Mosaic Attenuation

Definition:

• A CT pattern characterized by a heterogeneous appearance of lung attenuation, presenting as alternating regions of abnormally low and relatively normal or increased lung density.
• This pattern can result from small airways disease, pulmonary vascular disease, or infiltrative parenchymal disease.

Comment:

• When mosaic attenuation is caused by small airways disease, as in follicular bronchiolitis, the hypoattenuated areas correspond to lobules with air trapping and reflex vasoconstriction, leading to decreased perfusion.
• Its presence, especially in a former smoker with RA, strongly suggests small airway obstruction and is a common finding in RA-associated bronchiolitis.

Citation:

• Hansell, D. M.
• Radiology
• 2008.

Definition:

• These are pulmonary opacities that are typically 1-4 mm in diameter and located within the center of the secondary pulmonary lobules.
• They are characteristically separated from the pleural surface and interlobular septa by a few millimeters of normal-appearing lung parenchyma.
• They represent pathologies centered on the terminal bronchioles and associated peribronchiolar alveoli.

Comment:

• In the context of chronic rheumatoid arthritis (RA) and follicular bronchiolitis (FB), centrilobular nodules typically represent hyperplasia of bronchiole-associated lymphoid tissue (BALT) or inflammatory cellular infiltrates surrounding small airways.
• These findings are highly suggestive of inflammatory small airways disease, which is a known pulmonary manifestation of RA.

Citation:

• Kinney, P.
• Respiratory Medicine Case Reports
• 2018.

• The abnormal retention of gas within the lung parenchyma distal to an airway obstruction during exhalation.
• On expiratory CT, it manifests as areas of lung parenchyma that exhibit less than the normal increase in attenuation and/or lack of volume reduction compared to normal lung.

Comment:

• Air trapping is a direct consequence of small airway narrowing or obstruction, which is characteristic of inflammatory bronchiolitis like follicular bronchiolitis.
• In patients with rheumatoid arthritis, it is frequently observed in obliterative bronchiolitis, a severe form of small airways disease, and can be accentuated by surrounding normal lung or ground-glass opacities.

Citation:

• Tan, R.
• American Journal of Roentgenology
• 2006.

• An area of hazy increased lung attenuation on CT where the underlying bronchial and vascular markings remain visible.
• It indicates partial filling of airspaces, interstitial thickening, or increased capillary blood volume, rather than complete consolidation.

Comment:

• In the context of follicular bronchiolitis and rheumatoid arthritis, GGO may represent active inflammation, cellular infiltrates, or edema within the alveolar walls or airspaces, often adjacent to affected bronchioles.
• It is a non-specific finding but can be seen in various interstitial lung diseases associated with RA.

Citation:

• Wittram, C.
• American Journal of Roentgenology
• 2003.

• Abnormally increased thickness of the bronchial walls, which can be diffuse or localized on CT imaging.
• It is a non-specific sign that reflects chronic inflammation, edema, or hypertrophy of the bronchial wall components.

Comment:

• In follicular bronchiolitis, bronchial wall thickening results from the inflammatory process and lymphoid hyperplasia occurring in and around the small airways, contributing to luminal narrowing.
• This finding is consistent with chronic airways inflammation, a known feature of RA-associated lung disease, particularly in former smokers.

Citation:

• Grenier, P.
• Radiographics
• 1998.

• Thickening of the interlobular septa, which are thin connective tissue structures that define the boundaries of secondary pulmonary lobules and contain pulmonary venules and lymphatics.
• This thickening can be characterized as smooth, nodular, or irregular.

Comment:

• While not a primary feature of pure bronchiolitis, interlobular septal thickening in a patient with RA and follicular bronchiolitis may indicate coexisting interstitial lung disease, lymphatic congestion, or early fibrotic changes.
• The presence of irregular septal thickening often suggests interstitial fibrosis, which is a recognized complication of RA.

Citation:

• Akira, M.
• Journal of Computer Assisted Tomography
• 1998.

• Mosaic attenuation is a CT finding characterized by a patchwork pattern of regions with differing lung densities, appearing like inlaid tiles.
• It is a nonspecific sign with a broad differential diagnosis that falls into three main categories: small airway disease, occlusive vascular disease, and infiltrative parenchymal disease.
• The key to diagnosis is determining whether the darker (lucent) areas or the brighter (denser) areas are abnormal, which is often clarified with expiratory CT scans to assess for air trapping.

• FB is most often secondary to an underlying systemic disease.
• Connective Tissue Diseases: The most common causes are autoimmune conditions, particularly rheumatoid arthritis (RA) and Sjögren’s syndrome.
• Immunodeficiency Disorders: It can be associated with both congenital and acquired immunodeficiencies, such as Common Variable Immunodeficiency (CVID) and AIDS.
• Infections: Chronic or recurrent infections can also trigger FB.
• Idiopathic: In rare cases, no underlying cause is found, and it is termed primary or idiopathic follicular bronchiolitis.

