High-precision image-guided proton irradiation of mouse brain sub-volumes.

BACKGROUND AND PURPOSE: Proton radiotherapy offers the potential to reduce normal tissue toxicity. However, clinical safety margins, range uncertainties, and varying relative biological effectiveness (RBE) may result in a critical dose in tumor-surrounding normal tissue. To assess potential adverse effects in preclinical studies, image-guided proton mouse brain irradiation and analysis of DNA damage repair was established. MATERIAL AND METHODS: We designed and characterized a setup to shape proton beams with 7 mm range in water and 3 mm in diameter and commissioned a Monte Carlo model for in vivo dose simulation. Cone-beam computed tomography and orthogonal X-ray imaging were used to delineate the right hippocampus and position the mice. The brains of three C3H/HeNRj mice were irradiated with 8 Gy and excised 30 min later. Initial DNA double-strand breaks were visualized by staining brain sections for cell nuclei and γH2AX. Imaged sections were analyzed with an automated and validated processing pipeline to provide a quantitative, spatially resolved radiation damage indicator. RESULTS: The analyzed DNA damage pattern clearly visualized the radiation effect in the mouse brains and could be mapped to the simulated dose distribution. The proton beam passed the right hippocampus and stopped in the central brain region for all evaluated mice. CONCLUSION: We established image-guided proton irradiation of mouse brains. The clinically oriented workflow facilitates (back-) translational studies. Geometric accuracy, detailed Monte Carlo dose simulations, and cell-based assessment enable a biologically and spatially resolved analysis of radiation response and RBE.

Correction for volume recombination in liquid ionization chambers at high dose-per-pulse.

PURPOSE: To determine the volume recombination at high dose-per-pulse in liquid ionization chambers (LIC) and to ascertain whether existing calculation methods verified in air-filled chambers may be used to calculate a correction factor. METHODS: Two LICs, one filled with 2,2,4-trimethylpentane (isooctane) the other with tetramethylsilane (TMS), were irradiated in a pulsed, 20 MeV electron beam. Via reference measurements with a Faraday cup, the saturation correction for volume recombination was determined for dose-per-pulse values ranging from about 5 mGy to 1 Gy for both chambers at a pulse duration of 693 ns. In addition, the isooctane chamber was irradiated with pulses of varying duration, ranging from 5 ps to 10 ms, at a dose-per-pulse of about 76.5 mGy. The dose-per-pulse-dependent measurements were compared to calculations based on Boag's models (with and without a free electron fraction), the two-dose-rate method, and a numerical calculation. The pulse duration dependent measurements were compared only to a numerical calculation that iteratively calculates the charge transport and loss in a 1D model of an ionization chamber. RESULTS: In TMS only Boag's model with a free electron fraction and the numerical calculation are in good agreement with the experimental data. However, in isooctane, good agreement is observed between the experimental data, the numerical calculation as well as the two-dose-rate method, and Boag's model including a free electron fraction. Only Boag's model without a free electron fraction shows a good agreement with lesser extend. Furthermore, the pulse duration-dependent data for isooctane are well described by the numerical model. CONCLUSION: With isooctane as an active medium, a LIC could be directly used in a field with high dose-per-pulse utilizing the well-established two-dose-rate method to correct the volume recombination. In addition, pulsed fields with variable pulse duration are easily modeled for this medium using a numerical calculation. Other media, as exemplified by the TMS-filled chamber, might require additional considerations, such as including a fraction of free electrons in the consideration of volume recombination.

Towards ion beam therapy based on laser plasma accelerators.

Only few ten radiotherapy facilities worldwide provide ion beams, in spite of their physical advantage of better achievable tumor conformity of the dose compared to conventional photon beams. Since, mainly the large size and high costs hinder their wider spread, great efforts are ongoing to develop more compact ion therapy facilities. One promising approach for smaller facilities is the acceleration of ions on micrometre scale by high intensity lasers. Laser accelerators deliver pulsed beams with a low pulse repetition rate, but a high number of ions per pulse, broad energy spectra and high divergences. A clinical use of a laser based ion beam facility requires not only a laser accelerator providing beams of therapeutic quality, but also new approaches for beam transport, dosimetric control and tumor conformal dose delivery procedure together with the knowledge of the radiobiological effectiveness of laser-driven beams. Over the last decade research was mainly focused on protons and progress was achieved in all important challenges. Although currently the maximum proton energy is not yet high enough for patient irradiation, suggestions and solutions have been reported for compact beam transport and dose delivery procedures, respectively, as well as for precise dosimetric control. Radiobiological in vitro and in vivo studies show no indications of an altered biological effectiveness of laser-driven beams. Laser based facilities will hardly improve the availability of ion beams for patient treatment in the next decade. Nevertheless, there are possibilities for a need of laser based therapy facilities in future.

Nature of the chemical bond of aqueous Fe2+ probed by soft X-ray spectroscopies and ab initio calculations.

Aqueous iron(II) chloride is studied by soft X-ray absorption, emission, and resonant inelastic Raman scattering techniques on the Fe L-edge and O K-edge using the liquid-jet technique. Soft X-ray spectroscopies allow in situ and atom-specific probing of the electronic structure of the aqueous complex and thus open the door for the investigation of chemical bonding and molecular orbital mixing. In this work, we combine theoretical ab initio restricted active space self-consistent field and local atomic multiplet calculations with experimental soft X-ray spectroscopic methods for a description of the local electronic structure of the aqueous ferrous ion complex. We demonstrate that the atomic iron valence final states dominate the resonant inelastic X-ray scattering spectra of the complex over the ligand-to-metal charge transfer transitions, which indicates a weak interaction of Fe(2+) ion with surrounding water molecules. Moreover, the oxygen K-edge also shows only minor changes due to the presence of Fe(2+) implying a small influence on the hydrogen-bond network of water.

DMSO-Water Clustering in Solution Observed in Soft X-ray Spectra.

The significant deviation from the ideality of dimethyl sulfoxide (DMSO)/water mixtures can be addressed based on the change of the local molecular orbitals of each solvent upon mixing. Oxygen K-edge absorption and emission spectra of DMSO/water solutions were measured using the liquid microjet technique. The spectra demonstrate that the hydrogen bond network in liquid water is already influenced at small DMSO concentrations, and at the molar fraction xDMSO = 0.43 we find strong evidence of DMSO-water clustering reflected by the influence on the occupied molecular orbitals.