Abstract
Cerebrovascular reactivity (CVR) is defined as the ratio of the cerebral blood flow (CBF) response to an increase in a vasoactive stimulus. We used changes in blood oxygenation level-dependent (BOLD) MRI as surrogates for changes of CBF, and standardized quantitative changes in arterial partial pressure of carbon dioxide as the stimulus. Despite uniform stimulus and test conditions, differences in voxel-wise BOLD changes between testing sites may remain, attributable to physiologic and machine variability. We generated a reference atlas of normal CVR metrics (voxel-wise mean and SD) for each of two sites. We hypothesized that there would be no significant differences in CVR between the two atlases enabling each atlas to be used at any site. A total of 69 healthy subjects were tested to create site-specific atlases, with 20 of those individuals tested at both sites. 38 subjects were scanned at Site 1 (17F, 37.5 ± 16.8 y) and 51 subjects were tested at Site 2 (22F, 40.9 ± 17.4 y). MRI platforms were: Site 1, 3T Magnetom Skyra Siemens scanner with 20-channel head and neck coil; and Site 2, 3T HDx Signa GE scanner with 8-channel head coil. To construct the atlases, test results of individual subjects were co-registered into a standard space and voxel-wise mean and SD CVR metrics were calculated. Map comparisons of z scores found no significant differences between white matter or gray matter in the 20 subjects scanned at both sites when analyzed with either atlas. We conclude that individual CVR testing, and atlas generation are compatible across sites provided that standardized respiratory stimuli and BOLD MRI scan parameters are used. This enables the use of a single atlas to score the normality of CVR metrics across multiple sites.
Highlights
The magnitude of cerebral hemodynamic responses to alterations in arterial partial pressure of CO2 (PaCO2), referred to as cerebrovascular reactivity (CVR), has increased understanding of the determinants of cerebral perfusion in many neurovascular disorders
CVR step and ramp atlas maps were created for all subjects scanned at either site, with 38 subjects in total scanned at Site 1 and 51 subjects scanned at Site 2
No significant difference between the CVR step and ramp for GM and WM were found between the two sites (P-values presented in Table 3, α = 0.05)
Summary
The magnitude of cerebral hemodynamic responses to alterations in arterial partial pressure of CO2 (PaCO2), referred to as cerebrovascular reactivity (CVR), has increased understanding of the determinants of cerebral perfusion in many neurovascular disorders. The vasodilatory stimulus in most instances is uncontrolled, impeding test standardization, which is required for research and clinical use. A standardized “brain stress test” would provide a uniform platform from which to assess and manage a wide variety of disorders affecting brain blood flow regulation, such as in steno-occlusive disease (Brawley et al, 1967; Brawley, 1968; Symon, 1969; Kleiser and Widder, 1992; Yonas et al, 1993; Webster et al, 1995; Molina et al, 1999; Markus and Cullinane, 2001; Ogasawara et al, 2002; Sasoh et al, 2003; Mandell et al, 2008, 2011; Fierstra et al, 2010; Silvestrini et al, 2011; Sobczyk et al, 2016), glioma (Fierstra et al, 2018a; Sebok et al, 2020), arteriovenous malformations (Fierstra et al, 2011), traumatic brain injury (Da Costa et al, 2016; Mutch et al, 2016) and remote stroke effects (Sebok et al, 2018; Hendrik Bas van Niftrik et al, 2020; Sebok et al, 2021). The third and final step, and the aim of this paper, is to validate the compatibility of data between sites and across MR platforms
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