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Biomedical subjects

M Birkner

Publications and source records attributed to M Birkner.

6 recordsLinked to original sources

Modelling individual geometric variation based on dominant eigenmodes of organ deformation: implementation and evaluation.

We present a method of modelling inter-fractional organ deformation and correlated motion of adjacent organ structures in terms of so-called eigenmodes. The method is based on a principal component analysis (PCA) of organ shapes and allows for reducing the large dimensionality of geometry information from multiple CT studies to a few-parametric statistical model of organ motion and deformation. Eigenmodes are 3D vectorfields of correlated displacements of the organ surface points and can be seen as fundamental 'modes' of the patient's geometric variability. The amount of variability represented by the eigenmodes is quantified in terms of corresponding eigenvalues. Weighted sums of eigenmodes describe organ displacements/deformations and can be used to generate new organ geometries. We applied the method to four patient datasets of prostate/rectum/bladder with N = 15-18 CTs to assess interfractional geometric variation. The spectrum of eigenvalues was found to be dominated by only few values, indicating that the geometric variability of prostate/bladder/rectum is governed by only few patient specific eigenmodes. We evaluated the capability of this approach to represent the measured organ samples by calculating the residual errors for the organ surface points, using a varying number of eigenmodes. The distribution of residual errors shows fast convergence with the number of eigenmodes. Using 4 dominating modes, the range of residual errors for the four patients was 1.3-2.0 mm (prostate), 1.4-1.9 mm (rectum) and 1.5-1.9 mm (bladder). Thus, individual geometric variation taken from multiple imaging data can be described accurately by few dominating eigenmodes, thereby providing the most important factors to characterize deformable organ motion, which can assist adaptive radiotherapy planning.

Algorithms↗

Treatment simulation approaches for the estimation of the distributions of treatment quality parameters generated by geometrical uncertainties.

Geometric uncertainties arise during treatment planning and treatment and mean that dose-dependent parameters such as EUD are random variables with a patient specific probability distribution. Treatment planning with highly conformal treatment techniques such as intensity modulated radiation therapy requires new evaluation tools which allow us to estimate this influence of geometrical uncertainties on the probable treatment dose for a planned dose distribution. Monte Carlo simulations of treatment courses with recalculation of the dose according to the daily geometric errors are a gold standard for such an evaluation. Distribution histograms which show the relative frequency of a treatment quality parameter in the treatment simulations can be used to evaluate the potential risks and chances of a planned dose distribution. As treatment simulations with dose recalculation are very time consuming for sufficient statistical accuracy, it is proposed to do treatment simulations in the dose parameter space where the result is mainly determined by the systematic and random component of the geometrical uncertainties. Comparison of the parameter space simulation method with the gold standard for prostate cases and a head and neck case shows good agreement as long as the number of fractions is high enough and the influence of tissue inhomogeneities and surface curvature on the dose is small.

Body Burden↗

Adapting inverse planning to patient and organ geometrical variation: algorithm and implementation.

Image guided radiotherapy has the potential to improve both tumour control and normal tissue sparing by including temporal patient specific geometry information into the adaptive planning process. In this study we present a practical method of image guided adaptive inverse planning based on computed tomography (CT) and portal image feedback during the treatment course. The method is based on a general description of the radiotherapy optimization problem subject to dynamic geometrical variations of the patient/organs. We will demonstrate the feasibility of off-line image feedback into the inverse planning process with the example of three prostate cancer patients. CT and portal images acquired during the early course of the treatment are used to predict the geometrical variation distribution of a patient and to re-optimize the treatment plan accordingly. We will study the convergence of the optimization problem with respect to the number of image measurements and adaptive feedback loops.

Algorithms↗

Tools for the analysis of dose optimization: II. Sensitivity analysis.

Dose optimization requires that the treatment goals be specified in a meaningful manner, but also that alterations to the specification lead to predictable changes in the resulting dose distribution. Within the framework of constrained optimization, it is possible to devise a tool that quantifies the impact on the objective of target volume coverage of any change to a dosimetric constraint of normal tissue or target dose homogeneity. This sensitivity analysis relies on properties of the Lagrange function that is associated with the constrained optimization problem, but does not depend on the method used to solve this problem. It is useful particularly in cases with multiple target volumes and critical normal structures, where constraints and objectives can interact in a non-intuitive manner.

Algorithms↗

Monte Carlo dose computation for IMRT optimization.

A method which combines the accuracy of Monte Carlo dose calculation with a finite size pencil-beam based intensity modulation optimization is presented. The pencil-beam algorithm is employed to compute the fluence element updates for a converging sequence of Monte Carlo dose distributions. The combination is shown to improve results over the pencil-beam based optimization in a lung tumour case and a head and neck case. Inhomogeneity effects like a broader penumbra and dose build-up regions can be compensated for by intensity modulation.

Algorithms↗

Properties of modified hepatitis B virus surface antigen particles carrying preS epitopes.

The current hepatitis B virus (HBV) vaccines contain the small (S) and middle (M) viral envelope proteins in particulate form but lack the large (L) protein. Although these particles elicit protective immunity to HBV, inclusion of the immunogenic preS1 region of the L protein may enhance their efficacy. To present preS1-derived epitopes on secretable subviral particles we rearranged the HBV envelope ORF by fusing part or all of the preS1 region to either the N or C terminus of the S protein. Fusion of the first 42 residues of preS1 to either site allowed efficient secretion of the modified particles and rendered the linked sequence accessible at the surface of the particle. Conversely, fusion of preS1 sequences to the C terminus of the M protein completely blocked secretion. This block to secretion could be rescued by provision of a heterologous N-terminal signal sequence. All these particles displayed preS1, preS2 and S protein antigenicity. In mice, each construct elicited high titres of preS1-specific antibodies which recognized the authentic L protein. Particles composed of the modified M protein also induced a preS2-specific response. Unexpectedly, however, neither particle elicited S protein-specific antibodies. Nonetheless, the genetic approach employed here represents a strategy to incorporate preS1-derived epitopes both in high density and in highly immunogenic form into their authentic carrier matrix.

Animals↗