Cerebrovascular reactivity measurements using simultaneous 15O-water PET and ASL MRI: Impacts of arterial transit time, labeling efficiency, and hematocrit

Dawn Holley,Brittney Williams,Audrey P Fan,David Yen-Ting Chen,Bin Shen,Andrea Otte,Moss Y Zhao,David D Shin,Jun-Hyung Park,Greg Zaharchuk,Jia Guo,Taghi Rostami,Magdalena J Sokolska,Yosuke Ishii,Mohammad Mehdi Khalighi,Kim Halbert

doi:10.1016/j.neuroimage.2021.117955

Abstract

Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t-test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.

Highlights

Cerebrovascular reactivity (CVR) is an important biomarker that can predict the risk of cerebrovascular diseases (Markus and Cullinane, 2001)
Using the dynamic positron emission tomography (PET) method as a reference, the primary findings of this study are (1) that the multi-post labeling delay (PLD) approach is the preferred pseudocontinuous ASL (PCASL) technique for CVR quantification and the impacts of individual arterial blood T1 and labeling efficiency were small; (2) the single-PLD PCASL method underestimated CVR and postACZ cerebral blood flow (CBF) due to the significant reduction in arterial transit time (ATT); and (3) VSASL is a feasible technique in measuring CVR of gray matter (GM) and insensitive to variations in the arterial blood T1 relaxation but should be used with care due to the potential artifact near the ventricles
We have investigated the ACZ-induced CVR quantification using simultaneous 15O-water PET and Arterial spin labeling (ASL) magnetic resonance imaging (MRI)

Summary

Introduction

Cerebrovascular reactivity (CVR) is an important biomarker that can predict the risk of cerebrovascular diseases (Markus and Cullinane, 2001). The terms cerebrovascular reactivity and cerebrovascular reserve are frequently used to describe the CBF change in response to vasodilation or vasoconstriction. Cerebrovascular reactivity refers to the process of changing CBF induced by a stimulus and is the focus of this work; cerebrovascular reserve refers to the maximum capacity for CBF to reach. Since two CBF measurements (before and after the vasoactive stimulus) are needed for the quantification of CVR, 15O-water is the preferred radiotracer for PET-based CVR measurement due to its short half-life (2.04 min), allowing separate CBF images to be obtained before and after the administration of the vasodilator. The tracer’s short half-life limits the widespread application of PET-based CVR measurements in most patients, since it requires considerable infrastructure and colocalization of scanner and cyclotron

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