Residency · Residency · Diagnostic Radiology

Diffuse Lung Disease: HRCT Pattern Approach

HRCT Technique

Acquisition Parameters

High-resolution CT of the lungs uses thin-section imaging at 1 to 1.5 mm slice thickness, reconstructed with a high spatial frequency (sharp or bone) algorithm to maximize parenchymal detail. Modern MDCT scanners acquire volumetric data that is then reconstructed at these thin sections. Both inspiratory and expiratory acquisitions should be obtained: expiratory images are essential for detecting air trapping, which manifests as mosaic attenuation where certain lobules fail to increase in density on expiration. Prone imaging is valuable for differentiating dependent atelectasis (which resolves when the patient lies prone) from true posterior lung disease (which persists). Intravenous contrast is not needed for most interstitial lung disease evaluations.

Secondary Pulmonary Lobule -- The Fundamental Unit

The secondary pulmonary lobule is the smallest structural unit of the lung bounded by connective tissue septa, and understanding its anatomy is the key to interpreting HRCT findings. Each lobule has three components: the centrilobular core, containing a pulmonary arteriole and bronchiole (normally invisible on HRCT); the interlobular septa, containing lymphatics and pulmonary veins (normally barely visible); and the lobular parenchyma, consisting of alveoli and capillaries. The location of disease within the lobule directly guides the differential diagnosis. Centrilobular disease suggests hypersensitivity pneumonitis or respiratory bronchiolitis. Perilobular or septal disease suggests lymphangitic carcinomatosis or pulmonary edema. Random distribution suggests miliary tuberculosis or hematogenous metastases.

The Four Pattern Approach

Pattern 1: Reticular (Linear) Pattern

The reticular pattern consists of a network of lines reflecting thickening of the lung interstitium. Findings include interlobular septal thickening, intralobular lines, honeycombing, and traction bronchiectasis. Honeycombing, defined as clustered thick-walled cystic spaces of 3 to 10 mm sharing walls in a subpleural location, represents end-stage fibrosis and architectural destruction. Traction bronchiectasis, the irregular dilatation of bronchi within fibrotic lung, is another reliable indicator of established fibrosis.

The key diseases producing a reticular pattern include usual interstitial pneumonia (UIP) and idiopathic pulmonary fibrosis (IPF), which show basal and peripheral predominant honeycombing with traction bronchiectasis; non-specific interstitial pneumonia (NSIP), characterized by ground-glass opacity with fine reticulation and relative subpleural sparing; asbestosis, which produces bilateral lower lobe fibrosis with associated pleural plaques; and connective tissue disease-related interstitial lung disease, which may show either a UIP or NSIP pattern.

Pattern 2: Nodular Pattern

The distribution of nodules within the secondary pulmonary lobule is the critical diagnostic feature. Perilymphatic nodules concentrate along interlobular septa, subpleural regions, and bronchovascular bundles. This distribution is characteristic of sarcoidosis (the most common cause), lymphangitic carcinomatosis, and the pneumoconioses (silicosis and coal workers' pneumoconiosis). Centrilobular nodules cluster in the center of the secondary pulmonary lobule and spare the pleural surface, distinguishing them from perilymphatic nodules. This pattern is seen in hypersensitivity pneumonitis (where the nodules are ground-glass in density), respiratory bronchiolitis (in smokers), and infectious bronchiolitis including endobronchial spread of tuberculosis. Random nodules are distributed without respect to lobular structures and suggest miliary tuberculosis, miliary fungal infection, or hematogenous metastases (which often show lower lobe predominance due to greater blood flow).

The tree-in-bud pattern deserves special mention: centrilobular branching linear and nodular opacities resembling a budding tree that represent mucus or pus filling centrilobular bronchioles. This pattern is characteristic of infectious bronchiolitis, endobronchial spread of tuberculosis, cystic fibrosis, and aspiration.

Pattern 3: High-Attenuation (Increased Density) Pattern

Ground-glass opacity (GGO) is a hazy increase in attenuation that does not obscure underlying structures. It is nonspecific, representing partial filling of alveoli, interstitial thickening, or increased capillary blood volume. Acute causes include pneumonia, pulmonary hemorrhage, edema, and acute eosinophilic pneumonia. Chronic causes include hypersensitivity pneumonitis, NSIP, and desquamative interstitial pneumonia (DIP). Consolidation is denser opacification that does obscure underlying vessels and bronchi, and is characteristic of organizing pneumonia (COP), chronic eosinophilic pneumonia, pulmonary alveolar proteinosis, and lepidic-pattern adenocarcinoma. The crazy paving pattern, where GGO is superimposed with interlobular septal thickening, has a classic association with pulmonary alveolar proteinosis but is also seen in PJP, ARDS, pulmonary hemorrhage, and adenocarcinoma.

