000 Tree-in-Bud sign

The Tree-in-Bud (TIB) sign is a radiological finding observed on high-resolution CT (HRCT) of the chest. It represents centrilobular branching opacities with a nodular appearance, resembling budding tree branches. This sign typically indicates a pathological process within the small airways, such as bronchioles, and is often associated with infectious or inflammatory diseases.

Tree in Bud
Ashley Davidoff
TheCommonVein.net

Anatomical Basis
The Small Airways

Alveolar Ducts and Alveolar Sacs

Small Airways
The diagram allows us to understand the the components and the position of the small airways starting in (a) which is a secondary lobule that is fed by a lobular bronchiole(lb) which enters into the secondary lobule and divides into terminal bronchioles (tb) which is the distal part of the conducting airways, and at a diameter of Ashley Davidoff MD TheCommonVein.net lungs-0744

Overview of the Anatomy of the Lungs Large Airways and Small Airways
This image shows the division of the airways in the lungs classified as large airways and small airways.
A large airway is considered any airway larger than 2mm, and therefore includes all the airways involved with transport of air except for the terminal bronchiole. Included as seen in image a, are the trachea, mainstem bronchi, lobar bronchi segmental and subsegmental airways and the 3 subsequent divisions of subsegmental bronchi and bronchioles till the last transporting airway – the respiratory bronchiole which is usually about 2mm and is considered a small airway Image (a) shows the airways starting in the trachea and continuing to the mainstem bronchi, lobar bronchi, segmental bronchi, and subsegmental bronchi.
Image b shows the structures that make up the small airways starting with the terminal bronchiole (tb) followed by the respiratory bronchiole (rb) alveolar duct, (ad) and alveolar sacs (as)
Image (c) shows the histologic makeup of the large airways that include a pseudostratified ciliated columnar epithelium with mucus secreting goblet cells a muscular layer (red) and a prominent cartilage layer (white) In the larger bronchioles (d) the epithelium remains as a pseudostratified, ciliated, columnar epithelium with prominent muscular layer (red). The columnar epithelium transitions to a stratified ciliated cuboidal epithelium by the terminal bronchiole s (f) both still with a muscular layer. The respiratory epithelium transitions from a cuboidal epithelium to a squamous epithelium (f) with alveoli and type I and II pneumocytes starting to branch (g)
Ashley Davidoff MD TheCommonVein.net lungs-0740nL

Pathophysiology

The Tree-in-Bud pattern results from:

Endobronchial spread of material:
- Mucus, pus, or other substances accumulate within the bronchioles.
Peribronchiolar inflammation:
- Thickening of the walls of small airways and their surrounding structures.
Distal airway obstruction:
- Often due to infection or inflammatory debris.

Radiological Features

Appearance:
- Centrilobular, branching opacities resembling a tree with buds on its branches.
- Composed of:
  - Linear structures (the “branches”): Reflect dilated or inflamed bronchioles.
  - Small nodules (the “buds”): Represent impacted bronchioles or peribronchiolar inflammation.
Location:
- Centrilobular distribution: Centered within secondary pulmonary lobules.
- Predominantly affects the lower lobes but may involve other areas depending on the underlying disease.
Associated Findings:
- Ground-glass opacities.
- Consolidation or airspace filling in advanced stages.

Common Causes

Infectious Causes:
- Bacterial:
  - Tuberculosis (particularly in active or post-primary stages).
  - Nontuberculous mycobacterial infections (e.g., Mycobacterium avium complex).
- Fungal:
  - Aspergillosis.
- Viral:
  - Viral pneumonias can rarely mimic this appearance.
- Parasitic:
  - Parasitic infections like ascariasis or strongyloidiasis can rarely cause TIB.
Inflammatory Conditions:
- Bronchiectasis:
  - Associated with chronic airway inflammation and infections.
- Cystic Fibrosis:
  - TIB is common due to recurrent infections.
- Hypersensitivity Pneumonitis:
  - Inflammatory reaction causing small airway involvement.
Aspiration:
- Recurrent aspiration leading to chronic bronchiolar inflammation.
Diffuse Panbronchiolitis:
- Seen primarily in East Asian populations, associated with chronic infection.
Connective Tissue Diseases:
- Rheumatoid arthritis-associated bronchiolitis.

