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 for human fMRI and thus interpretation of such data is confounded. Here we validate the signal source of layer-dependent SS-SI VASO fMRI using multi-modal imaging in a rat model 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). Quantified cortical layer profiling is demonstrated to be in agreement between VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical processing independent of confounding large draining veins which can hamper BOLD fMRI studies, (depending on slice positioning). Thus, a cross species comparison is enabled using VASO as a common measure. We find increased VASO based CBV reactivity (3.1 ± 1.2 fold increase) in humans compared to rats. 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 VASO fMRI as an appropriate method in neuroscience application studies, in which the presence of large draining intracortical and pial veins limits neuroscientific inference with BOLD fMRI.
Bibliographical note© 2021 The Authors.
Renzo Huber and Aneurin J Kennerley received funding from the York-Maastricht partnership for this project. Renzo Huber was funded from the NWO VENI project 016.Veni.198.032 for part of the study. Benedikt Poser is partially funded by the NWO VIDI grant 16.Vidi.178.052 and by the National Institute for Health grant (R01MH/111444) (PI David Feinberg). Rainer Goebel has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3). The preclinical studies presented here were supported by a United Kingdom Medical Research Council (MRC) grant MR/M013553/1 and Wellcome Trust (WT) Grant 093069/Z/10/Z. Sebastian Dresbach is supported by the ‘Robin Hood’ fund of the Faculty of Psychology and Neuroscience and the department of Cognitive Neuroscience. We thank Harald E Möller and the NMR-group of the MPI-CBS for supporting the part of this study that was conducted at the MPI in Leipzig. Parts of the human fMRI data were acquired with the great support of Scannexus BV, Maastricht, NL (www.scannexus.nl).
- Cerebral blood volume
- Concurrent imaging
- Depth-dependent fMRI
- Draining vein
- Optical imaging spectroscopy
- Somatosensory stimulation