Spectral Diffusion Analysis for idiopathic Normal Pressure Hydrocephalus Diagnosis

'Spectral Diffusion Analysis (SDA)' is an advanced diffusion MRI technique that separates diffusion signals into spectral components to estimate compartment-specific water dynamics. In the context of idiopathic normal pressure hydrocephalus (iNPH), SDA is used to quantify interstitial fluid changes, offering potential non-invasive biomarkers.

Why Use SDA in iNPH? Conventional imaging markers (e.g. DESH, Evans index) lack pathophysiological specificity. SDA provides a more precise assessment of:

Interstitial Fluid Volume Fraction

Interstitial Diffusivity

These metrics reflect:

• Expansion of extracellular (interstitial) space
• Impaired glymphatic or perivascular clearance
• Altered brain compliance

Key Study: Ishida S et al. (J Magn Reson Imaging. 2025 Jul 4. doi:10.1002/jmri.29834) – Retrospective study comparing 34 iNPH patients vs. healthy controls – Main findings:

• ↑ F_int in periventricular and centrum semiovale white matter
• ↓ D_int suggesting stagnation of interstitial fluid
• Diagnostic discrimination superior to ADC or FA

Clinical Implications:

• SDA-derived metrics may aid in:
  1. Early, pathophysiology-based diagnosis of iNPH
  2. Differentiation from other causes of ventriculomegaly (e.g., atrophy)
  3. Predicting shunt responsiveness
• Provides insight into the glymphatic dysfunction hypothesis of iNPH

Advantages:

• Non-invasive, quantitative
• Detects subtle extracellular fluid alterations before gross morphological changes
• Applicable in clinical MRI with multi-b-value acquisition

Limitations:

• Requires advanced MRI acquisition and post-processing
• Interpretation depends on validation of model assumptions
• Not yet widely available in routine clinical practice