Structural and functional identification of vasculogenic mimicry in vitro.

Vasculogenic mimicry (VM) describes a process by which cancer cells establish an alternative perfusion pathway in an endothelial cell-free manner. Despite its strong correlation with reduced patient survival, controversy still surrounds the existence of an in vitro model of VM. Furthermore, many studies that claim to demonstrate VM fail to provide solid evidence of true hollow channels, raising concerns as to whether actual VM is actually being examined. Herein, we provide a standardized in vitro assay that recreates the formation of functional hollow channels using ovarian cancer cell lines, cancer spheres and primary cultures derived from ovarian cancer ascites. X-ray microtomography 3D-reconstruction, fluorescence confocal microscopy and dye microinjection conclusively confirm the existence of functional glycoprotein-rich lined tubular structures in vitro and demonstrate that many of structures reported in the literature may not represent VM. This assay may be useful to design and test future VM-blocking anticancer therapies.

A quantitative comparison of the performance of three deformable registration algorithms in radiotherapy.

We present an evaluation of various non-rigid registration algorithms for the purpose of compensating interfractional motion of the target volume and organs at risk areas when acquiring CBCT image data prior to irradiation. Three different deformable registration (DR) methods were used: the Demons algorithm implemented in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom-developed piecewise methods using either a Normalized Correlation or a Mutual Information metric (featureletNC and featureletMI). These methods were tested on data acquired using a novel purpose-built phantom for deformable registration and clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity coefficient (DSC) between manually drawn contours and the contours generated by a derived deformation field of the structures in question was compared to the result obtained with rigid registration (RR). For the phantom, the piecewise methods were slightly superior, the featureletNC for the intramodality and the featureletMI for the intermodality registrations. For the prostate cases in less than 50% of the images studied the DSC was improved over RR. Deformable registration methods improved the outcome over a rigid registration for lung cases and in the phantom study, but not in a significant way for the prostate study. A significantly superior deformation method could not be identified.

High-performance GPU-based rendering for real-time, rigid 2D/3D-image registration and motion prediction in radiation oncology.

A common problem in image-guided radiation therapy (IGRT) of lung cancer as well as other malignant diseases is the compensation of periodic and aperiodic motion during dose delivery. Modern systems for image-guided radiation oncology allow for the acquisition of cone-beam computed tomography data in the treatment room as well as the acquisition of planar radiographs during the treatment. A mid-term research goal is the compensation of tumor target volume motion by 2D/3D Registration. In 2D/3D registration, spatial information on organ location is derived by an iterative comparison of perspective volume renderings, so-called digitally rendered radiographs (DRR) from computed tomography volume data, and planar reference x-rays. Currently, this rendering process is very time consuming, and real-time registration, which should at least provide data on organ position in less than a second, has not come into existence. We present two GPU-based rendering algorithms which generate a DRR of 512×512 pixels size from a CT dataset of 53 MB size at a pace of almost 100 Hz. This rendering rate is feasible by applying a number of algorithmic simplifications which range from alternative volume-driven rendering approaches - namely so-called wobbled splatting - to sub-sampling of the DRR-image by means of specialized raycasting techniques. Furthermore, general purpose graphics processing unit (GPGPU) programming paradigms were consequently utilized. Rendering quality and performance as well as the influence on the quality and performance of the overall registration process were measured and analyzed in detail. The results show that both methods are competitive and pave the way for fast motion compensation by rigid and possibly even non-rigid 2D/3D registration and, beyond that, adaptive filtering of motion models in IGRT.

Optimization of extracranial stereotactic radiation therapy of small lung lesions using accurate dose calculation algorithms.

BACKGROUND: The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. METHODS: A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron) and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. RESULTS: The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. CONCLUSION: The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction.