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Biomedical subjects

M Arnfield

Publications and source records attributed to M Arnfield.

6 recordsLinked to original sources

Biologic treatment planning for high-dose-rate brachytherapy.

PURPOSE: Interstitial brachytherapy treatment plans are conventionally optimized with respect to total target dose and dose homogeneity, which does not account for the biologic effects of dose rate. In an HDR implant, with a stepping source, the dose rate dramatically changes during the course of treatment, depending on location, as the source moves from dwell position to dwell position. These widely varying dose rates, together with the related sequencing of the dwell positions, may impart different biologic effects at points receiving the same total dose. This study applies radiobiologic principles to account for the potential biologic impact of dose delivery at varying dose rates within an HDR implant. METHODS AND MATERIALS: The model under study uses a generalized version of the linear-quadratic (LQ) cell kill formula to calculate the surviving fraction of cells subjected to HDR irradiation. Using a planar interstitial HDR implant with the dwell times optimized to produce a homogeneous dose distribution along a reference plane parallel to the implant plane, surviving fractions were compared at selected reference points subjected to the same total dose. Biologic effect homogeneity was compared to dose homogeneity by plotting the effects at the reference points. The effects were examined with LQ parameters alpha, beta, and sublethal repair time T(1) varied over a range typical of human cells. RESULTS: In a region in which dose is relatively uniform, surviving fraction for some values of the model parameters are found to vary by as much as an order of magnitude due to differences in the HDR irradiation profiles at different dose points. This effect is more pronounced for shorter repair times and smaller alpha/beta ratios, and increases with increasing total irradiation time. CONCLUSION: Conventional HDR treatment planning currently considers dose distribution as the primary indicator of clinical effect. Our results demonstrate that plans optimized to maximize homogeneity within a target volume may not reflect the effect of the sequential nature of HDR dose delivery on cell kill. Biologic effect modeling may improve our understanding and ability to predict the adverse effects of our treatment, such as fat necrosis and fibrosis. Accounting for irradiation history and repair kinetics in the evaluation of HDR brachytherapy plans may add an important new dimension to our planning capabilities.

Algorithms↗

Monte Carlo dose calculations for dynamic IMRT treatments.

Dose calculations for intensity modulated radiation therapy (IMRT) face new challenges due to the complex leaf geometry and time dependent nature of the delivery. A fast method of particle transport through a dynamic multileaf collimator (MLC) geometry that accounts for photon attenuation and first-scattered Compton photon production has been incorporated into an existing Monte Carlo code used for patient dose calculations. Dosimetric agreement between calculation and measurement for two photon energies and MLC types is within experimental error for the sliding window tests. For a patient IMRT field, the Monte Carlo calculations are closer to measured dose than similar superposition or pencil beam calculations.

Humans↗

Dynamic splitting of large intensity-modulated fields.

The aims of this paper are to describe a method of splitting large intensity-modulated fields that cannot be delivered as a single field and to verify the accuracy of our method. Some multi-leaf collimators may be operated in the dynamic mode to deliver intensity-modulated radiation treatments (IMRT) using the 'sliding window' technique. In this technique each pair of leaves sweeps over the treatment field while the beam is on. However, there are limitations on the width of the field that can be treated due to the limited length of the leaves. For instance, the leaf length of the Varian MLC is 14.5 cm. Since each leaf pair must travel from the left boundary to the right boundary of the beam aperture, the maximum width of the field aperture that can be accommodated in one sweep of leaves is also limited to 14.5 cm, in fact to a slightly smaller value. It has been shown that IMRT is more efficient when used to plan and deliver the large and boost fields simultaneously. In such situations, the fields must be large enough to cover simultaneously the volumes of the gross tumour, microscopic disease and electively treated regions. Such field sizes are often larger than 14.5 cm wide. In this paper, we present a dynamic 'feathering' technique to split the large intensity-modulated fields into smaller fields. In this technique, the component beams overlap each other by a small amount, and the intensity in the overlap region gradually decreases for one field component and increases for the other. The sum of intensities remains the same as for the original field. This method eliminates the field matching problems associated with the conventional step 'break' for static fields. The splitting process is integrated into the IMRT treatment procedure and the entire planning process is automated. Comparison of dose distributions calculated and measured in a phantom showed good agreement. Such a method can be applied to the 'step and shoot' technique as well. IMRT fields of widths up to 25 cm can be delivered by splitting only once, which is adequate for most treatments.

