on target information provided online to the system. The algorithms were implemented in a dynamic target tracking control system designed for a Siemens 160 MLC. To assess the quality of the new target tracking system in terms of dosimetric accuracy, experiments with various types of motion patterns using different phantom setups were performed. The phantoms were equipped with radiochromic films placed between solid water slabs. Dosimetric results of exemplary deliveries to moving targets with and without dynamic MLC tracking applied were compared in terms of the gamma criterion to the reference dose delivered to a static phantom. RESULTS: Our measurements indicated that dose errors for clinically relevant two-dimensional target motion can be compensated by the new control system during the dose delivery of open fields. For a clinical IMRT dose distribution, the gamma success rate was increased from 19% to 77% using the new tracking system. Similar improvements were achieved for the delivery of a complete IMRT treatment fraction to a moving lung phantom. However, dosimetric accuracy was limited by the system's latency of 400 ms and the finite leaf width of 5 mm in the isocenter plane. CONCLUSIONS: Different experimental setups representing different target tracking scenarios proved that the tracking concept, the new algorithms and the dynamic control system make it possible to effectively compensate for dose errors due to target motion in real-time. These early results indicate that the method is suited to increasing the accuracy and the quality of the treatment delivery for the irradiation of moving tumors.

Frese, M.C. Wilkens, J.J. Huber, P.E. Jensen, A.D. Oelfke, U. Taheri-Kadkhoda, Z (2011) Application of constant vs. variable relative biological effectiveness in treatment planning of intensity-modulated proton therapy.. Show Abstract full text

PURPOSE: To investigate in a simulation study whether using a variable relative biological effectiveness (RBE) in calculation and optimization of intensity-modulated proton therapy (IMPT) instead of using an RBE of 1.1 would result in significant changes in the RBE-weighted dose (RWD) distributions. METHODS AND MATERIALS: For 4 patients with head-and-neck tumors, three IMPT plans were prepared respectively. The first plan was physically optimized (IMPT-PO plan), and the RWD was calculated with a constant RBE of 1.1. Then the plan's RWD was recalculated (IMPT-R plan) using a variable RBE model taking into account the linear energy transfer (LET) and tissue-specific radiobiological parameters. The third IMPT plan was optimized using a biological optimization routine (IMPT-BO plan). RESULTS: Comparing the IMPT-PO and IMPT-R plans, we observed that the RWD in radioresistant tissues was more sensitive to the LET than in radiosensitive tissues. The IMPT-R plans were in general more inhomogeneous than the IMPT-PO plans. The differences of RWD distributions for all volumes between IMPT-PO and IMPT-BO plans complied with predefined dose-volume constraints. The average LET was significantly lower in IMPT-BO plans than in IMPT-R plans. CONCLUSION: In radioresistant normal tissues caution has to be used regarding the LET distribution because these are most sensitive to changes in the LET. Biological optimization of IMPT plans based on the organ-specific biological parameters and LET distributions is feasible.

Krauss, A. Nill, S. Tacke, M. Oelfke, U (2011) Electromagnetic real-time tumor position monitoring and dynamic multileaf collimator tracking using a Siemens 160 MLC: geometric and dosimetric accuracy of an integrated system.. Show Abstract full text

PURPOSE: Dynamic multileaf collimator tracking represents a promising method for high-precision radiotherapy to moving tumors. In the present study, we report on the integration of electromagnetic real-time tumor position monitoring into a multileaf collimator-based tracking system. METHODS AND MATERIALS: The integrated system was characterized in terms of its geometric and radiologic accuracy. The former was assessed from portal images acquired during radiation delivery to a phantom in tracking mode. The tracking errors were calculated from the positions of the tracking field and of the phantom as extracted from the portal images. Radiologic accuracy was evaluated from film dosimetry performed for conformal and intensity-modulated radiotherapy applied to different phantoms moving on sinusoidal trajectories. A static radiation delivery to the nonmoving target served as a reference for the delivery to the moving phantom with and without tracking applied. RESULTS: Submillimeter tracking accuracy was observed for two-dimensional target motion despite the relatively large system latency of 500 ms. Film dosimetry yielded almost complete recovery of a circular dose distribution with tracking in two dimensions applied: 2%/2 mm gamma-failure rates could be reduced from 59.7% to 3.3%. For single-beam intensity-modulated radiotherapy delivery, accuracy was limited by the finite leaf width. A 2%/2 mm gamma-failure rate of 15.6% remained with tracking applied. CONCLUSION: The integrated system we have presented marks a major step toward the clinical implementation of high-precision dynamic multileaf collimator tracking. However, several challenges such as irregular motion traces or a thorough quality assurance still need to be addressed.

