Abstract
Introduction: This study aimed to use a novel MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, to assess damage of the white matter and gray matter in multiple system atrophy (MSA). Furthermore, this study investigated whether the sT1w/T2w ratio was associated with cognitive impairment in MSA. Methods: The white matter and gray matter sT1w/T2w ratio of 37 MSA patients and 19 healthy controls were measured. Correlation analyses were used to evaluate the relationship between sT1w/T2w ratio values and clinical variables, and a multivariate analysis was used to identify independent factors associated with cognitive impairment in MSA. Results: MSA patients showed a higher white matter sT1w/T2w ratio value than controls (p < 0.001), and the white matter sT1w/T2w ratio value was significantly correlated with the International Cooperative Ataxia Rating Scale score (r = 0.377, p = 0.021) and the Addenbrooke’s cognitive examination III score (r = −0.438, p = 0.007). Cognitively impaired MSA patients had a significantly higher white matter sT1w/T2w ratio value than cognitively preserved MSA patients (p = 0.010), and the multiple logistic regression analysis revealed that the median white matter sT1w/T2w ratio value was independently associated with cognitive impairment in MSA. Conclusion: The sT1w/T2w ratio is sensitive to degenerative changes in the white matter that is associated with cognitive ability in MSA patients.
References
1.
Gilman
S
, Wenning
GK
, Low
PA
, Brooks
DJ
, Mathias
CJ
, Trojanowski
JQ
, Second consensus statement on the diagnosis of multiple system atrophy
. Neurology
. 2018 Aug
;71
(9
):670
–6
. .2.
Stankovic
I
, Krismer
F
, Jesic
A
, Antonini
A
, Benke
T
, Brown
RG
, Cognitive impairment in multiple system atrophy: a position statement by the neuropsychology task force of the MDS Multiple System Atrophy (MODIMSA) study group
. Mov Disord
. 2014 Jun
;29
(7
):857
–67
.3.
Wang
PS
, Yeh
CL
, Lu
CF
, Wu
HM
, Soong
BW
, Wu
YT
. The involvement of supratentorial white matter in multiple system atrophy: a diffusion tensor imaging tractography study
. Acta Neurol Belg
. 2017 Mar
;117
(1
):213
–20
. .4.
Hara
K
, Watanabe
H
, Bagarinao
E
, Kawabata
K
, Yoneyama
N
, Ohdake
R
, Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy
. J Neurol
. 2018 Sep
;265
(9
):2079
–87
. .5.
Kawabata
K
, Hara
K
, Watanabe
H
, Bagarinao
E
, Ogura
A
, Masuda
M
, Alterations in cognition-related cerebello-cerebral networks in multiple system atrophy
. Cerebellum
. 2019 Aug
;18
(4
):770
–80
. .6.
Yang
H
, Luo
X
, Yu
H
, Guo
M
, Cao
C
, Li
Y
, Altered resting-state voxel-level whole-brain functional connectivity in multiple system atrophy patients with cognitive impairment
. Clin Neurophysiol
. 2020 Jan
;131
(1
):54
–62
. .7.
Glasser
MF
, Van Essen
DC
. Mapping human cortical areas in vivo based on myelin content as revealed by T1- and T2-weighted MRI
. J Neurosci
. 2011 Aug
;31
(32
):11597
–616
. .8.
Arshad
M
, Stanley
JA
, Raz
N
. Test-retest reliability and concurrent validity of in vivo myelin content indices: myelin water fraction and calibrated T1w/T2w image ratio
. Hum Brain Mapp
. 2017 Apr
;38
(4
):1780
–90
.9.
Glasser
MF
, Goyal
MS
, Preuss
TM
, Raichle
ME
, Van Essen
DC
. Trends and properties of human cerebral cortex: correlations with cortical myelin content
. Neuroimage
. 2014 Jun
;93
(Pt 2
):165
–75
. .10.
Nakamura
K
, Chen
JT
, Ontaneda
D
, Fox
RJ
, Trapp
BD
. T1-/T2-weighted ratio differs in demyelinated cortex in multiple sclerosis
. Ann Neurol
. 2017 Oct
;82
(4
):635
–9
. .11.
Pelkmans
W
, Dicks
E
, Barkhof
F
, Vrenken
H
, Scheltens
P
, van der Flier
WM
, Gray matter T1-w/T2-w ratios are higher in Alzheimer’s disease
. Hum Brain Mapp
. 2019 Sep
;40
(13
):3900
–9
. .12.
Du
G
, Lewis
MM
, Sica
C
, Kong
L
, Huang
X
. Magnetic resonance T1w/T2w ratio: a parsimonious marker for Parkinson disease
. Ann Neurol
. 2019 Jan
;85
(1
):96
–104
. .13.
Misaki
M
, Savitz
J
, Zotev
V
, Phillips
R
, Yuan
H
, Young
KD
, Contrast enhancement by combining T1- and T2-weighted structural brain MR images
. Magn Reson Med
. 2015 Dec
;74
(6
):1609
–20
. .14.
Cooper
G
, Finke
C
, Chien
C
, Brandt
AU
, Asseyer
S
, Ruprecht
K
, Standardization of T1w/T2w ratio improves detection of tissue damage in multiple sclerosis
. Front Neurol
. 2019 Apr
;10
:334
. .15.
