Imaging blood-brain barrier dysfunction: A state-of-the-art review from a clinical perspective

Paulien Moyaert; Beatriz E Padrela; Catherine A Morgan; Jan Petr; Jan Versijpt; Frederik Barkhof; Michael T Jurkiewicz; Xingfeng Shao; Olujide Oyeniran; Tabitha Manson; Danny J J Wang; Matthias Günther; Eric Achten; Henk J M M Mutsaerts; Udunna C Anazodo

doi:10.3389/fnagi.2023.1132077

Imaging blood-brain barrier dysfunction: A state-of-the-art review from a clinical perspective

Front Aging Neurosci. 2023 Apr 17:15:1132077. doi: 10.3389/fnagi.2023.1132077. eCollection 2023.

Authors

Paulien Moyaert^{1

2

3}, Beatriz E Padrela^{4

5}, Catherine A Morgan^{6

7}, Jan Petr^{4

5

8}, Jan Versijpt³, Frederik Barkhof^{4

5

9}, Michael T Jurkiewicz¹⁰, Xingfeng Shao¹¹, Olujide Oyeniran^{2

12}, Tabitha Manson^{7

13}, Danny J J Wang¹¹, Matthias Günther¹⁴, Eric Achten¹, Henk J M M Mutsaerts^{4

5}, Udunna C Anazodo^{2

15}

Affiliations

¹ Department of Medical Imaging, Ghent University Hospital, Ghent, Belgium.
² Lawson Health Research Institute, London, ON, Canada.
³ Department of Neurology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.
⁴ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands.
⁵ Amsterdam Neuroscience, Brain Imaging, Amsterdam, Netherlands.
⁶ School of Psychology and Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
⁷ Centre for Advanced MRI, Auckland UniServices Limited, Auckland, New Zealand.
⁸ Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
⁹ Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, United Kingdom.
¹⁰ Department of Molecular Imaging, Western University, London, ON, Canada.
¹¹ Laboratory of FMRI Technology (LOFT), USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
¹² Department of Medical Biophysics, Western University, London, ON, Canada.
¹³ Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
¹⁴ Fraunhofer Institute for Digital Medicine, University of Bremen, Bremen, Germany.
¹⁵ Montreal Neurological Institute, McGill University, Montreal, QC, Canada.

Abstract

The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow of molecules from the blood to brain parenchyma, protecting the brain's microenvironment. If one of the BBB components starts to fail, its dysfunction can lead to a cascade of neuroinflammatory events leading to neuronal dysfunction and degeneration. Preliminary imaging findings suggest that BBB dysfunction could serve as an early diagnostic and prognostic biomarker for a number of neurological diseases. This review aims to provide clinicians with an overview of the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging methods for evaluating BBB integrity? And (3. Distribution) what is the potential of BBB imaging in different environments, particularly in resource limited settings? We conclude that further advances are needed, such as the validation, standardization and implementation of readily available, low-cost and non-contrast BBB imaging techniques, for BBB imaging to be a useful clinical biomarker in both resource-limited and well-resourced settings.

Keywords: blood-brain barrier dysfunction; diagnostic imaging; magnetic resonance imaging; neurodegeneration; positron emission tomography.

Publication types

Review

Grants and funding

PM is supported by a doctoral fellowship from Fonds voor Wetenschappelijk Onderzoek (FWO; http://www.fwo.be/en/). CM is supported by the Freemasons Foundation, New Zealand. FB is supported by the NIHR Biomedical Research Centre at UCLH. HM is supported by the Dutch Heart Foundation (03-004-2020-T049), the Eurostars-2 joint programme with co-funding from the European Union Horizon 2020 Research and Innovation Programme (ASPIRE E!113701), provided by the Netherlands Enterprise Agency (RvO), and the EU Joint Program for Neurodegenerative Disease Research, provided by Netherlands Organisation for Health Research and Development and Alzheimer Nederland (DEBBIE JPND2020-568-106) and the Canadian Institutes of Health Research (CIHR JPND 173743).