The Role of Dendritic Spines in Water Exchange Measurements With Diffusion MRI: Double Diffusion Encoding and...

Area of Science:

• Neuroimaging
• Biophysics
• Computational Neuroscience

Background:

• Diffusion MRI (dMRI) estimates water exchange rates in vivo, typically attributed to membrane permeability.
• Non-permeative geometric exchange, particularly in dendritic spines, may also influence these estimates.
• Understanding contributions to dMRI signals is crucial for accurate interpretation.

Purpose of the Study:

• To investigate the impact of geometric exchange between dendritic spines and shafts on dMRI-derived exchange estimates.
• To differentiate geometric exchange from permeative exchange using advanced dMRI analysis frameworks.

Main Methods:

• Monte Carlo simulations in synthetic dendrites with varied spine morphology, density, and membrane permeability.
• Generation of diffusion-weighted signals using multiple dMRI protocols (single, double diffusion encoding, free waveforms).
• Analysis using Kärger model, correlation tensor imaging, restriction-exchange, and multi-Gaussian exchange with transient kurtosis (tMGE).

Main Results:

• Dendritic spines created time-dependent diffusion MRI signal signatures similar to permeative exchange.
• Spine morphology and density modulated the observed effects, increasing exchange rate and microscopic kurtosis with density.
• The tMGE method successfully distinguished geometric from permeative exchange.

Conclusions:

• Non-permeative geometric exchange in dendritic spines significantly impacts dMRI exchange estimates.
• These findings necessitate consideration of geometric factors in future dMRI studies.
• dMRI exchange estimates may serve as a non-invasive proxy for dendritic spine density, with potential neurological disorder applications.