Reactivation TB with Transbronchial Spread

CT –Reactivation TB – Left Upper Lobe
CT scan in the axial plane of the left upper lobe of a 28-year-old immigrant with cough shows a focal subsegmental consolidation with focal cavitation subtended by a thick-walled subsegmental airway. There are extensive tree in bud changes indicating transbronchial spread. Lab tests confirmed a diagnosis of TB and the patient was treated with RISE, a 4-month treatment regimen of rifapentine-moxifloxacin for mycobacterium tuberculosis.
Ashley Davidoff MD TheCommonVein.net 255Lu 136075c

CT Active TB Transbronchial Spread with Extensive Tree in Bud Changes
39-year-old immigrant Vietnamese male presents night sweats fever and cough. CT in the axial plane through the mid chest shows innumerable micronodules resulting from transbronchial spread with resultant tree in bud pattern.
Ashley Davidoff MD TheCommonvein.net 135788c 006Lu

Mycobacterium Avium Complex (MAC)

MAI with tree in bud centrilobular nodules cavitating nodules bronchiolectasis
Ashley Davidoff MD TheCommonVein.net

Aspergillus

Bronchopneumonic Form

Small Airway Disease Ground Glass Micronodules and Probable Tree in Bud Sign
Axial Ct scan focused on the right lung base shows ground glass micronodules revealing a combination of centrilobular nodules and tree in bud sign indicating small airway disease
Diagnosis Aspergillus Infection
Ashley Davidoff TheCommonVein.net 219Lu-015

ABPA

Bronchiectasis

HP

CT Hypersensitivity Pneumonitis 7 years prior
CT in the axial (upper)and coronal plane (lower panels) show most prominent changes in the anterior segment of the left upper lobe
The findings are characterized and best appreciated in the upper right panel by evidence of small airway disease including tree in bud and centrilobular nodules most prominent in the periphery
Ashley Davidoff MD TheCommonVein.net 135835

CT in the axial (upper)and coronal plane (lower panels) show most prominent changes in the anterior segment of the left upper lobe
The findings are characterized and best appreciated in the upper right panel by evidence of small airway disease including tree in bud and centrilobular nodules most prominent in the periphery
Ashley Davidoff MD TheCommonVein.net 135835

Aspiration

Aspiration Pneumonia and Tree in Bud Changes
43 year female found unconscious CT showed finding in the posterior segment of the right upper lobe and consolidation and tree in bud changes reflecting acute aspiration pneumonia
Ashley Davidoff MD TheCommonVein.net consolidation pneumonia aspiration-43f004-ct-tree-in-bud

Differential Diagnosis

Conditions that may mimic the tree-in-bud sign include:

Miliary Nodules:
- Random distribution, not branching.
Vascular Disease:
- Centrilobular vascular opacities (e.g., pulmonary hemorrhage).
Sarcoidosis:
- Perilymphatic distribution of nodules rather than centrilobular.

Clinical Significance

The Tree-in-Bud sign indicates a small airway disease, often with infectious or inflammatory pathology.
It is important to correlate the radiological findings with clinical symptoms (e.g., cough, fever, dyspnea) and laboratory tests (e.g., sputum culture, serology).

Imaging Modalities

High-Resolution CT (HRCT):
- Gold standard for identifying and characterizing the TIB sign.
Chest X-Ray:
- Often non-specific and may miss subtle airway pathology.

