Orientationally invariant indices of axon diameter and density from diffusion MRI

Alexander, Daniel C.; Hubbard, Penny L.; Hall, Matt G.; Moore, Elizabeth A.; Ptito, Maurice; Parker, Geoffrey; Dyrby, Tim B.

doi:10.1016/j.neuroimage.2010.05.043

Cited by 644 publications

(1,029 citation statements)

References 42 publications

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“…The contrast in the in vivo results may therefore reflect the detection of relatively large axon radii in certain parts of the corpus callosum—although our fits from substrates containing gamma distributions of radii suggest that while qualitatively meaningful, our axon radius index values are likely to be overestimates. Nevertheless, while Alexander et al 4 and Dyrby et al 8 have suggested that only very weak sensitivity to axon radius index is available at clinical gradient strengths, we have shown that using suitable priors can ameliorate the situation.…”

Section: Discussionmentioning

confidence: 57%

“…Refs. 4 and 25). We denote the isotropic volume fraction with f i and the restricted volume fraction with f r , subject to

0 \leq f_{normali} + f_{normalr} \leq 1

.…”

Section: Methodsmentioning

confidence: 99%

“…Generative radii were

R \in {5, 10, 20}

μm, as in Ref. 4, with the optimization seeking a combination of pulse arrangements that jointly minimize average expected variance in the model parameters across these three values (although large relative to the expected radii in most tissue, they represent the domain where we expect some sensitivity at low gradient strength). No assumptions were made about the orientations of the axon bundles within the voxel, and gradient directions for each arrangement were therefore uniformly spread over the sphere.…”

Section: Methodsmentioning

confidence: 99%

“…The tissue models are typically built up from simple geometric shapes such as cylinders and spheres, but despite their simplicity they may be able to provide more direct tissue microstructure parameters than can be obtained from traditional diffusion‐weighted magnetic resonance imaging analysis 4, 5, 6. These model parameters may in turn offer greater interpretability and sensitivity as biomarkers.…”

Section: Introductionmentioning

confidence: 99%

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Microstructural parameter estimation in vivo using diffusion MRI and structured prior information

Clayden

Nagy

Weiskopf

et al. 2015

Magnetic Resonance in Med

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PurposeDiffusion MRI has recently been used with detailed models to probe tissue microstructure. Much of this work has been performed ex vivo with powerful scanner hardware, to gain sensitivity to parameters such as axon radius. By contrast, performing microstructure imaging on clinical scanners is extremely challenging.MethodsWe use an optimized dual spin‐echo diffusion protocol, and a Bayesian fitting approach, to obtain reproducible contrast (histogram overlap of up to 92%) in estimated maps of axon radius index in healthy adults at a modest, widely‐available gradient strength (35 mT m −1). A key innovation is the use of influential priors.ResultsWe demonstrate that our priors can improve precision in axon radius estimates—a 7‐fold reduction in voxelwise coefficient of variation in vivo—without significant bias. Our results may reflect true axon radius differences between white matter regions, but this interpretation should be treated with caution due to the complexity of the tissue relative to our model.ConclusionsSome sensitivity to relatively large axons (3–15 μm) may be available at clinical field and gradient strengths. Future applications at higher gradient strength will benefit from the favorable eddy current properties of the dual spin‐echo sequence, and greater precision available with suitable priors. Magn Reson Med, 2015. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Magn Reson Med 75:1787–1796, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

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Section: Discussionmentioning

confidence: 57%

“…Refs. 4 and 25). We denote the isotropic volume fraction with f i and the restricted volume fraction with f r , subject to

0 \leq f_{normali} + f_{normalr} \leq 1

.…”

Section: Methodsmentioning

confidence: 99%

“…Generative radii were

R \in {5, 10, 20}

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Microstructural parameter estimation in vivo using diffusion MRI and structured prior information

Clayden

Nagy

Weiskopf

et al. 2015

Magnetic Resonance in Med

Self Cite

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“…However, scan times are long and the high 7T magnetic field and maximum gradient strength (400 mT/m) are impossible to achieve on a live human scanners, that typically operate at 1.5-3T and can achieve maximum gradient strength between 30-60 mT/m. Alexander et al [4] demonstrates measurements of axon diameter and density in the live human brain on a standard clinical scanner using a simplified AxCalibre model and multi shell high angular resolution diffusion imaging (HARDI). The method relies on an experiment design optimization [5] to achieve sensitivity without the need of high gradient strengths and long acquisition times.…”

Section: Introductionmentioning

confidence: 99%

In-Vivo Estimates of Axonal Characteristics Using Optimized Diffusion MRI Protocols for Single Fibre Orientation

Schneider

Wheeler‐Kingshott

Alexander

2010

Medical Image Computing and Computer-Assisted Intervention – MICCAI 2010

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Abstract. This work presents diffusion MR protocols that allow estimation of axonal parameters like diameter and density in the live human brain. Previous approaches demand very high field experimental systems or suffer from long acquisition times and are therefore impractical for use in clinical studies. We propose a method that significantly reduces scan time by making use of the a-priori known fibre orientation in structures with well defined single fibre (SF) organisation like the corpus callosum (CC) and produces protocols that can be performed in under 25 minutes on a standard clinical system. Results from a computer simulation experiment show that our SF protocols can generate parameter estimates with similar precision to previously proposed orientation invariant (OI) protocols. Furthermore, we acquire the 20 minute long SF protocol and the 1 hour long OI protocol in a scan/rescan study on two healthy subjects and compare the axonal parameter maps from both protocols.

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Synaptic Density in Early Stages of Psychosis and Clinical High Risk

Blasco,

Nisha Aji,

Ramos-Jiménez

et al. 2024

JAMA Psychiatry

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ImportanceSynaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear.ObjectiveTo investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups.Design, Setting, and ParticipantsThis cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis).Main Outcomes and MeasuresSynaptic density was quantified with dynamic 90-minute [18F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density.ResultsA total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (F2,273 = 4.02, P = .02, Cohen F = 0.17; ROI: F5,273 = 360.18, P &lt; .01, Cohen F = 2.55) with a group × ROI interaction (F10,273 = 2.67, P &lt; .01, Cohen F = 0.32). Synaptic density was lower in cannabis users (F1,272 = 5.31, P = .02, Cohen F = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: F1,81 = 4.31, P = .04, Cohen F = 0.23; Scale of Psychosis-Risk Symptoms negative scores: F1,90 = 4.12, P = .04, Cohen F = 0.21). SV2A binding potential was significantly associated with neurite density index (F1,138 = 6.76, P = .01, Cohen F = 0.22).Conclusions and RelevanceThis study found that synaptic density reductions were present during the early stages of psychosis and its risk states and associated with negative symptoms. The implications of SV2A for negative symptoms in psychosis and CHR warrant further investigation. Future studies should investigate the impact of cannabis use on synaptic density in CHR longitudinally.

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Orientationally invariant indices of axon diameter and density from diffusion MRI

Cited by 644 publications

References 42 publications

Microstructural parameter estimation in vivo using diffusion MRI and structured prior information

Microstructural parameter estimation in vivo using diffusion MRI and structured prior information

In-Vivo Estimates of Axonal Characteristics Using Optimized Diffusion MRI Protocols for Single Fibre Orientation

Synaptic Density in Early Stages of Psychosis and Clinical High Risk

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