Biophysical modeling of low-energy ion irradiations with NanOx.

Background: Targeted radiotherapies with low-energy ions show interesting possibilities for the selective irradiation of tumor cells, a strategy particularly appropriate for the treatment of disseminated cancer. Two promising examples are boron neutron capture therapy (BNCT) and targeted radionuclide therapy with -particle emitters (TAT). The successful clinical translation of these radiotherapies requires the implementation of accurate radiation dosimetry approaches able to take into account the impact on treatments of the biological effectiveness of ions and the heterogeneity in the therapeutic agent distribution inside the tumor cells.

Prompt-gamma track-length estimator with time tagging from proton tracking.

The design of prompt-gamma detectors necessitates numerous Monte Carlo simulations to precisely develop and optimize the detection stages in proton therapy. Alongside the advancement of MC simulations, various variance reduction methods have been explored to speed-up calculations. Among these techniques, track-length estimators are interesting scoring methods for achieving both speed and accuracy in Monte Carlo simulations of rare events.

Imaging of polychromatic sources through Compton spectral reconstruction.

Study the performance of a spectral reconstruction method for Compton imaging of polychromatic sources and compare it to standard Compton reconstruction based on the selection of photopeak events.The proposed spectral and the standard photopeak reconstruction methods are used to reconstruct images from simulated sources emitting simultaneously photons of 140, 245, 364 and 511 keV. Data are simulated with perfect and realistic energy resolutions and including Doppler broadening.

Relative stopping power resolution in time-of-flight proton CT.

Proton computed tomography (CT) is similar to x-ray CT but relies on protons rather than photons to form an image. In its most common operation mode, the measured quantity is the amount of energy that a proton has lost while traversing the imaged object from which a relative stopping power map can be obtained via tomographic reconstruction. To this end, a calorimeter which measures the energy deposited by protons downstream of the scanned object has been studied or implemented as energy detector in several proton CT prototypes.

Estimate of the Biological Dose in Hadrontherapy Using GATE.

For the evaluation of the biological effects, Monte Carlo toolkits were used to provide an RBE-weighted dose using databases of survival fraction coefficients predicted through biophysical models. Biophysics models, such as the mMKM and NanOx models, have previously been developed to estimate a biological dose. Using the mMKM model, we calculated the saturation corrected dose mean specific energy z1D* (Gy) and the dose at 10% for human salivary gland (HSG) cells using Monte Carlo Track Structure codes LPCHEM and Geant4-DNA, and compared these with data from the literature for monoenergetic ions.

Monte Carlo simulations of nanodosimetry and radiolytic species production for monoenergetic proton and electron beams: Benchmarking of GEANT4-DNA and LPCHEM codes.

Purpose: In hadrontherapy, biophysical models can be used to predict the biological effect received by cancerous tissues and organs at risk. The input data of these models generally consist of information on nano/micro dosimetric quantities and, concerning some models, reactive species produced in water radiolysis. In order to fully account for the radiation stochastic effects, these input data have to be provided by Monte Carlo track structure (MCTS) codes allowing to estimate physical, physico-chemical, and chemical effects of radiation at the molecular scale.

Energy-adaptive calculation of the most likely path in proton CT.

This note addresses an issue faced by every proton computed tomography (CT) reconstruction software: the modelling and the parametrisation of the multiple Coulomb scattering power for the estimation of the most likely path (MLP) of each proton. The conventional approach uses a polynomial model parameterised as a function of depth for a given initial beam energy. This makes it cumbersome to implement a software that works for proton CT data acquired with an arbitrary beam energy or with energy modulation during acquisition.

A time-of-flight-based reconstruction for real-time prompt-gamma imaging in proton therapy.

We propose a novel prompt-gamma (PG) imaging modality for real-time monitoring in proton therapy: PG time imaging (PGTI). By measuring the time-of-flight (TOF) between a beam monitor and a PG detector, our goal is to reconstruct the PG vertex distribution in 3D. In this paper, a dedicated, non-iterative reconstruction strategy is proposed (PGTI reconstruction).

Influence of sub-nanosecond time of flight resolution for online range verification in proton therapy using the line-cone reconstruction in Compton imaging.

Online ion range monitoring in hadron therapy can be performed via detection of secondary radiation, such as prompt-rays, emitted during treatment. The promptemission profile is correlated with the ion depth-dose profile and can be reconstructed via Compton imaging. The line-cone reconstruction, using the intersection between the primary beam trajectory and the cone reconstructed via a Compton camera, requires negligible computation time compared to iterative algorithms.

Advanced Monte Carlo simulations of emission tomography imaging systems with GATE.

Built on top of the Geant4 toolkit, GATE is collaboratively developed for more than 15 years to design Monte Carlo simulations of nuclear-based imaging systems. It is, in particular, used by researchers and industrials to design, optimize, understand and create innovative emission tomography systems. In this paper, we reviewed the recent developments that have been proposed to simulate modern detectors and provide a comprehensive report on imaging systems that have been simulated and evaluated in GATE.

Influence of gold nanoparticles embedded in water on nanodosimetry for keV photon irradiation.

Purpose: For the past two decades, high-Z nanoparticles have been of high interest to improve the therapeutic outcomes of radiation therapy, especially for low-energy x-rays. Monte Carlo (MC) simulations have been used to evaluate the boost of dose deposition induced by Auger electrons near the nanoparticle surface, by calculating average energy deposition at the nanoscale. In this study, we propose to go beyond average quantities and quantify the stochastic nature of energy deposition at such a scale.

