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.

Ultra-high field functional Magnetic Resonance Imaging (fMRI) offers the spatial resolution to measure neural activity at the scale of cortical layers. Most fMRI studies make use of the Blood-Oxygen-Level Dependent (BOLD) signal, arising from a complex interaction of changes in cerebral blood flow (CBF) and volume (CBV), and venous oxygenation. However, along with cyto- and myeloarchitectural changes across cortical depth, laminar fMRI is confronted with additional confounds related to vascularization differences that exist across cortical depth. In the current study, we quantify how the non-uniform distribution of macro- and micro-vascular compartments, as measured with Gradient-Echo (GE) and Spin-Echo (SE) scan sequences, respectively, affect laminar BOLD fMRI responses following evoked hypercapnic and hyperoxic breathing conditions. We find that both macro- and micro-vascular compartments are capable of comparable theoretical maximum signal intensities, as represented by the M-scaling parameter. However, the capacity for vessel dilation, as reflected by the cerebrovascular reactivity (CVR), is approximately three times larger for the macro- compared to the micro-vasculature at superficial layers. Finally, there is roughly a 35% difference in CBV estimates between the macro- and micro-vascular compartments, although this relative difference is approximately uniform across cortical depth.

In the current study, we quantify vascular properties in relation to laminar BOLD fMRI signals for differently sized vascular compartments across cortical depth. Using hypercapnic and hyperoxic breathing conditions, while measuring from macro- and micro-vascular compartments, we estimate effects of dilation capacity, theoretical maximum signal intensity, and relative change in cerebral blood volume on laminar BOLD contrasts. We show that enlarged signals for larger pial veins are mainly caused by their capacity for dilation. BOLD signal differences between macro- and micro-vascular compartments are not likely caused by differences in theoretical maximum signal intensity, or relative changes in cerebral blood volume.

In this study, we investigate the vascular contribution to the BOLD signal by comparing purely non-neuronal-related changes in the BOLD signal induced by gas manipulations with neuronal-related hemodynamic changes in the BOLD signal for different vascular compartments. Different vascular compartments were targeted by employing gradient-echo and spin-echo in combination with cortical depth estimations and pial vein segmentations. Our findings suggest that the increase in macro-vascular baseline venous blood volume (CBVv0) is the main contributor to the large GE-BOLD signal increase towards the pial surface and that normalization for this CBVv0-dependence is possible using a hyperoxia breathing task.