• The disease is believed to result from chronic antigenic stimulation of the immune system within the lungs.
• This stimulation prompts a reactive, polyclonal hyperplasia of the lymphoid tissue (BALT) that naturally exists along the airways.
• The resulting lymphoid follicles grow and physically compress the bronchiolar lumen, leading to narrowing and obstruction.
• This obstruction is a key mechanism that leads to air trapping and other downstream effects.

• The primary structural change is the narrowing and obstruction of the small airways (bronchioles) due to peribronchiolar lymphoid follicles.
• Chronic inflammation leads to the infiltration of inflammatory cells into the bronchiolar walls.
• In some cases, this can lead to bronchial dilatation (bronchiectasis) secondary to the obstruction.
• Advanced or persistent inflammation may result in secondary fibrosis (scarring) and remodeling of the small airways.

• The narrowing of airways leads to airflow limitation and an obstructive ventilatory defect.
• Air can be inhaled but becomes trapped distal to the obstruction, a phenomenon known as “air trapping.”.
• This process impairs efficient gas exchange in the affected lung regions.
• Clinically, this manifests as progressive shortness of breath (dyspnea), especially on exertion, and chronic cough.

• Mosaic Attenuation: The Diagnostic Epicenter
  • Mosaic attenuation refers to a patchwork of differing lung densities on CT. It is a nonspecific finding with a broad differential diagnosis, making the analysis of the pattern crucial. The key is to determine whether the darker (lucent) or brighter (dense) areas are abnormal.
  • 1. Small Airway Disease (e.g., Follicular Bronchiolitis): This is the most common cause. The mosaic pattern arises from air trapping due to bronchiolar obstruction.
    • The lucent (darker) areas are abnormal, representing trapped air.
    • This leads to reflex hypoxic vasoconstriction, making vessels within the lucent areas appear smaller.
    • The denser (brighter) areas are normal lung, which may be relatively hyperperfused.
    • Expiratory CT is the key diagnostic tool: it accentuates the pattern, as the lucent, air-trapped areas fail to increase in density.
  • 2. Occlusive Vascular Disease (e.g., CTEPH): Here, the mosaic pattern is caused by differences in blood flow.
    • The lucent (darker) areas are also abnormal, representing regions of decreased blood flow (oligemia).
    • Vessels within the lucent areas are smaller, while vessels in the denser, normally perfused areas may be enlarged.
    • Unlike in airway disease, significant air trapping is typically absent on expiratory scans.
  • 3. Parenchymal/Infiltrative Disease: In this category, the abnormality is ground-glass opacity.
    • The denser (brighter) areas are abnormal, representing filling of the airspaces (e.g., with fluid, cells) or thickening of the interstitium.
    • The lucent areas represent the normal, unaffected lung.
• Clues Pointing to Follicular Bronchiolitis:
  • In the context of mosaic attenuation, the presence of diffuse centrilobular nodules (1-3 mm) is the hallmark finding that strongly suggests a cellular bronchiolitis like follicular bronchiolitis. These nodules correspond pathologically to the hyperplastic lymphoid follicles obstructing the airways.
  • Tree-in-bud opacities may also be present, indicating impacted bronchioles.
• Important Differential Diagnoses for Mosaic Attenuation:
  • Constrictive (Obliterative) Bronchiolitis: Also a small airway disease common in RA, it presents with mosaic attenuation and air trapping. However, it is a fibrotic process and typically lacks the prominent centrilobular nodules seen in follicular bronchiolitis.
  • Hypersensitivity Pneumonitis (HP): A classic cause of mosaic attenuation with air trapping. It can be distinguished by ill-defined ground-glass centrilobular nodules and the highly specific “headcheese sign,” a mixture of three densities (normal, low, and high attenuation).
  • Chronic Thromboembolic Pulmonary Hypertension (CTEPH): This vascular disease causes a mosaic perfusion pattern. It is distinguished by the lack of significant air trapping and the presence of direct vascular signs like intravascular webs, bands, or abrupt vessel cutoffs.

• There are no specific lab tests that diagnose follicular bronchiolitis itself. The diagnosis is histopathological, requiring a lung biopsy.
• Laboratory tests are essential to investigate for underlying causes.
• For suspected rheumatoid arthritis, tests include Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (anti-CCP).
• For suspected immunodeficiency, immunoglobulin levels (e.g., IgG, IgM) may be checked.

• The mainstay of treatment is managing the underlying associated condition.
• For cases associated with rheumatoid arthritis, immunosuppressive therapy with corticosteroids or other disease-modifying antirheumatic drugs (DMARDs) is used.
• For immunodeficiency-related cases, immunoglobulin replacement therapy may be indicated.
• Some cases have shown response to macrolide antibiotics like azithromycin, which have anti-inflammatory properties.

• The overall prognosis for follicular bronchiolitis is generally considered good.
• The outcome largely depends on the nature and successful management of the underlying or associated disease.
• In patients with immunodeficiency, the disease may be more progressive.

• This describes the pathophysiology of ground-glass opacity, which would appear as the denser, not the darker, part of a mosaic pattern.

