The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

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In prostate cancer radiotherapy, the accurate identification of the prostate and organs at risk in planning computer tomography (CT) images is an important part of the therapy planning and optimization. Manually contouring these organs can be a time consuming process and subject to intra-and inter-expert variability. Automatic identification of organ boundaries from these images is challenging due to the poor soft tissue contrast. Atlas-based approaches may provide a priori structural information by propagating manual expert delineations to a new individual space; however the inter-individual variability and registration errors may lead to biased results. Multiatlas approaches can partly overcome some of these difficulties by selecting the most similar atlases among a large data base but the definition of similarity measure between the available atlases and the query individual has still to be addressed. The purpose of this chapter is to explain atlas-based segmentation approaches and the evaluation of different atlas-based strategies to simultaneously segment prostate, bladder and rectum from CT images. A comparison between single and multiple atlases is performed. Experiments on atlas ranking, selection strategies and fusion decision rules are carried out to illustrate the presented methodology. Propagation of labels using two registration strategies are applied and the results of the comparison with manual delineations are reported.

Proinflammatory cytokines produced by immune cells play a central role in the increased intestinal epithelial permeability during inflammation. Expansion of visceral adipose tissue (VAT) is currently considered a consequence of intestinal inflammation. Whether VAT per se plays a role in early modifications of intestinal barrier remains unknown. The aim of this study was to demonstrate the direct role of adipocytes in regulating paracellular permeability of colonic epithelial cells (CECs). We show in adult rats born with intrauterine growth retardation, a model of VAT hypertrophy, and in rats with VAT graft on the colon, that colonic permeability was increased without any inflammation. This effect was associated with altered expression of tight junction (TJ) proteins occludin and ZO-1. In coculture experiments, adipocytes decreased transepithelial resistance (TER) of Caco-2 CECs and induced a disorganization of ZO-1 on TJs. Intraperitoneal administration of leptin to lean rats increased colonic epithelial permeability and altered ZO-1 expression and organization. Treatment of HT29-19A CECs with leptin, but not adiponectin, dose-dependently decreased TER and altered TJ and F-actin cytoskeleton organization through a RhoA-ROCK-dependent pathway. Our data show that adipocytes and leptin directly alter TJ function in CECs and suggest that VAT could impair colonic epithelial barrier.

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Accurate segmentation of the prostate and organs at risk in computed tomography (CT) images is a crucial step for radiotherapy planning. Manual segmentation, as performed nowadays, is a time consuming process and prone to errors due to the a high intra- and inter-expert variability. This paper introduces a new automatic method for prostate, rectum and bladder segmentation in planning CT using a geometrical shape model under a Bayesian framework. A set of prior organ shapes are first built by applying principal component analysis to a population of manually delineated CT images. Then, for a given individual, the most similar shape is obtained by mapping a set of multi-scale edge observations to the space of organs with a customized likelihood function. Finally, the selected shape is locally deformed to adjust the edges of each organ. Experiments were performed with real data from a population of 116 patients treated for prostate cancer. The data set was split in training and test groups, with 30 and 86 patients, respectively. Results show that the method produces competitive segmentations w.r.t standard methods (averaged dice = 0.91 for prostate, 0.94 for bladder, 0.89 for rectum) and outperforms the majority-vote multi-atlas approaches (using rigid registration, free-form deformation and the demons algorithm).

The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.