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Proton therapy is a fast growing treatment modality for cancer and is in selected cases preferred over conventional radiotherapy with photons because of the highly conformal dose distribution that can be achieved with protons due to their steep dose gradients. However, these steep gradients also make proton therapy sensitive to range uncertainties. Proton ranges are calculated from proton stopping powers relative to that in water (Relative Stopping Power, RSP). The RSPs needed for a treatment plan can be estimated from CT (Computed Tomography) data of a patient. High accuracy reference values of RSPs are required to assess the accuracy of these CT based estimates. In this paper we present a water phantom that enables accurate measurement of depth dose profiles in water. Experimental RSPs with a relative standard uncertainty smaller than 0.4% (1 σ ) for samples with a water equivalent thickness of about 2 cm can be derived from the measured depth dose distributions. Most CT based RSP estimates use an approximate RSP model based on the Bethe-Bloch formula without the shell, density, Barkas and Bloch correction. In the Geant4 Monte Carlo code these corrections are included and RSP calculations with this code are expected to be more accurate. In this work, a set of 32 well defined (composition and density), mostly clinically relevant materials is used to assess the correspondence between RSPs that were measured, that were estimated from the approximate RSP model and that were calculated from Monte Carlo simulations. With the measured RSPs we provide a ground-truth bench mark to test the validity of RSPs derived from CT imaging and Monte Carlo simulations.

In 2016 and 2017, the 8th and 9th 4D treatment planning workshop took place in Groningen (the Netherlands) and Vienna (Austria), respectively. This annual workshop brings together international experts to discuss research, advances in clinical implementation as well as problems and challenges in 4D treatment planning, mainly in spot scanned proton therapy. In the last two years several aspects like treatment planning, beam delivery, Monte Carlo simulations, motion modeling and monitoring, QA phantoms as well as 4D imaging were thoroughly discussed.This report provides an overview of discussed topics, recent findings and literature review from the last two years. Its main focus is to highlight translation of 4D research into clinical practice and to discuss remaining challenges and pitfalls that still need to be addressed and to be overcome.

Because of strong indications of multiple counting by the multi-channel scaler (MCS) during most of the experiments described in Dendooven et al (2015 Phys. Med. Biol. 60 8923–47), the production of short-lived positron emitters in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium was remeasured. The new results are reported here. With proper single counting of the MCS, the new production rates are 1.1 to 2.9 times smaller than reported in Dendooven et al (2015 Phys. Med. Biol. 60 8923–47). The omission of the conversion from MCS time bin to time unit in the previous data analysis was corrected, leading to an increase of the production rate by a factor of 2.5 or 10 for some nuclides. The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: 12N (T 1/2 = 11 ms) on carbon (5.3% of 11C), 29P (T 1/2 = 4.1 s) on phosphorus (23% of 30P) and 38mK (T 1/2 = 0.92 s) on calcium (173% of 38gK). The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, 12N dominates up to 70 s. On bone tissue, 38mK dominates the beam-on PET counts from 0.2–0.7 s until about 80–110 s. Considering nuclides created on phosphorus and calcium, the short-lived ones provide 8 times more decays than the long-lived ones during a 70 s irradiation. Bone tissue will thus be much better visible in beam-on PET compared to PET imaging after an irradiation. From the estimated number of 12N PET counts, we conclude that, for any tissue, except carbon-poor ones, 12N PET imaging potentially provides equal quality proton range information as prompt gamma imaging with an optimized knife-edge slit camera.

Thomas Schlathölter,1 Pierre Eustache,2 Erika Porcel,2 Daniela Salado,2 Lenka Stefancikova,2 Olivier Tillement,3 Francois Lux,3 Pierre Mowat,3 Aleksandra K Biegun,4 Marc-Jan van Goethem,4 Hynd Remita,5 Sandrine Lacombe2 1Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands; 2Institut des Sciences Moléculaires d’Orsay (ISMO), Univ. Paris Sud, CNRS, Université Paris Saclay, Orsay Cedex, 3Institut Lumière Matière, Villeurbanne Cedex, France; 4Kernfysisch Versneller Instituut – Center for Advanced Radiation Technology (KVI-CART), University of Groningen, Groningen, the Netherlands; 5Laboratoire de Chimie Physique, Universite Paris-Sud, Orsay Cedex, France Abstract: The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/µm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting. Keywords: gadolinium-based nanoparticles, platinum nanoparticles, nanosensitization, theranostics

The development of a proton radiography system to improve the imaging of patients in proton beam therapy is described. The system comprises gridpix based time projection chambers, which are based on the Timepix chip designed by the Medipix collaboration, for tracking the protons. This type of detector was chosen to have minimal impact on the actual determination of the proton tracks by the tracking detectors. To determine the residual energy of the protons, a $BaF _{2}$ crystal with a photomultiplier tube is used. We present data taken in a feasibility experiment with phantoms that represent tissue equivalent materials found in the human body. The obtained experimental results show a good agreement with the performed simulations.

