Imaging of IPF

Gamal Rabie Agmy, MD, FCCP Professor of chest Diseases, Assiut university

• Interstitial compartment is the portion of the lung sandwiched between the epithelial and endothelial basement membrane

• Expansion of the interstitial compartment by inflammation with or without fibrosis – Necrosis

– Hyperplasia

– Collapse of basement membrane

– Inflammatory cells

What is the Pulmonary

Interstitium?

The interstitium of the lung is not normally visible radiographic-

ally; it becomes visible only when disease (e.g., edema,

fibrosis, tumor) increases its volume and attenuation.

The interstitial space is defined as continuum of loose

connective tissue throughout the lung composed of three

subdivisions:

(i) the bronchovascular (axial), surrounding the bronchi,

arteries, and veins from the lung root to the level of the

respiratory bronchiole

(ii) the parenchymal (acinar), situated between the alveolar

and capillary basement membranes

(iii) the subpleural, situated beneath the pleura, as well as in

the interlobular septae.

The Lung Interstitium

Secondary pulmonary lobular

anatomy

The terminal bronchiole in the center

divides into respiratory bronchioles with

acini that contain alveoli.

Lymphatics and veins run within the

interlobular septa

Centrilobular area in blue (left)

and perilymphatic area in yellow

(right)

Ideal ILD doctor

Radiologist

Pathologist

Pulmonologist

Introduction

◙ Idiopathic pulmonary fibrosis (IPF) has

been defined by international guidelines as

a specific form of chronic, progressive,

fibrosing interstitial pneumonia of unknown

cause, occurring primarily in older adults,

limited to the lungs and associated with the

histopathological and/or radiological

pattern of usual interstitial pneumonia (UIP)

Diagnostic criteria

According to international guidelines , the

diagnosis of IPF requires the following:

1) exclusion of other known causes of interstitial lung

disease, e.g. domestic and occupational environmental

exposures, connective tissue disease and drug

toxicity;

2) the presence of a definite UIP pattern on HRCT in

patients not subjected to surgical lung biopsy; and

3) specific combinations of HRCT and surgical lung biopsy

patterns in patients subjected to surgical lung biopsy.

Radiography

Early in the disease, the most common radiographic changes are an

interstitial shadowing of small (1- to 2-mm), irregular opacities, which are

seen in about three fourths of patients. Less common are small, round

opacities, which are seen in one fifth of patients. This finding is generally

known as reticulonodular opacities. Septal lines are occasionally

observed. The distribution is predominantly basal.

Peripheral accentuation is also a

common feature, but it is more easily

appreciated on CT scans than on plain

chest radiographs.

The pattern is usually symmetrical.

Another common pattern is hazy, ground-

glass opacification, which is either

diffuse or patchy. Volume loss and a

raised diaphragm are seen in up to 60%

of patients. This may be accompanied by

basal discoid atelectasis.

Pleural disease is not typical of IPF. Its

presence should raise the possibility of

other conditions, such as asbestosis,

rheumatoid pulmonary disease, or

systemic lupus.

Pneumothorax, pneumomediastinum, or

both have been reported in a few patients;

these conditions have been associated

with bullae in the lung parenchyma.

With progression of alveolitis to fibrosis, the

initial fine lines become coarse, and small (2-

mm) cysts appear. These cysts coalesce and

increase to 5-7 mm in diameter; they appear as

ring opacities within the honeycomb lung.

As fibrosis worsens, the honeycombing

becomes coarser with larger honeycomb

cysts, and further volume loss occurs. In

advanced stages, there is radiographic

evidence of pulmonary arterial hypertension.

False positives/negatives

For symptomatic patients in whom the

diffusion capacity is abnormal, results of

chest radiography may be normal.

For other patients, the radiographic

appearances are abnormal before clinical

symptoms appear. Results of HRCT scanning

are abnormal for most patients with IPF.

Computed Tomography

Inconsistent with UIP

pattern (any one of

seven features)

Possible UIP

pattern (all

three features)

UIP pattern (all

four features)

•Upper or mid lung

predominance

•peribronchovascular

predominance

•extensive ground glass abnormality (extent >

reticular abnormality)

•profuse micronodules

(bilateral, predominantly

upper lobes) •discrete cysts (multiple

bilateral, away from areas of

honeycombing)

•diffuse mosaic

attenuation/air trapping (bilateral in three or more

lobes)

•subpleural basal

predominance

•reticular abnormality

•Absence of features listed as inconsistent

with UIP pattern

•subpleural basal

predominance

•reticular abnormality

•honeycombing with

or without traction

bronchiectasis

•Absence of features

listed as inconsistent

with UIP pattern

The Fleischner Society glossary provides both

radiological and pathological definitions for

honeycombing

Radiologically, honeycombing is characterised by

‘‘clustered cystic air spaces, cysts of comparable

diameters, and cyst diameters typically ,10 mm

surrounded by well-defined walls’’

The pathology is defined as ‘‘destroyed and fibrotic

lung tissue containing numerous cystic airspaces

with thick fibrous walls, representing the late stage

of various lung diseases, with complete loss of

acinar architecture’’

Rough Reticular Fine Reticular

Traction

Bronchiectasis

and

Interface

sign

Honey

combing

UIP UIP or NSIP

Mosiac pattern

Bronchiolitis

obliterans

Chronic EAA

Young woman Dry mouth Smoker

LAM LIP Histiocytosis

Using HRCT to prognosticate IPF and

monitor disease progression

1-Traction bronchiectasis

2-Honeycombing

3-Decreases DLCo

the extent of honeycombing at baseline and its progression on

follow-up HRCT were both found to be important predictors of

mortality in patients with fibrosing interstitial pneumonia.

Subjects who demonstrated progression of fibrosis extent on

HRCT over a period of 6 months and a decline in forced vital

capacity were identified as a particular sub-group of IPF

patients with the poorest outcomes. In fact this was shown to

be a superior predictor of outcome compared to baseline

HRCT fibrosis scores

False positives/negatives

One third of all cases of IPF are missed on

HRCT; a confident diagnosis of IPF is made

in about two thirds of cases

Nuclear Imaging In cases of IPF, perfusion lung scintigraphy shows

nonspecific, subsegmental mismatched perfusion defects.

These are not correlated with clinical severity.

Gallium-67 imaging has not proven to be of value in cases

of established IPF.

Technetium-99m diethylenetriamine penta-acetic acid

(DTPA) is cleared more rapidly when capillary permeability

is increased than when it is not, and the findings may

provide an index of lung inflammation.

Fluorodeoxyglucose (FDG) positron-emission tomography

(PET) may show FDG accumulation in the lung bases; such

findings correlate with the honeycomb fibrosis seen on

high-resolution HRCT