VASO‐based calculations of CBV change: Accounting for the dynamic CSF volume

While the noninvasiveness and high temporal resolution of blood oxygenation level-dependent (BOLD) imaging have led to its preferential status in functional MRI, the numerous contributors to the BOLD signal—cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood volume (CBV)—complicate its interpretation. Noninvasive acquisitions of CBF or CBV, using arterial spin labeling (ASL) (1) or vascular space occupancy-related methods (2,3), respectively, would not only lead to an improved understanding of BOLD, but also potentially offer superior stand-alone methods of fMRI. While quantitative ASL continues to suffer from issues such as transit time uncertainty and contamination from intravascular blood (4), interpretation of the VASO signal is also still under investigation (5–8). In particular, the impact of cerebrospinal fluid (CSF) on the VASO signal, both at rest (6,7,9) and during activation (6,8), has received recent attention. Partial volume effects within voxels containing CSF can significantly increase (or in some cases decrease) the magnitude of VASO signal changes (7). Furthermore, recent work (8) has suggested that a minor change in the CSF fraction with activation, such as the 5.6% decrease found by Donahue et al. (6) during visual stimulation, is sufficient to significantly impact the VASO signal. While the concurrent nulling of blood and CSF via VASO-FLAIR offers an efficient method of measuring simultaneous changes in blood and CSF with activation, this can only be achieved in single slices (6,9). In contrast, the MAGIC (Multiple Acquisitions with Global Inversion Cycling) VASO technique first proposed by Lu et al. (10) has recently been extended to whole brain coverage, with demonstration of effective nulling of either blood or CSF in separate acquisitions depending on the choice of inversion time (8). MAGIC VASO employs a series of global inversion pulses between groups of slices in order to keep the longitudinal blood signal close to zero throughout the entire volume acquisition. The impact of incomplete blood nulling in particular slices has been investigated and shown to be significant (8), thereby prohibiting the simplifications used in CBV calculations performed in some previous VASO studies (2,5,6,11). In addition, examination of the sensitivity of the VASO signal to local resting CBV indicates that a 50% underestimation of CBVrest would result in a 100% overestimation of the percent CBV change calculated from a simple VASO experiment (8). When assuming a uniform CBVrest across the brain, as some studies have done (2,5,11), such errors are not improbable given that resting CBV has been shown to vary from 2.5 to 8.7 mL / 100 mL in different regions (12). Consequently, it becomes apparent that global CBVrest maps must be used in calculations of percent CBV change from VASO. The present study is the first to use voxelspecific values obtained from a global CBVrest map to calculate ΔCBV from VASO. Our proposed technique uses separate acquisitions of blood-nulled and CSF-nulled VASO signals during rest and activation that allows for the calculation of relative changes in CBV while ACcounting for the Dynamic CSF volume (ACDC). To assess VASO ACDC, we employed a breath-holding paradigm to induce hypercapnia, which has been shown in numerous studies to cause widespread dilatation of the cerebral arterioles (13–19). To our knowledge, these are the first noninvasive whole-brain MRI measurements of CBV change that account for the change in local CSF fraction. These results are compared to VASO-based solutions that do not allow for CSF change and to previous literature on cerebral vascular reactivity. In addition, the relationship between relative changes in CSF and CBV is discussed with suggestions for further investigation.