Principal component-based image segmentation: a new approach to outline in vitro cell colonies

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Sharp dose profiles for high precision proton therapy using focused proton beams

Proton beam therapy has been developed to irradiate the tumor with higher precision and dose conformity compared to conventional X-ray irradiation. The dose conformity of this treatment modality may be further improved if narrower proton beams are used. Still, this is limited by multiple Coulomb scattering of protons through tissue. The primary aim of this work was to develop techniques to produce narrow proton beams and investigate the resulting dose profiles. We introduced and assessed three different proton beam shaping techniques: 1) metal collimators (100/150~MeV), 2) focusing of conventional- (100/150~MeV), and 3) focusing of high-energy (350~MeV, shoot-through) proton beams. Focusing was governed by the initial value of the Twiss parameter $\alpha$~($\alpha_0$), and can be implemented with magnetic particle accelerator optics. The dose distributions in water were calculated by Monte Carlo simulations using Geant4, and evaluated by target to surface dose ratio (TSDR) in addition to the transverse beam size~($\sigma_T$) at the target. The target was defined as the location of the Bragg peak or the focal point. The different techniques showed greatly differing dose profiles, where focusing gave pronouncedly higher relative target dose and efficient use of primary protons. Metal collimators with radii ~3.6~mm). In contrast, a focused beam of conventional (150~MeV) energy produced a very high TSDR (>~80) with similar $\sigma_T$ as a collimated beam. High-energy focused beams were able to produce TSDRs > 100 and $\sigma_T$ around 1.5~mm. From this study, it appears very attractive to implement magnetically focused proton beams in radiotherapy of small lesions or tumors in close vicinity to healthy organs at risk. This can also lead to a paradigm change in spatially fractionated radiotherapy.Comment: Submitted to Scientific Report

HYPER-RADIOSENSITIVITY AND INDUCED RADIORESISTANCE (HRS/IRR) : the effect of using different dose-rates for pre-exposure on the hyper-radiosensitivity in T-47D cells

Irradiating T-47D cells with doses below 1 Gy revealed that cells of this line express hyper-radiosensitivity (HRS). In the present study HRS has been investigated when a challenge dose was given 6 or 24 hours after a priming dose delivered with varying dose-rates. In addition the effect of a challenge dose to T-47D cells that had been pre-irradiated for several months by incorporated tritium was investigated. A 60Co-source at the Radium Hospital was used for all irradiations. It was chosen to give a fixed priming dose of 0.3 Gy, but dose-rates were varied between 0.045 Gy/h, 0.32 Gy/h, 0.9 Gy/h or high dose-rate (HDR) of 1 Gy/min. Immediately after the priming exposure, the cells were trypsinized and seeded in small flasks (25 cm2) and incubated for 6 or 24 hours before they received the HDR challenge doses. DNA histograms revealed that the T-47D cells in the cell culture used in the experiments with priming exposures of 0.32 and 0.045 Gy/h and also in one of the experiments with HDR priming, had been mixed with cells of another stemline. The mixed cell culture (denoted T-47Dmix) was also used in the experiment with incorporation of tritium into T-47d cells, but in this case it was found from DNA histograms that only the control cells were mixed, but that the cultures exposed to protracted low dose-rate (LDR) irradiation consisted of only T-47d cells. Investigations were made that suggested that the cells mixed into the T-47D cells were of the line NHIK 3025. The following was observed from the experiments: T-47D cells clearly express both HRS/IRR and the adaptive response in the low-dose range (below 1 Gy). NHIK 3025 cells do not express HRS/IRR. T-47D cells that had been pre-irradiated by tritium-decay electrons did not express HRS/IRR. T-47D cells with functional pRb adapted to the continuous irradiation with electrons from incorporated tritium, while the putative NHIK 3025 cells without functional pRb were eradicated by the same treatment. When priming doses were delivered with the lowest dose-rates used (i.e. 0.32 Gy/h and 0.045 Gy/h) the priming effect as measured 6 hours following the termination of the priming exposure seemed to be larger than when the priming dose was delivered with higher dose-rates (i.e. HDR or 0.9 Gy/h). 24 hours after the priming doses delivered with 0.32 Gy/h and 0.045 Gy/h, HRS was still absent (perhaps even further reduced), while 24 hours after a HDR priming dose HRS was partially restored. These results led to speculations concerning: The influence of micro-environmental conditioning effects on the radiation response of NHIK 3025 cells that are growing in a mixed culture with T-47D cells under conditions that would normally be lethal for NHIK 3025 cells. An alternative theory for HRS/IRR in which it is assumed that the repair processes of the cell are permanently induced. When radiation damages are so small, that the tissue as a whole would profit from cell suicide relative to repair with the danger of mis-repair, the repair processes are subdued by apoptosis. The involvement of pRb in the suppression of apoptosis of the alternative theory for HRS/IRR and in the adaptation of T-47D cells to continuous irradiation by decay electrons from incorporated tritium. The possibility that there are two different regulation pathways for induction of the cell-protective mechanisms that reduce HRS after pre-irradiation: One that is dose dependent, instantly induced by HDR irradiation but not by LDR irradiation, and which induces short-lasting mechanisms. Another pathway that works over time and is induced by LDR and probably also by HDR irradiation. The effect and duration of the mechanisms induced by this late-responding pathway depends on the duration of exposure

Low-Dose-Rate Irradiation for 1 Hour Induces Protection Against Lethal Radiation Doses but Does Not Affect Life Span of DBA/2 Mice

Prior findings showed that serum from DBA/2 mice that had been given whole-body irradiation for 1 hour at a low dose rate (LDR) of 30 cGy/h induced protection against radiation in reporter cells by a mechanism depending on transforming growth factor β3 and inducible nitric oxide synthase activity. In the present study, the effect of the 1 hour of LDR irradiation on the response of the preirradiated mice to a subsequent lethal dose and on the life span is examined. These DBA/2 mice were prime irradiated for 1 hour at 30 cGy/h. Two experiments with 9 and 9.5 Gy challenge doses given 6 weeks after priming showed increased survival in primed mice compared to unprimed mice followed up to 225 and 81 days after challenge irradiation, respectively. There was no overall significant difference in life span between primed and unprimed mice when no challenge irradiation was given. The males seemed to have a slight increase in lifespan after priming while the opposite was seen for the females

The dose-dependent impact of γ-radiation reinforced with backscatter from titanium on primary human osteoblasts

AbstractIn head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM). The hOBs were exposed to ionizing γ-irradiation in single doses of 2, 6 or 10 Gy. Twenty-one days post-irradiation, cell nuclei and collagen production were quantified. Cytotoxicity and indicators of differentiation were measured and compared to unirradiated controls. Radiation with backscatter from titanium significantly reduced the number of hOBs but increased the alkaline phosphatase activity in both types of medium when adjusted to the relative cell number on day 21. Irradiated hOBs on the TiF-surface produced similar amounts of collagen as unirradiated controls when cultured in DM. The majority of osteogenic biomarkers significantly increased on day 21 when the hOBs had been exposed to 10 Gy, while the opposite or no effect was observed after lower doses. High doses reinforced with backscatter from titanium resulted in smaller but seemingly more differentiated subpopulations of osteoblasts