Pattern 4: Low-Attenuation (Decreased Density/Cystic) Pattern

Lung cysts are well-defined, thin-walled (less than 2 mm), round air-containing spaces. Lymphangioleiomyomatosis (LAM) produces diffuse, uniform, round thin-walled cysts throughout both lungs, typically in women of reproductive age, and is associated with tuberous sclerosis complex. Langerhans cell histiocytosis (LCH) produces irregular, bizarre-shaped cysts and nodules with upper and mid-lung predominance, sparing the costophrenic angles, and occurs in smokers. Lymphocytic interstitial pneumonia (LIP) produces scattered thin-walled cysts with ground-glass opacity and is associated with Sjogren syndrome and HIV. Birt-Hogg-Dube syndrome produces basilar and medial cysts and is associated with renal tumors and skin fibrofolliculomas.

Emphysema causes parenchymal destruction without a visible wall. Centrilobular emphysema is upper lobe predominant and smoking-related. Panlobular emphysema is lower lobe predominant and associated with alpha-1 antitrypsin deficiency. Paraseptal emphysema is subpleural and associated with spontaneous pneumothorax in young adults.

Mosaic attenuation and air trapping manifest as geographic areas of differing lung density. On expiratory images, hypolucent areas (regions that fail to increase in density) represent air trapping from small airway disease. This finding is characteristic of hypersensitivity pneumonitis, constrictive bronchiolitis, and asthma.

HRCT Pattern Summary

Key Disease Entities in Detail

Usual Interstitial Pneumonia (UIP) / Idiopathic Pulmonary Fibrosis (IPF)

The definite UIP pattern on HRCT consists of subpleural, basal predominant honeycombing with or without traction bronchiectasis, in the absence of features inconsistent with UIP. When this pattern is present in the appropriate clinical context, surgical lung biopsy is not required for a diagnosis of IPF, sparing the patient a morbid procedure. The probable UIP pattern shows subpleural, basal predominant reticulation with traction bronchiectasis but without honeycombing, and may or may not require biopsy depending on multidisciplinary discussion. Features that are inconsistent with UIP include upper or mid-lung predominance, peribronchovascular predominance, extensive ground-glass opacity out of proportion to reticulation, profuse micronodules, air trapping on expiratory images (which suggests hypersensitivity pneumonitis), and consolidation.

Non-Specific Interstitial Pneumonia (NSIP)

In NSIP, ground-glass opacity is the predominant finding, unlike UIP where reticulation dominates. Subpleural sparing, where a thin rim of normal-appearing lung is seen between the GGO and the pleural surface, is relatively characteristic. The pattern is basal predominant and symmetric. Two subtypes are recognized: cellular NSIP, consisting mostly of GGO and carrying a better prognosis, and fibrotic NSIP, which shows GGO with reticulation and traction bronchiectasis. NSIP has a strong association with connective tissue diseases such as scleroderma, polymyositis/dermatomyositis, and rheumatoid arthritis, and generally carries a better prognosis than UIP/IPF.

Hypersensitivity Pneumonitis (HP)

Acute and subacute HP present with centrilobular ground-glass nodules, ground-glass opacity, and air trapping on expiratory images, with upper and mid-lung predominance or diffuse distribution. Chronic (fibrotic) HP can mimic UIP, but upper and mid-lung predominance of fibrosis and the presence of air trapping help distinguish it from IPF. The exposure history is critical and should always be sought (birds, mold, feather duvets, hot tubs, farming exposures). The three-density sign, a combination of GGO, normal lung, and mosaic attenuation visible on the same HRCT section, is suggestive of HP.

