Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders

Menno D. Stellingwerff; Murtadha L. Al-Saady; Kwok Shing Chan; Adam Dvorak; José P. Marques; Shannon Kolind; Stefan D. Roosendaal; Nicole I. Wolf; Frederik Barkhof; Marjo S. van der Knaap; Petra J.W. Pouwels

doi:10.1111/jon.13167

Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders

Menno D. Stellingwerff, Murtadha L. Al-Saady, Kwok Shing Chan, Adam Dvorak, José P. Marques, Shannon Kolind, Stefan D. Roosendaal, Nicole I. Wolf, Frederik Barkhof, Marjo S. van der Knaap, Petra J.W. Pouwels^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Background and purpose: Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole-brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi-compartment relaxometry diffusion-informed MWI: MCR-DIMWI, and multi-echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI). Methods: For 9 patients with different leukodystrophies (age range 0.4-62.4 years) and 15 control subjects (2.3-61.3 years), T1-weighted MRI, fluid-attenuated inversion recovery, multi-echo gradient echo with variable flip angles, METRICS, and multi-shell diffusion-weighted imaging were acquired on 3 Tesla. MCR-DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi-level analyses were performed. Results: MCR-DIMWI and METRICS-derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR-DIMWI-MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS-MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR-DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other. Conclusion: This proof-of-concept study shows that MCR-DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders.

Original language	English
Pages (from-to)	61-77
Number of pages	17
Journal	Journal of Neuroimaging
Volume	34
Issue number	1
Early online date	4 Nov 2023
DOIs	https://doi.org/10.1111/jon.13167
Publication status	Published - Feb 2024

Bibliographical note

Funding Information:
We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN-RND, project ID 739510). The work of Kwok-Shing Chan and José Marques is part of the research program FOM-N-31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co-owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands.

Funding Information:
We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN‐RND, project ID 739510). The work of Kwok‐Shing Chan and José Marques is part of the research program FOM‐N‐31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co‐owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands.

Publisher Copyright:
© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.

Funding

We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN-RND, project ID 739510). The work of Kwok-Shing Chan and José Marques is part of the research program FOM-N-31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co-owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands. We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN‐RND, project ID 739510). The work of Kwok‐Shing Chan and José Marques is part of the research program FOM‐N‐31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co‐owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands.

Funders	Funder number
VU University Medical Center
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	P112686CA00
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

brain
MCR-DIMWI
metrics
myelin water imaging
NODDI
tissue microstructure

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10.1111/jon.13167

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Cite this

@article{3f7d34267f5a4761a60652f0cddb23b9,

title = "Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders",

abstract = "Background and purpose: Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole-brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi-compartment relaxometry diffusion-informed MWI: MCR-DIMWI, and multi-echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI). Methods: For 9 patients with different leukodystrophies (age range 0.4-62.4 years) and 15 control subjects (2.3-61.3 years), T1-weighted MRI, fluid-attenuated inversion recovery, multi-echo gradient echo with variable flip angles, METRICS, and multi-shell diffusion-weighted imaging were acquired on 3 Tesla. MCR-DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi-level analyses were performed. Results: MCR-DIMWI and METRICS-derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR-DIMWI-MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS-MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR-DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other. Conclusion: This proof-of-concept study shows that MCR-DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders.",

keywords = "brain, MCR-DIMWI, metrics, myelin water imaging, NODDI, tissue microstructure",

author = "Stellingwerff, {Menno D.} and Al-Saady, {Murtadha L.} and Chan, {Kwok Shing} and Adam Dvorak and Marques, {Jos{\'e} P.} and Shannon Kolind and Roosendaal, {Stefan D.} and Wolf, {Nicole I.} and Frederik Barkhof and {van der Knaap}, {Marjo S.} and Pouwels, {Petra J.W.}",

note = "Funding Information: We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN-RND, project ID 739510). The work of Kwok-Shing Chan and Jos{\'e} Marques is part of the research program FOM-N-31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co-owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands. Funding Information: We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN‐RND, project ID 739510). The work of Kwok‐Shing Chan and Jos{\'e} Marques is part of the research program FOM‐N‐31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co‐owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands. Publisher Copyright: {\textcopyright} 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.",

year = "2024",

month = feb,

doi = "10.1111/jon.13167",

language = "English",

volume = "34",

pages = "61--77",

journal = "Journal of Neuroimaging",

issn = "1051-2284",

publisher = "Wiley-Blackwell",

number = "1",

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TY - JOUR

T1 - Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders

AU - Stellingwerff, Menno D.