To improve the quality of cancer treatment with protons, a translation of X-ray Computed Tomography (CT) images into a map of the proton stopping powers needs to be more accurate. Proton stopping powers determined from CT images have systematic uncertainties in the calculated proton range in a patient of typically 3-4\% and even up to 10\% in region containing bone~\cite{USchneider1995,USchneider1996,WSchneider2000,GCirrone2007,HPaganetti2012,TPlautz2014,GLandry2013,JSchuemann2014}. As a consequence, part of a tumor may receive no dose, or a very high dose can be delivered in healthy ti\-ssues and organs at risks~(e.g. brain stem)~\cite{ACKnopf2013}. A transmission radiograph of high-energy protons measuring proton stopping powers directly will allow to reduce these uncertainties, and thus improve the quality of treatment. The best way to obtain a sufficiently accurate radiograph is by tracking individual protons traversing the phantom (patient)~\cite{GCirrone2007,TPlautz2014,VSipala2013}. In our simulations we have used an ideal position sensitive detectors measuring a single proton before and after a phantom, while the residual energy of a proton was detected by a BaF$_{2}$ crystal. To obtain transmission radiographs, diffe\-rent phantom materials have been irradiated with a 3x3~cm$^{2}$ scattered proton beam, with various beam energies. The simulations were done using the Geant4 simulation package~\cite{SAgostinelli2003}. In this study we focus on the simulations of the energy loss radiographs for various proton beam energies that are clinically available in proton radiotherapy., Comment: 6 pages, 6 figures, Presented at Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, 7-12 June, 2015, Krak\'ow, Poland

A set of differential cross-section data of the 1 H(d, pp)n breakup reaction at 130 MeV deuteron beam energy has been measured in the domain of very forward polar angles with the use of the Germanium Wall detector at the Forschungszentrum Julich. The data obtained for over 1000 kinematical points (112 geometries) are compared with the theoretical predictions based on various models of the three-nucleon (3N) dynamics. They comprise: the realistic nucleon-nucleon potentials alone or combined with the three-nucleon force (3NF), the coupled-channel calculations with the explicit treatment of the Δ-isobar excitation and finally, the potentials derived from chiral perturbation theory. In the part of the phase space studied, the Coulomb interaction between protons has a strong impact on the differential cross section of the breakup reaction. The strongest Coulomb effects are found in regions where the relative energy of the two protons is the smallest. In these regions the data are well reproduced exclusively by calculations which include the electromagnetic repulsion between protons. In spite of the dominance of the Coulomb force in the phase space studied, the contribution of 3NF effects is also observed.

A large set of cross-section data for the H-1 (d,pp)n breakup reaction was measured at 130 MeV deuteron beam energy with the Germanium Wall setup covering the range of very forward polar angles. In the investigated part of the phase-space, the dynamics is dominated by the Coulomb force influence. The data are compared with results of theoretical calculations based on the realistic Argonne V18 potential supplemented with the long-range electromagnetic component. The predictions also include the Urbana IX three nucleon force model. The cross-section data reveal seizable Coulomb force effects.

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeteris applied for reconstruction of the tracks and energies of individual high energy protons. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam., Comment: 21 pages, 8 figures

Precise and large sets of cross section, vector $A_{x}, A_{y}$ and tensor$ A_{xx}, A_{xy}, A_{yy}$ analyzing power data for the $^{1}H\left ( d, pp \right )n$ breakup reactions were measured at 100 and 130 MeV deuteron beam energies with the SALAD and BINA detectors at KVI and the Germanium Wall setup at FZ-Jülich. Results are compared with various theoretical approaches which model the three-nucleon system dynamics. The cross section data reveal a sizable three-nucleon force (3NF) and Coulomb force influence. In case of the analyzing powers very low sensitivity to these effects was found and the data are well describe by 2N models only. For $A_{xy}$ at 130 MeV, serious disagreements were observed when 3NF models are included in the calculations.

Proton radiography is a novel imaging modality that allows direct measurement of the proton energy loss in various tissues. Currently, due to the conversion of so-called Hounsfield units from X-ray Computed Tomography (CT) into relative proton stopping powers (RPSP), the uncertainties of RPSP are 3-5% or higher, which need to be minimized down to 1% to make the proton treatment plans more accurate.In this work, we simulated a proton radiography system, with position-sensitive detectors (PSDs) and a residual energy detector (RED). The simulations were built using Geant4, a Monte Carlo simulation toolkit. A phantom, consisting of several materials was placed between the PSDs of various Water Equivalent Thicknesses (WET), corresponding to an ideal detector, a gaseous detector, silicon and plastic scintillator detectors. The energy loss radiograph and the scattering angle distributions of the protons were studied for proton beam energies of 150 MeV, 190 MeV and 230 MeV. To improve the image quality deteriorated by the multiple Coulomb scattering (MCS), protons with small angles were selected. Two ways of calculating a scattering angle were considered using the proton's direction and position.A scattering angle cut of 8.7 mrad was applied giving an optimal balance between quality and efficiency of the radiographic image. For the three proton beam energies, the number of protons used in image reconstruction with the direction method was half the number of protons kept using the position method. (C) 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd.

