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Diffusion prepared pseudo-continuous arterial spin labeling reveals blood–brain barrier dysfunction in patients with CADASIL

  • Magnetic Resonance
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

Diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of the blood–brain barrier (BBB). We aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and to analyze the association between the BBB water exchange rate and MRI/clinical features of these patients.

Methods

Forty-one patients with CADASIL and thirty-six age- and sex-matched controls were scanned with DP-pCASL MRI to estimate the BBB water exchange rate (kw). The MRI lesion burden, the modified Rankin scale (mRS), and the neuropsychological scales were also examined. The association between kw and MRI/clinical features was analyzed.

Results

Compared with that in the controls, kw in patients with CADASIL was decreased at normal-appearing white matter (NAWM) (t =  − 4.742, p < 0.001), cortical gray matter (t =  − 5.137, p < 0.001), and deep gray matter (t =  − 3.552, p = 0.001). After adjustment for age, gender, and arterial transit time, kw at NAWM was negatively associated with the volume of white matter hyperintensities (β =  − 0.754, p = 0.001), whereas decreased kw at NAWM was independently associated with an increased risk of abnormal mRS scale (OR = 1.058, 95% CI: 1.013–1.106, p = 0.011) in these patients.

Conclusions

This study found that the BBB water exchange rate was decreased in patients with CADASIL. The decreased BBB water exchange rate was associated with an increased MRI lesion burden and functional dependence of the patients, suggesting the involvement of BBB dysfunction in the pathogenesis of CADASIL.

Clinical relevance statement

DP-pCASL reveals BBB dysfunction in patients with CADASIL. The decreased BBB water exchange rate is associated with MRI lesion burden and functional dependence, indicating the potential of DP-pCASL as an evaluation method for disease severity.

Key Points

• DP-pCASL reveals blood–brain barrier dysfunction in patients with CADASIL.

• Decreased BBB water exchange rate, an indicator of BBB dysfunction detected by DP-pCASL, was associated with MRI/clinical features of patients with CADASIL.

• DP-pCASL can be used as an evaluation method to assess the severity of disease in patients with CADASIL.

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Abbreviations

ASL:

Arterial spin labeling

ATT:

Arterial transit time

BBB:

Blood–brain barrier

CADASIL:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

CBF:

Cerebral blood flow

CGM:

Cortical gray matter

CMBs:

Cerebral microbleeds

DCE-MRI:

Dynamic contrast-enhanced MRI

DGM:

Deep gray matter

DP-pCASL:

Diffusion prepared pseudo-continuous ASL

MD-pCASL:

Multi-delay pseudo-continuous ASL

MMSE:

Mini-Mental State Examination

MoCA:

Montreal Cognitive Assessment

mRS:

Modified Rankin scale

NAWM:

Normal-appearing white matter

ROIs:

Regions of interest

SAS:

Zung’s Self-Rating Anxiety Scale

SDMT:

Symbol Digit Modality Test

SDS:

Zung’s Self-Rating Depression Scale

TMT:

Trail Making Test

WMH:

White matter hyperintensity

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Acknowledgements

The authors acknowledge Yue Wu, Dongbiao Sun, and Dixuan Wu (Institute of Biophysics, Chinese Academy of Sciences) for their contribution to MRI data acquisition. The authors also appreciate the support of Weili Yang (Department of Neurology, Peking University First Hospital) for administrative assistance. Partial technical support for the imaging optimization was provided by Dr. Jing An (Siemens Shenzhen Magnetic Resonance Ltd).

Funding

This study has received funding from the National Natural Science Foundation of China (82101355, 81961128030, 82001804), Scientific Research Seed Fund of the Peking University First Hospital (2021SF06), Key Technologies Research and Development Program of China (2016YFC1300605), National Science and Technology Innovation 2030 Major Program (2022ZD0211901), Youth Innovation Promotion Association of the CAS (2022093), US National Institutes of Health (R01NS114382), and Ministry of Science and Technology of China (2019YFA0707103).

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Author notes

  1. Chen Ling and Jinyuan Zhang contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Neurology, Peking University First Hospital, Beijing, China

    Chen Ling, Li Bai, Yunchuang Sun, Fan Li, Zhaoxia Wang & Yun Yuan

  2. Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China

    Chen Ling, Li Bai, Yunchuang Sun, Fan Li, Zhaoxia Wang & Yun Yuan

  3. State Key Laboratory of Brain and Cognitive Science, Beijing MR Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    Jinyuan Zhang, Zhixin Li, Rong Xue, Yan Zhuo & Zihao Zhang

  4. University of Chinese Academy of Sciences, Beijing, China

    Jinyuan Zhang, Zhixin Li, Rong Xue, Yan Zhuo & Zihao Zhang

  5. Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine University of Southern California, CA, Los Angeles, USA

    Xingfeng Shao & Danny J. J. Wang

  6. Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Qi Yang

  7. Key Lab of Medical Engineering for Cardiovascular Disease, Ministry of Education, Beijing, China

    Qi Yang

  8. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing, China

    Qi Yang

  9. Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China

    Zihao Zhang

  10. Department of Neurology, Keck School of Medicine University of Southern California, CA, Los Angeles, USA

    Danny J. J. Wang

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  1. Chen Ling
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Corresponding authors

Correspondence to Qi Yang, Zihao Zhang or Yun Yuan.

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The scientific guarantor of this publication is Prof. Zihao Zhang.

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.

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

Ethical approval

This study was approved by the Institutional Review Board and Ethics Committee of Peking University First Hospital.

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Ling, C., Zhang, J., Shao, X. et al. Diffusion prepared pseudo-continuous arterial spin labeling reveals blood–brain barrier dysfunction in patients with CADASIL. Eur Radiol 33, 6959–6969 (2023). https://doi.org/10.1007/s00330-023-09652-7

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