CONTENTS

• Ground-glass opacity (GGO)
• Initial approach to GGO
• Subtypes of GGO
  • Diffuse GGO
  • Mosaic GGO
  • Crazy-paving ➡️
  • GGO in a nodular configuration:
    • Centrilobular GGO nodules ➡️
    • Non-centrilobular GGO nodules
  • GGO involved in larger nodules:
    • Halo sign ➡️
    • Reverse halo sign ➡️
• Mosaic attenuation
  • (1) Mosaic GGO
  • (2) Mosaic 2/2 small airway disease
  • (3) Mosaic 2/2 pulmonary HTN
  • (Related: GGO with spared areas)
• Three-density sign (headcheese sign)
• Questions & discussion

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ground-glass opacity (GGO)

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definition of ground-glass opacity (GGO)

• Ground-glass opacity on CT scan is defined as a hazy increase in lung opacity that doesn't obscure the lung vasculature (as opposed to consolidation, which does obscure the vasculature).
  • ⚠️ The term “ground-glass” is also used to describe a hazy opacity on chest X-ray. This is an incorrect abuse of the term. Properly defined GGO should be used only to describe this abnormality as seen on CT scan.
• Causes of ground-glass opacity are extremely broad, encompassing a diverse range of lung pathology (which is often less clinically severe than consolidation).

histological causes of ground-glass opacity:

• Partial alveolar filling process, with various substances:
  • Exudate.
  • Fluid.
  • Blood.
• Mild interstitial process that causes interstitial thickening:
  • (a) This may represent reversible inflammation. Among patients with interstitial lung disease and predominantly ground-glass opacity on CT scan, ~75% of patients are found to have inflammation on surgical biopsy.(Murray 2022)
  • (b) This may represent irreversible fibrosis that is below the resolution of the CT scan (especially in the presence of other findings of fibrotic lung disease, such as coarse reticulation, architectural distortion, traction bronchiectasis, and honeycombing).(Murray 2022)
• Partial alveolar collapse.
• Increased blood flow or venous engorgement, causing dilation of the microvasculature.

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initial approach to GGO

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Some degree of ground-glass opacities is often seen on a complex CT scan alongside an array of other abnormalities – this is nonspecific. Below is the approach to a CT scan wherein diffuse ground-glass opacities is a predominant or sole abnormality. 

[1] Evaluate tracheal configuration & ensure adequate scan quality

• ⚠️ Expiratory CT scans may mimic ground-glass opacification.(Shepard 2019)
• If the posterior tracheal membrane is flattened or bowed anteriorly, this suggests that the CT scan was inappropriately obtained during expiration.(24791617)

[2] Qualify the GGO & the scan

• Distribution on axial scan, e.g.:
  • Diffuse.
  • Centrilobular.
  • Peribronchovascular.
  • Peripheral.
  • Subpleural. (24791617)
• Distribution on coronal scan, e.g.:
  • Upper lung predominant.
  • Lower lung predominant.
• Evaluate for additional abnormalities, e.g.:
  • Interlobular septal thickening.
  • Intralobular interstitial thickening (fibrosis).
  • Cysts (causes of cysts plus GGO are discussed here: 📖)
  • Traction bronchiectasis.
  • Air trapping. (24791617)

[3] GGO is often broken down into several categories:

• Diffuse GGO. 📖
• Mosaic attenuation (patchy/lobular GGO). 📖
• Crazy paving (GGO plus septal thickening). 📖
• GGO itself takes on a nodular configuration:
  • Centrilobular GGO nodules. 📖
  • Non-centrilobular GGO nodules. 📖
• GGO occurs in relationship to larger nodules:
  • Halo sign. 📖
  • Reverse halo sign. 📖

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diffuse ground-glass opacities

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The following disorders are suggested by finding diffuse, bilateral GGO. 

infection, especially:

• Pneumocystis. 📖
• Viral pneumonias, including:
  • Herpesviruses:
    • CMV. 📖
    • HSV. 📖
  • COVID. 📖
  • RSV. 📖

interstitial lung disease

• HP 📖 (hypersensitivity pneumonitis, acute or subacute).
  • Perhaps the most common cause of diffuse GGO in normal hosts.(Walker 2019)
• NSIP 📖 (nonspecific interstitial pneumonitis).
• DIP 📖 (desquamative interstitial pneumonia).
• OP 📖 (organizing pneumonia).
• LIP 📖 (lymphocytic interstitial pneumonia).
• Eosinophilic pneumonia, including AEP (acute eosinophilic pneumonia).

