The goal of conformal radiation techniques is to improve local tumour control through dose escalation to target volumes while at the same time sparing surrounding healthy tissue. Respiratory motion is known to be the largest intra-fractional organ motion and the most significant source of uncertainty in treatment planning for chest lesions. A method to account for the effects of respiratory motion is to use four-dimensional radiotherapy. While analytical models are useful, it is essential that the motion problem in radiotherapy is addressed by both modeling as well as experimentally studies so that different obstacles can be overcome before clinical implementation of a motion compensation method. Validation of techniques aimed at measuring and minimizing the effects of respiratory motion require a realistic dynamic deformable phantom for use as a gold standard. In this work we present the design, construction, performance and deformable image registration of a novel breathing, tissue equivalent phantom with a deformable lung that can reproducibly emulate 3D non-isotropic lung deformations according to any real lung-like breathing pattern. The phantom consists of a Lucite cylinder filled with water containing a latex balloon stuffed with dampened natural sponges. The balloon is attached to a piston that mimics the human diaphragm. Nylon wires and Lucite beads, emulating vascular and bronchial bifurcations, were glued at various locations, uniformly throughout the sponges. The phantom is capable of simulating programmed irregular breathing patterns with varying periods and amplitudes. A deformable, tissue equivalent tumour, suitable for holding radiochromic film for dose measurements was embedded in the sponge. Experiments for 3D motion assessment, motion reproducibility as well as deformable image registration and validation are presented using the deformable phantom.

The thesis presents a comparison of four techniques used for stereotactic radiosurgery, consisting of the static conformal beam, static cone-based, proton therapy, and the Gamma Knife techniques. The comparisons involved six test cases in which phantom target lesions were created in the center of the modified anthropomorphic RandoRTM head. The phantom lesions presented in the study were extreme irregular cases that ranged in shape and volume and were near a critical structure to receive minimal dose during treatment planning. The best treatment plans from each technique for all studies were selected and the extracted data was analyzed using physical and biological parameters. Correlations between integral biological effective dose (normal brain) and normal tissue complication probability were analyzed as a function of dose conformity (PITV), and correlations between tumor control probability and integral biological effective dose (tumor) as a function of dose homogeneity (MDPD) were analyzed, as well. These parameter pairings showed strong links. The static conformal beam and the proton SOBP techniques consistently provided low PITV and MDPD values for all cases, including the most irregular and complicated cases. Higher PITV and MDPD values, typically associated with static cone-based and the Gamma Knife techniques, were due to normal tissue and tumor tissue, respectively, being irradiated at higher dose levels than the prescribed dose. For these cases, as the PITV increased, the NTCP increased, as well, due to high doses created within the normal tissue found within the prescription isodose surface.

Thesis (Ph.D.). / Written for the Dept. of Physics. Title from title page of PDF (viewed 2008/05/09). Includes bibliographical references.

Thesis (M.Sc.). / Written for the Medical Physics Department. Title from title page of PDF (viewed 2008/12/09). Includes bibliographical references.

Thesis (Ph.D.). / Written for the Dept. of Physics. Title from title page of PDF (viewed 2009/06/08). Includes bibliographical references.

In the investigation of radiation accidents, it is of great importance to estimate the dose absorbed by exposed persons in order to plan their therapy. Although occasionally in these situations physical dose measurements are possible, most often biological methods are required for dose estimation. The aim of this investigation was to assess the suitability of the cytokinesis blocked (CB) micronucleus assay as a biodosimetric method using lymphocytes irradiated in vivo. The approach adopted to achieve this was to estimate whole body doses by relating micronuclei yields in patients undergoing radiotherapy treatment with an in vitro radiation dose-response curve. These biologically derived estimates were then compared with the corresponding doses obtained by physical measurement and calculation. As a first approach a study was performed of the in vitro dose-response of gamma-ray induced micronuclei following cytokinesis-block in the lymphocytes of peripheral blood samples obtained from 4 healthy donors. The results indicated that the distribution of the induced micronuclei were overdispersed. Furthermore, a linear dose-response relationship was established when a curve was fitted to the data by an iteratively reweighted least squares method. By means of an analysis of covariance it was demonstrated that this result is in agreement with the dose-response relationships found by various other workers (Fenech et al., 1985; Fenech et al., 1986; Fenech et al., 1989; Balasem et al., 1992, and Slabbert, 1993). To assess the suitability and accuracy of dose assessment using the CB micronucleus assay for in vivo exposure of lymphocytes, blood samples obtained from 8 patients undergoing radiotherapy before, during and after treatment were examined. The physical doses of these patients were determined according to conventional radiation treatment plans and cumulative dose-volume histograms. The dose-volume histograms permitted calculation of integral doses and subsequently the estimate of equivalent whole-body doses. The results of the CB micronucleus assay applied to peripheral blood lymphocytes of 6 patients undergoing fractionated partial-body irradiation showed a dose-related increase in micronucleus frequency in each of the patients studied. This demonstrated that micronuclei analysis may serve as a quantitative biological measure of such exposures. The pooled data of these patients compared to the pooled data of the healthy donors show that there was no statistically significant difference between in vitro and in vivo results, however a slightly lower induced micronuclei frequency was observed after in vivo exposure. When the biological dose estimates for equivalent whole-body doses obtained from the in vitro dose response curve were compared with calculated physical doses, it was found that: biologically estimated dose = 0.936 physical dose. However, there was inadequate statistical evidence to discard the hypothesis that the gradient of the equation was equal to one. Therefore, the analysis of micronuclei induced in lymphocytes in vivo yields highly quantitative information on the equivalent whole-body dose. The negative binomial method was used for analysing the micronucleus data from two patients who received single, relatively larger tumour doses of 10 Gy each, with the objective to obtain estimates of the exposed body fraction and the dose to this fraction. The dose estimates to the irradiated volume were found to be within 30% of the physical tumour dose. The irradiated volume estimates seemed to be higher than the physically calculated volumes but by discarding the correction for the loss of cells due to interphase death the agreement was good between the physically and biologically determined integral doses. This study has revealed that the CB micronucleus assay appears to offer a reliable, consistent and relatively rapid biological method of whole body dose estimation. It is recognised that further corroborative work using the techniques described in this thesis is required for estimating localized exposure.

No description available.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser. I publikationen felaktig serieuppgift: Linköping studies in health sciences ; 989.

Thesis--University of Oklahoma. / Bibliography: leaves 115-119.

Thesis--University of Oklahoma. / Bibliography: leaves 90-92.