Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study.

To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated. A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma

Niveaux dexposition en tomodensitométrie multicoupes pédiatrique : Résultats de lenquête dosimétrique SFIPP/IRSN 2007-2008

Purpose. To evaluate current exposure levels from pediatric MDCT examinations in order to issue recommendations for the routine clinical practice that may be used for establishing future diagnostic reference levels (DRL).Materials and methods. A survey was conducted at hospital sites affiliated with the SFIPP (Société Francophone d'Imagerie Pédiatrique et Prénatale). Tube potential and volume computed tomography dose index (CTDI) vol. values were obtained for three age groups (1, 5 and 10 years) for typical scanning indications of eight anatomical regions.Results. Twenty of 29 sites provided us with a copy of their protocols. All ages groups combined, 97% of protocols used a tension level ≤120 kVp. For age groups 1, 5 and 10 years respectively, the 75th percentiles of dose distributions were : 31, 39.5 and 49.5 mGy for the «head» protocol; 24, 22 and 24 mGy for «head and neck»; 11, 11, and 11mGy for «paranasal sinuses»; 46, 71 and 87 mGy for «petrous bone»; 3, 3.5 and 5.5 mGy for «chest»; 2, 3 and 4 mGy for «low dose lung»; 4, 4.5 and 7 mGy for «abdomen-pelvis»; 7, 11 and 12 mGy for «bone». The inter-center discrepancy for doses were still high.Conclusion. This study provided an evaluation of current practices in reference centers for pediatric imaging and allowed readjustment of MDCT dose recommendations. It could help in the development of DRLS for pediatric MDCT.Objectif. Évaluer les niveaux actuels d’exposition en scanner multicoupes pédiatrique et en déduire des recommandations pour la pratique pouvant servir de base à l’élaboration de futurs niveaux de référence diagnostiques (NRD). Matériels et méthodes. Une enquête de pratique a été réalisée auprès des sites hospitaliers correspondants de la SFIPP (Société Francophone d’Imagerie Pédiatrique et Prénatale). Les valeurs protocolaires de haute tension et de dose théorique absorbée (IDSV) ont été relevées pour trois âges types (1, 5 et 10 ans) et des indications types sur huit régions anatomiques. Résultats. Vingt des 29 sites contactés ont transmis leurs protocoles. Tous âges confondus, 97 % des protocoles comportaient un niveau de haute tension ≤ 120 kV. Pour les âges de 1, 5 et 10 ans respectivement, les 75es centiles des distributions de dose étaient : 31, 39,5 et 49,5 mGy pour le protocole « crâne » ; 24, 22 et 24 mGy pour le « massif facial » ; 11, 11 et 11 mGy pour les « sinus » ; 46, 71 et 87 mGy pour les « rochers » ; 3, 3,5 et 5,5 mGy pour le « thorax standard » ; 2, 3 et 4 mGy pour le « poumon basse dose » ; 4, 4,5 et 7 mGy pour « l’abdomen-pelvis » ; 7, 11 et 12 mGy pour l’« os ». Les écarts dosimétriques intercentres restaient élevés. Conclusion. L’étude a permis d’évaluer les pratiques actuelles au sein de centres radiopédiatriques de référence et de réajuster les recommandations dosimétriques. Elle pourrait servir de base pour l’établissement de NRD en scanographie pédiatrique

Expositions radiologiques à visée diagnostique pendant l'enfance et risque de cancer Bilan des connaissances et perspectives