other

• DAD 📖 (diffuse alveolar damage).
• Heart failure. 📖
• DAH 📖 (diffuse alveolar hemorrhage).
• Aspiration pneumonitis. 📖
• Exposures:
  • Drug toxicity.
  • EVALI (E-cigarette and vaping-induced acute lung injury).
• Less likely:
  • PAP 📖 (pulmonary alveolar proteinosis) – Usually presents as crazy-paving, but can occasionally present as isolated diffuse ground-glass opacities.(15671387)
  • Bronchoalveolar carcinoma. 📖 Usually causes more focal GGO. Diffuse GGO is possible, but when this occurs it's usually associated with consolidation as well.

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mosaic attenuation

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definition of mosaic attenuation

• Mosaic attenuation refers to areas of variable attenuation on CT scan that are lobular or multilobular in size (like a patchwork quilt composed of two different fabrics). (28212835) 

approach to mosaic attenuation

• Mosaic attenuation can generally be categorized into three bins:
  • Ground-glass opacities (parenchymal disease) – hyperattenuating lung is abnormal.
  • Small airway disease causing air trapping (hypoattenuated lung is abnormal).
  • Vascular disease causing areas of hypoperfused lung (hypoattenuated lung is abnormal).
• The first step is to sort out which category the patient belongs to. Several clues may be utilized to sort out the etiology of mosaic attenuation, as summarized in the figure below.
• The following three sections explore in detail the characteristics and causes of mosaic attenuation within each category.

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[#1/3] mosaic attenuation due to patchy GGO (~50%) 

radiologic features

• The abnormality is increased lung attenuation within areas of GGO.
• There is no difference in the vessel caliber between different lung areas.
• Ground-glass opacities may be poorly marginated, without sharp borders between normal and abnormal parenchyma (unlike airway or vascular disease).(26730869)
• Other features that may suggest parenchymal disease:(36202482)
  • Septal thickening (mosaic GGO with septal thickening suggests: diffuse alveolar hemorrhage, heart failure, pneumocystis, diffuse alveolar damage, or organizing pneumonia). However, the possibility of PVOD/PCH (pulmonary venooclusive disease/pulmonary capillary hemangiomatosis) should also be considered, if there are signs of pulmonary hypertension.(26274445)
  • Fibrosis (e.g., reticulation, traction bronchiectasis).
  • Nodules (but not including centrilobular nodules, which would suggest small airway involvement).
  • Pleural effusion.

causes of mosaic GGO opacities

• Infection:
  • Pneumocystis.
  • Viral.
  • Mycobacterial.
  • Bronchopneumonia (e.g., mycoplasma).
• Pulmonary edema:
  • Heart failure.
  • DAD (diffuse alveolar damage).(31704148)
• Eosinophilic pneumonia:
  • AEP (acute eosinophilic pneumonia).
  • CEP (chronic eosinophilic pneumonia).
• Interstitial lung diseases:
  • HP (hypersensitivity pneumonia).
  • OP (organizing pneumonia).
  • Lipoid pneumonia.
  • NSIP (nonspecific interstitial pneumonia).
  • PAP (pulmonary alveolar proteinosis).
  • DIP (desquamative interstitial pneumonia).(31704148)
  • Sarcoidosis.
• Bronchoalveolar carcinoma.

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[#2/3] mosaic attenuation due to small airway obstruction (~33%) 

clinical features

• Wheeze could be suggestive.
• Pulmonary function testing may show an obstructive pattern.

radiologic features

• The primary abnormality is reduced lung attenuation due to gas trapping. This is often accompanied by a reduced vessel caliber in the darker lung tissue (a pattern which may be seen in either vascular or airway disease).
• Other evidence of airway disease may be present:
  • Centrilobular nodules (including tree-in-bud opacities), although this may also occur among patients with pulmonary hypertension due to PCH (pulmonary capillary hemangiomatosis).
  • Bronchial wall thickening (however, bronchial wall thickening may also be seen in some diseases that cause mosaic GGO, including heart failure, bronchopneumonia, or organizing pneumonia).
  • Bronchiectasis, especially if bronchiectatic airways supply regions of the lungs which are hypoattenuated due to hyperinflation. This must be distinguished from traction bronchiectasis, which is associated with parenchymal lung disease. Traction bronchiectasis will be localized to hyperattenuated areas of GGO (e.g., in the context of organizing pneumonia, diffuse alveolar damage, or nonspecific interstitial pneumonitis).(26274445)
  • Mucus plugging.
  • Global lung hyperinflation may occur in very severe cases.
• Expiratory CT scan may be used to clarify this, when in doubt:
  • In small airway disease:
    • Normal (denser) lung tissue is compressed on expiration, thereby becoming denser.
    • Hyperlucent lung stays the same size and density (due to gas trapping).
    • The net effect is to accentuate differences in density. Thus, expiratory CT scan may be useful to reveal occult gas trapping which may not be visible on a standard inspiratory CT scan.
  • Vascular disease or parenchymal disease: all parts of the lung become smaller and denser to a similar degree.(26730869)