Schell, S. Wilkens, J.J. Oelfke, U (2010) Radiobiological effect based treatment plan optimization with the linear quadratic model.. Show Abstract full text

As an approach towards more biology-oriented treatment planning for external beam radiation therapy, we present the incorporation of local radiation damage models into three dimensional treatment planning. This allows effect based instead of dose based plan optimization which could potentially better match the biologically relevant tradeoff between target and normal tissues. In particular, our approach facilitates an effective comparison of different fractionation schemes. It is based on the linear quadratic model to describe the biological radiation effect. Effect based optimization was integrated into our inverse treatment planning software KonRad, and we demonstrate the resulting differences between conventional and biological treatment planning. Radiation damage can be analyzed both qualitatively and quantitatively in dependence of the fractionation scheme and tissue specific parameters in a three dimensional voxel based system. As an example the potential advantages as well as the associated risks of hypofractionation for prostate cancer are analyzed and visualized with the help of effective dose volume histograms. Our results suggest a very conservative view regarding alternative fractionation schemes since uncertainties in biological parameters are still too big to make reliable clinical predictions.

Bangert, M. Oelfke, U (2010) Spherical cluster analysis for beam angle optimization in intensity-modulated radiation therapy treatment planning.. Show Abstract full text

An intuitive heuristic to establish beam configurations for intensity-modulated radiation therapy is introduced as an extension of beam ensemble selection strategies applying scalar scoring functions. It is validated by treatment plan comparisons for three intra-cranial, pancreas, and prostate cases each. Based on a patient specific matrix listing the radiological quality of candidate beam directions individually for every target voxel, a set of locally ideal beam angles is generated. The spherical distribution of locally ideal beam angles is characteristic for every treatment site and patient: ideal beam angles typically cluster around distinct orientations. We interpret the cluster centroids, which are identified with a spherical K-means algorithm, as irradiation angles of an intensity-modulated radiation therapy treatment plan. The fluence profiles are subsequently optimized during a conventional inverse planning process. The average computation time for the pre-optimization of a beam ensemble is six minutes on a state-of-the-art work station. The treatment planning study demonstrates the potential benefit of the proposed beam angle optimization strategy. For the three prostate cases under investigation, the standard treatment plans applying nine coplanar equi-spaced beams and treatment plans applying an optimized non-coplanar nine-beam ensemble yield clinically comparable dose distributions. For symmetric patient geometries, the dose distribution formed by nine equi-spaced coplanar beams cannot be improved significantly. For the three pancreas and intra-cranial cases under investigation, the optimized non-coplanar beam ensembles enable better sparing of organs at risk while guaranteeing equivalent target coverage. Beam angle optimization by spherical cluster analysis shows the biggest impact for target volumes located asymmetrically within the patient and close to organs at risk.

Krauss, A. Nill, S. Oelfke, U (2011) The comparative performance of four respiratory motion predictors for real-time tumour tracking.. Show Abstract full text

Prediction of respiratory motion is essential for real-time tracking of lung or liver tumours in radiotherapy to compensate for system latencies. This study compares the performance of respiratory motion prediction based on linear regression (LR), neural networks (NN), kernel density estimation (KDE) and support vector regression (SVR) for various sampling rates and system latencies ranging from 0.2 to 0.6 s. Root-mean-squared prediction errors are evaluated on 12 3D lung tumour motion traces acquired at 30 Hz during radiotherapy treatments. The effect of stationary predictor training versus continuous predictor retraining as well as full 3D motion processing versus independent coordinate-wise motion processing is investigated. Model parameter optimization is performed through a grid search in the model parameter space for each predictor and all considered latencies, sampling rates, training schemes and 3D data-processing modes. Comparison of the predictors is performed in the clinically applicable setting of patient-independent model parameters. The considered predictors roughly halve the prediction errors compared to using no prediction. When averaging over all sampling rates and latencies, prediction errors normalized to errors of using no prediction of 0.44, 0.46, 0.49 and 0.55 for NN, SVR, LR and KDE are observed. The small differences between the predictors emphasize the relative importance of adequate model parameter optimization compared to the actual prediction model selection. Thorough model parameter tuning is therefore essential for fair predictor comparisons.

Kang, J.H. Wilkens, J.J. Oelfke, U (2008) Non-uniform depth scanning for proton therapy systems employing active energy variation.. Show Abstract full text

In proton scanning systems that employ active energy variation for depth modulation, a switch of the particle energy might typically require 1-2 s. For plans comprising many energy slices, these seconds could sum up to a non-negligible fraction of the total treatment duration. We have applied the Nyquist-Shannon sampling theorem to determine an efficient spatial arrangement of Bragg peaks in a target volume. This pre-determined schedule of increasing energy spacing with higher energy allows us to reduce the number of used energy slices without compromising the physical dosimetric quality of a plan. Our results suggest that the advantage of such a simple implementation would be especially significant for larger, deep-seated tumors such as the prostate; the number of energy slices was cut by a factor of 2-6.

