Pathological basis of acute and chronic inflammation: imaging correlates

Overview

Inflammation is the biological response of vascularised tissue to harmful stimuli, including pathogens, damaged cells, toxic compounds, or radiation. A critical conceptual distinction underpins all of radiology's interaction with inflammatory disease: infection and inflammation are not synonymous. Infection is caused by microorganisms; inflammation is the host tissue response, arising from the Latin inflammare, "to ignite" or "set alight", which may occur in the presence or absence of an infectious agent. This distinction drives fundamental differences in imaging appearances, temporal evolution, and clinical management.

The inflammatory cascade is complex and multifactorial. It involves the vascular system, immune system, and cellular responses (including microglial activation as the primary component of the brain's innate immune response). The CNS functions as a unique microenvironment that responds differently from other organ systems to infiltrating immune cells; brain white matter is especially susceptible to inflammatory disease. Imaging reflects the consequences of these pathways, oedema, cellular infiltration, necrosis, fibrosis, and granuloma formation, rather than the underlying molecular events.

Pathological Basis of Acute Inflammation

Vascular Phase

Acute inflammation is initiated within seconds to minutes of tissue injury. The initial vascular response involves transient arteriolar vasoconstriction followed by sustained vasodilatation. Increased vascular permeability allows protein-rich exudate to leak into the interstitium, driven by endothelial cell contraction and direct endothelial injury. This produces:

• Oedema: accumulation of fluid in the extracellular space
• Cellular exudate: emigration of leucocytes (predominantly neutrophils in the acute phase) into tissue

Cellular Phase

Neutrophil recruitment follows a sequence of margination, rolling, adhesion, and transmigration. In tissues, neutrophils perform phagocytosis and release proteolytic enzymes and reactive oxygen species, destroying both the injurious agent and surrounding tissue. This is the substrate for suppuration (pus formation) and eventual abscess formation.

Pneumonia: The Prototypical Acute Pulmonary Inflammatory Response

Microorganisms enter the lung via three routes: tracheobronchial (inhalation/aspiration), pulmonary vasculature (haematogenous), or direct spread from mediastinum/chest wall/upper abdomen. Tracheobronchial infection produces three pathological and radiographic subtypes:

Important caveat: Radiographic pattern prediction of causative pathogen is notoriously unreliable in practice; viral and bacterial co-infection is common.

Outcomes of Acute Inflammation

Pathological Basis of Chronic Inflammation

Chronic inflammation arises when an acute inflammatory response fails to resolve, due to persistent infection, autoimmune activation, foreign body reaction, or unknown triggers. The cellular hallmark shifts from neutrophil-dominated to macrophage- and lymphocyte-dominated infiltration, often accompanied by plasma cells.

Key Pathological Features

• Macrophage activation: The central cellular actor. Activated macrophages can fuse to form multinucleated giant cells characteristic of granulomatous inflammation.
• Lymphocytic infiltration: Reflects ongoing adaptive immune activation; perivascular lymphocytic cuffing is a key histological marker.
• Granuloma formation: Aggregates of activated epithelioid macrophages, often with central necrosis (caseating) or without (non-caseating). Tuberculosis produces caseating granulomas; sarcoidosis produces non-caseating epithelioid granulomas.
• Fibrosis: Progressive replacement of inflamed tissue with collagen, driven by fibroblast activation via TGF-β and other mediators.
• Tissue destruction and remodelling: Concurrent cycles of injury and repair lead to architectural distortion, calcification, and contracture.
• Obliterative processes: Chronic bronchiolar inflammation and fibrosis can cause irreversible circumferential submucosal fibrosis → bronchiolar narrowing or obliteration (obliterative bronchiolitis), in the absence of intraluminal granulation tissue.

Granulomatous Inflammation, Special Category

Granulomatous inflammation is a subtype of chronic inflammation characterised by discrete collections of epithelioid macrophages. The major imaging-relevant causes:

Imaging Appearances: Acute vs Chronic Inflammation by Modality

Radiography and Fluoroscopy

Acute inflammation:

• Soft-tissue swelling, loss of fat planes
• Air-space consolidation in pneumonia (lobar/bronchopneumonia pattern with air bronchograms in bacterial pneumonia; perihilar patchy opacities in viral pneumonia)
• Periarticular soft-tissue swelling in septic arthritis
• Disc space narrowing and endplate erosion in early discitis

Chronic inflammation:

• Calcification (dystrophic): calcified lymph nodes in healed granulomatous disease; calcified granulomas in lung parenchyma; broncholithiasis (calcified endo/peribronchial node with associated obstruction)
• Sclerosis and bone remodelling in chronic osteomyelitis or healed tuberculous infection
• Gibbus deformity in spinal tuberculosis from chronic vertebral collapse (acute angulation on lateral view)
• Bronchiectasis as a sequela of obliterative bronchiolitis or recurrent infection
• Hyperinflation in obliterative bronchiolitis (air trapping; chest radiograph often normal or shows only subtle peripheral attenuation)

Computed Tomography

CT demonstrates inflammation through its effect on tissue density, enhancement pattern, and architectural change.

