Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1

Dinesh K Deelchand; James M Joers; Adarsh Ravishankar; Tianmeng Lyu; Uzay E. Emir; Diane Hutter; Christopher M. Gomez; Khalaf O. Bushara; Christophe Lenglet; Lynn E Eberly; Gulin Oz

doi:10.1002/mdc3.12804

Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1

Dinesh K Deelchand, James M Joers, Adarsh Ravishankar, Tianmeng Lyu, Uzay E. Emir, Diane Hutter, Christopher M. Gomez, Khalaf O. Bushara, Christophe Lenglet, Lynn E Eberly, Gulin Oz

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Spinocerebellar ataxia type 1 (SCA1) causes progressive degeneration of the cerebellum and brainstem. Volumetric magnetic resonance imaging (MRI) was shown to be more sensitive to disease progression than the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia (SARA), in longitudinal studies, and magnetic resonance spectroscopy (MRS) was shown to detect neurochemical abnormalities with high sensitivity cross-sectionally in SCA1.

Objectives: The objectives of this study were to compare the sensitivities to change of volumetric MRI, MRS, and SARA in a 3-year longitudinal study in SCA1.

Methods: A total of 16 early-to-moderate stage patients with SCA1 (SARA 0-14) and 21 matched healthy participants were scanned up to 3 times with 1.5-year intervals. Ataxia severity was assessed with SARA. T 1-weighted images and magnetic resonance spectra from the cerebellar vermis, cerebellar white matter, and pons were acquired at 3T.

Results: The pontine total N-acetylaspartate-to- myo-inositol ratio was the most sensitive MRS measure to change (-3.9 ± 4.6%/yr in SCA1 vs. -0.3 ± 3.5%/yr in controls; P < 0.02), and the pontine volume was the most sensitive MRI measure to change (-2.6 ± 1.2%/yr in SCA1 vs. -0.1 ± 1.2 in controls; P < 0.02). Effect size (mean percent change/standard deviation of percent change) of pontine volume was highest (-2.13) followed by pontine N-acetylaspartate-to- myo-inositol ratio (-0.84) and SARA (+0.60). The pontine N-acetylaspartate-to- myo-inositol ratio was abnormal for 1 premanifest patient at all visits and predicted study withdrawal as a result of disease progression in 3 patients.

Conclusion: Both MRI and MRS were more sensitive to disease progression than SARA in SCA1. Pontine volume was most sensitive to change, whereas MRS may have more sensitivity at the premanifest stage and predictive value for disease progression.

Original language	English (US)
Pages (from-to)	549-558
Number of pages	10
Journal	Movement Disorders Clinical Practice
Volume	6
Issue number	7
DOIs	https://doi.org/10.1002/mdc3.12804
State	Published - Sep 1 2019

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Publisher Copyright:
© 2019 International Parkinson and Movement Disorder Society

Keywords

biomarker
effect size
magnetic resonance spectroscopy
volumetry

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10.1002/mdc3.12804

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Deelchand, D. K., Joers, J. M., Ravishankar, A., Lyu, T., Emir, U. E., Hutter, D., Gomez, C. M., Bushara, K. O., Lenglet, C., Eberly, L. E., & Oz, G. (2019). Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1. Movement Disorders Clinical Practice, 6(7), 549-558. https://doi.org/10.1002/mdc3.12804

Deelchand, DK , Joers, JM, Ravishankar, A, Lyu, T, Emir, UE, Hutter, D, Gomez, CM, Bushara, KO, Lenglet, C , Eberly, LE & Oz, G 2019, 'Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1', Movement Disorders Clinical Practice, vol. 6, no. 7, pp. 549-558. https://doi.org/10.1002/mdc3.12804

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title = "Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1",

abstract = "Background: Spinocerebellar ataxia type 1 (SCA1) causes progressive degeneration of the cerebellum and brainstem. Volumetric magnetic resonance imaging (MRI) was shown to be more sensitive to disease progression than the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia (SARA), in longitudinal studies, and magnetic resonance spectroscopy (MRS) was shown to detect neurochemical abnormalities with high sensitivity cross-sectionally in SCA1.Objectives: The objectives of this study were to compare the sensitivities to change of volumetric MRI, MRS, and SARA in a 3-year longitudinal study in SCA1.Methods: A total of 16 early-to-moderate stage patients with SCA1 (SARA 0-14) and 21 matched healthy participants were scanned up to 3 times with 1.5-year intervals. Ataxia severity was assessed with SARA. T 1-weighted images and magnetic resonance spectra from the cerebellar vermis, cerebellar white matter, and pons were acquired at 3T. Results: The pontine total N-acetylaspartate-to- myo-inositol ratio was the most sensitive MRS measure to change (-3.9 ± 4.6%/yr in SCA1 vs. -0.3 ± 3.5%/yr in controls; P < 0.02), and the pontine volume was the most sensitive MRI measure to change (-2.6 ± 1.2%/yr in SCA1 vs. -0.1 ± 1.2 in controls; P < 0.02). Effect size (mean percent change/standard deviation of percent change) of pontine volume was highest (-2.13) followed by pontine N-acetylaspartate-to- myo-inositol ratio (-0.84) and SARA (+0.60). The pontine N-acetylaspartate-to- myo-inositol ratio was abnormal for 1 premanifest patient at all visits and predicted study withdrawal as a result of disease progression in 3 patients. Conclusion: Both MRI and MRS were more sensitive to disease progression than SARA in SCA1. Pontine volume was most sensitive to change, whereas MRS may have more sensitivity at the premanifest stage and predictive value for disease progression.",