Ziegenhein, P. Wilkens, J.J. Nill, S. Ludwig, T. Oelfke, U (2008) Speed optimized influence matrix processing in inverse treatment planning tools.. Show Abstract full text

An optimal plan in modern treatment planning tools is found through the use of an iterative optimization algorithm, which deals with a high amount of patient-related data and number of treatment parameters to be optimized. Thus, calculating a good plan is a very time-consuming process which limits the application for patients in clinics and for research activities aiming for more accuracy. A common technique to handle the vast amount of radiation dose data is the concept of the influence matrix (DIJ), which stores the dose contribution of each bixel to the patient in the main memory of the computer. This study revealed that a bottleneck for the optimization time arises from the data transfer of the dose data between the memory and the CPU. In this note, we introduce a new method which speeds up the data transportation from stored dose data to the CPU. As an example we used the DIJ approach as is implemented in our treatment planning tool KonRad, developed at the German Cancer Research Center (DKFZ) in Heidelberg. A data cycle reordering method is proposed to take the advantage of modern memory hardware. This induces a minimal eviction policy which results in a memory behaviour exhibiting a 2.6 times faster algorithm compared to the naive implementation. Although our method is described for the DIJ approach implemented in KonRad, we believe that any other planning tool which uses a similar approach to store the dose data will also benefit from the described methods.

Tacke, M.B. Nill, S. Häring, P. Oelfke, U (2008) 6 MV dosimetric characterization of the 160 MLC, the new Siemens multileaf collimator.. Show Abstract full text

New technical developments constantly aim at improving the outcome of radiation therapy. With the use of a computer-controlled multileaf collimator (MLC), the quality of the treatment and the efficiency in patient throughput is significantly increased. New MLC designs aim to further enhance the advantages. In this article, we present the first detailed experimental investigation of the new 160 MLC, Siemens Medical Solutions. The assessment included the experimental investigation of typical MLC characteristics such as leakage, tongue-and-groove effect, penumbra, leaf speed, and leaf positioning accuracy with a 6 MV treatment beam. The leakage is remarkably low with an average of 0.37% due to a new design principle of slightly tilted leaves instead of the common tongue-and-groove design. But due to the tilt, the triangular tongue-and-groove effect occurs. Its magnitude of approximately 19% is similar to the dose defect measured for MLCs with the common tongue-and-groove design. The average longitudinal penumbra measured at depth d(max) = 15 mm with standard 100 x 100 mm2 fields is 4.1 +/- 0.5 mm for the central range and increases to 4.9 +/- 1.3 mm for the entire field range of 400 x 400 mm2. The increase is partly due to the single-focusing design and the large distance between the MLC and the isocenter enabling a large patient clearance. Regarding the leaf speed, different velocity tests were performed. The positions of the moving leaves were continuously recorded with the kilovoltage-imaging panel. The maximum leaf velocities measured were 42.9 +/- 0.6 mm/s. In addition, several typical intensity-modulated radiation therapy treatments were performed and the delivery times compared to the Siemens OPTIFOCUS MLC. An average decrease of 11% in delivery time was observed. The experimental results presented in this article indicate that the dosimetric characteristics of the 160 MLC are capable of improving the quality of dose delivery with respect to precision and dose conformity.

Rau, A.W. Nill, S. Eidens, R.S. Oelfke, U (2008) Synchronized tumour tracking with electromagnetic transponders and kV x-ray imaging: evaluation based on a thorax phantom.. Show Abstract full text

Intrafractional organ motion remains a source of error in conformal radiotherapy of dynamic targets such as tumours of the lung or of the prostate. The purpose of this work was to devise a method for the continuous and routine measurement of intrafractional organ motion. The method consists of a combination of an electromagnetic (EM), internal marker-based tracking system with the on-board kilovoltage x-ray imaging system of a modern treatment machine. The EM system continuously tracks the target, while x-ray images can be acquired simultaneously if demand arises. An image processing algorithm has been developed to automatically localize and track the EM markers in the x-ray images. We have demonstrated simultaneous target tracking using the EM system and x-ray imaging of a mobile target inside a programmable thorax phantom. The target motion was very well reproduced by both systems. The comparability of the target locations reported by both systems was established (better than 0.25 mm up to target velocities of 3 cm s(-1)). One immediate use of the synchronized system was shown: the generation of a 4D cone beam computed tomography data set using the EM system for the measurement of motion. In conclusion, we have developed a system for the routine measurement of intrafractional motion that continuously provides the 3D position of the target with the ability to acquire images of the treatment field only when needed, thereby eliminating avoidable imaging dose to the patient.

Weichsel, J. Fuchs, T. Lefebvre, E. d'Humières, E. Oelfke, U (2008) Spectral features of laser-accelerated protons for radiotherapy applications.. Show Abstract full text

Laser-induced particle accelerators have been recognized as a potential proton source for radiotherapeutic applications in recent years. However, there are still major difficulties--especially regarding the resulting proton spectra--to overcome for a successful application in the clinic. Here we elaborate on the physics of double-layer targets to propose a tentative 'optical gantry' setup. The spectral requirements for a quality dose deposition of the fast protons are estimated. Plasma simulations of the one-dimensional expansion of microstructured targets are performed according to various target dimensions, rear proton densities and substrate masses. Subsequently, the dependence of the resulting proton spectra on these parameters is evaluated and compared to previously published analytical considerations. Quasi-monoenergetic proton beams, which would be suitable for high-quality dose delivery, could be achieved from pure proton targets if one were able to select out the rear layer of those targets. However, much more realistic heavy substrate layered targets are not able to preserve this high spectral standard, partly due to a second Coulomb-expansion in the center-of-mass frame of the fast protons. This expansion can be mitigated by a reduction of the total positive charge in the rear layer, resulting in a comparable spectral quality as the previous target types. In conclusion, the promising spectral results as well as an estimation of the total number of fast protons which can be expected from such a setup, suggest that the introduction of laser-based proton accelerators into the clinic might be possible in the future.