Acute inflammation:

• Oedema: Reduced attenuation in affected parenchyma
• Fat stranding: Increased attenuation of mesenteric or pericolonic fat due to exudate (diverticulitis, appendicitis, epiploic appendagitis, the latter showing a hyperattenuating rim sign around a fat-density lesion adjacent to the colon)
• Abscess: Rim-enhancing fluid collection, often with surrounding inflammatory stranding; thick, irregular walls with avid enhancement in pyogenic abscess
• Bowel wall thickening: Avidly enhancing mucosa with low-density submucosal oedema in acute Crohn's flare
• Lymphadenopathy: Reactive nodes with preserved fatty hilum; suppurative nodes may show central necrosis
• Vasculitis (acute): Circumferential wall thickening of large vessels with hyperattenuation on non-enhanced CT; active Takayasu arteritis produces circumferential aortic wall thickening with corresponding FDG uptake

Chronic inflammation:

• Fibrosis: Progressive soft-tissue density without oedema; reticular opacities in the lung
• Calcification: Calcified granulomas, calcified lymph nodes (healed TB/histoplasmosis), peritoneal calcification
• Periaortic fibrosis: Circumferential soft-tissue rind around the aorta in inflammatory aortitis or IgG4-related periaortitis; associated retroperitoneal fibrosis. The native aorta is resistant to infection, but vessel abnormality (atherosclerosis, pre-existing aneurysm, cystic medial necrosis) renders it vulnerable to infectious aortitis, now most commonly caused by Staphylococcus aureus and Salmonella (formerly syphilis and tuberculosis prior to effective antimicrobial therapy)
• Cold abscesses (TB): Thin-walled, smooth rim enhancement, minimal surrounding inflammatory change
• Chronic spondylodiscitis: Sclerosis, deformity, paraspinal calcification; disc height loss

Differentiating pyogenic from tuberculous spinal infection on CT/MRI:

Magnetic Resonance Imaging

MRI is the most sensitive modality for characterising inflammation in the CNS, spine, and musculoskeletal system.

Acute inflammation:

• $T_2$/STIR hyperintensity: hallmark of oedema and inflammatory infiltrate
• Diffusion restriction ($\downarrow$ ADC): pyogenic abscess (viscous pus, highly restricted); acute infarction; active demyelination
• Post-gadolinium enhancement: breakdown of blood-brain barrier (BBB) or blood-tissue barrier; patterns include solid, rim, leptomeningeal, sulcal, and vessel-wall
• Acute meningitis: Sulcal/leptomeningeal FLAIR hyperintensity (failure of CSF suppression due to elevated protein and cellularity); leptomeningeal enhancement on post-contrast $T_1$. Complications include hydrocephalus, venous thrombosis, ventriculitis, and infarction
• Ventriculitis: Linear ependymal enhancement; periventricular FLAIR signal change; abnormally swollen choroid plexi (choroid plexitis); may follow abscess rupture into ventricles or arise from leptomeningitis/shunt infection; in chronic ventriculitis, periventricular calcification may be seen (classically in TORCH infections)
• Acute MS plaques: $T_2$/FLAIR hyperintense; incomplete ring ("open-ring") enhancement facing cortex; active plaques show BBB breakdown

Chronic inflammation:

• $T_1$ hypointense, $T_2$ hyperintense lesions with variable enhancement depending on activity
• Chronic inactive (burned-out) MS plaques: Hypocellular, myelin loss, no active inflammation, glial scarring, $T_2$ hyperintense, non-enhancing, depressed/excavated on gross pathology; do not reliably indicate new active disease
• Chronic active MS plaques: Continuing inflammation around outer borders; dense macrophages at plaque edge; may show smouldering rim enhancement
• Fibrous tissue: $T_1$ and $T_2$ hypointense (dense collagen low signal on all sequences)
• Granulomatous leptomeningitis (neurosarcoidosis, tuberculous meningitis): dural/leptomeningeal thickening with intense enhancement; cranial nerve sheath enhancement; infundibular and hypothalamic involvement particularly characteristic of neurosarcoidosis
• Synovitis: Intermediate $T_2$ synovial thickening, smooth in tuberculous arthritis; irregular with avid post-contrast enhancement in pyogenic arthritis; pyogenic abscesses thick-walled with pronounced surrounding inflammation; tuberculous cold abscesses smooth, thin-walled with less prominent surrounding change
• Spondylodiscitis: Vertebral body $T_1$ hypointensity and STIR hyperintensity; disc signal alteration; epidural/paraspinal collection with rim enhancement

MS plaque pathology, histological and imaging correlates:

MR Spectroscopy (CNS applications):