Algorithms↗

The impact of fluctuations in intensity patterns on the number of monitor units and the quality and accuracy of intensity modulated radiotherapy.

The purpose of this work is to examine the potential impact of the frequency and amplitude of fluctuations ("complexity") in intensity distributions on intensity-modulated radiotherapy (IMRT) dose distributions. The intensity-modulated beams are efficiently delivered using a multileaf collimator (MLC). Radiation may be delivered through a continuous (dynamic mode) or discrete (step-and-shoot) sequence of windows formed by the leaves. Algorithms and software that convert optimized intensity distributions into leaf trajectories apply approximate empirical corrections to account for the various effects associated with MLC characteristics, such as the rounded leaf tips, tongue-and-groove leaf design, leaf transmission, leaf scatter, and collimator scatter upstream from the MLC. Typically, the difference between inter- and intraleaf transmissions is ignored. In this paper, using a schematic example of IMRT for head and neck carcinomas, we demonstrate that complex anatomy and severe optimization constraints produce complex intensity patterns. Using idealized intensity patterns we also demonstrate that, for complex intensity patterns, the average window width tends to be smaller and, for the same dose received by the tumor, the number of MUs is larger. We found that as the complexity increases, so does the contribution of radiation transmitted through and scattered from the leaves ("indirect radiation") to the total delivered dose. As a consequence, the lowest deliverable intensity in complex intensity patterns may be significantly greater than that required to provide adequate protection for some normal tissues. Furthermore, since corrections for leaf transmission and scatter effects are approximate and the difference between inter- and intraleaf transmission is ignored, the accuracy of the delivered dose may be affected. Using the results of a simple experiment and a typical intensity-modulated beam for a head and neck case as examples, we show the effect of window width and complexity on the accuracy and deliverability of intensity patterns. Some possible strategies for improving the accuracy and for relaxing the lower limit on deliverable intensity are discussed.

Biophysical Phenomena↗

Nuclear magnetic resonance spectroscopy and sensitizer-adduct measurements of photodynamic therapy-induced ischemia in solid tumors.

Dunning R3327-AT prostate carcinomas growing in Fischer X Copenhagen rats were treated with interstitial photodynamic therapy (PDT--15 mg/kg Photofrin II 4 hours before illumination with 630-nm light via four parallelly implanted optical fibers) at different light intensities. Forty to 60 minutes after treatment, 31P-nuclear magnetic resonance spectra of tumors in anesthetized animals were obtained at 2.35 Tesla using surface coil localization. Areas under resonance peaks were normalized to the area under the peak of a phosphorus standard positioned at a fixed distance on the opposite side of the surface coil. Tumor concentrations of phosphomonoesters and phosphodiesters showed no change after tumor light doses up to 3000 J. Phosphocreatine, alpha-adenosine triphosphate (ATP), beta-ATP, and gamma-ATP signals decreased and inorganic phosphate signals increased with increasing light doses. The intratumor pH did not change significantly at these short times after PDT. In other R3327-AT and R3327-H tumor-bearing animals, [3H]misonidazole was administered 30 minutes prior to PDT treatments of both tumors. Twenty-four hours later, the tumors were resected in toto, and levels of retained [3H]misonidazole were determined in lased tumor specimens by liquid scintillation procedures. The amount of [3H]misonidazole activity in tumor tissue (covalently bound after hypoxic reduction) increased with light doses up to 3000 J. Sensitizer-adduct formation was found to correlate with the ratio of the concentration of inorganic phosphate to that of beta-ATP, both of which are presumed measures of tumor oxygenation status. These measurements have high-lighted the heterogenous nature of the oxygenation status of these experimental tumors. The precision of each assay for estimating tumor oxygenation is discussed.

Adenosine Triphosphate↗

Cylindrical irradiator fiber tip for photodynamic therapy.

In photodynamic therapy (PDT) the uniform distribution of intratumor or externally applied light is desirable but often difficult to achieve. An optical fiber tip producing cylindrical or lateral light emission can facilitate the application of laser energy by direct implantation of the tip into solid tumors or within tubular cavities of the body such as the bronchus or esophagus. A procedure is described for fabricating such a fiber tip, the main component of which is a hollow glass cylinder containing a light-scattering material. Light distributions emitted from the tip in air are documented. Useful properties of the tip include good light distribution, durability, heat resistance, and simplicity of construction.

Adenocarcinoma↗