Dose/Sensitivity in Proton Computer Tomography

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Merging Orthovoltage X-Ray Minibeams spare the proximal tissues while producing a solid beam at the target

© 2019, The Author(s). Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.3 mm), planar beams, called minibeams, which are known from synchrotron x-ray experiments to spare tissues. Furthermore, the slight divergence of the OXM array make the individual minibeams gradually broaden, thus merging with their neighbors at a given tissue depth to produce a solid beam. In this way the proximal tissues, including the cerebral cortex, can be spared. Here we present experimental results with radiochromic films to characterize the method’s dosimetry. Furthermore, we present our Monte Carlo simulation results for physical absorbed dose, and a first-order biologic model to predict tissue tolerance. In particular, a 220-kVp orthovoltage beam provides a 5-fold sharper lateral penumbra than a 6-MV x-ray beam. The method can be implemented in arc-scan, which may include volumetric-modulated arc therapy (VMAT). Finally, OXM’s low beam energy makes it ideal for tumor-dose enhancement with contrast agents such as iodine or gold nanoparticles, and its low cost, portability, and small room-shielding requirements make it ideal for use in the low-and-middle-income countries

Development of High-Speed Fluorescent X-Ray Micro-Computed Tomography

A high-speed fluorescent x-ray CT (FXCT) system using monochromatic synchrotron x rays was developed to detect very low concentration of medium-Z elements for biomedical use. The system is equipped two types of high purity germanium detectors, and fast electronics and software. Preliminary images of a 10mm diameter plastic phantom containing channels field with iodine solutions of different concentrations showed a minimum detection level of 0.002 mg I/ml at an in-plane spatial resolution of 100µm. Furthermore, the acquisition time was reduced about 1/2 comparing to previous system. The results indicate that FXCT is a highly sensitive imaging modality capable of detecting very low concentration of iodine, and that the method has potential in biomedical applications

Measurement of rocking curve wings at high x-ray energies

Measurements done recently at the NSLS have indicated that the level of intensity found in the wings of diffraction peaks from silicon at higher x-ray energies (>20keV) far exceeds the value which would be predicted based on the dynamical theory. We have measured Si(220) double crystal rocking curves at the 40keV fundamental and harmonics with various crystal scattering geometries: Bragg-Bragg, Laue-Bragg, Laue-Lauel. The comparison of the Bragg and Laue case diffraction geometries was done to determine scattering volume effects. Comparisons with dynamical theory calculations will be discussed. These measurements have been carried out in order to assess the level of harmonic contamination which will be present from a double crystal monochromator being designed for the X17 Superconducting Wiggler Beamline

In situ Biological Dose Mapping Estimates the Radiation Burden Delivered to ‘Spared’ Tissue between Synchrotron X-Ray Microbeam Radiotherapy Tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to ‘spared’ tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30–40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies

Going beyond histology. Synchrotron micro-computed tomography as a methodology for biological tissue characterization: from tissue morphology to individual cells

Current light microscopic methods such as serial sectioning, confocal microscopy or multiphoton microscopy are severely limited in their ability to analyse rather opaque biological structures in three dimensions, while electron optical methods offer either a good three-dimensional topographic visualization (scanning electron microscopy) or high-resolution imaging of very thin samples (transmission electron microscopy). However, sample preparation commonly results in a significant alteration and the destruction of the three-dimensional integrity of the specimen. Depending on the selected photon energy, the interaction between X-rays and biological matter provides semi-transparency of the specimen, allowing penetration of even large specimens. Based on the projection-slice theorem, angular projections can be used for tomographic imaging. This method is well developed in medical and materials science for structure sizes down to several micrometres and is considered as being non-destructive. Achieving a spatial and structural resolution that is sufficient for the imaging of cells inside biological tissues is difficult due to several experimental conditions. A major problem that cannot be resolved with conventional X-ray sources are the low differences in density and absorption contrast of cells and the surrounding tissue. Therefore, X-ray monochromatization coupled with a sufficiently high photon flux and coherent beam properties are key requirements and currently only possible with synchrotron-produced X-rays. In this study, we report on the three-dimensional morphological characterization of articular cartilage using synchrotron-generated X-rays demonstrating the spatial distribution of single cells inside the tissue and their quantification, while comparing our findings to conventional histological techniques

MOSFET dosimetry for microbeam radiation therapy at the European Synchrotron Radiation Facility

Preclinical experiments are carried out with ~20–30 μm wide, ~10 mm high parallel microbeams of hard, broad-‘‘white’’-spectrum x rays (~50–600 keV) to investigate microbeam radiation therapy (MRT) of brain tumors in infants for whom other kinds of radiotherapy are inadequate and/or unsafe. Novel physical microdosimetry (implemented with MOSFET chips in the ‘‘edge-on’’ mode) and Monte Carlo computer-simulated dosimetry are described here for selected points in the peak and valley regions of a microbeam-irradiated tissue-equivalent phantom. Such microbeam irradiation causes minimal damage to normal tissues, possible because of rapid repair of their microscopic lesions. Radiation damage from an array of parallel microbeams tends to correlate with the range of peak-valley dose ratios (PVDR). This paper summarizes comparisons of our dosimetric MOSFET measurements with Monte Carlo calculations. Peak doses at depths \u3c22 mm are 18% less than Monte Carlo values, whereas those depths \u3e22 mm and valley doses at all depths investigated (2 mm–62 mm) are within 2–13% of the Monte Carlo values. These results lend credence to the use of MOSFET detector systems in edge-on mode for microplanar irradiation dosimetry

CT imaging of small animals using monochromatized synchrotron x rays

Rats and chicken embryos were imaged in vivo with a prototype Multiple Energy Computed Tomography (MECT) system using monochromatized x rays from the X17 superconducting wiggler at the National Synchrotron Light Source. The CT configuration coated of a horizontal low-divergence, fan-shaped beam, 70 mm wide and 0.5 mm high, and a subject rotating about a vertical aids. A linear-array high-purity Ge detector with 140 elements, each 0.5 mm wide and 6 mm thick, was used with a data acquisition system that provides a linear response over almost six orders of magnitude of detector current. The dual photon absorptiometry (DPA) algorithm was applied to images of the rat head acquired at 20 and 45 keV to obtain two new images, one representing the low-Z, and the other the intermediate-Z clement group. The results indicate that the contrast resolution and the quantification accuracy of the images improve stepwise; first, with the monochromatic beam and, second, the DPA method. The system is a prototype for a brain scanner