Pflugfelder, D. Wilkens, J.J. Nill, S. Oelfke, U (2008) A comparison of three optimization algorithms for intensity modulated radiation therapy.. Show Abstract full text

In intensity modulated treatment techniques, the modulation of each treatment field is obtained using an optimization algorithm. Multiple optimization algorithms have been proposed in the literature, e.g. steepest descent, conjugate gradient, quasi-Newton methods to name a few. The standard optimization algorithm in our in-house inverse planning tool KonRad is a quasi-Newton algorithm. Although this algorithm yields good results, it also has some drawbacks. Thus we implemented an improved optimization algorithm based on the limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) routine. In this paper the improved optimization algorithm is described. To compare the two algorithms, several treatment plans are optimized using both algorithms. This included photon (IMRT) as well as proton (IMPT) intensity modulated therapy treatment plans. To present the results in a larger context the widely used conjugate gradient algorithm was also included into this comparison. On average, the improved optimization algorithm was six times faster to reach the same objective function value. However, it resulted not only in an acceleration of the optimization. Due to the faster convergence, the improved optimization algorithm usually terminates the optimization process at a lower objective function value. The average of the observed improvement in the objective function value was 37%. This improvement is clearly visible in the corresponding dose-volume-histograms. The benefit of the improved optimization algorithm is particularly pronounced in proton therapy plans. The conjugate gradient algorithm ranked in between the other two algorithms with an average speedup factor of two and an average improvement of the objective function value of 30%.

Biederer, J. Dinkel, J. Remmert, G. Jetter, S. Nill, S. Moser, T. Bendl, R. Thierfelder, C. Fabel, M. Oelfke, U. Bock, M. Plathow, C. Bolte, H. Welzel, T. Hoffmann, B. Hartmann, G. Schlegel, W. Debus, J. Heller, M. Kauczor, H.-.U (2009) 4D-Imaging of the lung: reproducibility of lesion size and displacement on helical CT, MRI, and cone beam CT in a ventilated ex vivo system.. Show Abstract full text

PURPOSE: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT). METHODS AND MATERIALS: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility. RESULTS: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16). CONCLUSIONS: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement.

Fuchs, T. Szymanowski, H. Oelfke, U. Glinec, Y. Rechatin, C. Faure, J. Malka, V (2009) Treatment planning for laser-accelerated very-high energy electrons.. Show Abstract full text

In recent experiments, quasi-monoenergetic and well-collimated very-high energy electron (VHEE) beams were obtained by laser-plasma accelerators. We investigate their potential use for radiation therapy. Monte Carlo simulations are used to study the influence of the experimental characteristics such as beam energy, energy spread and initial angular distribution on the dose distributions. It is found that magnetic focusing of the electron beam improves the lateral penumbra. The dosimetric properties of the laser-accelerated VHEE beams are implemented in our inverse treatment planning system for intensity-modulated treatments. The influence of the beam characteristics on the quality of a prostate treatment plan is evaluated. In comparison to a clinically approved 6 MV IMRT photon plan, a better target coverage is achieved. The quality of the sparing of organs at risk is found to be dependent on the depth. The bladder and rectum are better protected due to the sharp lateral penumbra at low depths, whereas the femoral heads receive a larger dose because of the large scattering amplitude at larger depths.

Heath, E. Unkelbach, J. Oelfke, U (2009) Incorporating uncertainties in respiratory motion into 4D treatment plan optimization.. Show Abstract full text

The purpose of this work is to investigate robust 4D optimization techniques which account for respiratory motion uncertainties. Two robust optimization techniques were applied to generate 4D optimized lung treatment plans. The probabilistic optimization approach minimizes the dose variance in the target volume while the worst case optimization minimizes a weighted combination of the nominal and worst case dose distributions which occur in the presence of respiratory motion variation. The two 4D optimization approaches were compared with a margin-based midventilation planning approach in five lung patients. Respiratory motion amplitude and baseline variations were quantified from tidal volume measurements during planning 4D CT acquisition. A similar target coverage was obtained for all three approaches, although the 4D optimization methods tended to be better at sparing the organs at risk. Both robust planning methods are suited for automatic determination of treatment plans which ensure target dose conformality under respiratory motion variations, while minimizing the dose burden of healthy lung tissue.

