Back to search

JPND-EU Joint Programme - Neurodege

Developing BBB-ASL as non-invasive early biomarker of Alzheimer’s disease

Alternative title: DEBBIE

Awarded: NOK 6.5 mill.

Alzheimer?s Disease (AD) causes the majority of dementia cases. One of its earliest signs is the loss of the Blood-Brain-Barrier (BBB) integrity, which can be imaged with positron emission tomography (PET) and magnetic resonance imaging (MRI) and may be related to disease progression. Arterial spin labelling (ASL) is an MRI technique for truly non-invasive measurement of brain blood perfusion including the vascular permeability or BBB integrity. However, for BBB integrity measurement it cannot be used reliably in a clinical setting due to long scan times. We hypothesize that this can be overcome by developing innovative techniques to allow for patient-specifically tuned BBB permeability assessments. The DEBBIE consortium will develop and focus on automatic WP1) Calibration of MRI acquisition parameters based on the patient?s hemodynamic status at scan time, WP2) Standardization of image processing for atlas-based correction of between-scanner and between-patient confounders, WP3) Validation of this integrated MRI solution by comparing it with PET and proteomic markers, and WP4) Application in several ongoing longitudinal AD studies to evaluate its clinical value. The DEBBIE consortium will provide a sensitive, non-invasive, and early biomarker of cognitive decline to identify essential pathologies underlying loss of cognition, paving the way for precision interventions. During 2021, existing ASL data have been processed for publication, biomarker techniques (based on cerebrospinal fluid measurements) for small-scale pathology and BBB dysfunction have been further developed and patients have been rutted for new BBB-ASL MRI recordings. At the same time, the protocol for MRI examinations is fully developed and ready for implementation per. 301121.

Alzheimer’s Disease (AD) causes the majority of dementia cases. The cerebral disease is devastating and incurable. AD painfully slowly destroys biographic memory, affects thinking and procedural skills leading to a complete dependency on family or health care services and death. While the incidence of AD rises in an ageing population, AD can also hit younger persons (presenile AD). One of its earliest and dynamic signs is the loss of the Blood-Brain-Barrier (BBB) integrity, which can be imaged with positron emission tomography (PET) and magnetic resonance imaging (MRI). While most methods require contrast agents, arterial spin labelling (ASL) is an MRI technique for truly non-invasive measurement of perfusion, allowing the measurement of several hemodynamic and physiological parameters including the vascular permeability or BBB integrity. ASL is currently the only technique for mapping local changes in BBB integrity without the use of contrast-enhancing agents or radioactive tracers. However, for BBB integrity measurement it cannot be used reliably in a clinical setting due to often rather long scan times and sensitivity to patient-specific hemodynamic variations. We hypothesize that these challenges can be overcome by developing and integrating innovative techniques to allow for patient-specifically tuned BBB permeability assessments. The DEBBIE consortium will develop and focus on automatic WP1) Calibration of MRI acquisition parameters based on the patient’s hemodynamic status at scan time, WP2) Standardization of image processing for atlas-based correction of between-scanner and between-patient confounders, WP3) Validation of this integrated MRI solution by comparing it with PET, and WP4) Application in several ongoing longitudinal AD studies to evaluate its clinical value. This work will allow the DEBBIE consortium to provide a sensitive, non-invasive, and early biomarker of cognitive decline.

Funding scheme:

JPND-EU Joint Programme - Neurodege