Ultrasound

• Acute soft-tissue infection: Increased echogenicity and loss of fascial planes in cellulitis; hypoechoic or complex fluid collection in abscess; increased Doppler flow in adjacent soft tissue
• Acute hepatitis: Hepatomegaly; periportal echogenicity ("starry sky" pattern in some viral hepatitis)
• Acute synovitis/septic arthritis: Joint effusion with synovial thickening; hypervascularity on Doppler
• Chronic inflammation: Synovial hypertrophy; pannus formation; loss of normal tissue planes; fibrosis with increased echogenicity
• Bowel (Crohn's disease): Mural thickening with submucosal oedema and increased Doppler vascularity in active disease; contrast-enhanced ultrasound useful for bowel wall microvascularisation assessment

Nuclear Medicine

FDG-PET/CT:

• Acute and active chronic inflammation demonstrate elevated $\text{SUV}_{\max}$ due to increased glucose metabolism in activated leucocytes
• Active vasculitis (e.g. Takayasu arteritis): Circumferential aortic and large-vessel FDG uptake, correlates with active disease and can detect inflammatory activity before structural vessel wall changes appear on CT; PET is particularly useful in early/acute-phase diagnosis where symptoms are vague
• Sarcoidosis: Mediastinal and hilar FDG-avid lymphadenopathy; panda sign/lambda sign on $^{67}$Ga scintigraphy
• Osteomyelitis: Three-phase bone scan (increased flow, blood pool, and delayed phase); $^{67}$Ga and labelled white cell scans used in chronic/subacute infection

Systematic Approach to Imaging Inflammatory Disease

1. Identify the dominant pattern: Oedema/exudate (acute) vs fibrosis/calcification/architectural distortion (chronic)
2. Determine distribution: Focal vs multifocal vs systemic; vascular vs airspace vs interstitial; perivascular vs parenchymal
3. Assess enhancement pattern: Solid, rim, leptomeningeal, sulcal, vessel-wall
4. Evaluate for suppuration/necrosis: Abscess identification is critical for management
5. Identify chronicity markers: Calcification, sclerosis, fibrosis, architectural remodelling
6. Correlate with clinical context: Immunocompromised? Known autoimmune disease? Exposure history? IgG4 serology?
7. Identify complications: Mass effect, vessel thrombosis, fistula formation, spinal cord compression, hydrocephalus, ventriculitis

Differential Diagnosis: Inflammation vs Malignancy vs Ischaemia

Key Pitfalls and Exam-Relevant Points

• Infection ≠ inflammation: Infection is caused by microorganisms; inflammation is the host response. Autoimmune, iatrogenic, radiation-induced, and paraneoplastic inflammatory processes share imaging features with infectious disease but require entirely different management.

• PET/CT: granulomatous disease mimicking malignancy: TB, sarcoidosis, and active vasculitis produce FDG uptake indistinguishable from neoplasm. Biopsy and clinical correlation are frequently required.

• Underestimating cold abscess: Tuberculous cold abscesses lack typical surrounding inflammatory oedema. Their thin, smooth walls and minimal surrounding reaction reflect attenuated host response and may lead to underestimation of disease extent.

• "Burned out" MS plaques do not enhance: Chronic inactive plaques reflect glial scarring and absent active inflammation. Non-enhancing lesions on follow-up MRI must not be assumed to represent new active disease, only enhancing lesions reliably indicate active BBB breakdown.

• Chronic periaortic fibrosis vs retroperitoneal malignancy: IgG4-related periaortitis produces a soft-tissue rind around the aorta mimicking lymphoma or retroperitoneal sarcoma. The rind morphology, absence of discrete nodal masses, systemic IgG4 elevation, and association with inflammatory aneurysm are discriminating features. Many previously "idiopathic" inflammatory aortitis cases represent undiagnosed IgG4-related disease.

• Lobar consolidation is not always bacterial: Klebsiella, Legionella, and viral infections can produce lobar patterns. Radiographic pattern prediction of causative pathogen is notoriously unreliable and should not be used in isolation.

• Ventriculitis on MRI: Linear ependymal enhancement, periventricular FLAIR signal change, and abnormally swollen choroid plexi indicate ventriculitis, a serious complication of adjacent abscess rupture or meningitis. FLAIR and post-contrast $T_1$ sequences are essential. Periventricular calcification in chronic ventriculitis is a classic TORCH infection finding.

• Pyogenic vs tuberculous spinal infection: Failure to consider TB in the appropriate context (multilevel disease, cold abscess, thoracic predominance, insidious onset) leads to diagnostic delay. Imaging features are distinct and should prompt targeted microbiological workup.

• Syphilitic gummata: Consist of dense lymphocytic and plasma cell infiltrate surrounding a central caseous necrotic core, with vascular proliferation and endarteritis. Two neuroimaging patterns: dural-based lesion mimicking meningioma, and medial temporal lobe abnormality mimicking herpes encephalitis. Ring or diffuse enhancement; dural tail in one-third.

• Enhancement alone is imperfect for activity assessment in chronic inflammation: Fibrotic tissue may enhance variably due to chronic vascularity. Serial imaging and clinical correlation are necessary.

Sources

• Fleischner Society guidelines (pulmonary nodule management)
• ACR Appropriateness Criteria (American College of Radiology)