Imaging of response to anti-angiogenic drugs

Les nouveaux traitements, comme les molécules antiangiogéniques, agissent sur des cibles spécifiques. Leur effet sur la taille tumorale est parfois absent ou retardé. De nouvelles techniques d’imagerie fonctionnelle s’intéressent à une caractéristique physiologique plutôt que la taille tumorale, et pourraient mettre en évidence des modifications en réponse au traitement apparaissant plus précocement. L’imagerie dynamique de la microcirculation suit la biodistribution d’un agent de contraste, et analyse la vascularisation tumorale. L’imagerie par résonance magnétique pondérée en diffusion permet de distinguer l’eau libre, de l’eau restreinte dans les tissus, reflétant la cellularité tumorale. L’imagerie par résonance magnétique par effet BOLD reflète l’oxygénation tissulaire en quantifiant le rapport déoxy/oxyhémoglobine. Les études testant ces techniques sont cependant préliminaires et nécessitent des études à grande échelle pour évaluer leur rôle dans la réponse aux traitements ciblés en oncologie.New therapies, such as anti-angiogenic drugs, target specific molecules. Their effect on tumor size is sometimes absent or delayed. New techniques of functional imaging do not detect changes in size, but rather a physiological characteristic, and could reveal changes in response to treatment which arise earlier. Dynamic contrast-enhanced (DCE) imaging follows the biodistribution of a contrast agent and analyzes tumor vascularization. Diffusion-weighted magnetic resonance imaging quantifies restriction to diffusion of water in tissues, reflecting tumor cellularity. BOLD magnetic resonance imaging reflects tissue oxygenation by quantifying the ratio between deoxygenated and oxygenated hemoglobin. Studies testing these techniques are still preliminary. It is therefore necessary to organize large scale studies to evaluate their potential role in response to targeted therapies in oncology

Género y trabajo: La identidad ocupacional de las operadoras de Telmex, de Gabriel Pérez Pérez

Dynamical contrast enhanced (DCE) imaging allows non invasive access to tissue micro-vascularization. It appears as a promising tool to build imaging biomark-ers for diagnostic, prognosis or anti-angiogenesis treatment monitoring of cancer. However, quantitative analysis of DCE image sequences suffers from low signal to noise ratio (SNR). SNR may be improved by averaging functional information in a large region of interest when it is functionally homogeneous. We propose a novel method for automatic segmentation of DCE image sequences into functionally homogeneous regions, called DCE-HiSET. Using an observation model which depends on one parameter a and is justified a posteri-ori, DCE-HiSET is a hierarchical clustering algorithm. It uses the p-value of a multiple equivalence test as dissimilarity measure and consists of two steps. The first exploits the spatial neighborhood structure to reduce complexity and takes advantage of the regularity of anatomical features, while the second recovers (spatially) disconnected homogeneous structures at a larger (global) scale. Given a minimal expected homogeneity discrepancy for the multiple equivalence test, both steps stop automatically by controlling the Type I error. This provides an adaptive choice for the number of clusters. Assuming that the DCE image sequence is functionally piecewise constant with signals on each piece sufficiently separated, we prove that DCE-HiSET will retrieve the exact partition with high probability as soon as the number of images in the sequence is large enough. The minimal expected homogeneity discrepancy appears as the tuning parameter controlling the size of the segmentation. DCE-HiSET has been implemented in C++ for 2D and 3D image sequences with competitive speed. Keywords : DCE imaging, automatic clustering, hierarchical segmentation, equivalence testComment: 58 page

Evaluation of antiangiogenic treatment effects on tumors' microcirculation by Bayesian physiological pharmacokinetic modeling and magnetic resonance imaging.

International audienceA physiological pharmacokinetic (PBPK) model was used to estimate tumor microcirculation in nude mice with a grafted tumor. The kinetics of a rapid clearance blood pool agent, Vistarem, were investigated by dynamic MRI after bolus administration. Signal enhancements were recorded in arterial blood and in tumor tissue. To analyze these data, we developed a whole-body mathematical model of the agent's biodistribution using physiological parameters. The model included six compartments: arterial and venous plasma, tumor (split into capillaries and interstitium), and the rest of the body (also split into capillaries and interstitium). As an application, changes in tumor microcirculation parameters were evaluated in mice receiving either an antiangiogenic treatment (ZD4190) or a placebo. The analysis was performed in a Bayesian framework, and the model was fitted to experimental data using Markov Chain Monte Carlo techniques. Results showed a significant difference in tumor microcirculation between the two groups of mice when the microcirculation parameters are considered together. This whole-body physiological model enables to analyze jointly data in tumor tissue and in arterial blood. This leads to accurate estimates of microcirculation parameters and the evaluation of their uncertainty

Assessment of rotator cuff.

<p>Assessment of rotator cuff.</p

Description of clinical evaluation of patients and healthy volunteers.

<p>Description of clinical evaluation of patients and healthy volunteers.</p