Correlation of FMISO simulations with pimonidazole-stained tumor xenografts: A question of O2 consumption?

PURPOSE: To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors. METHODS: Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively. Hoechst and CD31 images were used to generate maps of perfused blood vessels on which tissue oxygenation and the accumulation of the hypoxia tracer FMISO were mathematically simulated. The model includes a Michaelis-Menten relation to describe the oxygen consumption inside tissue. The maximum oxygen consumption rate M0 was chosen as the parameter for a tumor-specific optimization as it strongly influences tracer distribution. M0 was optimized on each tumor slice to reach optimum correlations between FMISO concentration 4 h postinjection and pimonidazole staining intensity. RESULTS: After optimization, high pixel-based correlations up to R(2) = 0.85 were found for individual tissue sections. Experimental pimonidazole images and FMISO simulations showed good visual agreement, confirming the validity of the approach. Median correlations per tumor model varied significantly (p < 0.05), with R(2) ranging from 0.20 to 0.54. The optimum maximum oxygen consumption rate M0 differed significantly (p < 0.05) between tumor models, ranging from 2.4 to 5.2 mm Hg/s. CONCLUSIONS: It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo. Good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M0, whose optimum value differed significantly between tumor models.

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator.

PURPOSE: We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilovoltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data. METHODS: We have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multi-channel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm(2). The results were compared against Monte Carlo simulations. RESULTS: Dose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%-3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios. CONCLUSIONS: EBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated.

A fast analytic dose calculation method for arc treatments for kilovoltage small animal irradiators.

Arc treatments require calculation of dose for collections of discrete gantry angles. The sampling of angles must balance between short computation time of small angle sets and the better calculation reliability of large sets. In this paper, an analytical formula is presented that allows calculation of dose delivered during continuous rotation of the gantry. The formula holds valid for continuous short arcs of up to about 30° and is derived by integrating a dose formula over gantry angles within a small angle approximation. Doses for longer arcs may be obtained in terms of doses for shorter arcs. The formula is derived with an empirical beam model in water and extended to inhomogeneous media. It is validated with experimental data obtained by applying arc treatment using kV small animal irradiator to a phantom of solid water and lung-equivalent material. The results are a promising step towards efficient 3D dose calculation and inverse planning purposes. In principle, this method also applies to VMAT dose calculation and optimization but requires extensions.

SU-E-T-163: Thin-Film Organic Photocell (OPV) Properties in MV and KV Beams for Dosimetry Applications.

PURPOSE: To characterize dosimetric properties of low-cost thin film organic-based photovoltaic (OPV) cells to kV and MV x-ray beams for their usage as large area dosimeter for QA and patient safety monitoring device. METHODS: A series of thin film OPV cells of various areas and thicknesses were irradiated with MV beams to evaluate the stability and reproducibility of their response, linearity and sensitivity to absorbed dose. The OPV response to x-rays of various linac energies were also characterized. Furthermore the practical (clinical) sensitivity of the cells was determined using IMRT sweeping gap test generated with various gap sizes. To evaluate their potential usage in the development of low cost kV imaging device, the OPV cells were irradiated with kV beam (60-120 kVp) from a fluoroscopy unit. Photocell response to the absorbed dose was characterized as a function of the organic thin film thickness and size, beam energy and exposure for kV beams as well. In addition, photocell response was determined with and without thin plastic scintillator. RESULTS: Response of the OPV cells to the absorbed dose from kV and MV beams are stable and reproducible. The photocell response was linearly proportional to the size and about slightly decreasing with the thickness of the organic thin film, which agrees with the general performance of the photocells in visible light. The photocell response increases as a linear function of absorbed dose and x-ray energy. The sweeping gap tests performed showed that OPV cells have sufficient practical sensitivity to measured MV x-ray delivery with gap size as small as 1 mm. CONCLUSIONS: With proper calibration, the OPV cells could be used for online radiation dose measurement for quality assurance and patient safety purposes. Their response to kV beam show promising potential in development of low cost kV radiation detection devices.