Modélisation Biomécanique pour l'Imagerie de Prostate

In 2012 in France, prostate cancer was the most frequent cancer with 53 465 new cases estimated and 8 876 deaths. Transrectal prostate biopsy is the only method used to prove the presence of cancer with a histopathologic study. Twelve biopsies are evenly punctured all around the prostate by the urologist as well as targeted areas. This is generally done with the guidance of endorectal ultrasound images. The difficulties for the urologist are to perform this 3D task precisely and accurately based on 2D imaging. Moreover image acquisition itself contributes to prostate motion and deformation. It is within this framework that we proposed the development of patient-specific biomechanical model of prostate. This model can be used in a clinical time and is based only on 3D ultrasonographic volumes. The model allows the urologist to monitor the deformations and the displacements of the prostate and to follow targeted areas. Firstly, we were interested in building a validation workflow for prototyping and conducting a large-scale test to evaluate the impact of each necessary step before the dynamic simulation. An initial test was conducted with a realistic deformable prostate phantom. This experiment is based on more than 800 simulations allowing us to complete a statistical survey. We then developed and validated tools, such as the calibration of a robot probe-holder to improve the workflow and to perform real patient data acquisitions. An evaluation of the impact of each parameter of the biomechanical model was achieved on a realistic deformable prostate phantom. Finally, we had the opportunity to apply our workflow on one patient biopsy session acquisition. Results are encouraging and shows good perspectives to our work.Le cancer de prostate était, en France en 2012, le premier cancer masculin avec plus de 53 465 nouveaux cas par an et 8 876 décès. La biopsie transrectale de prostate est la méthode utilisée afin de déterminer de manière histopathologique la présence ou non du cancer. Le plus souvent, l’urologue ponctionne la prostate en douze positions, équiréparties sur l’ensemble la prostate ainsi que des zones cibles. Ceci se fait classiquement sous guidage échographique endorectal. La difficulté pour l’urologue est de pouvoir réaliser cette cartographie de prostate de manière précise alors qu’il ne dispose, le plus souvent, que d’une imagerie 2D et que l’acquisition des images elle-même contribue à déplacer et déformer la prostate.C’est dans ce cadre que nous proposons le développement d’un modèle biomécanique de prostate patient-spécifique, utilisable en temps clinique, basé uniquement sur l’acquisition d’échographies transrectales. Ce modèle apporte un moyen de prendre en compte les déplacements et déformations de la prostate ainsi que des zones cibles. Pour cela, nous nous sommes intéressés à la construction d’une chaîne de validation permettant le prototypage et le test à grande échelle de paramètres sur des données issues de bancs expérimentaux ou cliniques afin d’évaluer l’impact de chaque étape jusqu’à la simulation biomécanique. Au cours de cette thèse, une première phase de test a été réalisée sur un fantôme réaliste de prostate afin d’étudier l’impact des paramètres de nos modèles au travers d’une étude statistique basée sur plus de 800 simulations. Des conclusions de ce premier essai, nous avons développé et validé des outils permettant l’acquisition de données cliniques tels que le calibrage d’un robot porte-sonde ou le développement d’une méthode de collision basée sur des contraintes projectives. Un premier test patient a pu être réalisé au cours de cette thèse et montre des résultats encourageants pour la poursuite de ces travaux

Hand-Eye Calibration of a Robot -UltraSound Probe System without any 3D Localizers

International audience3D UltraSound (US) probes are used in clinical applications for their ease of use and ability to obtain intra-operative volumes. In surgical navigation applications a calibration step is needed to localize the probe in a general coordinate system. This paper presents a new hand-eye calibration method using directly the kinematic model of a robot and US volume registration data that does not require any 3D localizers. First results show a targeting error of 2.34 mm on an experimental setup using manual segmentation of five beads in ten US volumes

Using CamiTK for rapid prototyping of interactive Computer Assisted Medical Intervention applications

Computer Assisted Medical Intervention (CAMI hereafter) is a complex multi-disciplinary field. CAMI research requires the collaboration of experts in several fields as diverse as medicine, computer science, mathematics, instrumentation, signal processing, mechanics, modeling, automatics, optics, etc

Risk factors for poor health and performance in European broiler production systems

Background Conventional broilers are currently one of the most efficient protein converters. Although decades of progress in genetic selection and feed formulation have lead to high standards of efficient broiler production, still a lot of variability is found between farms and between successive flocks. The aim of this study was to investigate risk- and/or protective factors for poor health and performance in conventional broiler-farms in Europe by developing eight multivariable linear mixed models. Three different models were used to investigate mortality (overall, first week, after first week), three models for performance variables (growth, feed conversion, European production index) and two models were related to slaughterhouse data (i.e. dead on arrival and condemnation rate). Results Several factors related to management and housing were significantly associated with health and performance of broilers. The following factors were associated with increased mortality: floor quality, neonatal septicemia, ventilation type and other professional activities of the farmer. The factors associated with performance were chick sex, coccidiosis infections, necrotic enteritis, dysbacteriosis, light intensity adaptations, ventilation type, comparing daily flock results with previous flock results by farmer, daily check of feed and water system and type of feed. For dead on arrival three risk factors were identified i.e. daily growth, type of light adaptation and type of drinkers system. For condemnation rate seven risk factors were found, i.e. type of drinking system, daily growth, feed withdrawal time, type of ventilation, house size, septicemia after seven days and type of feed. Conclusions These results imply that a multifactorial approach is required with adaptations involving both improvements in management, housing, health programs and an increasing level of professionalism of the farmer in order to improve broiler performance and health

An IL28B Genotype-Based Clinical Prediction Model for Treatment of Chronic Hepatitis C

BACKGROUND:Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. METHODS:HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC). RESULTS:Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. CONCLUSION:A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC

Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms

Background: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. Methods and Findings: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. Conclusions: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome

Soluble Serum CD81 Is Elevated in Patients with Chronic Hepatitis C and Correlates with Alanine Aminotransferase Serum Activity

Aim: Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity. Patients and Methods: Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry. Results: Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027). Conclusion: CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis

Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; PPeer reviewe