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Amide signal intensities may be reduced in the motor cortex and the corticospinal tract of ALS patients

  • Magnetic Resonance
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Abstract

Objectives

The aim of the study is to assess amide concentration changes in ALS patients compared with healthy controls by using quantitative amide proton transfer (APT) and multiparameter magnetic resonance imaging, and testing its correlation with clinical scores.

Methods

Sixteen ALS patients and sixteen healthy controls were recruited as part of the Canadian ALS Neuroimaging Consortium, and multimodal magnetic resonance imaging was performed at 3 T, including APT and diffusion imaging. Lorentz fitting was used to quantify the amide effect. Clinical disability was evaluated using the revised ALS functional rating scale (ALSFRS-R), and its correlation with image characteristics was assessed. The diagnostic performance of different imaging parameters was evaluated with receiver operating characteristic analysis.

Results

Our results showed that the amide peak was significantly different between the motor cortex and other gray matter territories within the brain of ALS patients (p < 0.001). Compared with controls, amide signal intensities in ALS were significantly reduced in the motor cortex (p < 0.001) and corticospinal tract (p = 0.046), while abnormalities were not detected using routine imaging methods. There was no significant correlation between amide and ALSFRS-R score. The diagnostic accuracy of the amide peak was superior to that of diffusion imaging.

Conclusions

This study demonstrated changes of amide signal intensities in the motor cortex and corticospinal tract of ALS patients.

Key Points

• The neurodegenerative disease amyotrophic lateral sclerosis (ALS) has a lack of objective imaging indicators for diagnosis and assessment.

• Analysis of amide proton transfer imaging revealed changes in the motor cortex and corticospinal tract of ALS patients that were not visible on standard magnetic resonance imaging.

• The diagnostic accuracy of the amide peak was superior to that of diffusion imaging.

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Abbreviations

ADC:

Apparent diffusion coefficient

ALS:

Amyotrophic lateral sclerosis

ALSFRS-R:

Revised ALS functional rating scale

ANCOVA:

Analysis of covariance

APT:

Amide proton transfer

ASICs:

Acid-sensing ion channel

CALSNIC:

Canadian ALS neuroimaging consortium

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

MT:

Magnetization transfer

NOE:

Nuclear Overhauser effect

RIPK1:

Receptor-interacting serine/threonine-protein kinase 1

ROC:

Receiver operating characteristic

ROI:

Region of interest

WASSR:

Water saturation shift reference

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Acknowledgments

Grateful acknowledgment is made to Dr. Mark D. Pagel from MD Anderson Cancer Center and Dr. Edward A. Randtke from the University of Arizona for technical assistance with pulse sequence implementation.

Funding

This study has received funding from the Canadian Institutes of Health Research to A.H.W.; the ALS Society of Canada and Brain Canada to S.K.; the Natural Science Foundation of China (grant numbers 81471730, 31870981) to R.W.; the 2020 La Ka Shing Foundation Cross-DisciplinaryResearch Grant (grant number 2020LKSFG06C) to Z.D.; the Department of Education Guangdong Province (grant number 2020KZDZX1085) to Z.D. and the Natural Science Foundation of Guangdong Province (grant number 2018A030307057) to Z.D.

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Authors and Affiliations

  1. Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, China

    Zhuozhi Dai & Renhua Wu

  2. Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, T6G 2V2, Canada

    Zhuozhi Dai, Peter Seres & Alan H. Wilman

  3. Department of Medicine (Neurology), University of Alberta, Edmonton, Alberta, T6G 2S2, Canada

    Sanjay Kalra & Dennell Mah

  4. School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, Queensland, 4072, Australia

    Hongfu Sun

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  1. Zhuozhi Dai
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  2. Sanjay Kalra
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  4. Peter Seres
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  5. Hongfu Sun
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  6. Renhua Wu
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  7. Alan H. Wilman
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Correspondence to Renhua Wu or Alan H. Wilman.

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The scientific guarantor of this publication is Alan H. Wilman.

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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors, Professor Sanjay Kalra, has significant statistical expertise.

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Written informed consent was obtained from all subjects (patients) in this study.

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• case-control study

• performed at one institution

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Dai, Z., Kalra, S., Mah, D. et al. Amide signal intensities may be reduced in the motor cortex and the corticospinal tract of ALS patients. Eur Radiol 31, 1401–1409 (2021). https://doi.org/10.1007/s00330-020-07243-4

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