W. Enghardt

OncoRay- Center for Radiation Research in Oncology, Dresden, Saxony, Germany

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Publications (242)335.73 Total impact

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    ABSTRACT: Background and purpose: To improve precision of particle therapy, in vivo range verification is highly desirable. Methods based on prompt gamma rays emitted during treatment seem promising but have not yet been applied clinically. Here we report on the worldwide first clinical application of prompt gamma imaging (PGI) based range verification. Material and methods: A prototype of a knife-edge shaped slit camera was used to measure the prompt gamma ray depth distribution during a proton treatment of a head and neck tumor for seven consecutive fractions. Inter-fractional variations of the prompt gamma profile were evaluated. For three fractions, in-room control CTs were acquired and evaluated for dose relevant changes. Results: The measurement of PGI profiles during proton treatment was successful. Based on the PGI information, inter-fractional global range variations were in the range of ±2mm for all evaluated fractions. This is in agreement with the control CT evaluation showing negligible range variations of about 1.5mm. Conclusions: For the first time, range verification based on prompt gamma imaging was applied for a clinical proton treatment. With the translation from basic physics experiments into clinical operation, the potential to improve the precision of particle therapy with this technique has increased considerably.
    No preview · Article · Jan 2016 · Radiotherapy and Oncology
  • Y Tian · K Stützer · W Enghardt · M Priegnitz · S Helmbrecht · C Bert · F Fiedler
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    ABSTRACT: Particle therapy positron emission tomography (PT-PET) is an in vivo and non-invasive imaging technique to monitor treatment delivery in particle therapy. The inevitable patient respiratory motion during irradiation causes artefacts and inaccurate activity distribution in PET images. Four-dimensional (4D) maximum likelihood expectation maximisation (4D MLEM) allows for a compensation of these effects, but has up to now been restricted to regular motion for PT-PET investigations. However, intra-fractional motion during treatment might differ from that during acquisition of the 4D-planning CT (e.g. amplitude variation, baseline drift) and therefore might induce inaccurate 4D PET reconstruction results. This study investigates the impact of different irregular analytical one-dimensional (1D) motion patterns on PT-PET imaging by means of experiments with a radioactive source and irradiated moving phantoms. Three sorting methods, namely phase sorting, equal amplitude sorting and event-based amplitude sorting, were applied to manage the PET list-mode data. The influence of these sorting methods on the motion compensating algorithm has been analysed. The event-based amplitude sorting showed a superior performance and it is applicable for irregular motions with ⩽4 mm amplitude elongation and drift. For motion with 10 mm baseline drift, the normalised root mean square error was as high as 10.5% and a 10 mm range deviation was observed.
    No preview · Article · Jan 2016 · Physics in Medicine and Biology
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    ABSTRACT: Positron emission tomography (PET) is a clinically implemented method for in vivo verification of treatment delivery in ion-beam therapy. The dose distribution is the relevant measure but PET captures a β+ -activity distribution, that is created as a side product during the irradiation. Therefore, a prediction of the activity distribution is required. We present a simulation code that makes use of measured yields of β+ -emitters to perform this task. The yields are available in three reference materials. A conversion from X-ray gray values to a combination of these materials has been set up. The lateral properties of the ion beam are described by means of a formulation of Moliere’s scattering theory in thick targets. A model of the annihilation point density around an emitting nuclide has been implemented in the software to describe the movement of the positrons. Simulations of phantom experiments as well as of a real patient case were performed. The results are comparable or superior to the results obtained from an established condensed history Monte Carlo code. We conclude that measured yields can be used as raw data for the calculation of ion-beam-induced β+ -activity distribution instead of nuclear cross sections.
    No preview · Article · Nov 2015 · IEEE Transactions on Nuclear Science
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    ABSTRACT: A major weakness of ion beam therapy is the lack of tools for verifying the particle range in clinical routine. The application of the Compton camera concept for the imaging of prompt gamma rays, a by-product of the irradiation correlated to the dose distribution, is a promising approach for range assessment and even three-dimensional in vivo dosimetry. Multiple position sensitive gamma ray detectors arranged in scatter and absorber planes, together with an imaging algorithm, are required to reconstruct the prompt gamma emission density map. Conventional block detectors deployed in Positron Emission Tomography (PET), which are based on Lu2SiO5:Ce (LSO) and Bi4Ge3O12 (BGO) scintillators, are suitable candidates for the absorber of a Compton camera due to their high density and absorption efficiency with respect to the prompt gamma energy range (several MeV). We compare experimentally LSO and BGO block detectors in clinical-like radiation fields in terms of energy, spatial and time resolution. The high energy range compensates for the low light yield of the BGO material and boosts significantly its performance compared to the PET scenario. Notwithstanding the overall superiority of LSO, BGO catches up in the field of prompt gamma imaging and can be considered as a competitive alternative to LSO for the absorber plane due to its lower price and the lack of intrinsic radioactivity.
    No preview · Article · Sep 2015 · Journal of Instrumentation
