The Role of Dendritic Spines in Water Exchange Measurements With Diffusion MRI: Time-Dependent Single Diffusion Encoding MRI

Prior work has focused on restricted/hindered diffusion and membrane permeation; <b>diffusion-mediated exchange between the dendritic shaft and its spines</b> has remained understudied.</p><p dir="ltr">This study tests the hypothesis that water diffusion within <i>impermeable</i> spiny dendrites can produce time-dependent SDE signals <b>indistinguishable from those arising from permeative exchange</b>, and asks how strongly spine density affects exchange-time estimates.

The approach combines Monte-Carlo simulations on digital spiny-dendrite substrates with analytical solutions from the narrow escape problem.</p><h2 dir="ltr">Key findings</h2><ul><li><b>Spine–shaft and shaft–spine exchange times fall in the 1–50 ms range</b> — comparable to permeative exchange estimates reported in cortex.</li><li>A <b>modified two-compartment Kärger model</b> captures the time-dependent SDE signal along spiny dendrites well, but the exchange time it returns reflects <b>total spine volume fraction</b> rather than specific spine morphology.</li><li>Unaccounted diffusion-mediated exchange <b>substantially biases Neurite Exchange Imaging (NEXI)</b>, inflating the apparent exchange rate and the inferred membrane permeability in proportion to spine volume fraction.</li><li>An <b>extended three-compartment Kärger model</b> (and its <b>coarse-grained</b> version) incorporates both diffusion-mediated shaft↔spine exchange and permeative exchange with the extracellular space.