Tree in Beud in a Patient with Atypical TB MAI
Ashley Davidoff MD The CommonVein.net

Is a
- radiologic finding on chest CT
- Characterised by
  - small, peripheral nodules,
  - originating from a centrilobular location extending into
  - distal smaller airways as
  - soft tissue nodules
  - connected to
    - multiple contiguous,
    - linear branching opacities.
    - reminiscent of a tree in bud in the spring
- Representing
  - mucous plugging,
  - bronchial dilatation, and
  - wall thickening of bronchiolitis.
  - histopathological correlate
    - small airway plugging with
      - mucus,
      - pus, or
      - fluid, with
      - dilated intralobular bronchioles,
      - peribronchiolar inflammation, and
      - wall thickening.
Cause
- - commonly associated with
  - infectious etiologies
    - aspiration
    - endobronchial spread of Mycobacterium tuberculosis,
    - Pneumocystis jiroveci (Pneumocystis carinii) pneumonia
    - Also other infections
      - bacterial,
      - fungal,
      - viral, or
      - parasitic
    - invasive pulmonary aspergillosis.
      - various
        
        immunodeficiency states,
        
        congenital disorders (cystic fibrosis),
        
        malignancy (lymphoma),
        
        panbronchiolitis,

Respiratory bronchioles, alveolar sacs, and alveoli
This drawing shows about 3-4 respiratory bronchioles that serve to make a secondary lobule. Alveolar sacs and individual alveoli are also seen. The yellow border represents the visceral pleura on the surface.
Courtesy of: Ashley Davidoff, M.D.

Infection

small (2–4-mm) centrilobular nodules and
branching linear opacities of similar caliber
originating from a single stalk
- bronchial wall thickening with or without
- bronchiectasis.
Active TB
Postprimary active tuberculosis in a 34-year-old man with weight loss and a chronic cough. (a) High-resolution CT scan of the left lung shows a thick-walled cavity and multiple peripheral small nodules and branching linear structures (arrows). Note the thickening of the bronchial walls (arrowhead). (b) Photomicrograph (original magnification, ×400; hematoxylin-eosin stain) shows impacted caseous material (*) in small peripheral airways (arrow).
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005
TB
Post primary active tuberculosis in a 66-year-old woman with a chronic cough. High-resolution CT scans of the right lung show peripheral, poorly defined, small (2–4-mm-diameter) centrilobular nodules and branching linear opacities of similar caliber originating from a single stalk (the tree-in-bud pattern) in the lower lobe (arrow). These findings represent endobronchial spread of tuberculosis.
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

Postprimary active tuberculosis in a 66-year-old woman with a chronic cough. High-resolution CT scans of the right lung show peripheral, poorly defined, small (2–4-mm-diameter) centrilobular nodules and branching linear opacities of similar caliber originating from a single stalk (the tree-in-bud pattern) in the lower lobe (arrow). These findings represent endobronchial spread of tuberculosis.
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

Infection with M avium-intracellulare complex in a 44-year-old woman with malaise and a chronic cough. High-resolution CT scans of the right lung show multiple peripheral small nodules connected to branching linear opacities and a thick-walled cavity in the superior segment of the lower lobe. Note the thickening of the bronchial walls, bronchial dilatation, and mucus impaction. The diagnosis was confirmed with bronchoalveolar lavage.
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005
Aspergillus and Tree in Bud Sign

Tree in Bud Sign Bronchopulmonary Aspergillosis (ABPA)
CT scan through the chest shows medium sized bronchi, bronchioles and small airways impacted with fluid. This collage is presented to reveal tree in bud changes resulting from impaction in the smaller terminal bronchioles and respiratory units. The tree-in-bud pattern also results in small centrilobular nodules connected to multiple branching linear structures of similar caliber from a single stalk. Originally it was felt to result from endobronchial spread of Mycobacterium tuberculosis, but is is now recognized in diverse entities including peripheral airway diseases caused by infection (bacterial, fungal, viral, or parasitic), congenital disorders, idiopathic disorders (obliterative bronchiolitis, pan bronchiolitis), aspiration or inhalation of foreign substances, immunologic disorders, connective tissue disorders and peripheral pulmonary vascular diseases such as neoplastic pulmonary emboli.
In this case there are also dilated medium sized airways, impacted with soft tissue characteristic of the finger in glove sign and most likely due to allergic bronchopulmonary aspergillosis (ABPA)
Ashley Davidoff MD Ashley Davidoff MD TheCommonVein.net
47113c01

