COPDGene® : Genetic Epidemiology of COPD NA-MIC: All Hand Meeting Raúl San José & James Ross BWH

COPD: Chronic Obstructive Pulmonary Disease Overview COPD: Chronic Obstructive Pulmonary Disease Definition: “Airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.” Causes:

COPD: a growing disease Overview COPD: a growing disease Projected to be the third-leading cause of death by 2020 24 million people affected by COPD in US

COPD: The Diseases What is the underlying process? Overview COPD: The Diseases What is the underlying process? Slowly progressive irreversible destruction of the lung tissue Emphysema: air sacs that exchange gases Airway disease (Chronic Bronchitis): airways that conduct these gases End Result: Progressive shortness of breath Cough Sputum production

Overview Disease in Images Airway Diseases Emphysema Diseases

COPDGene Only 20% of smokers develop COPD Genetic factors Multi-center study funded by the National Heart, Lung and Blood Institute (NHLBI). Co-PIs: Drs. James Crapo, Edwin Silverman. 21 clinical sites 3 Image analysis centers: Denver Iowa BWH

COPDGene COPDGene: Hypothesis 1) Precise phenotypic characterization of COPD subjects using computed tomography, as well as clinical and physiological measures, will provide data that will enable the broad COPD syndrome to be segregated into clinically significant subtypes. 2) Genome-wide association studies will identify genetic determinants for COPD susceptibility that will provide insight into clinically relevant COPD subtypes. 3) Distinct genetic determinants influence the development of emphysema and airway disease.

COPDGene COPDGene: Goals Collect a large population of COPD subjects and smokers without COPD: 10,000 Two racial/ethnic groups: Non-Hispanic whites and Non-Hispanic African Americans Extensive Characterization (Chest CT scans) Inspiratory, Expiratory High resolution CT (0.7mm isotropic with 50% overlap) 2 reconstructions kernels (smooth and sharp) Use genome-wide association analysis to find inherited causes of COPD and COPD subtypes

COPDGene: Study Design

COPDGene: Current status Since Sept 2007 over 6500 subjects have been recruited. First 2500 have been fully analyzed.

Challenges Data management Image analysis: inspiration and expiration Data Analysis Challenges Data management Storage: 40,000 scans, 20 TB expected to archive full cohort Quality control: Initial and processing Querying and retrieval Image analysis: inspiration and expiration Lung area and lobes Airway segmentation Robust: outlier detection Minimal user input High-throughput analysis Batch analysis Grid deployment

Analysis Centers National Jewish (Denver): Drs. Lynch and Schroeder Data Analysis National Jewish (Denver): Drs. Lynch and Schroeder Q&A Emphysema and Airway analysis using VIDA Primary archiving center Result integration BWH (Boston): Dr. Washko High-throughput emphysema analysis New phenotypes Data replication University of Iowa: Dr. Hoffman COPDGene Phantom Analysis (Q&A) VIDA customization

BWH Pipeline Lung Imaging Platform Data Analysis BWH Pipeline Lung Imaging Platform ITK-based filters for lung extraction, lobe segmentation and parenchymal texture analysis Emphysema quantification Air trapping quantification Tracheal air correction VTK-based filters for airway measurements Command Line Tools Grid Wizard Enterprise for pipeline deployment Iterative Lobe segmentation in Slicer 3

BWH Pipeline Filters Tools itkLungConventions Data Analysis BWH Pipeline Filters itkLungConventions itkExtractLungLabelMapImageFilter itkPartialLungLabelMapImageFilter itkMergeLungLabelMapsImageFilter itkAutoThresholdAirwaySegmentationImageFilter itkWholeLungVesselAndAirwaySegmentationImageFilter itkSplitLeftAndRightLungsImageFilter itkLabelLungRegionsImageFilter itkAirwayGraphTraits itkImageToAirwayGraphFilter itkImageToAirwayGraphFunctor itkMinCostPathAirwaySegmentationImageToGraphFilter Tools ConvertDicom GeneratePartialLungLabelMap GenerateEmphysemaMeasures QualityControl ExtractLungLabelMap MergeLungLabelMaps GenerateHUStatistics SegmentationAssistant GenerateMedianFilteredImage SplitLeftAndRightLungs LabelLungRegions GenerateAirwayPhantom

Data Analysis BWH Pipeline

Data Quality: Dashboard Data Analysis Data Quality: Dashboard

Future Directions Airway Analysis Development of new airway phenotypes User-driven path extraction Fully automatic approach based on Scale-space particles Development of new airway phenotypes Role of airway density in disease New approaches for emphysema Multi scanner brand correction Automatic pipeline supervision and reporting Insp.-Exp. registration for lobar ventilation assessment