Investigating Neurovascular Coupling with Simultaneous High-Resolution fMRI and Calcium Recordings in Rats

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Dokumentart: Dissertation
Date: 2023-06-15
Source: • Chen X*, Jiang Y*, Choi S, Pohmann R, Scheffler K, Kleinfeld D, Yu X. Single-vessel cerebral blood flow velocity fMRI to map blood velocity by phase-contrast imaging. PLoS Biol. 2021 Sep 9;19(9):e3000923. *these authors contributed equally • Chen X, Sobczak F, Chen Y, Jiang Y, Qian C, Lu Z, Ayata C, Logothetis NK, Yu X. Mapping optogenetically-driven single-vessel fMRI with concurrent neuronal calcium recordings in the rat hippocampus. Nature communications. 2019;10(1):1-12. • Chen Y, Pais-Roldan P, Chen X, Frosz MH, Yu X. MRI-guided robotic arm drives optogenetic fMRI with concurrent Ca2+ recording. Nature communications. 2019;10(1):1-11. • He Y, Wang M, Chen X, Pohmann R, Polimeni JR, Scheffler K, Rosen BR, Kleinfeld D, Yu X. Ultra-slow single-vessel BOLD and CBV-based fMRI spatiotemporal dynamics and their correlation with neuronal intracellular calcium signals. Neuron. 2018;97(4):925-39. e5
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biologie
Advisor: Mallot, Hanspeter (Prof. Dr.)
Day of Oral Examination: 2021-11-08
DDC Classifikation: 570 - Life sciences; biology
Keywords: Funktionelle Kernspintomografie , Calcium , Hippocampus
Other Keywords:
neurovascular coupling
blood oxygen level dependent
cerebral blood volume
cerebral blood flow
License: Publishing license including print on demand
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Dissertation ist gesperrt bis zum 15.06.2023 !


Functional magnetic resonance imaging (fMRI) could indirectly infer brain activity from the tightly coupled vascular hemodynamic response (neurovascular coupling, NVC). Although the widespread applications of fMRI in animals and humans have revolutionized our capacity to visualize functional brain activity, the underlying regulatory mechanisms of NVC are not yet fully elucidated. The recent advent of ultra-high field MRI (B0 ≥ 7 T) affords increased sensitivity and specificity to achieve high-resolution fMRI mapping, which addresses us to establish and apply a high-resolution single-vessel fMRI mapping scheme with blood-oxygen-level-dependent (BOLD), cerebral-blood-volume (CBV), and phase-contrast (PC) MRI methods. Moreover, the technological advances in multimodal fMRI provide complementary readouts of neural activity with high spatiotemporal resolution and cellular specificity, bridging the gap between vascular hemodynamic signal and its underlying neural basis. Therefore, we are motivated to build our multimodal fMRI platform with simultaneous single-vessel fMRI mapping and fiber-based calcium recording in rats to explore distinct NVC events and deepen our present understanding of the NVC. First, the single-vessel fMRI mapping method was established in the cortex of rats, obtaining the sensory-evoked/resting-state BOLD or CBV-weighted fMRI signals from individual penetrating venules or arterioles, respectively. With concurrent single-vessel fMRI mapping and neuronal calcium recording, we found a robust correlation between vessel-specific resting-state fMRI fluctuations (< 0.1 Hz) and ultra-slow neuronal calcium oscillations under light anesthesia. In addition, the single-vessel fMRI mapping was extended to awake humans, demonstrating that the ultra-slow BOLD fluctuations have a strong spatial correlation with sulcus veins (3 T) and intracortical veins of the visual cortex (9.4 T). Second, the single-vessel fMRI mapping was further extended to the subcortical area to achieve large-scale hippocampal hemodynamic mapping in rats with optogenetic activation. To investigating the hippocampal neurovascular functions with our multimodal fMRI, we revealed the unique spatiotemporal patterns of the vessel-specific hippocampal hemodynamic responses associated with two hippocampal calcium events, i.e., optogenetically evoked vs. spreading depression-like calcium events. Based on the calcium events-related single-vessel hippocampal hemodynamic modeling, we demonstrated the significantly reduced neurovascular coupling efficiency during spreading depression-like calcium events. Third, the single-vessel BOLD/CBV fMRI mapping scheme was complemented with PC-MRI, permitting us to measure the blood flow velocity changes from both individual penetrating venules and arterioles in the somatosensory cortex of rats. This high-resolution PC-based blood flow velocity mapping method offers us a qualitative assessment of blood flow velocity changes at the level of the individual vessels, pointing out a new path to study the underlying NVC mechanisms. Lastly, an MRI-guided robotic arm (MgRA) was built and applied to real-time position the optical fiber into the rat brain with high target precision, presenting great advantages over the common stereotaxic-assisted fiber implantation. Combining the whole-brain fMRI mapping with MgRA-guided rat brain interventions, e.g., circuit-specific optogenetic activation, GCamp-mediated calcium recording, or microinjection, this multimodal fMRI approach could offer us a powerful tool to assess the circuit-specific brain functions in rats.

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