Invasive bronchiolar aspergillosis in a patient who underwent bone marrow transplantation. (a) High-resolution CT scan (lung window) shows peripheral branching structures (arrow) associated with focal areas of consolidation in the right lower lobe. (b) Corresponding photograph of the autopsy specimen shows multiple yellowish acinar nodules (arrows). (c) Photomicrograph (original magnification, ×250; periodic acid–Schiff stain) of a lung biopsy specimen shows complete destruction of the bronchiolar wall (arrowheads) by Aspergillus organisms (arrow).
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

Other Infections

Staphylococcus Aureus

S aureus bronchiolitis in a 32-year-old man with acquired immunodeficiency syndrome (AIDS). (a) High-resolution CT scan shows small peripheral centrilobular nodules and branching linear opacities, resulting in the tree-in-bud pattern. (b) Photomicrograph (original magnification, ×400; hematoxylin-eosin stain) shows inflammatory material composed of leukocytes filling the bronchiolar lumen (arrow).
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

Hemophilus Influenza

H influenzae pneumonia in a 49-year-old woman with breast cancer, fever, and a productive cough. High-resolution CT scan shows diffuse centrilobular nodules and branching linear opacities, resulting in the tree-in-bud pattern.
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

CMV

Cytomegalovirus pneumonia in a 51-year-old man with chronic myelogenous leukemia who underwent bone marrow transplantation. (a) Thin-section CT scan of the right lung shows centrilobular ground-glass opacities in addition to nodules and tree-in-bud opacities (arrow). (b) Photomicrograph (original magnification, ×400; hematoxylin-eosin stain) shows cytomegalic inclusion bodies in the lung tissue (arrows).
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

Respiratory Syncytial Virus

Tree in Bud Sign with Lymphadenopathy
87 year old male with history of cough and suspicion of aspiration shows barium aspiration into the proximal trachea (upper right) The scout view ( upper right) shows an infiltrate at the right base, Thickened airways in the right lower lobe (2nd row left ) is associated with a pneumonic infiltrate in the right lower lobe (lower right) consistent with aspiration. There are thickened airways to the lingula (3rd and 4th row) with magnified view showing tree in bud changes (right sided images 3rd and 4th row)
These findings likely relate to infection, often fungal or granulomatous
Ashley Davidoff MD Ashley Davidoff MD TheCommonVein.net

Inflammatory Diseases

Aspiration and Tree in Bud

Aspiration Pneumonia and Tree in Bud Sign
87 year old male with history of cough and suspicion of aspiration shows barium aspiration into the proximal trachea (upper right) The scout view ( upper right) shows an infiltrate at the right base, Thickened airways in the right lower lobe (2nd row left ) is associated with a pneumonic infiltrate in the right lower lobe (lower right) consistent with aspiration. There are thickened airways to the lingula (3rd and 4th row) with magnified view showing tree in bud changes (right sided images 3rd and 4th row)
All these finding likely relate to aspiration though lingula involvement is not usual
Ashley Davidoff MD Ashley Davidoff MD TheCommonVein.net

Diffuse aspiration bronchiolitis in a 61-year-old woman with achalasia who experienced recurrent aspiration of foreign particles. Thin-section CT scan shows multiple centrilobular areas of increased attenuation with a characteristic tree-in-bud appearance. Esophageal dilatation with an air-fluid level is also seen.
Rossi, SE et al Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview RadioGraphics Vol. 25, No. 3 2005

Asthma

Inhalation Bronchiolitis

Obliterative Bronchiolitis aka (bronchiolitis obliterans is also known and constrictive bronchiolitis) association to lung transplant and bone marrow transplant