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

Chakwizira, Arthur LU ; Şimşek, Kadir ; Szczepankiewicz, Filip LU orcid ; Palombo, Marco and Nilsson, Markus LU (2026) In NMR in Biomedicine 39(7).
Abstract

Time-dependent diffusion MRI enables the estimation of water exchange rates in vivo. Most studies attribute these estimates to membrane permeability. However, non-permeative geometric exchange may also contribute. The present study investigates the contribution of geometric exchange between dendritic spines and shafts to diffusion MRI-derived exchange estimates. Monte Carlo simulations were performed in synthetic dendrites with varying spine morphology, density and membrane permeability. Diffusion-weighted signals were generated using multiple protocols—including single diffusion encoding, double diffusion encoding and free waveforms—and were analysed using four frameworks: the Kärger model (via kurtosis time-dependence), correlation... (More)

Time-dependent diffusion MRI enables the estimation of water exchange rates in vivo. Most studies attribute these estimates to membrane permeability. However, non-permeative geometric exchange may also contribute. The present study investigates the contribution of geometric exchange between dendritic spines and shafts to diffusion MRI-derived exchange estimates. Monte Carlo simulations were performed in synthetic dendrites with varying spine morphology, density and membrane permeability. Diffusion-weighted signals were generated using multiple protocols—including single diffusion encoding, double diffusion encoding and free waveforms—and were analysed using four frameworks: the Kärger model (via kurtosis time-dependence), correlation tensor imaging, restriction-exchange and multi-Gaussian exchange with transient kurtosis (tMGE). Dendritic spines were found to impart similar time-dependence signatures on the diffusion-weighted signal as permeative exchange (signal decrease with diffusion time). The effect was modulated by both spine morphology and density. Both the exchange rate and microscopic kurtosis increased with spine density. The tMGE method demonstrated the ability to disentangle geometric from permeative exchange. In conclusion, we demonstrate that non-permeative exchange in dendritic spines has a non-negligible impact on exchange estimates obtained with diffusion MRI and should be considered in future studies. Tentatively, we propose that diffusion MRI exchange estimates may provide a non-invasive proxy for dendritic spine density, with potential applications in studies of neurological disorders.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dendritic spines, diffusion MRI, double diffusion encoding, exchange, free waveforms, time-dependence
in
NMR in Biomedicine
volume
39
issue
7
article number
e70315
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:105041038533
  • pmid:42240476
ISSN
0952-3480
DOI
10.1002/nbm.70315
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2026 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.
id
315d0af4-b3d2-4423-bb4c-f311c3c91351
date added to LUP
2026-07-21 12:13:48
date last changed
2026-09-30 00:53:56
@article{315d0af4-b3d2-4423-bb4c-f311c3c91351,
  abstract     = {{<p>Time-dependent diffusion MRI enables the estimation of water exchange rates in vivo. Most studies attribute these estimates to membrane permeability. However, non-permeative geometric exchange may also contribute. The present study investigates the contribution of geometric exchange between dendritic spines and shafts to diffusion MRI-derived exchange estimates. Monte Carlo simulations were performed in synthetic dendrites with varying spine morphology, density and membrane permeability. Diffusion-weighted signals were generated using multiple protocols—including single diffusion encoding, double diffusion encoding and free waveforms—and were analysed using four frameworks: the Kärger model (via kurtosis time-dependence), correlation tensor imaging, restriction-exchange and multi-Gaussian exchange with transient kurtosis (tMGE). Dendritic spines were found to impart similar time-dependence signatures on the diffusion-weighted signal as permeative exchange (signal decrease with diffusion time). The effect was modulated by both spine morphology and density. Both the exchange rate and microscopic kurtosis increased with spine density. The tMGE method demonstrated the ability to disentangle geometric from permeative exchange. In conclusion, we demonstrate that non-permeative exchange in dendritic spines has a non-negligible impact on exchange estimates obtained with diffusion MRI and should be considered in future studies. Tentatively, we propose that diffusion MRI exchange estimates may provide a non-invasive proxy for dendritic spine density, with potential applications in studies of neurological disorders.</p>}},
  author       = {{Chakwizira, Arthur and Şimşek, Kadir and Szczepankiewicz, Filip and Palombo, Marco and Nilsson, Markus}},
  issn         = {{0952-3480}},
  keywords     = {{dendritic spines; diffusion MRI; double diffusion encoding; exchange; free waveforms; time-dependence}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{NMR in Biomedicine}},
  title        = {{The Role of Dendritic Spines in Water Exchange Measurements With Diffusion MRI : Double Diffusion Encoding and Free-Waveform MRI}},
  url          = {{http://dx.doi.org/10.1002/nbm.70315}},
  doi          = {{10.1002/nbm.70315}},
  volume       = {{39}},
  year         = {{2026}},
}