National audienceThe question of the risk of cancer associated with postnatal diagnostic medical exposure involving ionizing radiation in childhood is particularly relevant at the moment given the growing use of diagnostic examinations, especially computed tomography scans, in children. Compared to adults, pediatric patients are more sensitive to radiation and have more years of life expectancy and therefore more years at risk of cancer occurrence as compared to adults. This paper provides a description of diagnostic x-ray exposure in children in France and summarizes epidemiologic studies on subsequent risk of cancer. Overall, this review, based on 12 case-control studies and 6 cohort studies, shows no significant association between exposure to medical diagnostic radiation exposure and childhood cancer risk. The methodological limitations of these studies are discussed. As the expected cancer risks are low, epidemiological studies require very large sample sizes and long periods of follow-up in addition to a good dosimetry assessment to enable quantitative risk estimation. New cohort studies of young patients who underwent CT scans are currently underway within the European EPI-CT project. In the meantime, continued efforts to reduce doses and the number of radiological examinations in children are needed, including adhering to the " as long as reasonably achievable" (Alara) principle. © 2011 Elsevier Masson SAS.La question du risque de cancer associé à l’exposition médicale à visée diagnostique pendant l’enfance est particulièrement pertinente face à l’utilisation croissante des examens radiologiques, notamment des scanners, en pédiatrie. Les enfants représentent en effet une population particulièrement sensible aux rayonnements ionisants, caractérisée par une radiosensibilité de certains tissus accrue par rapport à celle des adultes et une espérance de vie longue, avec pour conséquence une probabilité plus élevée de développer un cancer. Cet article dresse un bilan de l’exposition des enfants aux rayonnements ionisants liée aux actes de diagnostic médical en France et propose une synthèse des études épidémiologiques sur le risque de cancer à long terme. Au total, à partir des résultats de 12 études cas–témoins et 6 études de cohortes analysées dans cette revue, il n’a pas été mis en évidence d’association significative entre l’exposition médicale à visée diagnostique pendant l’enfance et le risque de cancer. Les limites méthodologiques de ces études sont discutées. Le risque de cancer attendu étant faible, seules des études de grande taille, avec une longue période de suivi et des données dosimétriques de qualité seront capables de le mettre en évidence. Des études de cohortes portant sur plusieurs milliers de patients exposés au scanner pendant l’enfance sont actuellement en cours dans le cadre du projet européen EPI-CT. Parallèlement, la poursuite des efforts pour réduire les doses et le nombre des examens radiologiques dans l’enfance est toujours nécessaire, en respectant le principe as low as reasonably achievable (ALARA) en imagerie pédiatrique

Automatic exposure control in multichannel CT with tube current modulation to achieve a constant level of image noise: Experimental assessment on pediatric phantoms

Automatic exposure control (AEC) systems have been developed by computed tomography (CT) manufacturers to improve the consistency of image quality among patients and to control the absorbed dose. Since a multichannel helical CT scan may easily increase individual radiation doses, this technical improvement is of special interest in children who are particularly sensitive to ionizing radiation, but little information is currently available regarding the precise performance of these systems on small patients. Our objective was to assess an AEC system on pediatric dose phantoms by studying the impact of phantom transmission and acquisition parameters on tube current modulation, on the resulting absorbed dose and on image quality. We used a four-channel CT scan working with a patient-size and z -axis-based AEC system designed to achieve a constant noise within the reconstructed images by automatically adjusting the tube current during acquisition. The study was performed with six cylindrical poly(methylmethacrylate) (PMMA) phantoms of variable diameters (10- 32 cm) and one 5 years of age equivalent pediatric anthropomorphic phantom. After a single scan projection radiograph (SPR), helical acquisitions were performed and images were reconstructed with a standard convolution kernel. Tube current modulation was studied with variable SPR settings (tube angle, mA, kVp) and helical parameters (6- 20 HU noise indices, 80- 140 kVp tube potential, 0.8- 4 s. tube rotation time, 5- 20 mm x-ray beam thickness, 0.75-1.5 pitch, 1.25- 10 mm image thickness, variable acquisition, and reconstruction fields of view). CT dose indices (CTDIvol) were measured, and the image quality criterion used was the standard deviation of the CT number measured in reconstructed images of PMMA material. Observed tube current levels were compared to the expected values from Brooks and Di Chiro's [R.A. Brooks and G.D. Chiro, Med. Phys. 3, 237-240 (1976)] model and calculated values (product of a reference value multiplied by a dose ratio measured with thermoluminescent dosimeters). Our study demonstrates that this AEC system accurately modulates the tube current according to phantom size and transmission to achieve a stable image noise. The system accurately controls the tube current when changing tube rotation time, tube potential, or image thickness, with minimal variations of the resulting noise. Nevertheless, CT users should be aware of possible changes of tube current and resulting dose and quality according to several parameters: the tube angle and tube potential used for SPR, the x-ray beam thickness (tube current decreases and image noise increases when doubling x-ray beam thickness), the pitch value (a pitch decrease leads to a higher dose but also to a higher noise), and the acquisition field of view (FOV) (tube current is lower when using the small acquisition FOV compared to the large one, but the use of small acquisition FOV at 120 kVp leads to a peculiar increase of tube current and CTDIvol). © 2007 American Association of Physicists in Medicine

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part II, the cystic gland.