keywords = "biomarker, effect size, magnetic resonance spectroscopy, volumetry",

author = "Deelchand, {Dinesh K} and Joers, {James M} and Adarsh Ravishankar and Tianmeng Lyu and Emir, {Uzay E.} and Diane Hutter and Gomez, {Christopher M.} and Bushara, {Khalaf O.} and Christophe Lenglet and Eberly, {Lynn E} and Gulin Oz",

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doi = "10.1002/mdc3.12804",

language = "English (US)",

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T1 - Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1

AU - Deelchand, Dinesh K

AU - Joers, James M

AU - Ravishankar, Adarsh

AU - Lyu, Tianmeng

AU - Emir, Uzay E.

AU - Hutter, Diane

AU - Gomez, Christopher M.

AU - Bushara, Khalaf O.

AU - Lenglet, Christophe

AU - Eberly, Lynn E

AU - Oz, Gulin

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Spinocerebellar ataxia type 1 (SCA1) causes progressive degeneration of the cerebellum and brainstem. Volumetric magnetic resonance imaging (MRI) was shown to be more sensitive to disease progression than the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia (SARA), in longitudinal studies, and magnetic resonance spectroscopy (MRS) was shown to detect neurochemical abnormalities with high sensitivity cross-sectionally in SCA1.Objectives: The objectives of this study were to compare the sensitivities to change of volumetric MRI, MRS, and SARA in a 3-year longitudinal study in SCA1.Methods: A total of 16 early-to-moderate stage patients with SCA1 (SARA 0-14) and 21 matched healthy participants were scanned up to 3 times with 1.5-year intervals. Ataxia severity was assessed with SARA. T 1-weighted images and magnetic resonance spectra from the cerebellar vermis, cerebellar white matter, and pons were acquired at 3T. Results: The pontine total N-acetylaspartate-to- myo-inositol ratio was the most sensitive MRS measure to change (-3.9 ± 4.6%/yr in SCA1 vs. -0.3 ± 3.5%/yr in controls; P < 0.02), and the pontine volume was the most sensitive MRI measure to change (-2.6 ± 1.2%/yr in SCA1 vs. -0.1 ± 1.2 in controls; P < 0.02). Effect size (mean percent change/standard deviation of percent change) of pontine volume was highest (-2.13) followed by pontine N-acetylaspartate-to- myo-inositol ratio (-0.84) and SARA (+0.60). The pontine N-acetylaspartate-to- myo-inositol ratio was abnormal for 1 premanifest patient at all visits and predicted study withdrawal as a result of disease progression in 3 patients. Conclusion: Both MRI and MRS were more sensitive to disease progression than SARA in SCA1. Pontine volume was most sensitive to change, whereas MRS may have more sensitivity at the premanifest stage and predictive value for disease progression.

AB - Background: Spinocerebellar ataxia type 1 (SCA1) causes progressive degeneration of the cerebellum and brainstem. Volumetric magnetic resonance imaging (MRI) was shown to be more sensitive to disease progression than the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia (SARA), in longitudinal studies, and magnetic resonance spectroscopy (MRS) was shown to detect neurochemical abnormalities with high sensitivity cross-sectionally in SCA1.Objectives: The objectives of this study were to compare the sensitivities to change of volumetric MRI, MRS, and SARA in a 3-year longitudinal study in SCA1.Methods: A total of 16 early-to-moderate stage patients with SCA1 (SARA 0-14) and 21 matched healthy participants were scanned up to 3 times with 1.5-year intervals. Ataxia severity was assessed with SARA. T 1-weighted images and magnetic resonance spectra from the cerebellar vermis, cerebellar white matter, and pons were acquired at 3T. Results: The pontine total N-acetylaspartate-to- myo-inositol ratio was the most sensitive MRS measure to change (-3.9 ± 4.6%/yr in SCA1 vs. -0.3 ± 3.5%/yr in controls; P < 0.02), and the pontine volume was the most sensitive MRI measure to change (-2.6 ± 1.2%/yr in SCA1 vs. -0.1 ± 1.2 in controls; P < 0.02). Effect size (mean percent change/standard deviation of percent change) of pontine volume was highest (-2.13) followed by pontine N-acetylaspartate-to- myo-inositol ratio (-0.84) and SARA (+0.60). The pontine N-acetylaspartate-to- myo-inositol ratio was abnormal for 1 premanifest patient at all visits and predicted study withdrawal as a result of disease progression in 3 patients. Conclusion: Both MRI and MRS were more sensitive to disease progression than SARA in SCA1. Pontine volume was most sensitive to change, whereas MRS may have more sensitivity at the premanifest stage and predictive value for disease progression.

KW - biomarker

KW - effect size

KW - magnetic resonance spectroscopy

KW - volumetry

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Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1

Abstract

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