Introducing the concept of spiral microbeam radiation therapy (spiralMRT).

Motivation With interlaced microbeam radiation therapy (MRT) a first kilovoltage radiotherapy (RT) concept combining spatially fractionated entrance beams and homogeneous dose distribution at the target exists. However, this technique suffers from its high sensitivity to positioning errors of the target relative to the radiation source. With spiral microbeam radiation therapy (spiralMRT), this publication introduces a new irradiation geometry, offering similar spatial fractionation properties as interlaced MRT, while being less vulnerable to target positioning uncertainties.Methods The dose distributions achievable with spiralMRT in a simplified human head geometry were calculated with Monte Carlo simulations based on Geant4 and the dependence of the result on the microbeam pitch, total field size, and photon energy were analysed. A comparison with interlaced MRT and conventional megavoltage tomotherapy was carried out.Results SpiralMRT can deliver homogeneous dose distributions, while using spatially fractionated entrance beams. The valley dose of spiralMRT entrance beams is by up to 40% lower than the corresponding tomotherapy dose, thus indicating a better normal tissue sparing. The optimum photon energy is found to be around [Formula: see text].Conclusions SpiralMRT is a promising approach to delivering homogeneous dose distributions with spatially fractionated entrance beams, possibly decreasing normal tissue side effects in hypofractionated RT

The effect of magnetic field strength on the response of Gafchromic EBT-3 film.

With the advent of MRI-guided radiotherapy, the suitability of commercially available radiation dose detectors needs to be assessed. The aim of this study was to investigate the effect of the magnetic field (B-field) on the response of the Gafchromic EBT-3 films. Moreover, as an independent study, we contribute to clarifying the inconsistency of the results of recent published studies, on the effect of B-field on the sensitivity of Gafchromic films. A 60Co beam was used to irradiate film samples in an electromagnet. An in-house PMMA phantom was designed to fit in the 5 cm gap between the two poles of the magnet. The phantom consists of two symmetrical plates where a film can be inserted. The absorbed dose rate of the 60Co beam for zero B-field was measured using alanine pellets in a Farmer-type holder. A 12-point response curve was created, representing [Formula: see text] as a function of dose, for each of five different B-field strengths (0 T to 2 T). This study finds that there is at most a small effect of the magnetic field on the response of EBT-3 film. In terms of netOD (red channel) the change in response varied from ‒0.0011 at 0.5 T to 0.0045 at 2.0 T, with a standard uncertainty of 0.0030. If uncorrected, this would lead to an error in film-measured dose, for the red channel, of 2.4% at 2 T, with a standard uncertainty on dose of 1.4%. Results are also presented for B-field strengths of 0.5 T, 1 T and 1.5 T, which are all zero within the measurement uncertainty. Comparison between other studies is also presented. Considering the small change on dose determined with EBT-3 when irradiated under the presence of B-field and taking into account the overall uncertainty in dosimetry using EBT-3 film achieved in this work, EBT-3 is assessed to be a suitable detector for relative and absolute dosimetry, with appropriate corrections, in MRI-guided radiotherapy. The results of the current work also elucidate the inconsistency on the reports from previous studies and demonstrate the necessity of similar investigations by independent teams, especially if the existing results may be in conflict

Computational modelling of the cerebral cortical microvasculature: Effect of x-ray microbeams versus broad beam irradiation.

Microbeam Radiation Therapy is an innovative pre-clinical strategy which uses arrays of parallel, tens of micrometres wide kilo-voltage photon beams to treat tumours. These x-ray beams are typically generated on a synchrotron source. It was shown that these beam geometries allow exceptional normal tissue sparing from radiation damage while still being effective in tumour ablation. A final biological explanation for this enhanced therapeutic ratio has still not been found, some experimental data support an important role of the vasculature. In this work, the effect of microbeams on a normal microvascular network of the cerebral cortex was assessed in computer simulations and compared to the effect of homogeneous, seamless exposures at equal energy absorption. The anatomy of a cerebral microvascular network and the inflicted radiation damage were simulated to closely mimic experimental data using a novel probabilistic model of radiation damage to blood vessels. It was found that the spatial dose fractionation by microbeam arrays significantly decreased the vascular damage. The higher the peak-to-valley dose ratio, the more pronounced the sparing effect. Simulations of the radiation damage as a function of morphological parameters of the vascular network demonstrated that the distribution of blood vessel radii is a key parameter determining both the overall radiation damage of the vasculature and the dose-dependent differential effect of microbeam irradiation

Effect of the NΔ interaction on observables of the πNN and γNN systems

Effects on the hadronic and electromagnetic properties of the two-nucleon system above pion threshold, arising from the interaction of the Δ isobar with nucleons, are investigated. The instantaneous nucleon-Δ potential is based on the meson exchange. Two-body reactions connecting channels with at most one pion and one photon are studied. Processes leading to a three-body pion-two-nucleon final state are considered in the restricted kinematic domain in which the pion forms the P33 resonance with one of the nucleons. The nucleon-Δ potential is seen to increase the relative importance of the inelastic strength of two-nucleon spin-triplet states with respect to spin-singlet states, correcting a deficiency common in most existing models. Theoretical predictions are compared with recent experimental data for the various reactions. In particular, the differential cross section and the proton beam asymmetry for pp→nΔ++ (pπ+) are calculated, the latter observable being especially sensitive to the nucleon-Δ interaction

Line focus x-ray tubes-a new concept to produce high brilliance x-rays.

