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Ultra-strong diffusion-weighted MRI reveals cerebellar grey matter abnormalities in movement disorders

Tax, Chantal M W ; Genc, Sila ; MacIver, Claire L ; Nilsson, Markus LU ; Wardle, Mark ; Szczepankiewicz, Filip LU orcid ; Jones, Derek K and Peall, Kathryn J (2023) In NeuroImage: Clinical 38. p.1-9
Abstract

Structural brain MRI has proven invaluable in understanding movement disorder pathophysiology. However, most work has focused on grey/white matter volumetric (macrostructural) and white matter microstructural effects, limiting understanding of frequently implicated grey matter microstructural differences. Using ultra-strong spherical tensor encoding diffusion-weighted MRI, a persistent MRI signal was seen in healthy cerebellar grey matter even at high diffusion-weightings (b ​≥ 10,000 s/mm2). Quantifying the proportion of this signal (denoted fs), previously ascertained to originate from inside small spherical spaces, provides a potential proxy for cell body density. In this work, this approach was applied for the first time to a... (More)

Structural brain MRI has proven invaluable in understanding movement disorder pathophysiology. However, most work has focused on grey/white matter volumetric (macrostructural) and white matter microstructural effects, limiting understanding of frequently implicated grey matter microstructural differences. Using ultra-strong spherical tensor encoding diffusion-weighted MRI, a persistent MRI signal was seen in healthy cerebellar grey matter even at high diffusion-weightings (b ​≥ 10,000 s/mm2). Quantifying the proportion of this signal (denoted fs), previously ascertained to originate from inside small spherical spaces, provides a potential proxy for cell body density. In this work, this approach was applied for the first time to a clinical cohort, including patients with diagnosed movement disorders in which the cerebellum has been implicated in symptom pathophysiology. Five control participants (control group 1, median age 24.5 years (20-39 years), imaged at two timepoints, demonstrated consistency in measurement of all three measures - MD (Mean Diffusivity) fs, and Ds (dot diffusivity)- with intraclass correlation coefficients (ICC) of 0.98, 0.86 and 0.76, respectively. Comparison with an older control group (control group 2 (n = 5), median age 51 years (43-58 years)) found no significant differences, neither with morphometric nor microstructural (MD (p = 0.36), fs (p = 0.17) and Ds (p = 0.22)) measures. The movement disorder cohort (Parkinson's Disease, n = 5, dystonia, n = 5. Spinocerebellar Ataxia 6, n = 5) when compared to the age-matched control cohort (Control Group 2) identified significantly lower MD (p < 0.0001 and p < 0.0001) and higher fs values (p < 0.0001 and p < 0.0001) in SCA6 and dystonia cohorts respectively. Lobar division of the cerebellum found these same differences in the superior and inferior posterior lobes, while no differences were seen in either the anterior lobes or with Ds measurements. In contrast to more conventional measures from diffusion tensor imaging, this framework provides enhanced specificity to differences in restricted spherical spaces in grey matter (including small cells) by eliminating signals from cerebrospinal fluid and axons. In the context of human and animal histopathology studies, these findings potentially implicate the cerebellar Purkinje and granule cells as contributors to the observed signal differences, with both cell types having been implicated in several neurological disorders through both postmortem and animal model studies. This novel microstructural imaging approach shows promise for improving movement disorder diagnosis, prognosis, and treatment.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NeuroImage: Clinical
volume
38
article number
103419
pages
1 - 9
publisher
Elsevier
external identifiers
  • scopus:85159466236
  • pmid:37192563
ISSN
2213-1582
DOI
10.1016/j.nicl.2023.103419
language
English
LU publication?
yes
additional info
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
id
208a3c71-aed8-4e12-b1f4-71c839f011a8
date added to LUP
2023-06-01 13:51:10
date last changed
2024-06-15 03:42:56
@article{208a3c71-aed8-4e12-b1f4-71c839f011a8,
  abstract     = {{<p>Structural brain MRI has proven invaluable in understanding movement disorder pathophysiology. However, most work has focused on grey/white matter volumetric (macrostructural) and white matter microstructural effects, limiting understanding of frequently implicated grey matter microstructural differences. Using ultra-strong spherical tensor encoding diffusion-weighted MRI, a persistent MRI signal was seen in healthy cerebellar grey matter even at high diffusion-weightings (b ​≥ 10,000 s/mm2). Quantifying the proportion of this signal (denoted fs), previously ascertained to originate from inside small spherical spaces, provides a potential proxy for cell body density. In this work, this approach was applied for the first time to a clinical cohort, including patients with diagnosed movement disorders in which the cerebellum has been implicated in symptom pathophysiology. Five control participants (control group 1, median age 24.5 years (20-39 years), imaged at two timepoints, demonstrated consistency in measurement of all three measures - MD (Mean Diffusivity) fs, and Ds (dot diffusivity)- with intraclass correlation coefficients (ICC) of 0.98, 0.86 and 0.76, respectively. Comparison with an older control group (control group 2 (n = 5), median age 51 years (43-58 years)) found no significant differences, neither with morphometric nor microstructural (MD (p = 0.36), fs (p = 0.17) and Ds (p = 0.22)) measures. The movement disorder cohort (Parkinson's Disease, n = 5, dystonia, n = 5. Spinocerebellar Ataxia 6, n = 5) when compared to the age-matched control cohort (Control Group 2) identified significantly lower MD (p &lt; 0.0001 and p &lt; 0.0001) and higher fs values (p &lt; 0.0001 and p &lt; 0.0001) in SCA6 and dystonia cohorts respectively. Lobar division of the cerebellum found these same differences in the superior and inferior posterior lobes, while no differences were seen in either the anterior lobes or with Ds measurements. In contrast to more conventional measures from diffusion tensor imaging, this framework provides enhanced specificity to differences in restricted spherical spaces in grey matter (including small cells) by eliminating signals from cerebrospinal fluid and axons. In the context of human and animal histopathology studies, these findings potentially implicate the cerebellar Purkinje and granule cells as contributors to the observed signal differences, with both cell types having been implicated in several neurological disorders through both postmortem and animal model studies. This novel microstructural imaging approach shows promise for improving movement disorder diagnosis, prognosis, and treatment.</p>}},
  author       = {{Tax, Chantal M W and Genc, Sila and MacIver, Claire L and Nilsson, Markus and Wardle, Mark and Szczepankiewicz, Filip and Jones, Derek K and Peall, Kathryn J}},
  issn         = {{2213-1582}},
  language     = {{eng}},
  pages        = {{1--9}},
  publisher    = {{Elsevier}},
  series       = {{NeuroImage: Clinical}},
  title        = {{Ultra-strong diffusion-weighted MRI reveals cerebellar grey matter abnormalities in movement disorders}},
  url          = {{http://dx.doi.org/10.1016/j.nicl.2023.103419}},
  doi          = {{10.1016/j.nicl.2023.103419}},
  volume       = {{38}},
  year         = {{2023}},
}