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    ABSTRACT: Proton and light ion beams are applied to the therapeutic irradiation of cancer patients due to the favorable dose deposition of these particles in tissue. By means of accelerated ions, a high dose can be accurately deposited in the tumor while normal tissue is spared. Since minor changes in the patient’s tissue along the beam path can compromise the success of the treatment, an in-vivo monitoring of the dose deposition is highly desired. Cameras detecting the prompt γ-rays emitted during therapy are under investigation for this purpose. Due to the energy spectrum of prompt γ-rays with a range between a few keV and several MeV, it is reasonable to consider the utilization of electron-positron pair production events to reconstruct the origin of these prompt photons. The combined use as a pair production and Compton camera is expected to increase its efficiency. We evaluated if a pair production camera could be suitable in this context by means of Monte-Carlo simulations. Modelling of the pair production events taking place in a prototype detector dedicated to Compton imaging were performed. We analyzed the efficiency of the detector system regarding pair production and Compton events. The most crucial property of this pair production camera is the angular resolution. The results of this work indicate that the spatial resolution of the considered detection system used as pair production camera is, for principal reasons, insufficient for an application to range assessment in particle therapy. Furthermore, the efficiency of the pair production camera under study is one order of magnitude lower than the efficiency of the setup applied to the detection of Compton events.
    No preview · Article · Aug 2015 · IEEE Transactions on Nuclear Science
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    ABSTRACT: Ion beam therapy promises enhanced tumour coverage compared to conventional radiotherapy, but particle range uncertainties significantly blunt the achievable precision. Experimental tools for range verification in real-time are not yet available in clinical routine. The prompt gamma ray timing method has been recently proposed as an alternative to collimated imaging systems. The detection times of prompt gamma rays encode essential information about the depth-dose profile thanks to the measurable transit time of ions through matter. In a collaboration between OncoRay, Helmholtz-Zentrum Dresden-Rossendorf and IBA, the first test at a clinical proton accelerator (Westdeutsches Protonentherapiezentrum Essen, Germany) with several detectors and phantoms is performed. The robustness of the method against background and stability of the beam bunch time profile is explored, and the bunch time spread is characterized for different proton energies. For a beam spot with a hundred million protons and a single detector, range differences of 5 mm in defined heterogeneous targets are identified by numerical comparison of the spectrum shape. For higher statistics, range shifts down to 2 mm are detectable. A proton bunch monitor, higher detector throughput and quantitative range retrieval are the upcoming steps towards a clinically applicable prototype. In conclusion, the experimental results highlight the prospects of this straightforward verification method at a clinical pencil beam and settle this novel approach as a promising alternative in the field of in vivo dosimetry.
    Full-text · Article · Aug 2015 · Physics in Medicine and Biology
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    ABSTRACT: Irradiation with protons and light ions offers new possibilities for tumor therapy but has a strong need for novel imaging modalities for treatment verification. The development of new detector systems, which can provide an in vivo range assessment or dosimetry, requires an accurate knowledge of the secondary radiation field and reliable Monte Carlo simulations. This paper presents multiple measurements to characterize the prompt γ-ray emissions during proton irradiation and benchmarks the latest Geant4 code against the experimental findings. Within the scope of this work, the total photon yield for different target materials, the energy spectra as well as the γ-ray depth profile were assessed. Experiments were performed at the superconducting AGOR cyclotron at KVI-CART, University of Groningen. Properties of the γ-ray emissions were experimentally determined. The prompt γ-ray emissions were measured utilizing a conventional HPGe detector system (Clover) and quantitatively compared to simulations. With the selected physics list QGSP_BIC_HP, Geant4 strongly overestimates the photon yield in most cases, sometimes up to 50%. The shape of the spectrum and qualitative occurrence of discrete γ lines is reproduced accurately. A sliced phantom was designed to determine the depth profile of the photons. The position of the distal fall-off in the simulations agrees with the measurements, albeit the peak height is also overestimated. Hence, Geant4 simulations of prompt γ-ray emissions from irradiation with protons are currently far less reliable as compared to simulations of the electromagnetic processes. Deviations from experimental findings were observed and quantified. Although there has been a constant improvement of Geant4 in the hadronic sector, there is still a gap to close.
    No preview · Article · May 2015 · Physics in Medicine and Biology
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    Full-text · Article · Apr 2015
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    ABSTRACT: To guarantee equal access to optimal radiotherapy, a concept of patient assignment to photon or particle radiotherapy using remote treatment plan exchange and comparison - ReCompare - was proposed. We demonstrate the implementation of this concept and present its clinical applicability. The ReCompare concept was implemented using a client-server based software solution. A clinical workflow for the remote treatment plan exchange and comparison was defined. The steps required by the user and performed by the software for a complete plan transfer were described and an additional module for dose-response modeling was added. The ReCompare software was successfully tested in cooperation with three external partner clinics and worked meeting all required specifications. It was compatible with several standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow. The ReCompare software can be applied to support non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by remote treatment plan exchange and comparison. Copyright © 2015. Published by Elsevier GmbH.
    Full-text · Article · Feb 2015 · Zeitschrift für Medizinische Physik
  • C. Richter · G. Pausch · J. Seco · T. Bortfeld · W. Enghardt