Pineal cysts are a common incidental finding on brain MRI with resulting difficulties in differentiation between normal glands and pineal pathologies. The aim of this study was to assess the size and morphology of the cystic pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. In this retrospective multicenter study, 257 MR examinations (232 children, 0-5 years) were evaluated regarding pineal gland size (width, height, planimetric area, maximal cyst(s) size) and morphology. We performed linear regression analysis with 99 % prediction intervals of gland size versus age for the size parameters. Results were compared with a recent meta-analysis of pineoblastoma by de Jong et al. Follow-up was available in 25 children showing stable cystic findings in 48 %, cyst size increase in 36 %, and decrease in 16 %. Linear regression analysis gave 99 % upper prediction bounds of 10.8 mm, 10.9 mm, 7.7 mm and 66.9 mm(2), respectively, for cyst size, width, height, and area. The slopes (size increase per month) of each parameter were 0.030, 0.046, 0.021, and 0.25, respectively. Most of the pineoblastomas showed a size larger than the 99 % upper prediction margin, but with considerable overlap between the groups. We presented age-adapted normal values for size and morphology of the cystic pineal gland in children aged 0 to 5 years. Analysis of size is helpful in discriminating normal glands from cystic pineal pathologies such as pineoblastoma. We also presented guidelines for the approach of a solid or cystic pineal gland in hereditary retinoblastoma patients

Utilisation des données du programme de médicalisation des systèmes d'information (PMSI) dans les études épidémiologiques Application à la Cohorte Enfant Scanner

National audienceBackground: The "Cohorte Enfant Scanner", a study designed to investigate the risk of radiation-induced cancer after childhood exposure to CT (computed tomography) examinations, used clinical information contained in the "programme de médicalisation des systèmes d'information" (PMSI) database, the French hospital activities national program based upon diagnosis related groups (DRG). However, the quality and adequacy of the data for the specific needs of the study should be verified. The aim of our work was to estimate the percentage of the cohort's children identified in the PMSI database and to develop an algorithm to individualize the children with a cancer or a disease at risk of cancer from medical diagnoses provided by the DRGs database. Methods: Of the 1519 children from the "Cohorte Enfant Scanner", who had had a CT scan in the radiology department of a university hospital in 2002, a cross linkage was performed with the DRGs database. All hospitalizations over the period 2002-2009 were taken into account. An algorithm was constructed for the items "cancer" and "disease at risk for cancer" on a sample of 150 children. The algorithm was then tested on the entire population. Results: Overall, 74% of our population was identified in the DRGs database. The algorithm individualized cancer diagnoses with 91% sensitivity (95% confidence interval [95%CI]: 86%; 97%) and 98% specificity (95%CI: 97%; 99%) and 86% positive predictive value (95%CI: 80%; 93%). For the diagnosis of disease at risk for cancer, the sensitivity, specificity and positive predictive value were respectively 91% (95%CI: 84%; 98%), 94% (95%CI: 92%; 95%) and 52% (95%CI: 43%; 61%). Conclusion: The DRG database identified with excellent sensitivity and specificity children with diagnoses of cancer or disease at risk for cancer. Hence, potential confounding factors related to the disease of the child can be taken into account for analyses performed with the cohort. © 2012 Elsevier Masson SASPosition du problème : la Cohorte Enfant Scanner, qui étudie le risque de cancer radio-induit après exposition dans l’enfance à des examens scanographiques, pourrait bénéficier des informations cliniques contenues dans le programme de médicalisation des systèmes d’information (PMSI). Cependant, la qualité et l’adéquation des données aux besoins de l’étude doivent être vérifiées. L’objectif de notre travail était d’estimer le pourcentage d’enfants de la cohorte identifiés dans la base PMSI et de construire un algorithme pour individualiser les enfants présentant un cancer ou une pathologie à risque de cancer à partir des diagnostics cliniques de la base PMSI.Méthodes : un croisement des identifiants des 1519 enfants de la Cohorte Enfant Scanner ayant eu un scanner dans un service de radiopédiatrie hospitalo-universitaire en 2002 a été fait avec la base PMSI. Toutes les hospitalisations de l’enfant sur la période 2002–2009 ont été analysées. Un algorithme a été construit pour les items « cancer » et « pathologie à risque de cancer » sur un échantillon de 150 enfants. L’algorithme a ensuite été appliqué à l’ensemble de la population.Résultats : au total, 74 % de notre population a été identifiée dans la base PMSI. L’algorithme a permis d’individualiser les diagnostics de cancer avec une sensibilité de 91 % (intervalle de confiance à 95 %, [IC 95 %], 86 % ; 97 %), une spécificité de 98 % (IC 95 %, 97 % ; 99 %) et une valeur prédictive positive (VPP) de 86 % (IC 95 %, 80 % ; 93 %). Pour le diagnostic de pathologie à risque de cancer, la sensibilité, la spécificité et la VPP étaient respectivement de 91 % (IC 95 %, 84 % ; 98 %), 94 % (IC 95 %, 92 % ; 95 %) et 52 % (IC 95 %, 43 % ; 61 %).Conclusion : le PMSI a permis d’identifier avec d’excellentes sensibilité et spécificité les enfants présentant un cancer ou une pathologie à risque de cancer. Cela permettra de prendre en compte les facteurs de confusion éventuels liés à la pathologie de l’enfant dans les analyses de la Cohorte Enfant Scanner

