===== Interstitial Diffusivity (D<sub>int</sub>) =====

**Definition:**  
'''Interstitial Diffusivity''' ('''D<sub>int</sub>''') 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.

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**Physiological Basis:**
  * In healthy brain tissue, D<sub>int</sub> is influenced by:
    - **Extracellular matrix composition**
    - **Interstitial space geometry**
    - **Viscosity and flow resistance**
  * Interstitial water contributes to metabolic waste clearance, nutrient transport, and glymphatic circulation.

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**Measurement Techniques:**
  * Estimated using advanced diffusion MRI, especially:
    - [[Spectral diffusion analysis]]
    - [[Multi-compartment diffusion models]]
  * Requires high angular and multi-b-value data to isolate the extracellular component of water diffusion.

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**Clinical Relevance:**
  * ↓ D<sub>int</sub> → Suggests stagnation or restricted ISF flow  
    (e.g., in [[idiopathic normal pressure hydrocephalus]] or glymphatic failure)
  * ↑ D<sub>int</sub> → 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:
    - Interstitial flow efficiency
    - Parenchymal compliance
    - Glymphatic system status
  * Used in conjunction with [[F<sub>int</sub> — Interstitial Fluid Volume Fraction]] for characterization of brain fluid dynamics.

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**In iNPH:**
  * D<sub>int</sub> is often **reduced**, especially in periventricular white matter.
  * This may reflect impaired glymphatic flow and contribute to ventricular enlargement and white matter damage.

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**Related Concepts:**
  * [[Diffusivity (D)]]
  * [[Interstitial fluid dynamics]]
  * [[Spectral diffusion analysis]]
  * [[F<sub>int</sub> — Interstitial Fluid Volume Fraction]]
  * [[Glymphatic system]]