    No preview · Article · Dec 2014 · Physica Medica
  • A. Lühr · S. Löck · K. Roth · U. Just · M. Krause · M. Baumann · W. Enghardt

    No preview · Article · Dec 2014 · Radiotherapy and Oncology
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    ABSTRACT: The invention is related to a method for monitoring a range of a particle beam in a target. The method is using gamma detectors for detecting prompt gammas produced in the target. The time differences between the time of detecting a gamma quantum and a time of emission of a particle or a bunch of particles from the radiation device are determined. A statistical distribution of those time difference is used to deduce information related to the range of the beam. The invention is also related to an apparatus for monitoring a range based on measured time profiles of detected prompt gammas.
    Full-text · Patent · Sep 2014

  • No preview · Article · Sep 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Einleitung Die Partikeltherapie-Positronen-Emissions-Tomografie (PT-PET) ist die bisher einzige klinisch eingesetzte Methode zur Verifikation der Ionenstrahltherapie. Eine direkte Berechnung der Dosis aus der gemessenen Aktivität ist nicht möglich, weshalb die erhaltenen Bilder mit einer Referenz verglichen werden. Die vorliegende Arbeit untersucht die erreichbare Genauigkeit zweier Vergleichsverfahren für die Aktivitätsverteilungen anhand von reproduzierbaren Benchmark-Tests mit Phantomexperimenten. Dies stellt eine objektive Methode dar, um patientenbedingte Einflussfaktoren auszuschließen. Material und Methoden Zwei Arten von Phantomen wurden entwickelt, um wohldefinierte Abweichungen in der Aktivitätsverteilung zu erzeugen. Reine Reichweitendifferenzen wurden mittels des ersten Phantomtyps generiert, während der zweite Typ Kavitätenstrukturen simulierte. Die Phantome wurden mit 12C-Ionen bestrahlt. Die PT-PET-Messung wurde mit einem am Bestrahlungsplatz integrierten Kamerasystem durchgeführt. Verschiedene Messzeit-Szenarien wurden untersucht, unter der Annahme eines PET-Scanners direkt am Bestrahlungsplatz oder innerhalb des Bestrahlungsraumes. Die Bilddaten wurden mittels des Pearson-Korrelationskoeffizienten (PCC), eines Reichweiten-Vergleichsalgorithmus sowie einer speziellen Methode zur Erkennung gefüllter Kavitäten analysiert. Ergebnisse Reichweitendifferenzen konnten mit einer Genauigkeit von unter 2 mm erkannt werden. Der Reichweitenvergleichsalgorithmus lieferte hierbei leicht bessere Ergebnisse als die PCC-basierte Methode. Die Füllung einer Kavität konnte sicher erkannt werden, sofern deren Innendurchmesser mindestens 5 mm betrug. Schlussfolgerung Mit beiden Ansätzen ist eine objektive Beurteilung der PT-PET Daten möglich. Für klinisch realistische Dosisraten konnten vielversprechende Ergebnisse für ,,in-beam“ -und ,,in-room“ -PET erzielt werden.
    No preview · Article · Sep 2014 · Zeitschrift für Medizinische Physik
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    ABSTRACT: Proton and ion beams open up new vistas for the curative treatment of tumors, but adequate technologies for monitoring the compliance of dose delivery with treatment plans in real time are still missing. Range assessment, meaning the monitoring of therapy-particle ranges in tissue during dose delivery (treatment), is a continuous challenge considered a key for tapping the full potential of particle therapies. In this context the paper introduces an unconventional concept of range assessment by prompt-gamma timing (PGT), which is based on an elementary physical effect not considered so far: therapy particles penetrating tissue move very fast, but still need a finite transit time—about 1–2 ns in case of protons with a 5–20 cm range—from entering the patient's body until stopping in the target volume. The transit time increases with the particle range. This causes measurable effects in PGT spectra, usable for range verification. The concept was verified by proton irradiation experiments at the AGOR cyclotron, KVI-CART, University of Groningen. Based on the presented kinematical relations, we describe model calculations that very precisely reproduce the experimental results. As the clinical treatment conditions entail measurement constraints (e.g. limited treatment time), we propose a setup, based on clinical irradiation conditions, capable of determining proton range deviations within a few seconds of irradiation, thus allowing for a fast safety survey. Range variations of 2 mm are expected to be clearly detectable.
    No preview · Article · Aug 2014 · Physics in Medicine and Biology
