No abstract

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 ΔTOF(z) = 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.

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. The nucleon-nucleon potential (NNP) has been studied extensively by investigating the properties of bound nuclear systems, and, in more detail, via a comparison of high-precision two-nucleon scattering data with modern potentials based on the exchange of bosons [1,2,3]. A few of the modern NNPs were facilitated by a partialwave analysis (PWA), that provides a nearly modelindependent analysis of the available scattering data [4]. The modern NNPs reproduce the world data base with a reduced chi-square close to one and have, therefore, been accepted as high-quality benchmark potentials. The precision of modern NNPs has given confidence to study in detail the three-nucleon potential (3NP) which was already predicted in 1939 by Primakoff and Wilson [5]. Compelling evidence of 3NP effects came from various recent theoretical and experimental studies. For example, for light nuclei, Green's function Monte-Carlo calculations employing the high-quality NNPs clearly underestimate the experimental binding energies [2], and, therefore, show that NNPs are not sufficient to describe the three-nucleon and heavier systems accurately. In the last decade, high-precision data at intermediate energies in elastic Nd and dN scattering [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23] for a large energy range together with rigorous Faddeev calculations [24] * Electronic address: ramazani@kvi.nl † Electronic address: messchendorp@kvi.nl for the three-nucleon system have proven to be a sensitive tool to study the 3NP. In particular, a large sensitivity to 3NP effects exists in the minimum of the differential cross section [25,26]. Precision data for a large energy interval for the differential cross section and analyzing power came from recent experimental studies at KVI [7,8,9], RIKEN [10] and RCNP [12]. All these experiments had one common energy of 135 MeV/nucleon. Strikingly, the cross sections obtained at KVI were found to be significantly larger than those measured at RIKEN and at RCNP. The KVI data show significant deviation from predictions of state-of-the-art Faddeev calculations incorporating modern NNPs and 3NPs at this energy, whereas the results obtained at RIKEN and RCNP imply that the cross section can be described reasonably well exploiting the same potentials.This paper presents the results of a new measurement of the differential cross sections of the reaction 2 H( p, d)p at a proton-beam energy of 135 MeV, taken to provide additional data at 135 MeV/nucleon. These results are compared with the previously published data taken at intermediate energies. The data are obtained at KVI using a ne...

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.

Precision data are presented for the break-up reaction, 2 H( 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 H( p, 2 He)n channel. These results are compared to the 2 H( 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. Understanding the exact nature of the nuclear force is one of the long-standing questions in nuclear physics. In 1935, Yukawa successfully described the pair-wise nucleon-nucleon (NN) interaction as an exchange of a boson [1]. Current NN models are mainly based on Yukawa's idea and provide an excellent description of the high-quality database of proton-proton and neutron-proton scattering [2] and of the properties of the deuteron. However, for the simplest three-nucleon system, triton, three-body calculations employing NN forces clearly underestimate the experimental binding energies [3], demonstrating that NN forces are not sufficient to describe the three-nucleon system accurately. Some of the discrepancies between experimental data and calculations solely based on the NN interaction can be resolved by introducing an additional three-nucleon force (3NF). Most of the current models for the 3NF are based on a refined version of Fujita-Miyazawa's 3NF model [4], in which a 2π-exchange mechanism is incorporated by an intermediate ∆ excitation of one of the nucleons [5,6].The structure of the 3NF can be studied via a measurement of observables in three-nucleon scattering processes. More detailed information on the spin dependence of the 3NF can be obtained by measuring polarization observables such as the analyzing powers. For this, a series of * Electronic address: messchendorp@kvi.nl extensive studies of 3NF effects in elastic-scattering reactions have been performed at KVI and other laboratories. Precision measurements of the vector analyzing power of the proton in elastic proton-deuteron scattering have been performed at various beam energies ranging from 90 to 250 MeV [7,8,9,10,11]. Also, vector and tensor analyzing powers in elastic deuteron-proton scattering have been obtained at various beam energies ranging from 75 to 270 MeV [12,13,14,15,16,17]. In these measurements, systematic discrepancies between data and theoretical predictions which rigorously solve the Faddeev equations and using only NN potentials were observed. A large part of the discrepancies were removed by adding a 3NF to the NN potentials. Nevertheless, there are still unresolved problems specially at higher...

High-precision data for vector and tensor analyzing powers for the 1 H( d,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 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 xx and A yy are limited to very small kinematical regions, usually characterized by the lowest energy of the relative motion of the two protons.

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.

Abstract. We successfully identified several multibody final states in deuteron-deuteron scattering at 65 MeV/nucleon at KVI using a unique and advanced detection system called BINA. This facility enabled us to perform cross sections and polarization measurements with an improved statistical and systematic precision. The analysis procedure and a part of the results of the three-body break-up channel in the deuteron-deuteron scattering at 65 MeV/nucleon are presented.The physics phenomena of nuclei are for a large part understood by considering the interaction between their building blocks, the nucleons. In 1935 Yukawa described the nucleon-nucleon (NN) force by the exchange of massive mesons [1] in analogy to the electromagnetic interaction which can be represented by the exchange of of a massless photon. Several phenomenological nucleonnucleon potentials have been derived based on Yukawa's theory and are able to reproduce the whole bulk of data points in neutron-proton and proton-proton scattering with extremely high precision. These so-called high-quality NN potentials are used in Faddeev equations [2,3] to give an exact solution of the scattering problem of the threenucleon system. Already, for the simplest three-nucleon system, the triton, an exact solution of the three-nucleon Faddeev equations employing two-nucleon forces (2NFs) underestimates the experimental binding energy [4], showing that 2NFs are not sufficient to describe the threenucleon system accurately. The existence of an additional force, the three-nucleon (3N) interaction, was predicted by Primakov [5] and confirmed by a comparison between precision data and state-of-the-art calculations. In general, adding 3NF effects to the NN potentials gives a better agreement between the cross section data of the protondeuteron scattering and corresponding calculations [6][7][8][9][10][11][12][13][14][15][16][17], whereas a similar comparison for the spin observables yields various discrepancies [7][8][9][18][19][20][21][22]. This demona e-mail: ramazani@kvi.nl strated that spin-dependent parts of the 3NFs are poorly understood and that more studies in this field are needed.The 3NF effects are in general small in the threenucleon system. A complementary approach is to examine heavier systems for which the 3NF effects are significantly enhanced in magnitude. For this, it was proposed to study the four-nucleon system since the experimental database in the four-nucleon system is presently poor in comparison with that of the three-nucleon system. Most of the available data have been measured at very low energies, in particular below the three-body break-up threshold of 2.2 MeV. Also, theoretical developments are evolving rapidly at low energies [23][24][25][26], but lag behind at higher energies. The experimental database at intermediate energies is very limited [27][28][29]. This situation calls for extensive four-nucleon studies at intermediate energies. The goal of our work was to perform a comprehensive measurement of the cross sections and spin observab...