Currently hard coherent x-ray radiation at high photon fluxes can only be produced with large and expensive radiation sources, such as 3[Formula: see text] generation synchrotrons. Especially in medicine, this limitation prevents various promising developments in imaging and therapy from being translated into clinical practice. Here we present a new concept of highly brilliant x-ray sources, line focus x-ray tubes (LFXTs), which may serve as a powerful and cheap alternative to synchrotrons and a range of other existing technologies. LFXTs employ an extremely thin focal spot and a rapidly rotating target for the electron beam which causes a change in the physical mechanism of target heating, allowing higher electron beam intensities at the focal spot. Monte Carlo simulations and numeric solutions of the heat equation are used to predict the characteristics of the LFXT. In terms of photon flux and coherence length, the performance of the line focus x-ray tube compares with inverse Compton scattering sources. Dose rates of up to 180 Gy [Formula: see text] can be reached in 50 cm distance from the focal spot. The results demonstrate that the line focus tube can serve as a powerful compact source for phase contrast imaging and microbeam radiation therapy. The production of a prototype seems technically feasible

A cellular automaton model for spheroid response to radiation and hyperthermia treatments.

Thermo-radiosensitisation is a promising approach for treatment of radio-resistant tumours such as those containing hypoxic subregions. Response prediction and treatment planning should account for tumour response heterogeneity, e.g. due to microenvironmental factors, and quantification of the biological effects induced. 3D tumour spheroids provide a physiological in vitro model of tumour response and a systems oncology framework for simulating spheroid response to radiation and hyperthermia is presented. Using a cellular automaton model, 3D oxygen diffusion, delivery of radiation and/or hyperthermia were simulated for many ([Formula: see text]) individual cells forming a spheroid. The iterative oxygen diffusion model was compared to an analytical oxygenation model and simulations were calibrated and validated against experimental data for irradiated (0-10 Gy) and/or heated (0-240 CEM43) HCT116 spheroids. Despite comparable clonogenic survival, spheroid growth differed significantly following radiation or hyperthermia. This dynamic response was described well by the simulation ([Formula: see text] > 0.85). Heat-induced cell death was implemented as a fast, proliferation-independent process, allowing reoxygenation and repopulation, whereas radiation was modelled as proliferation-dependent mitotic catastrophe. This framework stands out both through its experimental validation and its novel ability to predict spheroid response to multimodality treatment. It provides a good description of response where biological dose-weighting based on clonogenic survival alone was insufficient

3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments.

For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that more closely resembles that of tumours in vivo and may thus be a superior in vitro cancer model than monolayer cultures. Here, the response of tumour spheroids formed from two established human cancer cell lines (HCT116 and CAL27) to single and combination treatments of radiation (0-20 Gy), and hyperthermia at 47 °C (0-780 CEM43) has been evaluated. Response was analysed in terms of spheroid growth, cell viability and the distribution of live/dead cells. Time-lapse imaging was used to evaluate mechanisms of cell death and cell detachment. It was found that sensitivity to heat in spheroids was significantly less than that seen in monolayer cultures. Spheroids showed different patterns of shrinkage and regrowth when exposed to heat or radiation: heated spheroids shed dead cells within four days of heating and displayed faster growth post-exposure than samples that received radiation or no treatment. Irradiated spheroids maintained a dense structure and exhibited a longer growth delay than spheroids receiving hyperthermia or combination treatment at (thermal) doses that yielded equivalent levels of clonogenic cell survival. We suggest that, unlike radiation, which kills dividing cells, hyperthermia-induced cell death affects cells independent of their proliferation status. This induces microenvironmental changes that promote spheroid growth. In conclusion, 3D tumour spheroid growth studies reveal differences in response to heat and/or radiation that were not apparent in 2D clonogenic assays but that may significantly influence treatment efficacy

Edge effects in 3D dosimetry: characterisation and correction of the non-uniform dose response of PRESAGE®.

Previous work has shown that PRESAGE® can be used successfully to perform 3D dosimetric measurements of complex radiotherapy treatments. However, measurements near the sample edges are known to be difficult to achieve. This is an issue when the doses at air-material interfaces are of interest, for example when investigating the electron return effect (ERE) present in treatments delivered by magnetic resonance (MR)-linac systems. To study this effect, a set of 3.5 cm-diameter cylindrical PRESAGE® samples was uniformly irradiated with multiple dose fractions, using either a conventional linac or an MR-linac. The samples were imaged between fractions using an optical-CT, to read out the corresponding accumulated doses. A calibration between TPS-predicted dose and optical-CT pixel value was determined for individual dosimeters as a function of radial distance from the axis of rotation. This data was used to develop a correction that was applied to four additional samples of PRESAGE® of the same formulation, irradiated with 3D-CRT and IMRT treatment plans, to recover significantly improved 3D measurements of dose. An alternative strategy was also tested, in which the outer surface of the sample was physically removed prior to irradiation. Results show that for the formulation studied here, PRESAGE® samples have a central region that responds uniformly and an edge region of 6-7 mm where there is gradual increase in dosimeter response, rising to an over-response of 24%-36% at the outer boundary. This non-uniform dose response increases in both extent and magnitude over time. Both mitigation strategies investigated were successful. In our four exemplar studies, we show how discrepancies at edges are reduced from 13%-37% of the maximum dose to between 2 and 8%. Quantitative analysis shows that the 3D gamma passing rates rise from 90.4, 69.3, 63.7 and 43.6% to 97.3, 99.9, 96.7 and 98.9% respectively