The novel proton radiography imaging technique has a large potential to be used in direct measurement of the proton energy loss (proton stopping power, PSP) in various tissues in the patient. The uncertainty of PSPs, currently obtained from translation of X-ray Computed Tomography (xCT) images, should be minimized from 3-5% or higher to less than 1%, to make the treatment plan with proton beams more accurate, and thereby better treatment for the patient.With Geant4 we simulated a proton radiography detection system with two position-sensitive and residual energy detectors. A complex phantom filled with various materials (including tissue surrogates), was placed between the position sensitive detectors. The phantom was irradiated with 150 MeVprotons and the energy loss radiograph and scattering angles were studied. Protons passing through different materials in the phantom lose energy, which was used to create a radiography image of the phantom. The multiple Coulomb scattering of a proton traversing different materials causes blurring of the image. To improve image quality and material identification in the phantom, we selected protons with small scattering angles.A good quality proton radiography image, in which various materials can be recognized accurately, and in combination with xCT can lead to more accurate relative stopping powers predictions.

Observables in proton-deuteron scattering are sensitive probes of the nucleon-nucleon interaction and three-nucleon force effects (3NF). Several facilities in the world, including Kernfysisch Versneller Instituut (KVI), allow a detailed study a few-nucleon interaction below the pion-production threshold exploiting polarized proton and deuteron beams. In this contribution we explored 3NF effects in the break-up scattering process by performing a measurement of differential cross section and the analyzing power, especially the x component of the analyzing power, using a 135 MeV polarized-proton beam impinging on a liquid-deuteron target. The proton-deuteron breakup reaction leads to a final state with three free particles and a rich phase space that allows us to study observables for continuous set of kinematical configurations of the outgoing nucleons. The results are interpreted with the help of state-of-the-art Faddeev calculations.

Therapeutic proton and heavier ion beams generate prompt gamma photons that may escape from the patient. In principle, this allows for real-time, in situ monitoring of the treatment delivery, in particular, the hadron range within the patient, by imaging the emitted prompt gamma rays. Unfortunately, the neutrons simultaneously created with the prompt photons create a background that may obscure the prompt gamma signal. To enhance the accuracy of proton dose verification by prompt gamma imaging, we therefore propose a time-of-flight (TOF) technique to reject this neutron background, involving a shifting time window to account for the propagation of the protons through the patient. Time-resolved Monte Carlo simulations of the generation and transport of prompt gamma photons and neutrons upon irradiation of a PMMA phantom with 100, 150 and 200 MeV protons were performed using Geant4 (version 9.2.p02) and MCNPX (version 2.7.D). The influence of angular collimation and TOF selection on the prompt gamma and neutron longitudinal profiles is studied. Furthermore, the implications of the proton beam microstructure (characterized by the proton bunch width and repetition period) are investigated. The application of a shifting TOF window having a width of Delta TOFz = 1.0 ns appears to reduce the neutron background by more than 99%. Subsequent application of an energy threshold does not appear to sharpen the distal falloff of the prompt gamma profile but reduces the tail that is observed beyond the proton range. Investigations of the influence of the beam time structure show that TOF rejection of the neutron background is expected to be effective for typical therapeutic proton cyclotrons.

High-precision tensor analyzing power T-20 data of the H-1(d, pp)n reaction at 130 MeV beam energy have been determined for 81 kinematical configurations. They are compared to theoretical predictions based on various approaches to describe the dynamics of the three-nucleon (3N) system. The calculations are performed using modern realistic nucleon-nucleon potentials combined with three-nucleon force (3NF) models or with an effective 3NF resulting from the explicit treatment of the Delta-isobar in coupled-channels (CC) calculations. Alternatively, the framework of chiral perturbation theory is used to generate consistent two-nucleon and three-nucleon potentials at the currently numerically attainable order. Results of the CC calculations with the Delta degrees of freedom and including long-range Coulomb force are also shown. In general all predictions are consistent with each other and describe the experimental T-20 results quite well. In a few configurations small inconsistencies between the data and the results of all approaches are observed. Predicted effects of the 3NF are not big and in most cases do not lead to an improved description of the data. The Coulomb force effects are also small in size and often opposite to the effects of TM99 3NF.