Determination of the Effective Local Lethal Function for the NanOx Model.

NanOx is a biophysical model recently developed in the context of hadrontherapy to predict the cell survival probability from ionizing radiation. It postulates that this may be factorized into two independent terms describing the cell response to two classes of biological events that occur in the sequence of an irradiation: the local lethal events that occur at nanometric scale and can by themselves induce cell death, and the non-local lethal events that lead to cell death by an effect of accumulation and/or interaction at a larger scale. Here we address how local lethal events are modeled in terms of the inactivation of undifferentiated nanometric targets via an "effective local lethal function ", which characterizes the response of each cell line to the spectra of "restricted specific energy".

Comparison of biophysical models with experimental data for three cell lines in response to irradiation with monoenergetic ions.

The relative biological effectiveness (RBE) in particle therapy is currently estimated using biophysical models. We compared experimental measurements to the α curves as function of linear energy transfer computed by the Local Effect Model (LEM I-IV), the Microdosimetric Kinetic Model (MKM) and the NanOx model for HSG, V79 and CHO-K1 cells in response to monoenergetic irradiations. Although the LEM IV and the MKM predictions accurately reproduced the trend observed in the data, NanOx yielded a better agreement than the other models for more irradiation configurations.

Study of the Influence of NanOx Parameters.

NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and diffusion of reactive chemical species. In order to further characterize the new framework, we discuss the meaning and relevance of most of the NanOx parameters by evaluating their influence on the linear-quadratic coefficient α and on the dose deposited to achieve 10% or 1% of cell survival, D 10 % or D 1 % , as a function of LET.

Relationship between radioadaptive response and individual radiosensitivity to low doses of gamma radiation: an extended study of chromosome damage in blood lymphocytes of three donors.

Purpose: Our study aimed at evaluating: 1) whether well-established variability in radioadaptive response (AR) in various donor blood lymphocytes might be attributed to inter-individual differences in radiosensitivity to different low dose levels; 2) whether AR is reproducibly present over time in the lymphocytes of AR-positive individuals. Experimental procedure: Whole blood samples of three donors were exposed to low doses (2-30 cGy) of γ-radiation alone (G phase) or followed by a 1 Gy challenge dose (late S/early G phase), and chromosome aberration were scored to assess the dose-response relationship and adaptive response, correspondingly. Three experiments were performed on blood samples of the same donors at six month intervals.

Corrigendum: Influence of Dose Rate on the Cellular Response to Low- and High-LET Radiations.

[This corrects the article on p. 58 in vol. 6, PMID: 27014633.

Experimental Comparison of Knife-Edge and Multi-Parallel Slit Collimators for Prompt Gamma Imaging of Proton Pencil Beams.

More and more camera concepts are being investigated to try and seize the opportunity of instantaneous range verification of proton therapy treatments offered by prompt gammas emitted along the proton tracks. Focusing on one-dimensional imaging with a passive collimator, the present study experimentally compared in combination with the first, clinically compatible, dedicated camera device the performances of instances of the two main options: a knife-edge slit (KES) and a multi-parallel slit (MPS) design. These two options were experimentally assessed in this specific context as they were previously demonstrated through analytical and numerical studies to allow similar performances in terms of Bragg peak retrieval precision and spatial resolution in a general context.

Influence of Dose Rate on the Cellular Response to Low- and High-LET Radiations.

Nowadays, head and neck squamous cell carcinoma (HNSCC) treatment failure is mostly explained by locoregional progression or intrinsic radioresistance. Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional RT or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient.

Assessment of Geant4 Prompt-Gamma Emission Yields in the Context of Proton Therapy Monitoring.

Monte Carlo tools have been long used to assist the research and development of solutions for proton therapy monitoring. The present work focuses on the prompt-gamma emission yields by comparing experimental data with the outcomes of the current version of Geant4 using all applicable proton inelastic models. For the case in study and using the binary cascade model, it was found that Geant4 overestimates the prompt-gamma emission yields by 40.

Modeling cell response to low doses of photon irradiation: Part 2--application to radiation-induced chromosomal aberrations in human carcinoma cells.

The biological phenomena observed at low doses of ionizing radiation (adaptive response, bystander effects, genomic instability, etc.) are still not well understood. While at high irradiation doses, cellular death may be directly linked to DNA damage, at low doses, other cellular structures may be involved in what are known as non-(DNA)-targeted effects.

Probabilistic models and numerical calculation of system matrix and sensitivity in list-mode MLEM 3D reconstruction of Compton camera images.

This paper addresses the problem of evaluating the system matrix and the sensitivity for iterative reconstruction in Compton camera imaging. Proposed models and numerical calculation strategies are compared through the influence they have on the three-dimensional reconstructed images. The study attempts to address four questions.

Modeling cell response to low doses of photon irradiation--Part 1: on the origin of fluctuations.

Intra- and inter-individual variability is a well-known aspect of biological responses of cells observed at low doses of radiation, whichever the phenomenon considered (adaptive response, bystander effects, genomic instability, etc.). There is growing evidence that low-dose phenomena are related to cell mechanisms other than DNA damage and misrepair, meaning that other cellular structures may play a crucial role.

Four-dimensional radiotherapeutic dose calculation using biomechanical respiratory motion description.

Purpose: Organ motion due to patient breathing introduces a technical challenge for dosimetry and lung tumor treatment by hadron therapy. Accurate dose distribution estimation requires patient-specific information on tumor position, size, and shape as well as information regarding the material density and stopping power of the media along the beam path. A new 4D dosimetry method was developed, which can be coupled to any motion estimation method.