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Frequency-dependence in multidimensional diffusion–relaxation correlation MRI of the brain : Overfitting or meaningful parameter?

Yon, Maxime LU ; Narvaez, Omar ; Martin, Jan LU ; Jiang, Hong LU ; Bernin, Diana LU ; Forssell-Aronsson, Eva ; Laun, Frederik ; Sierra, Alejandra and Topgaard, Daniel LU (2025) In Imaging Neuroscience 3.
Abstract

Time- or frequency-dependent (“restricted”) diffusion potentially provides useful information about cellular-scale structures in the brain but is challenging to interpret because of intravoxel tissue heterogeneity. Multidimensional diffusion–relaxation correlation MRI with tensor-valued diffusion encoding enables characterization of intravoxel heterogeneity in terms of nonparametric distributions of diffusion tensors and nuclear relaxation rates, and was recently augmented with explicit consideration of frequency-dependence to resolve the effects of restricted diffusion for distinct populations of tissue water. The simplest acquisition protocols for tensor-valued encoding unintentionally cover a frequency range of a factor 2–3, which... (More)

Time- or frequency-dependent (“restricted”) diffusion potentially provides useful information about cellular-scale structures in the brain but is challenging to interpret because of intravoxel tissue heterogeneity. Multidimensional diffusion–relaxation correlation MRI with tensor-valued diffusion encoding enables characterization of intravoxel heterogeneity in terms of nonparametric distributions of diffusion tensors and nuclear relaxation rates, and was recently augmented with explicit consideration of frequency-dependence to resolve the effects of restricted diffusion for distinct populations of tissue water. The simplest acquisition protocols for tensor-valued encoding unintentionally cover a frequency range of a factor 2–3, which can be extended in a more controlled way with oscillating gradient waveforms. While microimaging equipment with high-amplitude magnetic field gradients allows exploration of frequencies from tens to hundreds of Hz, clinical scanners with more moderate gradient capabilities are limited to narrower ranges that may be insufficient to observe restricted diffusion for brain tissues. We here investigate the effects of including or omitting frequency-dependence in the data inversion from isotropic and anisotropic liquids, excised tumor tissue, ex vivo mouse brain, and in vivo human brain. For microimaging measurements covering a wide frequency range, from 35 to 320 Hz at b-values over 4·109 sm−2, the inclusion of frequency-dependence drastically reduces fit residuals and avoids bias in the diffusion metrics for tumor and brain voxels with micrometer-scale structures. Conversely, for the case of in vivo human brain investigated in the narrow frequency range from 5 to 11 Hz at b = 3·109 sm−2, analyses with and without inclusion of frequency-dependence yield similar fit residuals and diffusion metrics for all voxels. These results indicate that frequency-dependent inversion may be generally applied to diffusion–relaxation correlation MRI data with and without observable effects of restricted diffusion.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diffusion MRI, frequency-dependent diffusion, Monte Carlo data inversion, multidimensional MRI, oscillating gradient spin echo (OGSE), spectrally modulated gradients, tensor-valued diffusion encoding
in
Imaging Neuroscience
volume
3
article number
IMAG.a.143
publisher
MIT Press
external identifiers
  • scopus:105017049046
  • pmid:40995460
ISSN
2837-6056
DOI
10.1162/IMAG.a.143
language
English
LU publication?
yes
id
9b3d5415-08a1-40e2-ae28-60be1821b508
date added to LUP
2025-11-26 15:15:31
date last changed
2025-11-27 03:00:03
@article{9b3d5415-08a1-40e2-ae28-60be1821b508,
  abstract     = {{<p>Time- or frequency-dependent (“restricted”) diffusion potentially provides useful information about cellular-scale structures in the brain but is challenging to interpret because of intravoxel tissue heterogeneity. Multidimensional diffusion–relaxation correlation MRI with tensor-valued diffusion encoding enables characterization of intravoxel heterogeneity in terms of nonparametric distributions of diffusion tensors and nuclear relaxation rates, and was recently augmented with explicit consideration of frequency-dependence to resolve the effects of restricted diffusion for distinct populations of tissue water. The simplest acquisition protocols for tensor-valued encoding unintentionally cover a frequency range of a factor 2–3, which can be extended in a more controlled way with oscillating gradient waveforms. While microimaging equipment with high-amplitude magnetic field gradients allows exploration of frequencies from tens to hundreds of Hz, clinical scanners with more moderate gradient capabilities are limited to narrower ranges that may be insufficient to observe restricted diffusion for brain tissues. We here investigate the effects of including or omitting frequency-dependence in the data inversion from isotropic and anisotropic liquids, excised tumor tissue, ex vivo mouse brain, and in vivo human brain. For microimaging measurements covering a wide frequency range, from 35 to 320 Hz at b-values over 4·10<sup>9</sup> sm<sup>−2</sup>, the inclusion of frequency-dependence drastically reduces fit residuals and avoids bias in the diffusion metrics for tumor and brain voxels with micrometer-scale structures. Conversely, for the case of in vivo human brain investigated in the narrow frequency range from 5 to 11 Hz at b = 3·10<sup>9</sup> sm<sup>−2</sup>, analyses with and without inclusion of frequency-dependence yield similar fit residuals and diffusion metrics for all voxels. These results indicate that frequency-dependent inversion may be generally applied to diffusion–relaxation correlation MRI data with and without observable effects of restricted diffusion.</p>}},
  author       = {{Yon, Maxime and Narvaez, Omar and Martin, Jan and Jiang, Hong and Bernin, Diana and Forssell-Aronsson, Eva and Laun, Frederik and Sierra, Alejandra and Topgaard, Daniel}},
  issn         = {{2837-6056}},
  keywords     = {{diffusion MRI; frequency-dependent diffusion; Monte Carlo data inversion; multidimensional MRI; oscillating gradient spin echo (OGSE); spectrally modulated gradients; tensor-valued diffusion encoding}},
  language     = {{eng}},
  publisher    = {{MIT Press}},
  series       = {{Imaging Neuroscience}},
  title        = {{Frequency-dependence in multidimensional diffusion–relaxation correlation MRI of the brain : Overfitting or meaningful parameter?}},
  url          = {{http://dx.doi.org/10.1162/IMAG.a.143}},
  doi          = {{10.1162/IMAG.a.143}},
  volume       = {{3}},
  year         = {{2025}},
}