causes of small airway obstruction with lobular hyperinflation

• Bronchiolitis obliterans (BO), including also DIPNECH (diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, which causes mosaic attenuation and nodules).
• HP (hypersensitivity pneumonitis).
• Sarcoidosis.
• Asthma.
• COPD (chronic bronchitis > emphysema).
• Bronchiectasis.

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[#3/3] mosaic attenuation due to pulmonary hypertension (aka, mosaic perfusion; ~16%)

clinical features

• Features of pulmonary hypertension may be present (e.g., cor pulmonale with peripheral edema).

radiological features

• The primary abnormality is reduced lung attenuation, often with reduced vessel caliber in the darker lung (this pattern is seen in both vascular or airway disease).
• Evidence of pulmonary hypertension:
  • Right ventricular dilation.
  • Main pulmonary artery enlargement.
  • (Further discussion of CT abnormalities in pulmonary hypertension: 📖)
• Morphologic abnormalities in pulmonary arteries.
  • Arteries may be dilated in higher-attenuation areas. A similar phenomenon can occur in mosaic patterns caused by airway obstruction (due to ventilation-perfusion matching). However, pulmonary arterial vasodilation is often more pronounced in patients with primary pulmonary vascular disease (e.g., the pulmonary artery may be larger than the adjacent bronchus).(26274445)
  • Other arterial abnormalities (e.g., thrombi, webs, abrupt occlusion, and/or luminal irregularities).

causes of mosaic perfusion: pulmonary hypertension

• Most commonly:
  • CTEPH (chronic thromboembolic pulmonary hypertension) – most common cause of substantial segmental or subsegmental mosaicism.(36202482)
  • PAH (pulmonary artery hypertension, aka group 1 pulmonary hypertension) – Mosaic pattern more often involves small scattered areas of low attenuation within lobules, and/or adjacent to pulmonary arteries.(26274445)
• Any etiology of pulmonary hypertension can cause mosaic perfusion. However, pulmonary hypertension due to cardiac (group 2) or pulmonary disease (group 3) is less likely to cause this.(26274445)

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special case: ground-glass opacification with lobular areas of spared lung

• This represents a subgroup of mosaic attenuation due to ground-glass opacification (the full differential diagnosis of which is listed above: 📖).
• If encountered, this may suggest the following disorders:
  • DAD (diffuse alveolar damage).
  • OP (organizing pneumonia).
  • Pneumocystis.

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three-density sign (headcheese sign)

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definition

• Combination of three features, with sharp borders between different areas:
  • (a) Lobular ground-glass opacities (GGO).
  • (b) Normal lung.
  • (c) Areas of reduced lung attenuation due to hyperinflation.
• This typically reflects a process that causes both air trapping and also patchy ground-glass opacification.

causes

• Subacute HP (hypersensitivity pneumonia) – the classic etiology.
• RB-ILD (respiratory bronchiolitis interstitial lung disease).
• Sarcoidosis.
• Bronchopneumonia (e.g., mycoplasma).
• DIP (desquamative interstitial pneumonitis).
• Two distinct processes: one causes mosaic GGO while the other causes small airway obstruction (e.g., diffuse alveolar hemorrhage in the context of asthma).(24361976) 

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non-centrilobular GGO nodules

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This is uncommonly encountered. The differential may include the following entities:

• Malignant or hyperplastic processes (especially if persistent).
  • Adenocarcinoma in situ.
  • Minimally invasive adenocarcinoma.
• OP (organizing pneumonia.
• Metastatic pulmonary calcification.
• Focal interstitial fibrosis.
• Focal inflammation.
• MMPH (multifocal micronodular pneumocyte hyperplasia) in the context of tuberous sclerosis.(24791617)

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questions & discussion

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