Positron emission tomography is so far the only method for in-vivo dose delivery verification in hadron therapy that is in clinical use. PET imaging during irradiation maximizes the number of detected counts and minimizes washout. In such a scenario, also short-lived positron emitters will be observed. As very little is known on the production of these nuclides, we determined which ones are relevant for proton therapy treatment verification. In order to be relevant, nuclides have to be produced close to the distal edge and thus at rather low proton energy. Therefore we measured the integral production of short-lived positron emitters in the stopping of 55 MeV protons in carbon, oxygen, phosphorus and calcium. The experiments were performed at the irradiation facility of the AGOR cyclotron at KVI-Center for Advanced Radiation Technology, University of Groningen. The positron emitters were identified based on their half-life. In order to do this, the proton beam was pulsed, i.e. delivered as a succession of beam-on and beam-off periods, and the time evolution of the 511 keV positron annihilation photons was recorded. A half-life analysis of the beam-off period allowed to determine the production rates of separate nuclides. The 511 keV photons were detected by a germanium clover detector [1]. A correction for the escape of positrons from the target, determined via MonteCarlo simulations, was applied. In the stopping of 55 MeV protons, the most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: 12N (T1/2 = 11 ms) on carbon (9% of the 11C production), 29P (T1/2 = 4.1 s) on phosphorus (20% of the 30P production) and 38mK (T1/2 = 0.92 s) on calcium (113% of the 38gK production). No short-lived nuclides are produced on water (i.e. oxygen). The experimental production rates are used to calculate the production on PMMA and a representative set of 4 tissue materials. [fig. 1] The number of decays per 55 MeV proton stopped in these materials, integrated over an irradiation, is calculated as function of the duration of the irradiation. The most noticeable result is that for an irradiation in (carbon-rich) adipose tissue, 12N will dominate the PET image up to an irradiation duration of 70 s. On bone tissue, 15O dominates over 12N after 8-15 s (depending on the carbon-to-oxygen ratio). Considering nuclides created on phosphorus and calcium, the short-lived ones provide 2.5 times more decays than the long-lived ones during a 70 s irradiation. Bone tissue will thus be better visible in beam-on PET compared to PET imaging after an irradiation. The results warrant detailed investigations into the energy-dependent production of 12N, 29P and 38mK and their effect on PET imaging during proton irradiations.

The quality of cancer treatment with protons critically depends on an accurate prediction of the proton stopping powers for the tissues traversed by the protons. Today, treatment planning in proton radiotherapy is based on stopping power calculations from densities of X-ray Computed Tomography (CT) images. This causes systematic uncertainties in the calculated proton range in a patient of typically 3-4%, but can become even 10% in bone regions [1-8]. This may lead to no dose in parts of the tumor and too high dose in healthy tissues [9]. A direct measurement of proton stopping powers with high-energy protons will allow reducing these uncertainties and will improve the quality of the treatment.Several studies have shown that a sufficiently accurate radiograph can be obtained by tracking individual protons traversing a phantom (patient) [4, 6, 10]. Our studies benefit from the gas-filled time projection chambers based on GridPix technology [11], developed at Nikhef, capable of tracking a single proton. A BaF2 crystal measuring the residual energy of protons was used. Proton radiographs of phantom consisting of different tissue-like materials were measured with a 30 x 30 mm(2) 150 MeV proton beam. Measurements were simulated with the Geant4 toolkit.First experimental and simulated energy radiographs are in very good agreement [12]. In this paper we focus on simulation studies of the proton scattering angle as it affects the position resolution of the proton energy loss radiograph. By selecting protons with a small scattering angle, the image quality can be improved significantly.

Extensive studies of three-nucleon force (3NF) effects in elastic proton-deuteron scattering have been performed at KVI and elsewhere in the past. In the present work, we explored 3NF effects in the break-up scattering process by performing high precision measurement of vector analyzing powers and differential cross sections using a 190 MeV polarized-proton beam on a liquid deuterium target. The experiment was performed by exploiting a new detector called Big Instrument for Nuclear-polarization Analysis, BINA. Its unique design enables coverage of almost the complete reaction phase space. Preliminary differential cross sections and vector analyzing powers are presented and results are compared with state-of-the-art three-nucleon calculations.

