Definition: 'Interstitial Diffusivity' ('Dint') refers to the rate at which water molecules diffuse within the brain’s interstitial (extracellular) space. It reflects the mobility of fluid in the parenchymal extracellular environment, distinct from intracellular or vascular compartments.

Physiological Basis:

• In healthy brain tissue, D_int is influenced by:
  1. Extracellular matrix composition
  2. Interstitial space geometry
  3. Viscosity and flow resistance
• Interstitial water contributes to metabolic waste clearance, nutrient transport, and glymphatic circulation.

Measurement Techniques:

• Estimated using advanced diffusion MRI, especially:
  1. Spectral diffusion analysis
  2. Multi-compartment diffusion models
• Requires high angular and multi-b-value data to isolate the extracellular component of water diffusion.

Clinical Relevance:

• ↓ D_int → Suggests stagnation or restricted ISF flow

(e.g., in idiopathic normal pressure hydrocephalus or glymphatic failure)

• ↑ D_int → May reflect increased ISF mobility or reduced structural barriers

(e.g., extracellular matrix degradation in aging or neurodegeneration)

Diagnostic Potential:

• May serve as a non-invasive biomarker of:
  1. Interstitial flow efficiency
  2. Parenchymal compliance
  3. Glymphatic system status
• Used in conjunction with F_int — Interstitial Fluid Volume Fraction for characterization of brain fluid dynamics.

In iNPH:

• D_int is often reduced, especially in periventricular white matter.
• This may reflect impaired glymphatic flow and contribute to ventricular enlargement and white matter damage.

Related Concepts:

• Diffusivity (D)
• Interstitial fluid dynamics
• Spectral diffusion analysis
• F_int — Interstitial Fluid Volume Fraction
• Glymphatic system