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 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.

AI-driven and automated MRI sequence optimization in scanner-independent MRI sequences formulated by a domain-specific language.

Introduction: The complexity of Magnetic Resonance Imaging (MRI) sequences requires expert knowledge about the underlying contrast mechanisms to select from the wide range of available applications and protocols. Automation of this process using machine learning (ML) can support the radiologists and MR technicians by complementing their experience and finding the optimal MRI sequence and protocol for certain applications. Methods: We define domain-specific languages (DSL) both for describing MRI sequences and for formulating clinical demands for sequence optimization. By using various abstraction levels, we allow different key users exact definitions of MRI sequences and make them more accessible to ML. We use a vendor-independent MRI framework (gammaSTAR) to build sequences that are formulated by the DSL and export them using the generic file format introduced by the Pulseq framework, making it possible to simulate phantom data using the open-source MR simulation framework JEMRIS to build a training database that relates input MRI sequences to output sets of metrics. Utilizing ML techniques, we learn this correspondence to allow efficient optimization of MRI sequences meeting the clinical demands formulated as a starting point. Results: ML methods are capable of capturing the relation of input and simulated output parameters. Evolutionary algorithms show promising results in finding optimal MRI sequences with regards to the training data. Simulated and acquired MRI data show high correspondence to the initial set of requirements. Discussion: This work has the potential to offer optimal solutions for different clinical scenarios, potentially reducing exam times by preventing suboptimal MRI protocol settings. Future work needs to cover additional DSL layers of higher flexibility as well as an optimization of the underlying MRI simulation process together with an extension of the optimization method.

Towards free breathing 3D ASL imaging of the human liver using prospective motion correction.

PURPOSE: Measurements of liver perfusion yield valuable information about certain diseases like carcinomas and cirrhosis. To assess perfusion, noninvasive arterial spin labeling (ASL) MRI has the potential to become an important alternative to contrast agent-based methods. Unfortunately, ASL perfusion-weighted images are highly susceptible to breathing motion. This work presents a prospective motion-compensation technique, tackling breathing motion during ASL experiments of the human liver. METHODS: Feasibility of 3D pseudo-continuous ASL imaging under free breathing is investigated by using a prospective motion-compensation technique with fat signal in additional 2D-EPI navigators. The proposed technique is compatible with strong signal suppression, occurring in background-suppressed pseudo-continuous ASL imaging. An additional retrospective 2D elastic registration algorithm is proposed to correct for residual elastic deformations. The technique is validated in 8 healthy volunteers. RESULTS: The prospective technique allowed a significant reduction of the cranial-caudal liver shifts during free breathing pseudo-continuous ASL experiments. Additional 2D elastic image registration allowed reduction of cranial-caudal liver motion to levels of timed breathing protocols. Artifacts in perfusion-weighted images could be reduced when compared with free-breathing ASL images without motion correction. CONCLUSION: The proposed technique is suitable for prospective compensation of liver motion in background-suppressed 3D pseudo-continuous ASL imaging. Future work focuses on further improving the quality of perfusion-weighted images.

Joint estimation and correction of motion and geometric distortion in segmented arterial spin labeling.

PURPOSE: Arterial spin labeling allows noninvasive measurement of cerebral blood flow by magnetically labeling inflowing blood, using it as endogenous tracer. Unfortunately, sensitivity to subject motion is high due to the subtractive nature of arterial spin labeling, which is especially problematic if Cartesian segmented 3D gradient and spin echo (GRASE) is applied. Using a 3D GRASE PROPELLER (3DGP) segmentation, retrospective correction of in-plane rigid body motion is possible before final combination of different segments. However, the standard 3DGP reconstruction is affected by off-resonance effects and has not yet been validated with different motion patterns and levels of background suppression. METHODS: The standard algorithm (1) and a Cartesian segmented 3D GRASE (2), as well as a new 3DGP reconstruction algorithm, which allows joint estimation of motion and geometric distortion (called 3DGP-JET), are validated in 5 healthy volunteers. Image quality of perfusion-weighted images was investigated for background suppression levels of 0%, 5%, and 10% in combination with no motion, as well as slow and fast intentional motion patterns during the scan. RESULTS: The proposed 3DGP-JET algorithm allowed robust estimation of field maps and motion for all scenarios, and greatly reduced motion-related artifacts in perfusion-weighted images when compared with Cartesian segmented 3D GRASE. CONCLUSION: Further improvements of the presented 3DGP-JET routine and a combination with prospective motion correction are recommended to compensate for through-plane motion, making the presented technique a good candidate for dealing with motion-related artifacts in arterial spin labeling images in clinical reality.

Robust Multi-TE ASL-Based Blood-Brain Barrier Integrity Measurements.

Multiple echo-time arterial spin labelling (multi-TE ASL) offers estimation of blood-tissue exchange dynamics by probing the T2 relaxation of the labelled spins. In this study, we provide a recipe for robust assessment of exchange time (Texch) as a proxy measure of blood-brain barrier (BBB) integrity based on a test-retest analysis. This includes a novel scan protocol and an extension of the two-compartment model with an "intra-voxel transit time" (ITT) to address tissue transit effects. With the extended model, we intend to separate the underlying two distinct mechanisms of tissue transit and exchange. The performance of the extended model in comparison with the two-compartment model was evaluated in simulations. Multi-TE ASL sequence with two different bolus durations was used to acquire in vivo data (n = 10). Cerebral blood flow (CBF), arterial transit time (ATT) and Texch were fitted with the two models, and mean grey matter values were compared. Additionally, the extended model also extracted ITT parameter. The test-retest reliability of Texch was assessed for intra-session, inter-session and inter-visit pairs of measurements. Intra-class correlation coefficient (ICC) and within-subject coefficient of variance (CoV) for grey matter were computed to assess the precision of the method. Mean grey matter Texch and ITT values were found to be 227.9 ± 37.9 ms and 310.3 ± 52.9 ms, respectively. Texch estimated by the extended model was 32.6 ± 5.9% lower than the two-compartment model. A significant ICC was observed for all three measures of Texch reliability (P < 0.05). Texch intra-session CoV, inter-session CoV and inter-visit CoV were found to be 6.6%, 7.9%, and 8.4%, respectively. With the described improvements addressing intra-voxel transit effects, multi-TE ASL shows good reproducibility as a non-invasive measure of BBB permeability. These findings offer an encouraging step forward to apply this potential BBB permeability biomarker in clinical research.