The many layers of BOLD. The effect of hypercapnic and hyperoxic stimuli on macro- and micro-vascular compartments quantified by CVR, M, and CBV across cortical depth

Abstract

Ultra-high field functional magnetic resonance imaging (fMRI) offers the spatial resolution to measure neuronal activity at the scale of cortical layers. However, cortical depth dependent vascularization differences, such as a higher prevalence of macro-vascular compartments near the pial surface, have a confounding effect on depth-resolved blood-oxygen-level dependent (BOLD) fMRI signals. In the current study, we use hypercapnic and hyperoxic breathing conditions to quantify the influence of all venous vascular and micro-vascular compartments on laminar BOLD fMRI, as measured with gradient-echo (GE) and spin-echo (SE) scan sequences, respectively. We find that all venous vascular and micro-vascular compartments are capable of comparable theoretical maximum signal intensities, as represented by the M-value parameter. However, the capacity for vessel dilation, as reflected by the cerebrovascular reactivity (CVR), is approximately two and a half times larger for all venous vascular compartments combined compared to the micro-vasculature at superficial layers. Finally, there is roughly a 35% difference in estimates of CBV changes between all venous vascular and micro-vascular compartments, although this relative difference was approximately uniform across cortical depth. Thus, our results suggest that fMRI BOLD signal differences across cortical depth are likely caused by differences in dilation properties between macro- and micro-vascular compartments.

On the influence of the vascular architecture on Gradient Echo and Spin Echo BOLD fMRI signals across cortical depth: a simulation approach based on realistic 3D vascular networks

“…On the other hand, superficial layers (pial surface) exhibit significant differences in the topology of the large vessels, leading to a less uniform fingerprint BOLD signal change in these layers. However, these simulation results support the necessity of addressing the bias of large vessels toward the pial surface in laminar fMRI data, for example, through filtering and/or normalization techniques 51,56 .…”

Laminar multi-contrast fMRI at 7T allows differentiation of neuronal excitation and inhibition underlying positive and negative BOLD responses

“…4). Since GRASE acquisition was utilized to generate T2-weighted BOLD contrast, we observed a plateau from middle to superficial layers with relatively lower amplitudes (∼5.5%) compared to EPI BOLD signals (∼14%) (Guidi et al, 2016; Schellekens et al, 2023). To the best of our knowledge, no study has reported detailed laminar profiles of β at 7T, while β is usually assumed to be 1 for UHF studies when the venous signal becomes negligible in extravascular BOLD signals (Griffeth & Buxton, 2011; Kida et al, 2000; Krieger et al, 2014).…”

“…This layer-specific vascular response may reflect the complex architecture of cortical vasculature probed by VASO and ASL. CBV changes reflect hypercapnia-induced vasodilation in both macro- and micro-vasculature, where CBV sampled from macro-vasculature (arterioles) are hypothesized to increase from deep to superficial layer but not for the micro-vasculature compartment (capillaries) (Schellekens et al, 2023). ASL signal primarily originates from capillary vessels, and peak of CBF increase in the deep layer is consistent with the higher microvascular density in middle to deep cortical layers (Shao et al, 2021).…”

Microvascular Specificity of Spin Echo BOLD fMRI: Impact of EPI Echo Train Length

“…During functional experiments, neurovascular coupling induces a CBV increase primarily in large veins and small arteries, which are much more capable at dilation than microvessels. 16 Consequently, our hyperoxia experiment might underestimate macrovascular contamination - and over-estimate the microvascular specificity - compared to an other-wise equivalent functional experiment.…”