The only method for in vivo dose delivery verification in proton beam radiotherapy in clinical use today is positron emission tomography (PET) of the positron emitters produced in the patient during irradiation. PET imaging while the beam is on (so called beam-on PET) is an attractive option, providing the largest number of counts, the least biological washout and the fastest feedback. In this implementation, all nuclides, independent of their half-life, will contribute. As a first step towards assessing the relevance of short-lived nuclides (half-life shorter than that of (10)C, T1/2 = 19 s) for in vivo dose delivery verification using beam-on PET, we measured their production in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: (12)N (T1/2 = 11 ms) on carbon (9% of (11)C), (29)P (T1/2 = 4.1 s) on phosphorus (20% of (30)P) and (38m)K (T1/2 = 0.92 s) on calcium (113% of (38g)K). No short-lived nuclides are produced on oxygen. The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, (12)N dominates up to 70 s. On bone tissue, (12)N dominates over (15)O during the first 8-15 s (depending on carbon-to-oxygen ratio). The short-lived nuclides created on phosphorus and calcium provide 2.5 times more beam-on PET counts than the long-lived ones produced on these elements during a 70 s irradiation. From the estimated number of (12)N PET counts, we conclude that, for any tissue, (12)N PET imaging potentially provides equal to superior proton range information compared to prompt gamma imaging with an optimized knife-edge slit camera. The practical implementation of (12)N PET imaging is discussed.

The treatment quality of cancer patients with a proton beam critically depends on accurate predictions of proton stopping powers. Uncertainties in proton range that occur from translation of an X-ray CT patient image, of typical 3–4% or more, lead to necessary enlargements of contours around the tumor, and thus delivery of unnecessary dose to healthy tissues. A 2-dimentional proton radiography imaging technique, in which proton stopping powers of various materials (tissues) are measured directly, can improve quality of proton treatment. The proton scattering angle, causing the image degradation, has to be studied with a special care.

Rich sets of high precision cross sections, vector and tensor analyzing powers for the [Formula: see text] breakup reaction were measured at 130 and 100 MeV beam energy with the use of detection systems covering large parts of the phase space. The cross section data allowed to establish evidences for three-nucleon force contributions and to confirm predictions of sizable effect of the Coulomb force in the breakup reaction. Analyzing power data are generally quite well described by theoretical predictions even with pure nucleon-nucleon interactions. However, in some regions discrepancies has been observed for tensor analyzing powers at 130 MeV.

Positron emission tomography is so far the only method for in-vivo dose delivery verification in hadron therapy that is in clinical use. A PET scanner placed in the treatment position (in-situ) will be able to obtain the highest number of counts, as it minimizes the decay of the positron emitting nuclei before the scan is started as well as reduces the effect of biological washout. We investigated the influence of the scan protocol, i.e. the moment when a scan in done in relation to the treatment delivery, on the ability to measure unacceptable deviations from the treatment plan. We developed a Geant4-based Monte-Carlo framework for proton therapy simulations. Four patient cases are studied: two head-and-neck, one sarcoma near the spine, and one breast cancer case. For each irradiation field, the production of the following PET isotopes is calculated: 15O, 11C, 10C, 14O, 30P, 38K, and 13N. The time sequence of the pencil beam scanning irradiation, the decay of the PET isotopes during the irradiation, and biological washout are included in the simulation. The production of these nuclei is then used to calculate a PET image for two scan protocols: a scan of 120 seconds after the first field, or a scan of 120 seconds after the last field. To mimic a typical scanner spatial resolution, the images are blurred using a Gaussian blurring function with 4 mm FWHM. Deviations from the treatment plan are simulated by shifting the patient 4 mm perpendicular to the field angle, or by increasing the patient density by 3%. The PET image is then simulated again for each scanning protocol. The ability of each protocol to detect these deviations from the treatment plan is investigated by comparing the planned and the modified PET image. Several analysis methods are used: line profiles coupled to the field-directions, structural similarity index analysis [1], and gamma index analysis. [2] Preliminary data shows that a difference in density is best detected by starting the scan directly after the first field. However, shifts perpendicular to the field directions are better detected when the scan is done after the last field, due to the increased activity and counting-rate.

One of the most important goals of modern nuclear physics is to contruct nuclear force model which properly describes the experimental data. To develop and test predictions of current models the breakup $^{1}H\left ( \vec{d}, pp \right )n$ reaction was investigated experimentally at 100 and 130 MeV deuteron beam energies. Rich set of data for cross section, vector and tensor analyzing powers was obtained with the use of the SALAD and BINA detectors at KVI and Germanium Wall setup at FZ-Jülich. Results are compared with various theoretical approaches which describe the three-nucleon (3N) system dynamics. For correct description of the cross section data both, three-nucleon force (3NF) and Coulomb force, have to be included into calculations and influence of those ingredients is seizable at specific parts of the phase space. In case of the vector analyzing powers very low sensitivity to any effects beyond nucleon-nucleon interaction was found. At 130 MeV, the $A_{xy}$ data are not correctly described when 3NF models are included into calculations.