Sarcoidosis

Sarcoidosis produces perilymphatic nodules distributed along bronchovascular bundles, interlobular septa, and subpleural surfaces, with upper and mid-lung predominance. Bilateral symmetric hilar and mediastinal lymphadenopathy is characteristic, described as the 1-2-3 sign or Garland triad (bilateral hilar plus right paratracheal nodes). The galaxy sign describes a large nodule surrounded by smaller satellite nodules. Fibrotic sarcoidosis shows upper lobe fibrosis, traction bronchiectasis, and posterior displacement of the main and upper lobe bronchi. The disease is staged radiographically:

Lymphangitic Carcinomatosis

Lymphangitic carcinomatosis produces smooth or nodular interlobular septal thickening, which is often unilateral or asymmetric (unlike the bilateral symmetric septal thickening of pulmonary edema). Bronchovascular bundles are thickened, but lung architecture is preserved without distortion. The disease may be unilateral or bilateral and is often accompanied by pleural effusion and lymphadenopathy. Common primary tumors include breast, lung, stomach, pancreas, prostate, and thyroid carcinomas.

<image>A four-panel HRCT diagram illustrating the four major diffuse lung disease patterns. Panel 1 (Reticular): subpleural honeycombing with stacked thick-walled cysts in the lung bases and traction bronchiectasis, labeled as UIP pattern. Panel 2 (Nodular): perilymphatic nodules distributed along interlobular septa, fissures, and bronchovascular bundles with bilateral hilar lymphadenopathy, labeled as sarcoidosis. Panel 3 (High-attenuation): bilateral ground-glass opacity with superimposed interlobular septal thickening creating the crazy-paving pattern, labeled as pulmonary alveolar proteinosis. Panel 4 (Low-attenuation/Cystic): multiple diffuse, round, thin-walled cysts of varying sizes uniformly distributed throughout both lungs with no nodules, labeled as lymphangioleiomyomatosis.</image>

<image>A diagram of the secondary pulmonary lobule on HRCT showing the anatomic compartments where different diseases localize. A single secondary pulmonary lobule is drawn as a polygonal structure bounded by interlobular septa. The centrilobular core contains the pulmonary arteriole and bronchiole (center dot). Three distributions of nodules are overlaid in different colors: (1) perilymphatic nodules (blue dots) along the septa and subpleural surface, (2) centrilobular nodules (red dots) clustered around the centrilobular core but sparing the pleural surface and septa, and (3) random nodules (green dots) scattered uniformly without lobular preference. A legend identifies each distribution and its top differential diagnoses.</image>

<image>A side-by-side comparison of UIP versus NSIP patterns on coronal HRCT reconstruction. The UIP panel shows basal and peripheral predominant honeycombing (clusters of thick-walled cysts) with traction bronchiectasis and minimal ground-glass opacity. The NSIP panel shows basal predominant ground-glass opacity with fine reticulation, subpleural sparing (a thin rim of normal-appearing lung between the GGO and the pleural surface), and traction bronchiectasis but no honeycombing. Key distinguishing features are listed in a comparison table below.</image>

Clinical Pearls

The definite UIP pattern on HRCT (subpleural basal honeycombing) is sufficiently specific that surgical lung biopsy is unnecessary for an IPF diagnosis in the appropriate clinical setting, sparing the patient a morbid procedure. If fibrosis is upper or mid-lung predominant rather than basal predominant, chronic hypersensitivity pneumonitis, sarcoidosis, or silicosis should be considered rather than UIP/IPF. Subpleural sparing is a helpful sign that favors NSIP over UIP. Perilymphatic nodules along fissures, septa, and bronchovascular bundles strongly suggest either sarcoidosis or lymphangitic carcinomatosis; the clinical history and symmetry of disease help differentiate them. The three-density sign (GGO, normal lung, and air trapping on a single slice) is suggestive of hypersensitivity pneumonitis. Expiratory images should always be obtained when evaluating suspected diffuse lung disease, because air trapping is an important finding in HP, constrictive bronchiolitis, and asthma that is invisible on inspiratory images alone. Prone imaging eliminates dependent atelectasis, which is particularly important when evaluating for basal fibrotic disease.

References

• Travis WD, et al. "An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias." American Journal of Respiratory and Critical Care Medicine, 2013
• Raghu G, et al. "Diagnosis of Idiopathic Pulmonary Fibrosis: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline." American Journal of Respiratory and Critical Care Medicine, 2018
• Lynch DA, et al. "Diagnostic Criteria for Idiopathic Pulmonary Fibrosis: A Fleischner Society White Paper." Lancet Respiratory Medicine, 2018
• Webb WR, Muller NL, Naidich DP. High-Resolution CT of the Lung, 5th ed. Wolters Kluwer, 2015
• Defined Patterns Approach: Miller WT, et al. "Hypersensitivity Pneumonitis and Its Mimics." RadioGraphics, 2019

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