• This is the correct mechanism for mosaic attenuation in small airway disease. Obstruction of the small airways causes air to be trapped during expiration.
• The body responds to the poor ventilation (hypoxia) in these trapped areas by constricting the blood vessels, shunting blood to better-ventilated lung. This combination of trapped, hypoventilated air and reduced blood flow makes these regions appear darker (hypoattenuated) on CT.
• [Arakawa H, Radiology, 1998]

• This describes reticulation, a finding in fibrotic lung diseases, not the primary cause of hypoattenuated mosaic patterns.

• This is the mechanism for mosaic attenuation in vascular diseases like CTEPH, not primary airway diseases. While it causes hypoattenuation, the root cause is vascular, not airway obstruction.

• This confuses the etiologies with the mechanism of the imaging sign. Follicular bronchiolitis is often autoimmune or idiopathic, not purely infectious.

• This incorrectly describes the pathophysiology for both conditions. Neither is primarily caused by alveolar filling or interstitial fibrosis as the source of mosaicism.

• This correctly differentiates the two root causes. In CTEPH, organized thrombi block pulmonary arteries, leading to reduced blood flow (oligemia) and hypoattenuation in the affected segments.
• In follicular bronchiolitis, inflammation obstructs the small airways, causing air trapping, with secondary (reflex) changes in perfusion.
• [Worthy SA, Radiology, 1997]

• This is incorrect. CTEPH does not cause significant air trapping because the airways are patent; the problem lies within the vessels.

• UIP is a fibrotic pattern characterized by basal, peripheral reticulation and honeycombing, not primarily mosaic attenuation and air trapping.

• Both follicular and constrictive bronchiolitis are small airway diseases common in RA that cause mosaic attenuation and air trapping.
• The key differentiator is that follicular bronchiolitis is a *proliferative* or *cellular* process, typically presenting with centrilobular nodules.
• Constrictive bronchiolitis is a *fibrotic* process where inflammation is minimal, and thus nodules are typically absent or scant, making mosaic attenuation the dominant finding.
• [Pipavath SJ, AJR, 2005]

• While sarcoidosis can cause mosaic patterns, its classic presentation is perilymphatic nodules along the bronchovascular bundles, septa, and pleura.

• Organizing pneumonia typically presents as consolidation or ground-glass opacities, often with a peripheral or peribronchial distribution (e.g., the “reverse halo sign”).

• PET/CT assesses metabolic activity and is not used to evaluate the functional mechanics of air trapping.

• Prone positioning is useful to differentiate dependent atelectasis (which resolves) from true ground-glass opacity, but it does not evaluate for air trapping.

• Contrast is essential for evaluating vascular causes (like CTEPH) but does not directly confirm or rule out air trapping. The primary question of air trapping must be answered first.

• This is the definitive, non-invasive method to differentiate mosaic attenuation caused by small airway disease from other causes.
• On expiration, normal lung increases in density, while areas of air trapping remain lucent and fail to decrease in volume. This accentuates the mosaic pattern and confirms airway obstruction as the cause.
• [Arakawa H, Radiology, 1998]

• This is the hallmark of Usual Interstitial Pneumonia (UIP) / Idiopathic Pulmonary Fibrosis (IPF), a pattern of advanced fibrosis.

• This is the classic combination for follicular bronchiolitis. The mosaic attenuation arises from air trapping, and the centrilobular nodules represent the histologic finding of peribronchiolar lymphoid follicle hyperplasia.
• [Howling SJ, Radiology, 1999]

• These are characteristic findings of chronic thromboembolic pulmonary hypertension (CTEPH), a vascular cause of mosaic attenuation.

• Crazy-paving (septal thickening superimposed on ground-glass opacity) is seen in conditions like pulmonary alveolar proteinosis, ARDS, and Pneumocystis pneumonia.

• Follicular bronchiolitis typically causes a two-density pattern: abnormal low attenuation (air trapping) and normal attenuation lung. Prominent ground-glass is less characteristic.

• The “headcheese” or “three-density” sign is considered highly specific for hypersensitivity pneumonitis (HP). It reflects the mixed pathology of HP: small airway obstruction causing air trapping (low density), active inflammation or fine fibrosis causing ground-glass opacity (high density), and interspersed areas of unaffected normal lung.
• [Silva CI, RadioGraphics, 2008]

• CTEPH is a vascular disease that causes a mosaic perfusion pattern (low and normal density) but does not typically involve ground-glass opacity as a primary feature.

• IPF is characterized by a fibrotic UIP pattern, not a three-density mosaic sign.

• Tree-in-bud opacities represent impacted, inflamed bronchioles and are a sign of small airway disease, not vascular disease.

• This is the hallmark of air trapping, confirming a small airway disease as the cause of the mosaic pattern.

• This is the key to identifying a vascular cause. The lucent areas are dark because of oligemia (less blood), so the vessels are small or absent. Blood is shunted to the normally perfused (denser) areas, making their vessels appear larger. The absence of significant air trapping on expiratory scans points away from an airway cause.
• [Castaner E, RadioGraphics, 2007]

• Bronchial wall thickening is a direct sign of airway inflammation or fibrosis and points towards an airway-centric cause.