Precise and large set of cross sections, vector A ( )x( ), A ( )y( ) and tensor A ( )xx( ), A ( )xy( ), A ( )yy( ) analyzing powers for the (1) H(d, pp)n breakup reactions were measured at 100 and 130 MeV deuteron beam energies with the use of the SALAD and BINA detectors at KVI and Germanium Wall setup at FZ-Jülich. Results are compared with various theoretical approaches which model the three-nucleon (3N) system dynamics. The calculations are based on different two-nucleon (2N) potentials which can be combined with models of the three-nucleon force (3NF) and other pieces of the dynamics can also be included like the Coulomb interaction and relativistic effects. The cross sections data reveal seizable 3NF and Coulomb force influence. In case of analyzing powers very low sensitivity to the effects was found and the data are well describe by 2N models only. At 130 MeV for A ( )xy( ) serious disagreements appear when 3NF models are included into calculations.

The PANDA detection system at FAIR, Germany, is designed to study antiproton-proton annihilations, in order to investigate among others the realm of charm-meson states and glueballs, which has still much to reveal. The yet unknown properties of this field are to be unraveled through studying QCD phenomena in the non-perturbative regime. The multipurpose PANDA detector will be capable of tracking, calorimetry, and particle identification, and is foreseen to run at high luminosities providing average reaction rates up to 20 Million interactions/s. The envisaged physics program requires measurements of photons and charged particles with excellent energy, position, and time resolutions. The electromagnetic calorimeter (EMC) will serve as one of the basic components of the detector setup and comprises cooled Lead-Tungstate (PbWO4) crystals. This paper presents the mechanical design of the Forward End-cap calorimeter and analyses the response of this detector component in conjunction with the full EMC and the complete PANDA detector. The simulation studies are focused on the performance of the planned EMC with respect to the energy and spatial resolution of the reconstructed photons. Results of the Monte Carlo simulations, excluding very low-energy photons, have been validated by data obtained from a prototype calorimeter and shown to fulfil the requirements imposed by the PANDA physics program., Comment: 22 Pages, 24 Figures, 4 Tables

High-quality vector analyzing power data for the $^{1}H\left ( d,pp \right )n$ breakup reaction and elastic scattering at 100MeV beam energy have been measured in a large part of the phase space for these processes. The results are compared to theoretical predictions obtained using the charge-dependent Bonn potential alone or combined with the three-nucleon force TM99 as well as to the results of calculations in the coupled-channel approach, with or without the inclusion of the Coulomb interaction. In the studied observables, effects of the 3NF and the Coulomb force are almost absent. The pairwise NN interactions alone are sufficient to describe the experimental results.

Precise monitoring of the particle range inside the body, preferably in real-time, is a primary interest in quality assurance of particle therapy. Prompt-gamma (PG) detection aims at this task, but such a system is technically challenging to implement. For mechanically collimated PG detection, neutron-induced background radiation originating in the collimator material is a major issue. We study by Monte-Carlo simulations (Geant4), the influence of different collimator designs and their geometric parameters - such as distance to source, size and septa thickness - on the correlation between transmitted PG profiles and the longitudinal depth-dose profile. The impact of background rejection by time-of-flight (TOF) is also addressed. A single-parallel-slit collimator scanned along the beam axis was primarily studied and results show that the background can be efficiently reduced by TOF discrimination. Due to reduced statistics, signal integration from neighbouring pencil-beams was further considered, accounting for typical clinical proton fluences. Furthermore, first direct-comparison results between multi-slat collimation and a knife-edge-slit collimator are presented, obtained both by simulation and analytical calculations of their geometric performances. Advantages and disadvantages of both approaches are highlighted and some design improvements are proposed. Energy thresholding was also addressed, showing that a low-energy threshold of 4 MeV increases the signal-to-background ratio in all simulation results, a factor mostly important if TOF rejection cannot be applied.

Set of vector analyzing power data of the (d) over barp elastic scattering and H-1((d) over bar, pp)n breakup reactions at 130-MeV deuteron beam energy has been measured in the domain of very forward polar angles. The results are compared with theoretical predictions originating from various approaches: realistic nucleon-nucleon (NN) potentials and the NN potentials combined with a three-nucleon force (3NF) model and with predictions based on the ChPT framework. In case of the breakup process, none of the theoretical calculations reveal sensitivity to any of the dynamical effects such as 3NF or Coulomb interaction and they describe the experimental data equally well. For the elastic scattering, the Coulomb correction appears not negligible at very small theta(c.m.)(d). The effect seems to be confirmed by the data.

The aim of this work is to seek for an optimal angular detection of prompt photons emitted perpendicularly to the beam direction using a time-of-flight technique, which enables a huge neutron background rejection. A homogeneous PMMA phantom was studied. The prompt photon profile correlates well with the dose distal fall-off when the proper selection of θ=90°±0.7° of the emitted prompt gamma rays is made. The correlation to the dose can be detected with the present method with an accuracy of up to 4 mm at 50% height of the prompt gamma rays profile.

