Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis

Thomas Welton, Jerome J. Maller, R. Marc Lebel, Ek T. Tan, Dominic B. Rowe, Stuart M. Grieve

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: To construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS). Methods: Clinical and MRI data were obtained from 21 ALS patients (aged 54 ± 14 years, 33% female) and 63 age- and gender-matched controls (aged 48 ± 18 years, 43% female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression. Results: The ALS group had mild-to-moderate impairment (disease duration: 1.8 ± 0.8 years; ALS functional rating scale 40.2 ± 6.0; forced vital capacity 83% ± 22%). No age or gender differences were present between groups. We found significant group differences in diffusion kurtosis metrics (apparent, mean, radial and axial kurtosis: p < .01) and iron deposition in the motor cortex (p = .03). Within the ALS group, we found significant relationships between motor cortex volume, apparent diffusion and disease duration (adjusted R2 = 0.27, p = .011); and between the apparent and radial kurtosis metrics and ALS functional rating scale (adjusted R2 = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83% (81% sensitivity, 85% specificity) and an area-under-the-curve of 0.86. Conclusion: Diffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.

LanguageEnglish
Article number101953
Pages1-8
Number of pages8
JournalNeuroImage: Clinical
Volume24
DOIs
Publication statusPublished - 22 Jul 2019

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Amyotrophic Lateral Sclerosis
Motor Cortex
Iron
Biomarkers
Linear Models
Cerebrovascular Circulation
Vital Capacity
Area Under Curve
Angiography
Sensitivity and Specificity

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Amyotrophic lateral sclerosis (178)
  • Diffusion kurtosis imaging (additional)
  • DWI (128)
  • Magnetic resonance imaging (120)
  • Motor cortex (311)

Cite this

Welton, Thomas ; Maller, Jerome J. ; Lebel, R. Marc ; Tan, Ek T. ; Rowe, Dominic B. ; Grieve, Stuart M. / Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis. In: NeuroImage: Clinical. 2019 ; Vol. 24. pp. 1-8.
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abstract = "Objective: To construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS). Methods: Clinical and MRI data were obtained from 21 ALS patients (aged 54 ± 14 years, 33{\%} female) and 63 age- and gender-matched controls (aged 48 ± 18 years, 43{\%} female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression. Results: The ALS group had mild-to-moderate impairment (disease duration: 1.8 ± 0.8 years; ALS functional rating scale 40.2 ± 6.0; forced vital capacity 83{\%} ± 22{\%}). No age or gender differences were present between groups. We found significant group differences in diffusion kurtosis metrics (apparent, mean, radial and axial kurtosis: p < .01) and iron deposition in the motor cortex (p = .03). Within the ALS group, we found significant relationships between motor cortex volume, apparent diffusion and disease duration (adjusted R2 = 0.27, p = .011); and between the apparent and radial kurtosis metrics and ALS functional rating scale (adjusted R2 = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83{\%} (81{\%} sensitivity, 85{\%} specificity) and an area-under-the-curve of 0.86. Conclusion: Diffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.",
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Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis. / Welton, Thomas; Maller, Jerome J.; Lebel, R. Marc; Tan, Ek T.; Rowe, Dominic B.; Grieve, Stuart M.

In: NeuroImage: Clinical, Vol. 24, 101953, 22.07.2019, p. 1-8.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis

AU - Welton, Thomas

AU - Maller, Jerome J.

AU - Lebel, R. Marc

AU - Tan, Ek T.

AU - Rowe, Dominic B.

AU - Grieve, Stuart M.

N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/7/22

Y1 - 2019/7/22

N2 - Objective: To construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS). Methods: Clinical and MRI data were obtained from 21 ALS patients (aged 54 ± 14 years, 33% female) and 63 age- and gender-matched controls (aged 48 ± 18 years, 43% female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression. Results: The ALS group had mild-to-moderate impairment (disease duration: 1.8 ± 0.8 years; ALS functional rating scale 40.2 ± 6.0; forced vital capacity 83% ± 22%). No age or gender differences were present between groups. We found significant group differences in diffusion kurtosis metrics (apparent, mean, radial and axial kurtosis: p < .01) and iron deposition in the motor cortex (p = .03). Within the ALS group, we found significant relationships between motor cortex volume, apparent diffusion and disease duration (adjusted R2 = 0.27, p = .011); and between the apparent and radial kurtosis metrics and ALS functional rating scale (adjusted R2 = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83% (81% sensitivity, 85% specificity) and an area-under-the-curve of 0.86. Conclusion: Diffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.

AB - Objective: To construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS). Methods: Clinical and MRI data were obtained from 21 ALS patients (aged 54 ± 14 years, 33% female) and 63 age- and gender-matched controls (aged 48 ± 18 years, 43% female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression. Results: The ALS group had mild-to-moderate impairment (disease duration: 1.8 ± 0.8 years; ALS functional rating scale 40.2 ± 6.0; forced vital capacity 83% ± 22%). No age or gender differences were present between groups. We found significant group differences in diffusion kurtosis metrics (apparent, mean, radial and axial kurtosis: p < .01) and iron deposition in the motor cortex (p = .03). Within the ALS group, we found significant relationships between motor cortex volume, apparent diffusion and disease duration (adjusted R2 = 0.27, p = .011); and between the apparent and radial kurtosis metrics and ALS functional rating scale (adjusted R2 = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83% (81% sensitivity, 85% specificity) and an area-under-the-curve of 0.86. Conclusion: Diffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.

KW - Amyotrophic lateral sclerosis (178)

KW - Diffusion kurtosis imaging (additional)

KW - DWI (128)

KW - Magnetic resonance imaging (120)

KW - Motor cortex (311)

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