What does increased signaling on a Magnetic Resonance Imaging (MRI) scan indicate?

Increased Signal on MRI: Clinical Interpretation

Increased signal intensity on MRI represents tissue with higher water content, appearing bright on T2-weighted, FLAIR, or STIR sequences, and indicates edema, inflammation, demyelination, ischemia, or other pathological processes depending on the anatomic location and clinical context. 1

Fundamental MRI Signal Characteristics

The appearance of "increased signal" depends critically on the specific MRI sequence used:

• T2-weighted and FLAIR sequences: Increased signal (hyperintensity) reflects elevated tissue water content from edema, inflammation, gliosis, demyelination, or ischemic injury 2, 1
• STIR sequences: Highly sensitive for detecting increased water content in tissues, representing bone marrow edema, inflammatory changes, or stress reactions in musculoskeletal imaging 3
• Diffusion-weighted imaging (DWI): Restricted diffusion (bright signal) indicates cytotoxic edema from acute cellular injury, most commonly seen in acute stroke 2

Anatomic Location-Specific Interpretation

Brain Parenchyma

White matter hyperintensities on T2/FLAIR sequences have distinct etiologies based on patient age and distribution:

• Age >50 years with vascular risk factors: Most commonly represents cerebral small vessel disease (chronic microvascular ischemic changes), appearing as small (<6 mm), non-enhancing lesions in deep white matter and periventricular regions 1
• Periventricular distribution: Chronic microvascular ischemia causes myelin loss, axonal damage, gliosis, and perivascular space dilation, significantly increasing risk of cognitive impairment, stroke, and mortality 1
• Multiple sclerosis: Requires typical lesions in at least two characteristic regions (periventricular, juxtacortical, infratentorial, or spinal cord), with ovoid lesions ≥3 mm perpendicular to corpus callosum ("Dawson's fingers") 2, 1

Critical red flags that suggest alternative diagnoses include:

• Enhancement persisting >3 months (consider sarcoidosis or vascular malformation) 2
• Leptomeningeal enhancement (neurosarcoidosis, granulomatous disease, or in progressive MS on post-contrast FLAIR) 2
• Punctate/miliary enhancement (CLIPPERS, vasculitis, PML, Susac syndrome) 2
• Purely cortical enhancement (subacute ischemia) 2

Spinal Cord

Increased T2 signal intensity in the spinal cord indicates intramedullary pathology from compression, inflammation, ischemia, demyelination, or trauma 4:

• Cervical spondylotic myelopathy: T2 hyperintensity appears in 65-80% of patients with moderate-to-severe disease, representing edema, gliosis, myelomalacia, or ischemic injury 4
• Prognostic significance: Combined T1 hypointensity with T2 hyperintensity indicates irreversible myelomalacia and predicts poor surgical outcomes 4
• Multiple sclerosis: Focal lesions occupying <50% of cord cross-section, extending <2 vertebral segments 4
• Neuromyelitis optica: Longitudinally extensive lesions with central cord predilection 4

Red flags in spinal cord imaging include:

• Swelling with long segments (neuromyelitis optica spectrum disorders, anti-MOG-IgG disease) 2
• Preferential involvement of caudal spine (anti-MOG-IgG disease) 2
• "Snake eye" or "owl's eye" sign of bilateral anterior grey matter horn hyperintensities (ischemia/infarction) 2

Musculoskeletal Tissues

Increased signal on STIR sequences in bone and soft tissue represents 3:

• Bone marrow edema: Indicates inflammation, stress reactions, or traumatic injury (sensitivity 79-82%, specificity 89-97%) 3
• Fascial fluid/edema: Particularly important for detecting necrotizing fasciitis (93% sensitivity) 3
• Sacroiliac joints: Active inflammation in axial spondyloarthropathy, though bone marrow edema can be nonspecific in up to 30% of healthy controls 3

Critical principle: STIR should never be used in isolation—always combine with T1-weighted sequences to differentiate acute inflammatory changes from chronic structural changes 3

Special Context: Amyloid-Modifying Therapy (ARIA-E)

In patients receiving anti-amyloid immunotherapy, increased signal on FLAIR sequences represents Amyloid-Related Imaging Abnormalities with Edema (ARIA-E) 2:

• Manifests as increased signal in parenchyma and/or leptomeninges, most commonly in parietal, occipital, and frontal lobes 2
• Represents vasogenic edema (increased extracellular fluid from capillary endothelial permeability) rather than cytotoxic edema 2
• Usually transient, not associated with restricted diffusion or tissue necrosis 2
• Leptomeningeal involvement may represent proteinaceous fluid effusion rather than subarachnoid hemorrhage 2

Temporal Evolution and Clinical Significance

Acute vs. chronic changes require different interpretation:

• Acute hemorrhage: High density on CT within 1 week, or extracellular methemoglobin (high signal on T1/T2) on MRI within 2 weeks 2
• Vasogenic edema: Transient, reversible, without restricted diffusion 2
• Cytotoxic edema: Restricted diffusion on DWI from acute cellular damage (e.g., stroke) 2
• Chronic changes: Gliosis, myelomalacia, or fibrosis developing over time 4, 5

Practical Clinical Algorithm

For brain white matter hyperintensities:

1. Patient >50 years with vascular risk factors: Attribute to cerebral small vessel disease; aggressively optimize vascular risk factors (blood pressure, statins, diabetes management, smoking cessation) 1
2. Patient <50 years without vascular risk factors: Consider follow-up MRI in 3-6 months; if new lesions appear in characteristic MS locations, pursue MS evaluation with lumbar puncture and evoked potentials 1
3. Any age with atypical features (enhancement >3 months, leptomeningeal involvement, mass effect): Pursue alternative diagnoses 2

For spinal cord T2 hyperintensity:

1. Acute onset: Consider ischemia, trauma, or acute inflammatory process 4
2. Subacute/chronic with compression: Assess for surgical candidacy; absence of T2 signal predicts best recovery, while T1 hypointensity + T2 hyperintensity predicts poor outcomes 4
3. No compression with longitudinally extensive lesion: Evaluate for neuromyelitis optica, ADEM 4
4. Focal lesion <2 segments: Consider MS, obtain contrast-enhanced images 4

For musculoskeletal STIR hyperintensities:

1. Always obtain T1-weighted images to differentiate acute from chronic changes 3
2. Bone marrow edema in sacroiliac joints: Deep lesions extending ≥1 cm from articular surface are more specific for pathologic inflammation 3
3. Fascial edema with clinical concern for infection: STIR has 93% sensitivity for necrotizing fasciitis; fascial thickening ≥3 mm has 86% sensitivity 3

Common Pitfalls to Avoid

• Do not diagnose MS from a single small white matter lesion: Lesions <3 mm do not meet McDonald criteria, and MS requires lesions in ≥2 characteristic regions 1
• Do not assume all periventricular hyperintensities are pathologic: Symmetric linear hyperintensities abutting lateral ventricles ("periventricular capping") and lesions <3 mm are normal variants 1
• Do not interpret STIR hyperintensities without T1-weighted images: Up to 30% of healthy controls show bone marrow edema in sacroiliac joints 3
• Do not assume enhancement always indicates active disease: Vascular structures and developmental venous anomalies can mimic pathologic enhancement 2