Ultra-high resolution blood volume fMRI and BOLD fMRI in humans at 9.4 T: Capabilities and challenges

Abstract

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

Validating layer-specific VASO across species

“…The somatosensory CBV changes in response to whisker stimulation peak in the range of 5%-10% (compared to the baseline CBV). Such amplitudes are consistent with previously reported ΔCBV estimates in the pre-clinical domain (Hillman et al 2007;Kennerley et al 2005;2012a;Lee et al 2001;Tian et al 2010), whereas they are about 5-10 times smaller than previously reported VASO signal changes in humans (Beckett et al 2020;Chai et al 2019;Finn et al 2019;Guidi et al 2017;Huber et al 2018;Kurban et al 2020;Persichetti et al 2020;Yang and Yu 2019;Yu et al 2019).…”

“…Slice selective slab-inversion (SS-SI) VASO is widely used across the literature for non-invasive imaging of microvascular layer-specific signal responses (Beckett et al 2020;Chai et al 2019;Finn et al 2019;Guidi et al 2017;Huber et al 2018;Kurban et al 2020;Persichetti et al 2020;Yang and Yu 2019;Yu et al 2019).…”

Comparison of BOLD and CBV using 3D EPI and 3D GRASE for cortical layer fMRI at 7T

“…In addition to the inflow effects commonly seen in BOLD images, all VASO sequences are at risk of artifacts due to the inflowing of uninverted blood to the imaging volume, e.g. in areas of very short arrival time such as large arteries (70), potentially reducing any observed VASO signal change. The use of shorter TIs with adjusted inversion efficiency, as performed here, can help avoid these artifacts.…”

Optogenetic assessment of VIP, PV, SOM and NOS inhibitory neuron activity and cerebral blood flow regulation in mouse somato-sensory cortex

“…arterial spin labeling) 20 or CBV fMRI (e.g. vascular space occupancy or VASO) [21][22][23] to detect brain dysfunction as well as monitor disease progression.…”