High-precision data for vector and tensor analyzing powers for the $^{1}\mathrm{H}$$(\mathrm{dP\vec},\mathit{pp})n$ reaction at a 130-MeV deuteron beam energy have been measured over a large part of the phase space. Theoretical predictions based on various approaches to describe the three nucleon ($3N$) system reproduce very well the vector analyzing power data and no three-nucleon force effect is observed for these observables. Tensor analyzing powers are also very well reproduced by calculations in almost the whole studied region, but locally certain discrepancies are observed. For ${A}_{\mathit{xy}}$ such discrepancies usually appear, or are enhanced, when model $3N$ forces, TM99 or Urbana, are included. Problems of all theoretical approaches with describing ${A}_{\mathit{xx}}$ and ${A}_{\mathit{yy}}$ are limited to very small kinematical regions, usually characterized by the lowest energy of the relative motion of the two protons.

Precision data are presented for the break-up reaction, $^2{\rm H}(\vec p,pp)n$, within the framework of nuclear-force studies. The experiment was carried out at KVI using a polarized-proton beam of 190 MeV impinging on a liquid-deuterium target and by exploiting the detector, BINA. Some of the vector-analyzing powers are presented and compared with state-of-the-art Faddeev calculations including three-nucleon forces effect. Significant discrepancies between the data and theoretical predictions were observed for kinematical configurations which correspond to the $^2{\rm H}(\vec p,^2$He$)n$ channel. These results are compared to the $^2{\rm H}(\vec p,d)p$ reaction to test the isospin sensitivity of the present three-nucleon force models. The current modeling of two and three-nucleon forces is not sufficient to describe consistently polarization data for both isospin states., 4 pages, 3 figures, submitted to PRL

High precision vector and tensor analyzing powers for the 1H(d, pp)n breakup reaction were measured at 130 MeV beam energy with the detection system covering a large part of the phase space. Results are compared with rigorous theoretical calculations based on realistic nucleon-nucleon potentials, also with so-called three-nucleon force included, as well as on chiral perturbation theory. Theoretical predictions generally describe data quite well although in some regions discrepancies have been observed, what indicates incompleteness of the present-day treatment of the three nucleon system dynamics.

A systematic study of three-nucleon force (3NF) effects in break-up reactions has been carried out at KVI at several energies. In this article, the p + d -> p + p + n reaction with a polarized-proton beam of 190 MeV will be discussed. The experiment was performed by exploiting a new detector called BINA. Some results for high-precision vector analyzing powers and differential cross sections are presented and compared with state-of-the-art Faddeev calculations with or without 3NF.

Differential cross sections and vector analyzing powers for the p + d -> p + d reaction have been measured using a new experimental setup (BINA) at KVI. The data are compared with published results and are found to be significantly different.

Observables in elastic proton-deuteron scattering are sensitive probes of the nucleon-nucleon interaction and three-nucleon force effects. The present experimental data base for this reaction is large, but contains a large discrepancy between data sets for the differential cross section taken at 135 MeV/nucleon by two experimental research groups. This paper reviews the background of this problem and presents new data taken at KVI. Differential cross sections and analyzing powers for the $^{2}{\rm H}(\vec p,d){p}$ and ${\rm H}(\vec d,d){p}$ reactions at 135 MeV/nucleon and 65 MeV/nucleon, respectively, have been measured. The data differ significantly from previous measurements and consistently follow the energy dependence as expected from an interpolation of published data taken over a large range at intermediate energies., Comment: 5 pages, 4 figures, submitted to PRC

The three-nucleon system is the simplest non-trivial testing ground in which the quality of modern nucleon-nucleon interaction models, as well as additional dynamical ingredients referred to as three-nucleon forces, can be probed quantitatively by means of a rigorous technique of solving the Faddeev equations. A large set of high precision, exclusive cross-section data for the (1)H((d) over right arrow, pp)n breakup reaction at 130 MeV was obtained at KVI, Groningen. It allowed to establish for the first time a clear evidence of the three-nucleon force contributions to the cross sections of the breakup process and to confirm recent predictions of sizable influences of the Coulomb force in this reaction.

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.

Purpose: To investigate the production and effect of short-lived positron emitters when using PET for in-vivo range verification during a proton therapy irradiation. Methods: The integrated production of short-lived positron emitters in the stopping of 55 MeV protons was measured in water, carbon, phosphorus and calcium targets. The experimental production rates are used to calculate the production on PMMA and a representative set of 4 tissue materials. The number of decays integrated over an irradiation in these materials is calculated as function of the duration of the irradiation, considering irradiations with the same total number of protons. Results: The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: 12-N (T1/2 = 11 ms) on carbon (9.5% of the 11-C production), 29-P (T1/2 = 4.1 s) on phosphorus (20% of the 30-P production) and 38m-K (T1/2 = 0.92 s) on calcium (113% of the 38g-K production). No short-lived nuclides are produced on water. The most noticeable Result is that for an irradiation in (carbon-rich) adipose tissue, 12-N will dominate the PET image up to an irradiation duration of 70 s. On bone tissue, 15-O dominates over 12-N after 7–15 s (depending on the carbon-to-oxygenmore » ratio). Conclusions: The presence of 12-N needs to be considered in PET imaging during proton beam irradiations as, depending on tissue composition and PET scanning protocol, it may noticeably deteriorate image quality due to the large positron range blurring. The results presented warrant investigations into the energy-dependent production of 12-N, 29-P and 38m-K and their effect on PET imaging during proton irradiations.« less