Reitz, I. Hesse, B.-.M. Nill, S. Tücking, T. Oelfke, U (2009) Enhancement of image quality with a fast iterative scatter and beam hardening correction method for kV CBCT.. Show Abstract full text

The problem of the enormous amount of scattered radiation in kV CBCT (kilo voltage cone beam computer tomography) is addressed. Scatter causes undesirable streak- and cup-artifacts and results in a quantitative inaccuracy of reconstructed CT numbers, so that an accurate dose calculation might be impossible. Image contrast is also significantly reduced. Therefore we checked whether an appropriate implementation of the fast iterative scatter correction algorithm we have developed for MV (mega voltage) CBCT reduces the scatter contribution in a kV CBCT as well. This scatter correction method is based on a superposition of pre-calculated Monte Carlo generated pencil beam scatter kernels. The algorithm requires only a system calibration by measuring homogeneous slab phantoms with known water-equivalent thicknesses. In this study we compare scatter corrected CBCT images of several phantoms to the fan beam CT images acquired with a reduced cone angle (a slice-thickness of 14 mm in the isocenter) at the same system. Additional measurements at a different CBCT system were made (different energy spectrum and phantom-to-detector distance) and a first order approach of a fast beam hardening correction will be introduced. The observed image quality of the scatter corrected CBCT images is comparable concerning resolution, noise and contrast-to-noise ratio to the images acquired in fan beam geometry. Compared to the CBCT without any corrections the contrast of the contrast-and-resolution phantom with scatter correction and additional beam hardening correction is improved by a factor of about 1.5. The reconstructed attenuation coefficients and the CT numbers of the scatter corrected CBCT images are close to the values of the images acquired in fan beam geometry for the most pronounced tissue types. Only for extreme dense tissue types like cortical bone we see a difference in CT numbers of 5.2%, which can be improved to 4.4% with the additional beam hardening correction. Cupping is reduced from 20% to 4% with scatter correction and 3% with an additional beam hardening correction. After 3 iterations (small phantoms) and 6 to 7 iterations (large phantoms) the algorithm converges. Therefore the algorithm is very fast, that means 1.3 seconds per projection for 3 iterations on a standard PC.

Ulrich, S. Nill, S. Oelfke, U (2007) Development of an optimization concept for arc-modulated cone beam therapy.. Show Abstract full text

In this paper, we propose an optimization concept for a rotation therapy technique which is referred to as arc-modulated cone beam therapy (AMCBT). The aim is a reduction of the treatment time while achieving a treatment plan quality equal to or better than that of IMRT. Therefore, the complete dose is delivered in one single gantry rotation and the beam is modulated by a multileaf collimator. The degrees of freedom are the field shapes and weights for a predefined number of beam directions. In the new optimization loop, the beam weights are determined by a gradient algorithm and the field shapes by a tabu search algorithm. We present treatment plans for AMCBT for two clinical cases. In comparison to step-and-shoot IMRT treatment plans, it was possible by AMCBT to achieve dose distributions with a better dose conformity to the target and a lower mean dose for the most relevant organ at risk. Furthermore, the number of applied monitor units was reduced for AMCBT in comparison to IMRT treatment plans.

Thieke, C. Küfer, K.-.H. Monz, M. Scherrer, A. Alonso, F. Oelfke, U. Huber, P.E. Debus, J. Bortfeld, T (2007) A new concept for interactive radiotherapy planning with multicriteria optimization: first clinical evaluation.. Show Abstract full text

BACKGROUND AND PURPOSE: Currently, inverse planning for intensity-modulated radiotherapy (IMRT) can be a time-consuming trial and error process. This is because many planning objectives are inherently contradictory and cannot reach their individual optimum all at the same time. Therefore in clinical practice the potential of IMRT cannot be fully exploited for all patients. Multicriteria (multiobjective) optimization combined with interactive plan navigation is a promising approach to overcome these problems. PATIENTS AND METHODS: We developed a new inverse planning system called "Multicriteria Interactive Radiotherapy Assistant (MIRA)". The optimization result is a database of patient specific, Pareto-optimal plan proposals. The database is explored with an intuitive user interface that utilizes both a new interactive element for plan navigation and familiar dose visualizations in form of DVH and isodose projections. Two clinical test cases, one paraspinal meningioma case and one prostate case, were optimized using MIRA and compared with the clinically approved planning program KonRad. RESULTS: Generating the databases required no user interaction and took approx. 2-3h per case. The interactive exploration required only a few minutes until the best plan was identified, resulting in a significant reduction of human planning time. The achievable plan quality was comparable to KonRad with the additional benefit of having plan alternatives at hand to perform a sensitivity analysis or to decide for a different clinical compromise. CONCLUSIONS: The MIRA system provides a complete database and interactive exploration of the solution space in real time. Hence, it is ideally suited for the inherently multicriterial problem of inverse IMRT treatment planning.