AU - Al-Saady, Murtadha L.

AU - Chan, Kwok Shing

AU - Dvorak, Adam

AU - Marques, José P.

AU - Kolind, Shannon

AU - Roosendaal, Stefan D.

AU - Wolf, Nicole I.

AU - Barkhof, Frederik

AU - van der Knaap, Marjo S.

AU - Pouwels, Petra J.W.

N1 - Funding Information: We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN-RND, project ID 739510). The work of Kwok-Shing Chan and José Marques is part of the research program FOM-N-31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co-owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands. Funding Information: We want to thank Marije Voermans, Stephanie van der Stadt, Hemmo Yska, and Petra Kroonenburg for their help in acquiring the MRI data, Paul Groot for IT support, Bram Coolen for help in implementing the MRI sequences, and Dushyant Kumar for sharing analysis software. The authors affiliated with Amsterdam Leukodystrophy Center are members of the European Reference Network “Rare Neurological Disorders” (ERN‐RND, project ID 739510). The work of Kwok‐Shing Chan and José Marques is part of the research program FOM‐N‐31/16PR1056 supported by the Dutch Research Council (NWO). Nicole Wolf is a consultant for Ionis, Orchard, Vigil Neuro, Passage Bio, and Lilly and coinvestigator for Ionis, Takeda/Shire, and Vigil Neuro for several leukodystrophy trials, without personal payment. She is co‐owner of Aer Beatha, a company for asthma treatment. Marjo van der Knaap is a consultant for Calico (VWM) and coinvestigator for Ionis (Alexander disease trial), without personal payment. She is on patent P112686US00 “therapeutic effects of Guanabenz treatment in vanishing white matter” and on patent P112686CA00 “the use of Guanabenz in the treatment of VWM,” both for the VU University Medical Center, Amsterdam, The Netherlands. Publisher Copyright: © 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.

PY - 2024/2

Y1 - 2024/2

N2 - Background and purpose: Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole-brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi-compartment relaxometry diffusion-informed MWI: MCR-DIMWI, and multi-echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI). Methods: For 9 patients with different leukodystrophies (age range 0.4-62.4 years) and 15 control subjects (2.3-61.3 years), T1-weighted MRI, fluid-attenuated inversion recovery, multi-echo gradient echo with variable flip angles, METRICS, and multi-shell diffusion-weighted imaging were acquired on 3 Tesla. MCR-DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi-level analyses were performed. Results: MCR-DIMWI and METRICS-derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR-DIMWI-MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS-MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR-DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other. Conclusion: This proof-of-concept study shows that MCR-DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders.

AB - Background and purpose: Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole-brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi-compartment relaxometry diffusion-informed MWI: MCR-DIMWI, and multi-echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI). Methods: For 9 patients with different leukodystrophies (age range 0.4-62.4 years) and 15 control subjects (2.3-61.3 years), T1-weighted MRI, fluid-attenuated inversion recovery, multi-echo gradient echo with variable flip angles, METRICS, and multi-shell diffusion-weighted imaging were acquired on 3 Tesla. MCR-DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi-level analyses were performed. Results: MCR-DIMWI and METRICS-derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR-DIMWI-MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS-MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR-DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other. Conclusion: This proof-of-concept study shows that MCR-DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders.

KW - brain

KW - MCR-DIMWI

KW - metrics

KW - myelin water imaging

KW - NODDI

KW - tissue microstructure

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ER -

Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders

Abstract

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