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    ABSTRACT: Für die translationale Krebsforschung sind präklinische in-vivo-Untersuchungen an Kleintieren unverzichtbar, um Erkenntnisse aus in-vitro-Zellexperimenten vor der klinischen Einführung zu validieren. Bei der Konzeption solcher Tierexperimente müssen verschiedene biologische, technische und methodische Aspekte betrachtet werden. Dieser Übersichtsartikel gibt eine umfangreiche Zusammenfassung zur Bestrahlung von Kleintieren wie Mäusen und Ratten basierend auf relevanten Publikationen dieses Forschungsgebietes. Klinische Bestrahlungsgeräte für Teletherapie und Brachtytherapie sowie dedizierte Bestrahlungsgeräte für die Forschung sind zur Bestrahlung von Kleintieren geeignet. Dies hängt jedoch wesentlich vom Tiermodell und den Forschungszielen ab. Geeignete Lösungen werden vorgestellt, welche die verfügbaren Technologien der humanen Strahlentherapie auf die präklinische Forschung mit Kleintieren übertragen. Des Weiteren werden wichtige Entscheidungshilfen für die Experimentplanung zusammengefasst, die zur Erzielung zuverlässiger, klinisch relevanter Ergebnisse zu beachten sind.
    No preview · Article · Aug 2014 · Zeitschrift für Medizinische Physik
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    ABSTRACT: In the context of ion beam therapy, particle range verification is a major challenge for the quality assurance of the treatment. One approach is the measurement of the prompt gamma rays resulting from the tissue irradiation. A Compton camera based on several position sensitive gamma ray detectors, together with an imaging algorithm, is expected to reconstruct the prompt gamma ray emission density map, which is correlated with the dose distribution. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), a Compton camera setup is being developed consisting of two scatter planes: two CdZnTe (CZT) cross strip detectors, and an absorber consisting of one Lu2SiO5 (LSO) block detector. The data acquisition is based on VME electronics and handled by software developed on the ROOT framework. The setup has been tested at the linear electron accelerator ELBE at HZDR, which is used in this experiment to produce bunched bremsstrahlung photons with up to 12.5 MeV energy and a repetition rate of 13 MHz. Their spectrum has similarities with the shape expected from prompt gamma rays in the clinical environment, and the flux is also bunched with the accelerator frequency. The charge sharing effect of the CZT detector is studied qualitatively for different energy ranges. The LSO detector pixel discrimination resolution is analyzed and it shows a trend to improve for high energy depositions. The time correlation between the pulsed prompt photons and the measured detector signals, to be used for background suppression, exhibits a time resolution of 3 ns FWHM for the CZT detector and of 2 ns for the LSO detector. A time walk correction and pixel-wise calibration is applied for the LSO detector, whose resolution improves up to 630 ps. In conclusion, the detector setup is suitable for time-resolved background suppression in pulsed clinical particle accelerators. Ongoing tasks are the quantitative comparison with simulations and the test of imaging algorithms. Experiments at proton accelerators have also been performed and are currently under analysis.
    No preview · Article · May 2014 · Journal of Instrumentation
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    ABSTRACT: The recent advancements in the field of laser-driven particle acceleration have made Laser-driven Ion Beam Therapy (L-IBT) an attractive alternative to the conventional particle therapy facilities. To bring this emerging technology to clinical application, we introduce the broad energy assorted depth dose deposition model which makes efficient use of the large energy spread and high dose-per-pulse of Laser Accelerated Protons (LAP) and is capable of delivering homogeneous doses to tumors. Furthermore, as a key component of L-IBT solution, we present a compact iso-centric gantry design with 360° rotation capability and an integrated shot-to-shot energy selection system for efficient transport of LAP with large energy spread to the patient. We show that gantry size could be reduced by a factor of 2-3 compared to conventional gantry systems by utilizing pulsed air-core magnets.
    Full-text · Article · Mar 2014 · Applied Physics B