Kang, J.H. Wilkens, J.J. Oelfke, U (2007) Demonstration of scan path optimization in proton therapy.. Show Abstract full text

A three-dimensional (3D) intensity modulated proton therapy treatment plan to be delivered by magnetic scanning may comprise thousands of discrete beam positions. This research presents the minimization of the total scan path length by application of a fast simulated annealing (FSA) optimization algorithm. Treatment plans for clinical prostate and head and neck cases were sequenced for continuous raster scanning in two ways, and the resulting scan path lengths were compared: (1) A simple back-and-forth, top-to-bottom (zigzag) succession, and (2) an optimized path produced as a solution of the FSA algorithm. Using a first approximation of the scanning dynamics, the delivery times for the scan sequences before and after path optimization were calculated for comparison. In these clinical examples, the FSA optimization shortened the total scan path length for the 3D target volumes by approximately 13%-56%. The number of extraneous spilled particles was correspondingly reduced by about 13%-54% due to the more efficient scanning maps that eliminated multiple crossings through regions of zero fluence. The relative decrease in delivery time due to path length minimization was estimated to be less than 1%, due to both a high scanning speed and time requirements that could not be altered by optimization (e.g., time required to change the beam energy). In a preliminary consideration of application to rescanning techniques, the decrease in delivery time was estimated to be 4%-20%.

Wilkens, J.J. Oelfke, U (2008) Direct comparison of biologically optimized spread-out bragg peaks for protons and carbon ions.. Show Abstract full text

PURPOSE: In radiotherapy with hadrons, it is anticipated that carbon ions are superior to protons, mainly because of their biological properties: the relative biological effectiveness (RBE) for carbon ions is supposedly higher in the target than in the surrounding normal tissue, leading to a therapeutic advantage over protons. The purpose of this report is to investigate this effect by using biological model calculations. METHODS AND MATERIALS: We compared spread-out Bragg peaks for protons and carbon ions by using physical and biological optimization. The RBE for protons and carbon ions was calculated according to published biological models. These models predict increased RBE values in regions of high linear energy transfer (LET) and an inverse dependency of the RBE on dose. RESULTS: For pure physical optimization, protons yield a better dose distribution along the central axis. In biologically optimized plans, RBE variations for protons were relatively small. For carbon ions, high RBE values were found in the high-LET target region, as well as in the low-dose region outside the target. This means that the LET dependency and dose dependency of the RBE can cancel each other. We show this for radioresistant tissues treated with two opposing beams, for which the predicted carbon RBE within the target volume was lower than outside. CONCLUSIONS: For tissue parameters used in this study, the model used does not predict a biologic advantage of carbon ions. More reliable model parameters and clinical trials are necessary to explore the true potential of radiotherapy with carbon ions.

Tacke, M. Nill, S. Oelfke, U (2007) Real-time tracking of tumor motions and deformations along the leaf travel direction with the aid of a synchronized dynamic MLC leaf sequencer.. Show Abstract full text

Advanced radiotherapeutical techniques like intensity-modulated radiation therapy (IMRT) are based on an accurate knowledge of the location of the radiation target. An accurate dose delivery, therefore, requires a method to account for the inter- and intrafractional target motion and the target deformation occurring during the course of treatment. A method to compensate in real time for changes in the position and shape of the target is the use of a dynamic multileaf collimator (MLC) technique which can be devised to automatically arrange the treatment field according to real-time image information. So far, various approaches proposed for leaf sequencers have had to rely on a priori known target motion data and have aimed to optimize the overall treatment time. Since for a real-time dose delivery the target motion is not known a priori, the velocity range of the leading leaves is restricted by a safety margin to c x v(max) while the following leaves can travel with an additional maximum speed to compensate for the respective target movements. Another aspect to be considered is the tongue and groove effect. A uniform radiation field can only be achieved if the leaf movements are synchronized. The method presented in this note is the first to combine a synchronizing sequencer and real-time tracking with a dynamic MLC. The newly developed algorithm is capable of online optimizing the leaf velocities by minimizing the overall treatment time while at the same time it synchronizes the leaf trajectories in order to avoid the tongue and groove effect. The simultaneous synchronization is performed with the help of an online-calculated mid-time leaf trajectory which is common for all leaf pairs and which takes into account the real-time target motion and deformation information.

Stützel, J. Oelfke, U. Nill, S (2008) A quantitative image quality comparison of four different image guided radiotherapy devices.. Show Abstract full text

PURPOSE: A study to quantitatively compare the image quality of four different image guided radiotherapy (IGRT) devices based on phantom measurements with respect to the additional dose delivered to the patient. METHODS: Images of three different head-sized phantoms (diameter 16-18 cm) were acquired with the following four IGRT-CT solutions: (i) the Siemens Primatom single slice fan beam computed tomography (CT) scanner with an acceleration voltage of 130 kV, (ii) a Tomotherapy HI-ART II unit using a fan beam scanner with an energy of 3.5 MeV and (iii) the Siemens Artíste prototype, providing the possibility to perform kV (121 kV) and MV (6 MV) cone beam (CB) CTs. For each device three scan protocols (named low, normal, high) were selected to yield the same weighted computed tomography dose index (CTDI(w)). Based on the individual inserts of the different phantoms the image quality achieved with each device at a certain dose level was characterized in terms of homogeneity, spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and electron density-to-CT-number conversion. RESULTS: Based on the current findings for head-sized phantoms all devices show an electron density-to-CT-number conversion almost independent of the imaging parameters and hence can be suited for treatment planning purposes. The evaluation of the image quality, however, points out clear differences due to the different energies and geometries. The Primatom standard CT scanner shows throughout the best performance, especially for soft tissue contrast and spatial resolution with low imaging doses. Reasonable soft tissue contrast can be obtained with slightly higher doses compared to the CT scanner with the kVCB and the Tomotherapy unit. In order to get similar results with the MVCB system a much higher dose needs to be applied to the patient. CONCLUSION: Considering the entire investigations, especially in terms of contrast and spatial resolution, a rough tendency for decreasing image quality can be given: Primatom, Artíste prototype kVCB, Tomotherapy, Artíste prototype MVCB.