Diagnostic Performance of Magnetic Resonance Imaging and Computed Tomography for Advanced Retinoblastoma: A Systematic Review and Meta-analysis.

PURPOSE: To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies. METHODS: Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed. MAIN OUTCOME MEASURES: Sensitivity and specificity of MRI and CT in detecting tumor extent. RESULTS: Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%-78%), 74% (95% CI, 52%-88%), and 88% (95% CI, 20%-100%), respectively, and specificities of 94% (95% CI, 84%-98%), 72% (95% CI, 31%-94%), and 99% (95% CI, 86%-100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses. CONCLUSIONS: Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few-mostly old-studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed

Radiation exposure from CT in early childhood A French large-scale multicentre study

International audienceObjectives The increasing use of CT scans in the paediatric population raises the question of a possible health impact of ionising radiation exposure associated with CT scans. The aim of this study was to describe the pattern of CT use in early childhood. Methods In 14 major French paediatric radiology departments, children undergoing at least 1 CT scan before age 5, between 2000 and 2006, were included. For each examination, absorbed organ doses were calculated. Results 43% of the 27 362 children in the cohort were aged less than 1 year during their first exposure, with 9% being aged less than 1 month. The mean number of examinations per child was 1.6 (range 1-43). The examinations included head in 63% of the cases, chest in 21%, abdomen and pelvis in 8% and others in 8%. Brain and eye lenses received the highest cumulative doses from head examinations, with mean organ dose values of 22 mGy (maximum 1107 mGy) and 26 mGy (maximum 1392 mGy), respectively. The mean cumulative effective dose was 3.2 mSv (range 0.1-189 mSv). Conclusion CT scan exposure in childhood is responsible for relatively high doses to radiosensitive organs. The rather large dose range according to the protocols used requires their optimisation. The cohort follow-up will study the risk of long-term radiation-induced cancer. © 2012 The British Institute of Radiology

Suivi d’enfants exposés aux rayonnements ionisants dans le cadre de procédures radiologiques à visée diagnostique

Compte tenu de la radiosensibilité accrue des enfants aux rayonnements ionisants, notre objectif est d’évaluer les risques de cancers solides et de leucémies à long terme associés aux expositions médicales reçues pendant l’enfance. Deux études de cohorte sont réalisées par le Laboratoire d’épidémiologie de l’Institut de radioprotection et de sûreté nucléaire (IRSN). L’une, la « Cohorte Enfant Scanner » porte sur les enfants nés après le 01/01/1995 et exposés aux rayonnements ionisants lors de scanners réalisés entre 2000 et 2013. L’autre porte sur les enfants exposés lors de procédures de cardiologie interventionnelle avant l’âge de 10 ans entre 2000 et 2013. Pour chacune des cohortes, une évaluation rétrospective individuelle de l’exposition sera réalisée par l’Unité d’expertise en radioprotection médicale de l’IRSN. Un suivi passif en termes de cancers solides et de leucémies sera réalisé grâce aux données des registres de cancers pédiatriques et aux données de mortalité. La « Cohorte Enfant Scanner » est constituée de plus 80 000 enfants et s’inscrit dans le projet européen EPI-CT, qui regroupe 9 cohortes nationales. À terme, la cohorte des enfants en cardiologie interventionnelle regroupera plus de 8 000 enfants. Ces études de cohortes, avec un suivi prolongé, permettront d’étudier l’impact sur la santé des expositions radiologiques reçues pendant l’enfance