DEveloping BBB-ASL as non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD): Study design

IF 1.9 Q3 CLINICAL NEUROLOGY
Beatriz Padrela , Amnah Mahroo , Mervin Tee , Markus Sneve , Paulien Moyaert , Oliver Geier , Joost Kuijer , Soetkin Beun , Wibeke Nordhøy , Yufei David Zhu , Mareike Buck , Daniel Hoinkiss , Simon Konstandin , Jörn Huber , Julia Wiersinga , Roos Rikken , Diederick de Leeuw , Håkon Grydeland , Lynette Tippett , Erin Cawston , Henk J.M.M. Mutsaerts
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引用次数: 0

Abstract

Introduction

Arterial spin labeling (ASL) MRI, a non-invasive technique for imaging perfusion, now allows studying BBB permeability. The DEveloping BBB-ASL as a non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD) multi-cohort study integrates this modified BBB-ASL technique in several healthy and diseased populations (Table 1) to study methodological and clinical research questions (Table 2) on the ability of BBB-ASL as an early AD biomarker.

Methods

DEBBIE-AD will enroll various cohorts with subjective cognitive decline, mild cognitive impairment, and AD dementia, as well as age-matched healthy controls, at seven sites (Table 1). Our newly developed BBB-ASL sequence — implemented with the vendor-independent MRI framework gammaSTAR — will be added to multiple MRI protocols. The BBB-ASL sequence combines time-encoded multi-post labeling delay pseudo-continuous ASL with a multi-echo 3D GRASE readout, allowing estimating CBF, ATT, and the BBB time of exchange (Tex). Data analyses will be conducted using ExploreASL. Beyond MRI standard sequences, including T1w, T2w, FLAIR, DWI, the DEBBIE clinical outcomes include amyloid-PET and blood and CSF fluid biomarkers (Table 1).

Expected Results

Preliminary testing of the BBB-ASL has been conducted on 3T systems (different Siemens Heathineers scanners) in different cohorts at multiple sites. Data processing with ExploreASL includes FSL-FABBER4 for quantification, allowing harmonized image processing. An example of the mean and standard deviation Tex maps of two DEBBIE cohorts is shown in Figure 1 to illustrate the similarities of the Tex patterns from two cohorts of similar-aged healthy adults from different sites.

Discussion

The DEBBIE-AD study aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies. The presented sequence may provide novel and unique insights into the staging of BBB permeability changes in groups at greater risk of developing AD, which may, in turn, provide new targets for treatment.

开发作为阿尔茨海默病非侵入性早期生物标志物的 BBB-ASL (DEBIE-AD):研究设计
导言动脉自旋标记(ASL)磁共振成像(MRI)是一种用于成像灌注的非侵入性技术,现在可用于研究 BBB 的通透性。开发作为阿尔茨海默病非侵入性早期生物标志物的 BBB-ASL 多队列研究(DEBBIE-AD)在多个健康和患病人群(表 1)中整合了这种改良的 BBB-ASL 技术,以研究 BBB-ASL 作为阿尔茨海默病早期生物标志物的方法学和临床研究问题(表 2)。方法DEBBIE-AD 将在七个研究机构(表 1)招募主观认知能力下降、轻度认知功能障碍和注意力缺失性痴呆症患者以及年龄匹配的健康对照组。我们新开发的BBB-ASL序列--通过独立于供应商的磁共振成像框架gammaSTAR实现--将被添加到多个磁共振成像方案中。BBB-ASL序列将时间编码的多后标记延迟伪连续ASL与多回波三维GRASE读出相结合,可以估计CBF、ATT和BBB交换时间(Tex)。数据分析将使用 ExploreASL 进行。除了包括 T1w、T2w、FLAIR、DWI 在内的 MRI 标准序列外,DEBIE 的临床结果还包括淀粉样蛋白-PET 以及血液和脑脊液生物标记物(表 1)。ExploreASL 的数据处理包括用于量化的 FSL-FABBER4,从而实现了统一的图像处理。图 1 显示了两个 DEBBIE 队列的 Tex 图的平均值和标准偏差,以说明来自不同部位的两个年龄相仿的健康成人队列的 Tex 模式的相似性。 讨论 DEBBIE-AD 研究旨在为 BBB-ASL 测量 BBB 通透性的能力提供证据,并证明其在 AD 相关病理中的实用性。所展示的序列可能会为AD高危人群的BBB通透性变化分期提供新颖独特的见解,进而为治疗提供新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cerebral circulation - cognition and behavior
Cerebral circulation - cognition and behavior Neurology, Clinical Neurology
CiteScore
2.00
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审稿时长
14 weeks
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