Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

CT Im a g in g Ph e n ot yp e s in COPD

Raúl San José Est épar, Ph.D.

Laboratory of Mathematics in Imaging

Applied Chest Imaging Laboratory
Surgical Planning Laboratory
Brigham and Women’s Hospital

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

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:


CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

COPD: a growing disease

Projected to be the third-leading cause of death by
2020
24 million people affected by COPD in US

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Disease in Images

Airway Diseases


Emphysema Diseases


CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Quantitative CT

• CT is the modality of choice for quantitative

lung imaging
– Good contrast between tissue classes: air,
connective tissue, blood
• Partial Volume Effect
– Physical metric: Density
• Subject to artifacts and measurement conditions
– High resolution
• No high enough for the disease site


CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

What can we get from CT?

Airway
Phenotypes

Size
Effective Linear Attenuation Coefficient
CT
Edge Detection

HRCT Morphology & Shape

Density

Dynamic
Emphysema MSCT (INSP EXP)
Phenotypes
Registration
Gas trapping
Deformation
Parenchyma interdependence

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

CT-based biomarkers: Accuracy vs

Precision
• How do we want to measure?
– Accurate: the right” answer  no bias
– Precise: errors are as small as possible
–
– What is the main difference?

Accurate, not precise Precise, but not accurate

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Wall thickness

• Wall thickness measurements are a clear example

where accuracy has overplayed precision

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Emphysema phenotypes

Cluster-based analysis
Shape-based analysis

Size

Texture-based analysis Morphology & Shape

Effective Linear Attenuation Coefficient

Density

Histogram-based
analysis

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Histogram-based measurements
• Low Attenuation Areas % (LAA%)
– Conceptually more appealing
– Histopathologic correlates
• 15th Percentile (Per15th)
– More normally distributed
– More sensitive to early changes


CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Issues

• Lung density is influenced by

– BMI
– Noise
– CT protocol
• Inter-center (or inter scanner) variability in CT
measures of emphysema
• Volume dependence of emphysema measures


CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Cluster-based analysis (power law)

• Power law for the distribution of air pocket sizes.
• Related to the fractal dimension of the alveolar
surface.
• Sensitivity to early-stage disease
• Mishima, PNSA 1999

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Shape-based analysis

• Descriptor of diaphragm
curvature
• Correlated with DLCO%
and VA
• Enhance information
provided by
histogram-based
metrics.

Keller, Reeves, Yankelevitz et al, Proc

SPIE, 2009

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Texture-based analysis
• Exploit pixel relations: higher order order statistics
and other image features.
• Require training stage.
• Long processing time.
• It has the potential of being less sensitive to scanner
variability.

Xu, TMI, 2006

CT Imaging Phenotypes in COPD
 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Airway Phenotypes

Airway size
Tree morphology

Size

Effective Linear Attenuation CoefficientAirway Power Morphology & Shape

Density

Peak Wall Attenuation

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Airway Size

• Small airways are the site of

obstruction
– Difficult to measure at current
resolutions
– Distal thickening is related to proximal
effects (Nakano,2005)
• Airway size phenotypes
– Wall Thickness
– Wall Area % (WA%)
– Pi10: Extrapolated square root of wall
area of an ideal airway of 10 mm
internal Perimeter.
CT Imaging Phenotypes in COPD
 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Wall thickness: THE airway

phenotype?
-Some open-ended questions
·Does inflammation and airway remodeling merely leads to airway
thickening?
·What is the CT-intensity telling about the diseases?

-
-CT measures the linear attenuation coefficient of the underlying
tissue structures. This can be used as a indirect measurement for
density (no without many caveats)
-Hypothesis:
·Airway wall compositions changes due to mural remodeling can be
detectable by CT X-ray attenuation
·Changes in wall X-ray attenuation may correlate with degree of expiratory
airflow obstruction

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Preliminary Evidences

-Micro-CT of an hamartoma:

-Normal Airway: Histology vs CT

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Wall X-ray Attenuation

-Washko et al, JAP 2009. Gender and Airway Wall Attenuation

-Increased Wall at t enuat ion w it h 900

800
disease progression. 700
600

CT Density*
-Wall at t enuat ion shows higher 500 Males
correlat ion wit h FEV1% 400 Female
300
predict ed (R= -0.47, 200
100
P< 0.0001) t han wall t hickness 0
(R= -0.34, P< 0.0001). Normal 1 2 3/4
GOLD Stage

-In a m ult ivariat e analysis, percent age of em physem a and

wall at t enuat ion w ere significant predict ors of FEV1%
predicted (P<0.0001), but not wall thickness.

-
CT Imaging Phenotypes in COPD
 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Mass Conversation Principle

-Developm ent of a new phenot ype t hat has as prim ary goal t o be
precise while capturing the main airway components: morphology and
composition

-Scanner can be approximate as a linear system: mass has to be preserved.

-
CT (h(x))

mass mass

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Airway Power

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Simulation: Power vs Wall thickness

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Simulation: Power vs Wall

Attenuation

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Simulation: Power vs Parenchyma

Attenuation

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

COPDGene Phantom

-Four scanners: Philips, GE, Siem ens and GE (Low dose)

-Two reconst ruct ion kernels

-Each t ube is used as it s own cont rol

-A precise m et ric should be st able across brands and prot ocols

-
CTP666-4 CTP666-3 CTP666-2
CTP666-1
CTP666-5 CTP666-6

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Relative error per scanner

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Relative error between lose dose and

high dose

CT Imaging Phenotypes in COPD

Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Relative error for all possible

combinations

CT Imaging Phenotypes in COPD

 Introduction Emphysema Airways Airway Power Lung Cancer Workshop VII

Conclusions

• CT is the primary imaging tool to

characterize COPD
– COPD phenotypes are still a moving target
• Shared quantitative challenges due to
scanner variability
– Reverse engineer scanner effects
– Exploit signal invariant properties to define
new metrics


CT Imaging Phenotypes in COPD