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Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis

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Abstract

Objectives

To explore the sensitivity of potential DTI-based biomarkers in detecting microstructural changes for whole-brain white matter in early stage amyotrophic lateral sclerosis (ALS), analyze the relationship between the DTI indices and disease status, and further clarify potential brain regions for disease monitoring and clinical assessment.

Methods

Thirty-three non-demented ALS patients and 32 age- and gender-matched subjects participated in this study. DTI data were acquired via 3.0T MRI scanner. Maps of diffusion-related indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were obtained. Tract-based spatial statistics (TBSS) were used to investigate whole-brain white matter changes of each index. Correlation analyses between both brain-wide and volume-of-interest (VOI)-wide white matter alterations and clinical factors including ALSFRS-R scores, disease duration, and progression rate were performed.

Results

Compared to healthy subjects, ALS patients showed significantly increased RD, MD and reduced FA, mainly along the corticospinal tract (CST) and the body of corpus callosum (CC). Increases in RD were broader than decreases in FA, in CST of both hemispheres. Meanwhile, involvement of several extra-motor regions was also revealed by RD. Significant positive correlation between ALSFRS-R scores and FA, negative correlation between ALSFRS-R and RD were found in left CST.

Conclusions

RD may be the most sensitive biomarker for the detection of early demyelination of white matter. Both RD and FA may serve as objective biomarkers for disease severity assessment. CST may be the most affected brain region in non-demented ALS.

Key Points

• Changes in RD were broader than those in FA in bilateral CST.

• Involvement of extra-motor regions was uncovered by RD.

• FA and RD in CST were related to ALSFRS-R scores.

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Abbreviations

AD:

Axial diffusivity

ALS:

Amyotrophic lateral sclerosis

ALSFRS-R :

Revised ALS Functional Rating Scale

CC:

Corpus callosum

CST:

Corticospinal tract

FA:

Fractional anisotropy

FTD:

Frontotemporal dementia

HC:

Healthy controls

LMN:

Lower motor neurons

MD:

Mean diffusivity

PLIC:

Posterior limb of internal capsule

RD:

Radial diffusivity

TBSS:

Tract-based spatial statistics

UMN:

Upper motor neurons

VOI:

Volumes-of-interest

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Acknowledgements

The authors sincerely thank all patients with ALS and their families, as well as the healthy volunteers who kindly agreed to participate in the present study.

Funding

This study has received funding by the Scientific Research project supported by Huashan Hospital, Fudan University (2016QD15, 2016QD085), the Science and Technology Commission of Shanghai Municipality (16410722800, 17411953700), and the National Natural Science Foundation of China (81301203).

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Author notes

  1. Yifang Bao and Liqin Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China

    Yifang Bao, Liqin Yang, Haiqing Li, Weijun Tang, Daoying Geng & Yuxin Li

  2. Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, China

    Yifang Bao, Liqin Yang, Haiqing Li, Weijun Tang, Daoying Geng & Yuxin Li

  3. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China

    Yan Chen

  4. Department of Radiotherapy, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China

    Biyun Zhang

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  1. Yifang Bao
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  3. Yan Chen
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Corresponding authors

Correspondence to Daoying Geng or Yuxin Li.

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The scientific guarantor of this publication is Yuxin Li.

Conflict of interest

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

No complex statistical methods were necessary for this paper.

Informed consent

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

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Institutional Review Board approval was obtained.

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

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Bao, Y., Yang, L., Chen, Y. et al. Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis. Eur Radiol 28, 4940–4948 (2018). https://doi.org/10.1007/s00330-018-5506-z

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