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
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-03-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/3/e081635.full |
| _version_ | 1826804470566092800 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Catherine Morgan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T01:25:07Z |
| format | Article |
| id | doaj.art-cb019857e39c403eb369f2a40b1fec37 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2025-03-17T01:55:04Z |
| publishDate | 2024-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-cb019857e39c403eb369f2a40b1fec372025-02-14T23:45:09ZengBMJ Publishing GroupBMJ Open2044-60552024-03-0114310.1136/bmjopen-2023-081635Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocolCatherine Morgan0Frederik Barkhof1David L Thomas2Saima Hilal3Moritz Brandt4Betty M Tijms5Majon Muller6Tormod Fladby7Jennifer Linn8Per Selnes9Atle Bjørnerud10Elsmarieke M van de Giessen11Beatriz Padrela12Amnah Mahroo13Mervin Tee14Markus H Sneve15Paulien Moyaert16Oliver Geier17Joost P A Kuijer18Soetkin Beun19Wibeke Nordhøy20Yufei David Zhu21Mareike A Buck22Daniel C Hoinkiss23Simon Konstandin24Jörn Huber25Julia Wiersinga26Roos Rikken27Diederick de Leeuw28Håkon Grydeland29Lynette Tippett30Erin E Cawston31Esin Ozturk-Isik32Anders Fjell33Kristine Walhovd34Lene Pålhaugen35Patricia Clement36Eric Achten37Udunna Anazodo38Klaus Eickel39Jan Petr40Matthias Günther41Henk J M M Mutsaerts421Department of Neurology, Southmead Hospital, Bristol, UK6 Department of Medical Physics & Biomedical Engineering, University College London Faculty of Engineering Sciences, London, UKDepartment of Brain Repair and Rehabilitation, University College London, London, UKMemory, Aging and Cognition Center, National University Health System, SingaporeDepartment of Neurology, Technische Universität Dresden, Dresden, GermanyNeurology, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsDepartment of Internal Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsDepartment of Neurology, Akershus University Hospital, Lorenskog, NorwayDepartment of Neurology, Faculty of Medicine, Babylon, IraqDepartment of Neurology, Akershus University Hospital, Lorenskog, NorwayOslo University Hospital, Oslo, NorwayRadiology & Nuclear Medicine, Amsterdam UMC location VUmc, Amsterdam, The NetherlandsDepartment of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyNational University Health System, SingaporeCenter for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, NorwayDepartment of Diagnostic Sciences, University Hospital Ghent, Gent, BelgiumDepartment of Physics and Computational Radiology, Oslo University Hospital, Oslo, NorwayDepartment of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsDepartment of Diagnostic Sciences, University Hospital Ghent, Gent, BelgiumDepartment of Physics and Computational Radiology, Oslo University Hospital, Oslo, NorwayBiomedical Engineering, University of California Davis, Davis, California, USAFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyDepartment of Internal Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsAmsterdam UMC Locatie VUmc, Amsterdam, NetherlandsAmsterdam UMC Locatie VUmc, Amsterdam, NetherlandsCenter for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, NorwayThe University of Auckland School of Psychology, Auckland, New ZealandThe University of Auckland Department of Pharmacology and Clinical Pharmacology, Auckland, New ZealandBogazici University Institute of Biomedical Engineering, Istanbul, TurkeyCenter for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, NorwayCenter for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, NorwayDepartment of Neurology, Akershus University Hospital, Lorenskog, NorwayDepartment of Diagnostic Sciences, University Hospital Ghent, Gent, BelgiumDepartment of Diagnostic Sciences, University Hospital Ghent, Gent, BelgiumLawson Health Research Institute, London, Ontario, CanadaFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyDepartment of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsFraunhofer Institute for Digital Medicine MEVIS, Bremen, GermanyDepartment of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, NetherlandsIntroduction 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.https://bmjopen.bmj.com/content/14/3/e081635.full |
| spellingShingle | 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 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 BMJ Open |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/14/3/e081635.full |
| work_keys_str_mv | AT catherinemorgan developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT frederikbarkhof developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT davidlthomas developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT saimahilal developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT moritzbrandt developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT bettymtijms developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT majonmuller developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT tormodfladby developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT jenniferlinn developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT perselnes developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT atlebjørnerud developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT elsmariekemvandegiessen developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT beatrizpadrela developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT amnahmahroo developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT mervintee developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT markushsneve developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT paulienmoyaert developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT olivergeier developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT joostpakuijer developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT soetkinbeun developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT wibekenordhøy developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT yufeidavidzhu developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT mareikeabuck developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT danielchoinkiss developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT simonkonstandin developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT jornhuber developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT juliawiersinga developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT roosrikken developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT diederickdeleeuw developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT hakongrydeland developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT lynettetippett developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT erinecawston developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT esinozturkisik developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT andersfjell developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT kristinewalhovd developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT lenepalhaugen developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT patriciaclement developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT ericachten developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT udunnaanazodo developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT klauseickel developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT janpetr developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT matthiasgunther developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol AT henkjmmmutsaerts developingbloodbrainbarrierarterialspinlabellingasanoninvasiveearlybiomarkerofalzheimersdiseasedebbieadaprospectiveobservationalmulticohortstudyprotocol |