[Show abstract][Hide abstract] 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.
Physics in Medicine and Biology 08/2015; 60(16):6247-6272. DOI:10.1088/0031-9155/60/16/6247 · 2.92 Impact Factor
[Show abstract][Hide abstract] 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.
Physics in Medicine and Biology 05/2015; 60(10):4197-4207. DOI:10.1088/0031-9155/60/10/4197 · 2.92 Impact Factor
[Show abstract][Hide abstract] 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.
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.
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.
[Show abstract][Hide abstract] 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.
Physics in Medicine and Biology 08/2014; 59(18):5399. DOI:10.1088/0031-9155/59/18/5399 · 2.92 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
Journal of Instrumentation 05/2014; 9(05):P05002. DOI:10.1088/1748-0221/9/05/P05002 · 1.53 Impact Factor
[Show abstract][Hide abstract] 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.
Applied Physics B 03/2014; 117(1). DOI:10.1007/s00340-014-5796-z · 1.63 Impact Factor
[Show abstract][Hide abstract] 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 [
Journal of Radiation Research 03/2014; 55 Suppl 1(Suppl 1):i143-i144. DOI:10.1093/jrr/rrt151 · 1.69 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Purpose: To investigate the possibility of detecting patient mispositioning in carbon-ion therapy with particle therapy positron emission tomography (PET) in an automated image registration based manner.Methods: Tumors in the head and neck (H&N), pelvic, lung, and brain region were investigated. Biologically optimized carbon ion treatment plans were created with TRiP98. From these treatment plans, the reference β(+)-activity distributions were calculated using a Monte Carlo simulation. Setup errors were simulated by shifting or rotating the computed tomography (CT). The expected β(+) activity was calculated for each plan with shifts. Finally, the reference particle therapy PET images were compared to the "shifted" β(+)-activity distribution simulations using the Pearson's correlation coefficient (PCC). To account for different PET monitoring options the inbeam PET was compared to three different inroom scenarios. Additionally, the dosimetric effects of the CT misalignments were investigated.Results: The automated PCC detection of patient mispositioning was possible in the investigated indications for cranio-caudal shifts of 4 mm and more, except for prostate tumors. In the rather homogeneous pelvic region, the generated β(+)-activity distribution of the reference and compared PET image were too much alike. Thus, setup errors in this region could not be detected. Regarding lung lesions the detection strongly depended on the exact tumor location: in the center of the lung tumor misalignments could be detected down to 2 mm shifts while resolving shifts of tumors close to the thoracic wall was more challenging. Rotational shifts in the H&N and lung region of +6° and more could be detected using inroom PET and partly using inbeam PET. Comparing inroom PET to inbeam PET no obvious trend was found. However, among the inroom scenarios a longer measurement time was found to be advantageous.Conclusions: This study scopes the use of various particle therapy PET verification techniques in four indications. The automated detection of patients' setup errors was investigated in a broad accumulation of data sets. The evaluation of introduced setup errors is performed automatically, which is of utmost importance to introduce highly required particle therapy monitoring devices into the clinical routine.
