Reproducibility of cerebrovascular reactivity measurements: A systematic review of neuroimaging techniques

Abstract

Cerebrovascular reactivity (CVR), the capacity of the brain to increase cerebral blood flow (CBF) to meet changes in physiological demand, is an important biomarker to evaluate brain health. Typically, this brain "stress test" is performed by using a medical imaging modality to measure the CBF change between two states: at baseline and after vasodilation. However, since there are many imaging modalities and many ways to augment CBF, a wide range of CVR values have been reported. An understanding of CVR reproducibility is critical to determine the most reliable methods to measure CVR as a clinical biomarker. This review focuses on CVR reproducibility studies using neuroimaging techniques in 32 articles comprising 427 total subjects. The literature search was performed in PubMed, Embase, and Scopus. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified 5 factors of the experimental subjects (such as sex, blood characteristics, and smoking) and 9 factors of the measuring technique (such as the imaging modality, the type of the vasodilator, and the quantification method) that have strong effects on CVR reproducibility. Based on this review, we recommend several best practices to improve the reproducibility of CVR quantification in neuroimaging studies.

Keywords: Cerebrovascular reactivity; brain stress test; cerebrovascular reserve; repeatability; reproducibility; systematic review.

Figure 1.

Search and screening results from three databases PubMed, Embase, and Scopus. After removing the duplicated papers, the title, abstract, and full text of each study was assessed using the inclusion and exclusion criteria.

Figure 2.

The range of CVR values using different modalities and vasodilators of all selected studies. (A) The range of CVR induced by ACZ was the largest among the three vasodilators. (B) The lowest wsCV was found in CVR induced by BH. (C) The range of CVR using PET and inhaling hypercapnia gas challenge was the lowest among all methods. Modalities that did not appear in any studies (N = 0) were excluded in the figure.

Figure 3.

The range of wsCV using different modalities and vasodilators of all selected studies. (A) The range of wsCV of CVR induced by ACZ was the largest among the three vasodilators. (B) the wsCV of CVR induced by BH showed the lowest range. (C) The hypercapnia gas challenge technique was adopted by the highest number of studies among all methods. Overall, PET with hypercapnia gas challenge is the most reproducible technique (indicated by * in the subplot C). Modalities that did not appear in any studies (N = 0) were excluded in the figure.

Figure 4.

The range of ICC using different modalities and vasodilators of all selected studies. (A) Only one TCD study employed ICC as the metric for reproducibility. (B) The ICC of CVR was the highest using 3 T MRI with the measurement repeated within a week. (C) The range of ICC was the largest using inhaling hypercapnia gas as the vasodilator. Modalities that did not appear in any studies (N = 0) were excluded in the figure.