Diagnostic tools – imaging and lung

function (humans)

David A Lynch, MB

Disclosures

Consultant: Research support:Perceptive Imaging Centocor, IncBoehringer Ingelheim Siemens IncGenentech NHLBIGileadIntermuneVeracytePfizer

Conflict of interestI 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

Possible UIP 51 9 4 0 64

Inconsistent with

UIP 55 16  4 0 75

Total 188 42 9 2 241Yagihashi 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

SemiquantitativeDensitometry/CT histogramTexture-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 0.004Treatment 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

R2= 0.23P<0.0001

R2= 0.30P<0.0001

R2= 0.20P<0.0001

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.

Normal lungReticular Abnormality

Textural analysis

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

THANKS!