1. Diagnostic tools – imaging and lung function (humans)
David A Lynch, MB

2. Disclosures Consultant: Research support:
Perceptive Imaging Centocor, Inc
Boehringer Ingelheim Siemens Inc
Genentech NHLBI
Gilead
Intermune
Veracyte
Pfizer

3. I ain’t going near no CT scanner
Conflict of interest
I ain’t going near no CT scanner
Jack

4. CT in human fibrotic lung disease
Technique
Terminology
Patterns of fibrosis
Quantification

5. High Resolution CT technique
Thin section ( mm)
Small field of view
Edge-enhancing reconstruction
Adequate inspiration
Absent motion
Prone and expiratory images very helpful
Multiplanar images
Standard window width (1500) and level (-700)
Mayo JR. CT evaluation of diffuse infiltrative lung disease: dose considerations and optimal technique. Journal of thoracic imaging. 2009;24(4):252-9.

8. Features of lung fibrosis
Reticular lines
Honeycombing
Ground glass attenuation or consolidation (uncommon)
Traction bronchiectasis/architectural distortion
Lobar volume loss
Hansell DM, et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):

9. Reticular abnormality with traction bronchiectasis

10. Reticular abnormality with honeycombing

11. Ground glass abnormality

12. Consolidation with traction bronchiectasis

13. Architectural distortion

14. Lobar volume loss

15. CT distribution Craniocaudal Upper lung predominant
Lower lung predominant
Mid lung predominant
Axial
Peripheral/subpleural
Peribronchovascular

16. Patterns of lung fibrosis in humans
UIP
NSIP
Hypersensitivity pneumonitis
Sarcoidosis
Organizing pneumonia
Idiopathic pleuroparenchymal fibroelastosis

18. UIP pattern Subpleural, basal predominance Reticular abnormality
Honeycombing with or without traction bronchiectasis
Absence of features inconsistent with UIP pattern
ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. AJRCCM, 2011 Mar 15;183(6):

19. Possible UIP Subpleural, basal predominance Reticular abnormality
Absence of features inconsistent with UIP pattern
ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. AJRCCM, 2011 Mar 15;183(6):

20. IPFNET: Concordance between CT and pathologic diagnoses
Pathology diagnosis
CT diagnosis
Definite UIP
Probable UIP
Possible UIP
Not UIP
Total
UIP 82 17 1 2
102 51 9 4 64
Inconsistent with UIP 55
16  75
188 42
241
Yagihashi et al. Soc Thorac Radiol 2014

21. NSIP Basal predominance Peribronchovascular/ subpleural sparing
Confluent pattern
Volume loss
Ground glass
Reticular
Traction bronchiectasis
Consolidation +/-
Honeycombing rare
Travis et al. Am J Respir Crit Care Med. 2008;177:1338

22. Fibrotic sarcoidosis

23. Fibrotic hypersensitivity pneumonitis
Upper, mid or lower lung predominance
Infiltrative
Centrilobular nodules
Irregular lines
Ground glass
Reticular opacity
Honeycombing
Obstructive
Air trapping
Cysts
Emphysema

24. Organizing pneumonia

25. Idiopathic pleuropulmonary fibroelastosis (IPPFE)
Rare entity
Upper lobe predominant
Dense pleural/subpleural fibrosis
Traction bronchiectasis and volume loss
Frankel SK. Chest 2004;126:

26. Bleomycin induced fibrosis in rabbits
Hirose et al. Am Rev Respir Dis Mar;147(3):730-8.
Lynch et al. Acad Radiol Feb;4(2):102-7

27. Bleomycin induced fibrosis in rabbits
Lynch et al. Acad Radiol Feb;4(2):102-7

28. Quantification of lung fibrosis
Semiquantitative
Densitometry/CT histogram
Texture-based methods

29. Relationship between semiquantitative assessment and physiologic impairment
Wells et al. Am J Respir Crit Care Med Vol 167. pp 962–969, 2003

30. Relationship between semiquantitative assessment and mortality: Multivariate
Baseline Variable
Hazard ratio
95% Confidence Interval
p Value
HRCT features
Overall extent of fibrosis
2.71
1.61, 4.55
<
% predicted DLCO
0.94
0.90, 0.98
0.004
Treatment assignment to IFN-γ1b
0.53
0.28, 0.99
0.04
Lynch DA, et al. Am J Respir Crit Care Med2005;172:

31. Histogram-based parameters
Courtesy: Stephen Humphries, National Jewish Health

32. Relationship between quantitative histogram assessment and physiologic impairment
Best et al., Radiology; 2003;208:

33. Multivariate analysis of predictors of mortality in IPF (n=167, 35 deaths)
Effect
Odds Ratio Estimates
95% Confidence Limits
Wald Chi-Square
Pr > ChiSq
Kurtosis at Baseline
0.579
0.32 to 1.049
3.249
0.0715
Mean Visual Fibrosis at Baseline CT
1.104
1.018 to 1.198
5.7171
0.0168
Best et al., Radiology; 2008 Mar;246(3): 33

34. Textural analysis Normal lung Reticular Abnormality
Courtesy: Stephen Humphries, National Jewish Health

35. Critical features of CT assessment of fibrosis
High resolution technique, with minimal motion
Standardized descriptive lexicon
Systematic categorization of fibrotic patterns
Quantification
Visual
Histogram based
Textural
Validation against physiology, pathology, outcome

36. THANKS!