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Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder

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Abstract

Objectives

Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS).

Methods

Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson’s correlation was used to analyze the correlation with clinical symptoms.

Results

The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r =  − 0.323, p < 0.05).

Conclusions

Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD.

Clinical relevance statement

Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder.

Key Points

• Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children.

• The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder.

• The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

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Abbreviations

AC-PC:

Anterior-posterior commissure

ADHD:

Attention-deficit/hyperactivity disorder

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DTI-ALPS:

Diffusion tensor image-analysis along the perivascular space

Dxassoc:

Diffusivity along the x-axis in association fiber area

Dxproj:

Diffusivity along the x-axis in projection fiber area

Dxsubc:

Diffusivity along the x-axis in subcortical fiber area

Dyassoc:

Diffusivity along the y-axis in association fiber area

Dyproj:

Diffusivity along the y-axis in projection fiber area

Dysubc:

Diffusivity along the y-axis in subcortical fiber area

Dzassoc:

Diffusivity along the z-axis in association fiber area

Dzproj:

Diffusivity along the z-axis in projection fiber area

Dzsubc:

Diffusivity along the z-axis in subcortical fiber area

FOV:

Field of view

FSE:

Fast spin-echo

ICC:

Interclass correlation coefficient

ICV:

Intracranial volume

ISF:

Interstitial fluid

NEX:

Number of excitations

SWI:

Susceptibility-weighted imaging

T1-FSPGR:

T1-weighted fast spoiled gradient recalled echo

T2WI:

T2-weighted imaging

TD:

Typical developing

TE:

Echo time

TR:

Repetition time

VRS:

Virchow-Robin spaces

WM:

White matter

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Acknowledgements

We would like to thank the participants and their families as well as the staff at the MRI in the First Affiliated Hospital of Sun Yat-sen University for making this study possible.

This article has been pre-printed on the Research Square, with the https://doi.org/10.21203/rs.3.rs-1922962/v1.

Funding

This study has received funding from the National Natural Science Foundation of China (grant number 82001439) and the Natural Science Fund Project of Guangdong Province (grant number 2022A1515011910).

Author information

Author notes

  1. Yingqian Chen, Miaomiao Wang, and Shu Su contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Yingqian Chen, Shu Su, Yan Dai, Mengsha Zou, Liping Lin, Jianping Chu & Zhiyun Yang

  2. Department of Radiology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Miaomiao Wang, Xianjun Li & Jian Yang

  3. MR Research, GE Healthcare, Beijing, China

    Long Qian

  4. Department of Pediatric, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Hongyu Zhang & Meina Liu

Authors
  1. Yingqian Chen
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  2. Miaomiao Wang
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  3. Shu Su
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  4. Yan Dai
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Corresponding authors

Correspondence to Jian Yang or Zhiyun Yang.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Zhiyun Yang.

Conflict of interest

One of the authors (Long Pian) is an employee of GE Healthcare.

The other 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’ parents in this study.

Ethical approval

This study was approved by the institutional review board of the First Affiliated Hospital of Sun Yat-sen University (No. [2019]328).

Study subjects or cohorts overlap

No study subjects or cohorts have been previously reported.

Methodology

• Prospective

• Cross-sectional study

• Performed at one institution

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Chen, Y., Wang, M., Su, S. et al. Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder. Eur Radiol 34, 1444–1452 (2024). https://doi.org/10.1007/s00330-023-10220-2

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