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

2. 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:

3. 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

4. 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

5. Overview
Disease in Images
Airway Diseases
Emphysema Diseases

6. 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

7. 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.

8. 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

9. COPDGene: Study Design

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

11. 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

12. 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

13. 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

14. 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

15. Data Analysis
BWH Pipeline

16. Data Quality: Dashboard
Data Analysis
Data Quality: Dashboard

17. 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