BMJ Open (Mar 2024)
Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol
- Catherine Morgan,
- Frederik Barkhof,
- David L Thomas,
- Saima Hilal,
- Moritz Brandt,
- Betty M Tijms,
- Majon Muller,
- Tormod Fladby,
- Jennifer Linn,
- Per Selnes,
- Atle Bjørnerud,
- Elsmarieke M van de Giessen,
- Beatriz Padrela,
- Amnah Mahroo,
- Mervin Tee,
- Markus H Sneve,
- Paulien Moyaert,
- Oliver Geier,
- Joost P A Kuijer,
- Soetkin Beun,
- Wibeke Nordhøy,
- Yufei David Zhu,
- Mareike A Buck,
- Daniel C Hoinkiss,
- Simon Konstandin,
- Jörn Huber,
- Julia Wiersinga,
- Roos Rikken,
- Diederick de Leeuw,
- Håkon Grydeland,
- Lynette Tippett,
- Erin E Cawston,
- Esin Ozturk-Isik,
- Anders Fjell,
- Kristine Walhovd,
- Lene Pålhaugen,
- Patricia Clement,
- Eric Achten,
- Udunna Anazodo,
- Klaus Eickel,
- Jan Petr,
- Matthias Günther,
- Henk J M M Mutsaerts
Affiliations
- Catherine Morgan
- The University of Auckland School of Psychology, Auckland, New Zealand
- Frederik Barkhof
- Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- David L Thomas
- Department of Brain Repair and Rehabilitation, University College London, London, UK
- Saima Hilal
- National University Health System, Singapore
- Moritz Brandt
- Department of Neurology, Faculty of Medicine, Babylon, Iraq
- Betty M Tijms
- Neurology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Majon Muller
- Department of Internal Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Tormod Fladby
- Department of Neurology, Akershus University Hospital, Lorenskog, Norway
- Jennifer Linn
- Department of Neurology, Faculty of Medicine, Babylon, Iraq
- Per Selnes
- Department of Neurology, Akershus University Hospital, Lorenskog, Norway
- Atle Bjørnerud
- Oslo University Hospital, Oslo, Norway
- Elsmarieke M van de Giessen
- Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Beatriz Padrela
- Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Amnah Mahroo
- Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
- Mervin Tee
- National University Health System, Singapore
- Markus H Sneve
- Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway
- Paulien Moyaert
- Lawson Health Research Institute, London, Ontario, Canada
- Oliver Geier
- Department of Physics and Computational Radiology, Oslo University Hospital, Oslo, Norway
- Joost P A Kuijer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Soetkin Beun
- Department of Diagnostic Sciences, University Hospital Ghent, Gent, Belgium
- Wibeke Nordhøy
- Department of Physics and Computational Radiology, Oslo University Hospital, Oslo, Norway
- Yufei David Zhu
- Biomedical Engineering, University of California Davis, Davis, California, USA
- Mareike A Buck
- University of Bremen, Bremen, Germany
- Daniel C Hoinkiss
- Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
- Simon Konstandin
- Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
- Jörn Huber
- Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
- Julia Wiersinga
- Department of Internal Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Roos Rikken
- Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Diederick de Leeuw
- Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Håkon Grydeland
- Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway
- Lynette Tippett
- The University of Auckland School of Psychology, Auckland, New Zealand
- Erin E Cawston
- The University of Auckland Department of Pharmacology and Clinical Pharmacology, Auckland, New Zealand
- Esin Ozturk-Isik
- Bogazici University Institute of Biomedical Engineering, Istanbul, Turkey
- Anders Fjell
- Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway
- Kristine Walhovd
- Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway
- Lene Pålhaugen
- Department of Neurology, Akershus University Hospital, Lorenskog, Norway
- Patricia Clement
- Department of Diagnostic Sciences, University Hospital Ghent, Gent, Belgium
- Eric Achten
- Department of Diagnostic Sciences, University Hospital Ghent, Gent, Belgium
- Udunna Anazodo
- Lawson Health Research Institute, London, Ontario, Canada
- Klaus Eickel
- Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
- Jan Petr
- Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- Matthias Günther
- Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany
- Henk J M M Mutsaerts
- Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
- DOI
- https://doi.org/10.1136/bmjopen-2023-081635
- Journal volume & issue
-
Vol. 14,
no. 3
Abstract
Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD).Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies.Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