Taheri-Kadkhoda, Z. Björk-Eriksson, T. Nill, S. Wilkens, J.J. Oelfke, U. Johansson, K.-.A. Huber, P.E. Münter, M.W (2008) Intensity-modulated radiotherapy of nasopharyngeal carcinoma: a comparative treatment planning study of photons and protons.. Show Abstract full text

BACKGROUND: The aim of this treatment planning study was to investigate the potential advantages of intensity-modulated (IM) proton therapy (IMPT) compared with IM photon therapy (IMRT) in nasopharyngeal carcinoma (NPC). METHODS: Eight NPC patients were chosen. The dose prescriptions in cobalt Gray equivalent (GyE) for gross tumor volumes of the primary tumor (GTV-T), planning target volumes of GTV-T and metastatic (PTV-TN) and elective (PTV-N) lymph node stations were 72.6 GyE, 66 GyE, and 52.8 GyE, respectively. For each patient, nine coplanar fields IMRT with step-and-shoot technique and 3D spot-scanned three coplanar fields IMPT plans were prepared. Both modalities were planned in 33 fractions to be delivered with a simultaneous integrated boost technique. All plans were prepared and optimized by using the research version of the inverse treatment planning system KonRad (DKFZ, Heidelberg). RESULTS: Both treatment techniques were equal in terms of averaged mean dose to target volumes. IMPT plans significantly improved the tumor coverage and conformation (P < 0.05) and they reduced the averaged mean dose to several organs at risk (OARs) by a factor of 2-3. The low-to-medium dose volumes (0.33-13.2 GyE) were more than doubled by IMRT plans. CONCLUSION: In radiotherapy of NPC patients, three-field IMPT has greater potential than nine-field IMRT with respect to tumor coverage and reduction of the integral dose to OARs and non-specific normal tissues. The practicality of IMPT in NPC deserves further exploration when this technique becomes available on wider clinical scale.

Merchant, T.E. Hua, C.-.H. Shukla, H. Ying, X. Nill, S. Oelfke, U (2008) Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function.. Show Abstract full text

BACKGROUND: To determine whether proton radiotherapy has clinical advantages over photon radiotherapy, we modeled the dose characteristics of both to critical normal tissue volumes using data from patients with four types of childhood brain tumors. PROCEDURES: Three-dimensional imaging and treatment planning data, including targeted tumor and normal tissues contours, were acquired for 40 patients, 10 each with optic pathway glioma (OPG), craniopharyngioma (CR), infratentorial ependymoma (EP), or medulloblastoma (MB). Dose-volume data were collected for the entire brain, temporal lobes, cochlea, and hypothalamus from each patient. The data were averaged and compared based on treatment modality (protons vs. photons) using dose-cognitive effects models. Outcomes were estimated over 5 years. RESULTS: Relatively small critical normal tissue volumes such as the cochlea and hypothalamus may be spared from radiation exposure when not adjacent to the primary tumor volume. Larger normal tissue volumes such as the supratentorial brain or temporal lobes receive less of the low and intermediate doses. When applied to longitudinal models of radiation dose-cognitive effects, these differences resulted in clinically significant higher IQ scores for patients with MB and CR and academic reading scores in patients with OPG. Extreme differences between proton and photon dose distributions precluded meaningful comparison of protons and photons for patients with EP. CONCLUSIONS: Differences in the overall dose distributions, as indicated by modeling changes in cognitive function, showed that a reduction in the lower-dose volumes or mean dose would have long-term, clinical advantages for children with MB, CR, and OPG.

Pflugfelder, D. Wilkens, J.J. Oelfke, U (2008) Worst case optimization: a method to account for uncertainties in the optimization of intensity modulated proton therapy.. Show Abstract full text

The sharp dose gradients which are possible in intensity modulated proton therapy (IMPT) not only offer the possibility of generating excellent target coverage while sparing neighbouring organs at risk, but can also lead to treatment plans which are very sensitive to uncertainties in treatment variables such as the range of individual Bragg peaks. We developed a method to account for uncertainties of treatment variables in the optimization based on a worst case dose distribution. The worst case dose distribution is calculated using several possible realizations of the uncertainties. This information is used by the objective function of the inverse treatment planning system to generate treatment plans which are acceptable under all considered realizations of the uncertainties. The worst case optimization method was implemented in our in-house treatment planning software KonRad in order to demonstrate the usefulness of this approach for clinical cases. In this paper, we investigated range uncertainties, setup uncertainties and a combination of both uncertainties. Using our method the sensitivity of the resulting treatment plans to these uncertainties is considerably reduced.

