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Anders Dyhr Sandgaard

Publications and source records attributed to Anders Dyhr Sandgaard.

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Predicting Mesoscopic Larmor Frequency Shifts in Ex Vivo Porcine Optic Nerve

Larmor frequency shifts in white matter (WM) vary with fiber orientation due to anisotropic microstructure. Since clinical voxels are significantly larger than these microscopic frequency variations, the measured signal represents a bulk average of local shifts. Accurate estimation of magnetic susceptibility therefore requires accounting for these underlying frequency distributions that exist below the imaging resolution. We evaluated whether Microstructure-informed Quantitative Susceptibility Mapping (μQSM) can predict orientation-dependent sub-voxel frequency shifts from orientationally dispersed hollow cylinders and spherical inclusions. Diffusion-weighted and multi-gradient-echo images were acquired from ex vivo pig optic nerves at multiple orientations relative to the main magnetic field using a 3T Siemens Connectom scanner. We also analyzed de-ironed optic nerves to try and separate the effects of myelin and iron on susceptibility. The estimated sub-voxel frequency shifts closely matched μQSM predictions, consistent with mesoscopic field perturbations generated by uniformly magnetized axons. De-ironing had minimal effect on the frequency shifts, indicating negligible iron contribution. μQSM accurately reproduces the orientation dependence of Larmor frequency shifts in optic nerve WM, providing new insight into their microstructural origin and supporting improved estimation of tissue magnetic susceptibility in Quantitative Susceptibility Mapping.

physics.med-ph

Axonal microstructure and compartmentalization impact the orientation and time dependence of mesoscopic transverse relaxation

In biological tissue, MR transverse relaxation stems from mechanisms spanning multiple scales, from molecular dipole-dipole interactions to mesoscopic field variations driven by tissue microstructure. While mesoscopic relaxation reflects cellular organization, its dynamics in white matter, specifically its dependence on axonal orientation and echo time, remain less investigated. This study employs theoretical frameworks and Monte-Carlo simulations using 3D EM-based white matter (WM) geometries to investigate how compartmentalization and realistic morphology drive these effects. Specifically, we simulate intra-axonal relaxation driven by magnetic fields induced by realistic axonal myelin sheaths and intra-axonal spheres as a model of iron-containing mitochondria. Our results confirm that orientation dependence of mesoscopic relaxation in WM is detectable and agrees with experimental observations. The time-dependence aligns with 1-dimensional short-range structural disorder, but at clinical echo times, this signature may be masked by dominant molecular relaxation. This work moves beyond idealized models to aid the development of more specific biophysical models of mesoscopic relaxation to achieve better biomarkers for neurodegenerative disease.

physics.med-ph

Predicting Mesoscopic Larmor Frequency Shifts in White Matter with Diffusion MRI -- A Monte-Carlo Study in axonal phantoms

This study aims to validate if MRI can measure anisotropic mesoscopic Larmor frequency shifts from white matter axonal microstructure relative to the B0 direction and if dMRI can estimate this anisotropy. Recent models describe how mesoscopic Larmor frequency shifts depend on induced magnetic fields by axons, described by an orientation distribution function. Using Monte-Carlo simulations of MRI signals in mesoscopic white matter axon substrates, we show MRI can estimate this mesoscopic frequency shift and dMRI can estimate its orientation dependence.

physics.med-ph

The Larmor frequency shift of a white matter magnetic microstructure model with multiple sources

Magnetic susceptibility imaging may provide valuable information about chemical composition and microstructural organization of tissue. However, its estimation from the MRI signal phase is particularly difficult as it is sensitive to magnetic tissue properties ranging from the molecular to macroscopic scale. The MRI Larmor frequency shift measured in white matter (WM) tissue depends on the myelinated axons and other magnetizable sources such as iron-filled ferritin. We have previously derived the Larmor frequency shift arising from a dense media of cylinders with scalar susceptibility and arbitrary orientation dispersion. Here we extend our model to include microscopic WM susceptibility anisotropy as well as spherical inclusions with scalar susceptibility to represent subcellular structures, biologically stored iron etc. We validate our analytical results with computer simulations and investigate the feasibility of estimating susceptibility using simple iterative linear least squares without regularization or preconditioning. This is done in a digital brain phantom synthesized from diffusion MRI (dMRI) measurements of an ex vivo mouse brain at ultra-high field.

physics.med-ph

Incorporating the effect of white matter microstructure in the estimation of magnetic susceptibility in ex-vivo mouse brain

Accurate estimation of microscopic magnetic field variations induced in biological tissue can be valuable for mapping tissue composition in health and disease. Here, we present an extension to Quantitative susceptibility mapping (QSM) to account for local white matter (WM) magnetic microstructure by using our previously presented model for solid cylinders with arbitrary orientations to describe axons in terms of concentric cylinders. Through computer simulations, we find that our model improves susceptibility estimation compared to QSM, and Susceptibility Tensor Imaging (STI) are substantially biased by the unaccounted-for structural anisotropy due to the mesoscopic frequency contribution, indicating the observed STI tensor might not represent susceptibility anisotropy as expected. Experiments in mouse brains acquired at ultrahigh field shows the mesoscopic contribution due to WM microstructure to be substantial. This in turn changed estimated susceptibility values up to 25% root-mean-squared-difference in WM compared to standard QSM. Our work underscores how microstructural field effects impact susceptibility estimates, and should not be neglected when imaging anisotropic tissue such as brain WM.

physics.med-ph

To mask or not to mask? Investigating the impact of accounting for spatial frequency distributions and susceptibility sources on QSM quality

Estimating magnetic susceptibility using MRI depends on inverting a forward relationship between the susceptibility and measured Larmor frequency. However, an often-overlooked constraint in susceptibility fitting is that the Larmor frequency is only measured inside the sample, and after background field removal, susceptibility sources should only reside inside the same sample. Here we test the impact of accounting for such effects in susceptibility fitting and demonstrate that such effects should not be ignored.

physics.med-ph

Larmor frequency shift from magnetized cylinders with arbitrary orientation distribution

We present a theoretical framework for the NMR and MRI measured Larmor frequency in media with magnetized microstructure using the mesoscopic Lorentz sphere and the principle of coarse graining. We obtain an analytical expression for infinite cylinders with arbitrary orientation dispersion and show how it depends on the fiber orientation distribution, measurable using diffusion MRI. Through simulations, we scrutinize the framework including the effect of the shape and size of the Lorentz cavity and validate our result for cylinders.

physics.med-ph