Validating layer-specific VASO across species

Cerebral blood volume (CBV) has been shown to be a robust and important physiological parameter for quantitative interpretation of functional (f)MRI, capable of delivering highly localized mapping of neural activity. Indeed, with recent advances in ultra-high-field (>=7T) MRI hardware and associated sequence libraries, it has become possible to capture non-invasive CBV weighted fMRI signals across cortical layers. One of the most widely used approaches to achieve this (in humans) is through vascular-space-occupancy (VASO) fMRI. Unfortunately, the exact contrast mechanisms of layer-dependent VASO fMRI have not been validated and thus interpretation of such data is confounded. Here we cross-validate layer-dependent VASO fMRI contrast in a preclinical rat model using well established (but invasive) imaging methods in response to neuronal activation (somatosensory cortex) and respiratory challenge (hypercapnia). In particular VASO derived CBV measures are directly compared to concurrent measures of total haemoglobin changes from high resolution intrinsic optical imaging spectroscopy (OIS). Through direct comparison of response magnitude, across time, negligible changes in hematocrit ratio during activation (neuronal or vascular) are inferred. Quantified cortical layer profiling is demonstrated and in agreement between both VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical excitatory and inhibitory processing independent of confounding large draining veins which hamper BOLD fMRI studies. While we find increased VASO based CBV reactivity (3.1 {+/-} 1.2 fold increase) in humans compared to rats it is demonstrated that this reflects differences in stimulus design rather than confounds of the VASO signal source. Together, our findings confirm that the VASO contrast is indeed a reliable estimate of layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent fMRI results and should supersede BOLD fMRI as the method of choice in neuroscience application studies. HighlightsO_LIOur goal is to validate layer-specific VASO fMRI with gold standard methods C_LIO_LILayer-specific VASO sequences are implemented for 7T imaging in humans and rats C_LIO_LIComparisons of VASO, optical imaging, and MION confirm the expected contrast origin C_LIO_LISomatosensory stimulation in humans and rats reveal the same layer-fMRI signatures C_LIO_LIWe confirm that VASO is a valid measure to estimate layer-specific neural activity C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/219378v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@4f9733org.highwire.dtl.DTLVardef@14fccd2org.highwire.dtl.DTLVardef@101edaorg.highwire.dtl.DTLVardef@598bae_HPS_FORMAT_FIGEXP M_FIG C_FIG