Sugiyama
A
, Yokota
H
, Hirano
S
, Cooper
G
, Mukai
H
, Koide
K
, Magnetic resonance T1w/T2w ratio in the middle cerebellar peduncle might be a sensitive biomarker for multiple system atrophy
. Eur Radiol
. 2021
;31
(6
):4277
–84
.16.
Takenoshita
S
, Terada
S
, Yoshida
H
, Yamaguchi
M
, Yabe
M
, Imai
N
, Validation of Addenbrooke’s cognitive examination III for detecting mild cognitive impairment and dementia in Japan
. BMC Geriatr
. 2019 Apr
;19
(1
):123
. .17.
So
M
, Foxe
D
, Kumfor
F
, Murray
C
, Hsieh
S
, Savage
G
, Addenbrooke’s cognitive examination III: psychometric characteristics and relations to functional ability in dementia
. J Int Neuropsychol Soc
. 2018 Sep
;24
(8
):854
–63
.18.
Smith
SM
, Jenkinson
M
, Woolrich
MW
, Beckmann
CF
, Behrens
TE
, Johansen-Berg
H
, Advances in functional and structural MR image analysis and implementation as FSL
. NeuroImage
. 2004
;23
(Suppl 1
):S208
–19
. .19.
Zhang
Y
, Brady
M
, Smith
S
. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm
. IEEE Trans Med Imaging
. 2001 Jan
;20
(1
):45
–57
. .20.
Smith
SM
, Jenkinson
M
, Johansen-Berg
H
, Rueckert
D
, Nichols
TE
, Mackay
CE
, Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
. NeuroImage
. 2006 Jul
;31
(4
):1487
–505
. .21.
Trojanowski
JQ
, Revesz
T
. Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy
. Neuropathol Appl Neurobiol
. 2007 Dec
;33
(6
):615
–20
. .22.
Konagaya
M
, Sakai
M
, Matsuoka
Y
, Konagaya
Y
, Hashizume
Y
. Multiple system atrophy with remarkable frontal lobe atrophy
. Acta Neuropathol
. 1999 Apr
;97
(4
):423
–8
. .23.
Papp
MI
, Kahn
JE
, Lantos
PL
. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivoponto cerebellar atrophy and Shy-Drager syndrome)
. J Neurol Sci
. 1989 Dec
;94
(1–3
):79
–100
.24.
Matsusue
E
, Fujii
S
, Kanasaki
Y
, Kaminou
T
, Ohama
E
, Ogawa
T
. Cerebellar lesions in multiple system atrophy: postmortem MR imaging-pathologic correlations
. AJNR Am J Neuroradiol
. 2009 Oct
;30
(9
):1725
–30
. .25.
Burzynska
AZ
, Preuschhof
C
, Bäckman
L
, Nyberg
L
, Li
SC
, Lindenberger
U
, Age-related differences in white matter microstructure: region-specific patterns of diffusivity
. Neuroimage
. 2010 Feb
;49
(3
):2104
–12
. .26.
Righart
R
, Biberacher
V
, Jonkman
LE
, Klaver
R
, Schmidt
P
, Buck
D
, Cortical pathology in multiple sclerosis detected by the T1/T2-weighted ratio from routine magnetic resonance imaging
. Ann Neurol
. 2017 Oct
;82
(4
):519
–29
. .27.
Uddin
MN
, Figley
TD
, Marrie
RA
, Figley
CR
; For the CCOMS Study Group
. Can T1w/T2w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1w/T2w ratios, GRASE-based T1w/T2w ratios and multi-echo GRASE-based myelin water fractions
. NMR Biomed
. 2018 Mar
;31
(3
).28.
Hagiwara
A
, Hori
M
, Kamagata
K
, Warntjes
M
, Matsuyoshi
D
, Nakazawa
M
, Myelin measurement: comparison between simultaneous tissue relaxometry, magnetization transfer saturation index, and T1w/T2w ratio methods
. Sci Rep
. 2018 Jul
;8
(1
):10554
. .29.
Brück
W
, Bitsch
A
, Kolenda
H
, Brück
Y
, Stiefel
M
, Lassmann
H
. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology
. Ann Neurol
. 1997 Nov
;42
(5
):783
–93
. .30.
Kanda
T
, Nakai
Y
, Aoki
S
, Oba
H
, Toyoda
K
, Kitajima
K
, Contribution of metals to brain MR signal intensity: review articles
. Jpn J Radiol
. 2016 Apr
;34
(4
):258
–66
. .31.
Kaindlstorfer
C
, Jellinger
KA
, Eschlböck
S
, Stefanova
N
, Weiss
G
, Wenning
GK
. The relevance of iron in the pathogenesis of multiple system atrophy: a viewpoint
. J Alzheimers Dis
. 2018
;61
(4
):1253
–73
. .32.
Visanji
NP
, Collingwood
JF
, Finnegan
ME
, Tandon
A
, House
E
, Hazrati
LN
. Iron deficiency in parkinsonism: region-specific iron dysregulation in Parkinson’s disease and multiple system atrophy
. J Parkinsons Dis
. 2013
;3
(4
):523
–37
.33.
Mills
JD
, Kim
WS
, Halliday
GM
, Janitz
M
. Transcriptome analysis of grey and white matter cortical tissue in multiple system atrophy
. Neurogenetics
. 2015 Apr
;16
(2
):107
–22
. .© 2021 S. Karger AG, Basel
2021
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
