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

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

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

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

High Resolution CT technique Thin section (0.625-1.5 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.

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):697-722.

Reticular abnormality with traction bronchiectasis

Reticular abnormality with honeycombing

Ground glass abnormality

Consolidation with traction bronchiectasis

Architectural distortion

Lobar volume loss

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

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

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):788-824

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):788-824

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

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

Fibrotic sarcoidosis

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

Organizing pneumonia

Idiopathic pleuropulmonary fibroelastosis (IPPFE) Rare entity Upper lobe predominant Dense pleural/subpleural fibrosis Traction bronchiectasis and volume loss Frankel SK. Chest 2004;126:2007-2013.

Bleomycin induced fibrosis in rabbits Hirose et al. Am Rev Respir Dis. 1993 Mar;147(3):730-8. Lynch et al. Acad Radiol. 1997 Feb;4(2):102-7

Bleomycin induced fibrosis in rabbits Lynch et al. Acad Radiol. 1997 Feb;4(2):102-7

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

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

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 < 0.0001 % 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;172:488-93.

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

Relationship between quantitative histogram assessment and physiologic impairment Best et al., Radiology; 2003;208:407-414

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):935-40. 33

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

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

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