Medical Physics 12/2013; 40(12):121718. DOI:10.1118/1.4829595 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The HADES (High Acceptance Di-Electron Spectrometer) is a tool designed for lepton pair (e+e−) spectroscopy in pion, proton and heavy ion induced reactions in the 1–2AGeV energy range. One of the goals of the HADES experiment is to study in-medium modifications of hadron properties like effective masses, decay widths, electromagnetic form factors etc. Such effects can be probed with vector mesons ( ρ,ω,ɸ ) decaying into e+e− channel. The identification of vector mesons by means of a HADES spectrometer is based on invariant mass reconstruction of e+e− pairs. The combined information from all spectrometer sub-detectors is used to reconstruct the di-lepton signal. The recent results from 2.2GeV p + p, 1AGeV and 2AGeV C+C experiments are presented. Diaz Medina, Jose, Jose.Diaz@uv.es
[Show abstract][Hide abstract] ABSTRACT: In the context of particle 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 Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and OncoRay, a Compton camera setup has been developed consisting of two scatter planes (CdZnTe cross strip detectors) and an absorber (Lu2SiO5 block detector). The data acquisition is based on VME electronics and handled by software developed on the ROOT framework. The setup was tested at the linear electron accelerator ELBE at HZDR, which was used to produce bunched bremsstrahlung photons with up to 12.5MeV. Their spectrum has similarities with the one expected from prompt gamma rays in the clinical case, and the flux is also bunched with the accelerator frequency. The spatial resolution for the CZT and LSO detector is analyzed and it showed a trend to improve for low and high energy depositions respectively. The time correlation between the pulsed prompt photons and the measured signals to be used for background discrimination exhibits a time resolution of 3 ns (2 ns) FWHM for the CZT (LSO) detector. A time walk correction and pixel calibration is applied for the LSO detector, whose resolution improved up to 630 ps. In conclusion, the detectors are suitable for time-resolved background suppression in pulsed clinical particle accelerators. Ongoing tasks are the test of the imaging algorithms and the quantitative comparison with simulations. Experiments at proton accelerators have been also performed and are now under analysis.
Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), 2013 IEEE; 10/2013
[Show abstract][Hide abstract] ABSTRACT: To investigate scanned-beam proton dose distribution reproducibility in the lung under high frequency jet ventilation (HFJV).
For 11 patients (12 lesions), treated with single-fraction photon stereotactic radiosurgery under HFJV, scanned-beam proton plans were prepared with the TRiP98 treatment planning system using 2, 3-4 and 5-7 beams. The planning objective was to deliver at least 95% of the prescription of 33Gy (RBE) to 98% of the PTV. Plans were subsequently recomputed on localization CT scans. Additionally, for selected cases, the effects of range uncertainties were investigated.
Median GTV V98% was 98.7% in the original 2-field plans and 93.7% in their recomputation (p=0.039). The respective values were 99.0% and 98.0% (p=0.039) for the 3-4-field plans and 100.0% and 99.6% (p=0.125) for the 5-7-field plans. CT calibration uncertainties of ±3.5% led to a GTV V98% reduction below 1.5 percentual points in most cases and reaching 3 percentual points for 2-field plans with beam undershoot.
Through jet ventilation, reproducible tumor fixation for proton radiotherapy of lung lesions is achievable, ensuring excellent target coverage in most cases. In few cases, non-optimal patient setup reproducibility induced density changes across beam entrance channels, leading to dosimetric deterioration between planning and delivery.
Radiotherapy and Oncology 10/2013; 109(1). DOI:10.1016/j.radonc.2013.09.013 · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For quality assurance in particle therapy, a non-invasive, in vivo range verification is highly desired. Particle therapy positron-emission-tomography (PT-PET) is the only clinically proven method up to now for this purpose. It makes use of the β(+)-activity produced during the irradiation by the nuclear fragmentation processes between the therapeutic beam and the irradiated tissue. Since a direct comparison of β(+)-activity and dose is not feasible, a simulation of the expected β(+)-activity distribution is required. For this reason it is essential to have a quantitatively reliable code for the simulation of the yields of the β(+)-emitting nuclei at every position of the beam path. In this paper results of the three-dimensional Monte-Carlo simulation codes PHITS, GEANT4, and the one-dimensional deterministic simulation code HIBRAC are compared to measurements of the yields of the most abundant β(+)-emitting nuclei for carbon, lithium, helium, and proton beams. In general, PHITS underestimates the yields of positron-emitters. With GEANT4 the overall most accurate results are obtained. HIBRAC and GEANT4 provide comparable results for carbon and proton beams. HIBRAC is considered as a good candidate for the implementation to clinical routine PT-PET.
Physics in Medicine and Biology 09/2013; 58(18):6355-6368. DOI:10.1088/0031-9155/58/18/6355 · 2.92 Impact Factor