Non-BOLD contrasts to improve the interpretability of high-resolution fMRI in humans
Creators: name: Huber, Laurentius
Publisher: name: F1000 Research Limited
Year: 2019

description: Methodological advancements of functional Magnetic Resonance Imaging (fMRI) in recent years allow researchers to approach the mesoscopic spatial regime of cortical layers and cortical columns. In principle, this could revolutionize the ability to tackle cortical information processing within micro-circuits and across brain systems. One of the major limitations of conventional gradient-echo BOLD fMRI, however, is that it probes neuronal activity changes only indirectly via evoked cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2) changes. Since, the resulting gradient-echo BOLD signal is mostly sensitive to ascending veins in the tissue and to pial veins, the achievable spatial specificity to neuronal activation is limited. Furthermore, the non-linear interaction of CBF, CBV and CMRO2 at high resolutions can hamper quantitative interpretations of the BOLD signal across cortical layer and columns with different baseline physiology. Measuring CBF, CBV or CMRO2 directly on a laminar and columnar level can overcome these limitations.<br>This presentation will introduce laminar non-BOLD fMRI methods, summarize resent advancements, and provide an overview of how to use these methods to improve the neuroscientific interpretability in application studies.<br>First, I will review the physiology of the cortical blood supply in the sub-millimeter regime and the corresponding practical challenges in high-resolution fMRI.<br>Then, I will review the most-widely used non-BOLD fMRI methods to measure high-resolution CBF, CBV and CMRO2 responses and discuss them with respect to their sequence parameter space, sensitivity, specificity and applicability. Specific focus will be on the methods of arterial spin labeling (ASL), vascular space occupancy (VASO) and calibrated fMRI.<br>Finally, I will conclude that non-BOLD methods at submillimeter resolution have an inherently low signal-to-noise ratio (SNR) are thus still challenging. However, their spatial specificity is improved, they are quantifiable, and, hence, the obtained results are physiologically interpretable. Therefore, they can potentially be superior alternatives to conventional GE-BOLD never the less.<br>This conclusion will be discussed in the light of recent neuroscientific application studies that pinpoint laminar and columnar microcircuits in visual cortex, sensorimotor cortex, and prefrontal cortex.<br><br>References<br>1. Polimeni, J.R., Fischl, B., Greve, D.N., and Wald, L.L. (2010). Laminar analysis of 7T BOLD using an imposed spatial activation pattern in human V1. Neuroimage 52, 1334–1346.<br>2. Kay, K., Jamison, K., Vizioli, L., Zhang, R., Margalit, E., and Ugurbil, K. (2018). A critical assessment of data quality and venous effects in ultra-high-resolution fMRI. BioRxiv 1–45.<br>3. Kim, S.-G., and Ogawa, S. (2012). Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J. Cereb. Blood Flow Metab. 32, 1188–1206.<br>4. Goense, J.B.M., Whittingstall, K., and Logothetis, N.K. (2012). Neural and BOLD responses across the brain. Wiley Interdiscip. Rev. Cogn. Sci. 3, 75–86.<br>5. Huber, L., Uludaǧ, K., and Möller, H.E. (2017). Non-BOLD contrast for laminar fMRI in humans: CBF, CBV, and CMRO2. Neuroimage ahead of print.<br>6. Huber, Finn, Handwerker ... Bandettini (2018). Unique functional digit representation in human motor cortex across columns and layers. In 48th Society for Neuroscience, p. 675.03.<br>7. Finn, Huber, Jangraw, and Bandettini (2018). Layer-dependent activity in human prefrontal cortex during working memory. BioRxiv 425249.<br>8. Huber, Handwerker, Jangraw ... Bandettini (2017). High-resolution CBV-fMRI allows mapping of laminar activity and connectivity of cortical cortical input and output in human M1.