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    ABSTRACT: Therapeutic irradiation with protons and ions is advantageous over radiotherapy with photons due to its favorable dose deposition. Additionally, ion beams provide a higher relative biological effectiveness than photons. For this reason, an improved treatment of deep-seated tumors is achieved and normal tissue is spared. However, small deviations from the treatment plan can have a large impact on the dose distribution. Therefore, a monitoring is required to assure the quality of the treatment. Particle therapy positron emission tomography (PT-PET) is the only clinically proven method which provides a non-invasive monitoring of dose delivery. It makes use of the β+-activity produced by nuclear fragmentation during irradiation. In order to evaluate these PT-PET measurements, simulations of the β+-activity are necessary. Therefore, it is essential to know the yields of the β+-emitting nuclides at every position of the beam path as exact as possible. We evaluated the three-dimensional Monte-Carlo simulation tool PHITS (version 2.30) [ 1] and the 1D deterministic simulation tool HIBRAC [ 2] with respect to the production of β+-emitting nuclides. The yields of the most important β+-emitting nuclides for carbon, lithium, helium and proton beams have been calculated. The results were then compared with experimental data obtained at GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Germany. GEANT4 simulations provide an additional benchmark [ 3]. For PHITS, the impact of different nuclear reaction models, total cross-section models and evaporation models on the β+-emitter production has been studied. In general, PHITS underestimates the yields of positron-emitters and cannot compete with GEANT4 so far. The β+-emitters calculated with an extended HIBRAC code were in good agreement with the experimental data for carbon and proton beams and comparable to the GEANT4 results, see [ 4] and Fig. 1. Considering the simulation results and its speed compared with three-dimensional Monte-Carlo tools, HIBRAC is a good candidate for the implementation in clinical routine PT-PET. Fig 1.Depth-dependent yields of the production of 11C and 15O during proton irradiation of a PMMA target with 140 MeV [ 4].
    Full-text · Article · Mar 2014 · Journal of Radiation Research
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    ABSTRACT: Identifying those patients who have a higher chance to be cured with fewer side effects by particle beam therapy than by state-of-the-art photon therapy is essential to guarantee a fair and sufficient access to specialized radiotherapy. The individualized identification requires initiatives by particle as well as non-particle radiotherapy centers to form networks, to establish procedures for the decision process, and to implement means for the remote exchange of relevant patient information. In this work, we want to contribute a practical concept that addresses these requirements. We proposed a concept for individualized patient allocation to photon or particle beam therapy at a non-particle radiotherapy institution that bases on remote treatment plan comparison. We translated this concept into the web-based software tool ReCompare (REmote COMparison of PARticlE and photon treatment plans). We substantiated the feasibility of the proposed concept by demonstrating remote exchange of treatment plans between radiotherapy institutions and the direct comparison of photon and particle treatment plans in photon treatment planning systems. ReCompare worked with several tested standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow. Our concept supports non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by providing expertise from a particle therapy center. The software tool ReCompare may help to improve and standardize this personalized treatment decision. It will be available from our website when proton therapy is operational at our facility.
    Full-text · Article · Feb 2014 · Radiation Oncology

Publication Stats

2k Citations
335.73 Total Impact Points

Institutions

  • 2008-2015
    • OncoRay- Center for Radiation Research in Oncology
      Dresden, Saxony, Germany
    • GSI Helmholtzzentrum für Schwerionenforschung
      Darmstadt, Hesse, Germany
  • 2006-2015
    • Technische Universität Dresden
      • Faculty of Medicine Carl Gustav Carus
      Dresden, Saxony, Germany
  • 1987-2015
    • Helmholtz-Zentrum Dresden-Rossendorf
      • Institute of Radiation Physics
      Dresden, Saxony, Germany
  • 2012-2013
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 2009
    • CERN
      • Technology Department (TE)
      Genève, Geneva, Switzerland
  • 1997-2008
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
  • 2007
    • Justus-Liebig-Universität Gießen
      • II. Physikalisches Institut
      Gießen, Hesse, Germany
  • 1998
    • Hungarian Academy of Sciences
      • Institute for Energy and Environmental Safety
      Budapest, Budapest fovaros, Hungary