Unkelbach, J. Oelfke, U (2005) Incorporating organ movements in IMRT treatment planning for prostate cancer: minimizing uncertainties in the inverse planning process.. Show Abstract full text

We investigate an off-line strategy to incorporate inter fraction organ movements in IMRT treatment planning. Nowadays, imaging modalities located in the treatment room allow for several CT scans of a patient during the course of treatment. These multiple CT scans can be used to estimate a probability distribution of possible patient geometries. This probability distribution can subsequently be used to calculate the expectation value of the delivered dose distribution. In order to incorporate organ movements into the treatment planning process, it was suggested that inverse planning could be based on that probability distribution of patient geometries instead of a single snapshot. However, it was shown that a straightforward optimization of the expectation value of the dose may be insufficient since the expected dose distribution is related to several uncertainties: first, this probability distribution has to be estimated from only a few images. And second, the distribution is only sparsely sampled over the treatment course due to a finite number of fractions. In order to obtain a robust treatment plan these uncertainties should be considered and minimized in the inverse planning process. In the current paper, we calculate a 3D variance distribution in addition to the expectation value of the dose distribution which are simultaneously optimized. The variance is used as a surrogate to quantify the associated risks of a treatment plan. The feasibility of this approach is demonstrated for clinical data of prostate patients. Different scenarios of dose expectation values and corresponding variances are discussed.

Glinec, Y. Faure, J. Malka, V. Fuchs, T. Szymanowski, H. Oelfke, U (2006) Radiotherapy with laser-plasma accelerators: Monte Carlo simulation of dose deposited by an experimental quasimonoenergetic electron beam.. Show Abstract full text

The most recent experimental results obtained with laser-plasma accelerators are applied to radio-therapy simulations. The narrow electron beam, produced during the interaction of the laser with the gas jet, has a high charge (0.5 nC) and is quasimonoenergetic (170 +/- 20 MeV). The dose deposition is calculated in a water phantom placed at different distances from the diverging electron source. We show that, using magnetic fields to refocus the electron beam inside the water phantom, the transverse penumbra is improved. This electron beam is well suited for delivering a high dose peaked on the propagation axis, a sharp and narrow tranverse penumbra combined with a deep penetration.

Oelfke, U. Tücking, T. Nill, S. Seeber, A. Hesse, B. Huber, P. Thilmann, C (2006) Linac-integrated kV-cone beam CT: technical features and first applications.. Show Abstract full text

One of the most prominent imaging techniques in image-guided radiotherapy (IGRT) is the acquisition of cone beam computed tomographies (CBCTs) at the linac with the patient in treatment position. CBCTs provide accurate 3-dimensional (3D) knowledge about the patient's anatomy for every treatment fraction and are therefore well suited for all adaptive corrections of errors related to interfractional uncertainties of the treatment process. In this paper, we first describe the technical development and implementation of this new imaging technique at our linac, i.e., the hardware components and their operating parameters are discussed in detail for a standard image acquisition of CBCTs. Then, an extension of this approach for the acquisition of complete images for extended field of views--the "shifted detector" technique--is presented followed by a first investigation of how CBCTs can be reliably used for adaptive dose calculations. Finally, a first clinical application, the process of automatic patient positioning based on CBCT images, is discussed. From our investigations, we conclude that the technical development of linac-integrated CBCTs bears an enormous potential for the correction of interfractional treatment errors. However, image quality and reconstruction speed of the images leave room for improvement. The development of clinical strategies for the optimal application of this new image modality in a clinical environment is one the major tasks for the future.

Maleike, D. Unkelbach, J. Oelfke, U (2006) Simulation and visualization of dose uncertainties due to interfractional organ motion.. Show Abstract full text

In this paper, we deal with the effects of interfractional organ motion during radiation therapy. We consider two problems: first, treatment plan evaluation in the presence of motion, and second, the incorporation of organ motion into IMRT optimization. Concerning treatment plan evaluation, we face the problem that the delivered dose cannot be predicted with certainty at the time of treatment planning but is associated with uncertainties. We present a method to simulate stochastic properties of the dose distribution. This provides the treatment planner with information about motion-related risks of different plans and may support the decision for or against a treatment plan. This information includes the display of probabilities of individual voxels to receive doses from a therapeutical interval or above critical levels, as well as a diagram that shows the variability of the dose volume histogram. Concerning the incorporation of organ motion into IMRT planning, we further analyse the approach of inverse planning based on probability distributions of possible patient geometries. We consider three different sources of uncertainty, namely uncertainty about the amplitude of motion, a systematic error and a random error. We analyse the impact of these sources of uncertainty on the optimized treatment plans for prostate cancer.

Korreman, S. Rasch, C. McNair, H. Verellen, D. Oelfke, U. Maingon, P. Mijnheer, B. Khoo, V (2010) The European Society of Therapeutic Radiology and Oncology-European Institute of Radiotherapy (ESTRO-EIR) report on 3D CT-based in-room image guidance systems: A practical and technical review and guide. full text