High precision cross-section data of the deuteron-proton breakup reaction at 130 MeV deuteron energy are compared with the theoretical predictions obtained with a coupled-channel extension of the CD Bonn potential with virtual Delta-isobar excitation, without and with inclusion of the long-range Coulomb force. The Coulomb effect is studied on the basis of the cross-section data set, extended in this work to about 1500 data points by including breakup geometries characterized by small polar angles of the two protons. The experimental data clearly prefer predictions obtained with the Coulomb interaction included. The strongest effects are observed in regions in which the relative energy of the two protons is the smallest., 9 pages, 3 figures, submitted to Physics Letters B

Vector and tensor analyzing powers of the 1H(d,pp)n breakup process have been measured at the beam energy of 130 MeV. The forthcoming results will be compared with predictions based on various 2N and 3N forces models in quest for a correct structure of the 3NF.

Comparison of the cross sections measured over a large part of the phase space of the deuteron‐proton breakup at 130 MeV with the results of rigorous, Faddeev‐like calculations is presented. Global analysis, including nearly 1200 data points, reveals a better agreement for theoretical predictions which include three‐nucleon force (3NF) model over the results obtained with only nucleon‐nucleon realistic potentials. A possible way to probe details of the 3NF models via studying “non‐standard” projections of the multi‐dimensional phase space is envisaged.

The measurement of exclusive deuteron-proton breakup for kinematics covering a large fraction of the available phase space has been performed using 130 MeV deuteron beam. High precision fivefold cross section data in 38 kinematical configurations have been compared to predictions of modern nuclear forces. To this aim the three-nucleon s3Nd Faddeev equations have been solved rigorously using the nucleon-nucleon (NN) potentials AV18, charge-dependent Bonn, Nijm I, and Nijm II alone, and combining them with the 2p-exchange Tucson-Melbourne three-nucleon force (TM 3NF) and with its modified version TM99, more consistent with chiral symmetry. The AV18 potential was also combined with the Urbana IX 3NF. Global comparison of the measured cross sections to pairwise NN force predictions only and with 3NF’s included clearly reveals the presence of 3NF effects. Our study demonstrates the usefulness of the kinematically complete breakup reaction studied in the full phase space to search for 3NF effects.

An experiment to measure cross sections and both, vector and tensor analyzing powers, for the 1H(d,pp)n breakup reaction at 130 MeV deuteron beam energy is presented. Employing a position-sensitive detection system covering a large solid angle enables probing of a significant part of the whole phase space. First results are presented and compared with the rigorous Faddeev calculations using modern NN and 3NF potentials.

Compared to external beam photon therapy, proton therapy offers significant advantages in ensuring complete tumor destruction while minimizing collateral damage to healthy tissue. The reason for this is the highly localized dose deposition of ions (Bragg peak). However, dose delivery with protons (and other ions) is less robust toward anatomical changes in the patient over the course of a treatment, proton range miscalculations, and patient motion. It is therefore essential that an in-situ treatment delivery verification tool becomes an integral part of proton therapy to reduce these risks and their subsequent complications. The purpose of this study is to design such a system and evaluate its usefulness in a clinical setting for patient treatment.

A therapeutic proton beam penetrating a patient generates a large number of prompt photons as well as neutrons, resulting from proton-induced nuclear reactions. This allows for obtaining longitudinal beam-profile images via the detection of selected prompt-gamma rays emitted perpendicularly to the beam direction. The significant neutron background on top of the prompt photons signal was observed. Thus, the goal of presented research is to propose the novel in-situ time-of-flight (TOF) technique for neutron background rejection in order to get the optimum signal from prompt-gamma rays escaping the irradiated object. Density heterogeneities within the patient affect the position of the Bragg peak. Due to potential morphological changes the Bragg peak position may vary during the course of treatment, which may lead to clinically significant under-dosage in the tumor or over-dosage in the organs-at-risk. The Bragg peak shifts due to target morphological modifications, whichmay occur in realistic radiotherapy scenarios (e.g. tumor or normal tissue swelling), can be detected with the presented method to within a few millimeters. We show a clinically relevant correlation between the prompt-gamma profiles and the target (patient) density.