scholarly journals Mesoscopic Mapping of Ictal Neurovascular Coupling in Awake Behaving Mice Using Optical Spectroscopy and Genetically Encoded Calcium Indicators

2021 ◽  
Vol 15 ◽  
Author(s):  
Fan Yang ◽  
Jing Li ◽  
Yan Song ◽  
Mingrui Zhao ◽  
James E. Niemeyer ◽  
...  
Keyword(s):  
Cerebral Blood Volume ◽  
Imaging Techniques ◽  
Neurovascular Coupling ◽  
Blood Oxygen Level Dependent ◽  
Epileptic Focus ◽  
Wide Field ◽  
Blood Oxygen Level ◽  
Optical Signals ◽  
Hemoglobin Oxygenation ◽  
Mapping Techniques

Unambiguously identifying an epileptic focus with high spatial resolution is a challenge, especially when no anatomic abnormality can be detected. Neurovascular coupling (NVC)-based brain mapping techniques are often applied in the clinic despite a poor understanding of ictal NVC mechanisms, derived primarily from recordings in anesthetized animals with limited spatial sampling of the ictal core. In this study, we used simultaneous wide-field mesoscopic imaging of GCamp6f and intrinsic optical signals (IOS) to record the neuronal and hemodynamic changes during acute ictal events in awake, behaving mice. Similar signals in isoflurane-anesthetized mice were compared to highlight the unique characteristics of the awake condition. In awake animals, seizures were more focal at the onset but more likely to propagate to the contralateral hemisphere. The HbT signal, derived from an increase in cerebral blood volume (CBV), was more intense in awake mice. As a result, the “epileptic dip” in hemoglobin oxygenation became inconsistent and unreliable as a mapping signal. Our data indicate that CBV-based imaging techniques should be more accurate than blood oxygen level dependent (BOLD)-based imaging techniques for seizure mapping in awake behaving animals.

scholarly journals Measurement of CMRO2 and its relationship with CBF in hypoxia with an extended calibrated BOLD method

2019 ◽  
Vol 40 (10) ◽  
pp. 2066-2080
Author(s):  
Yaoyu Zhang ◽  
Yayan Yin ◽  
Huanjie Li ◽  
Jia-Hong Gao
Keyword(s):  
Cerebral Blood Volume ◽  
Pulse Sequence ◽  
Blood Oxygen Level Dependent ◽  
Extended Model ◽  
Brain Health ◽  
Blood Oxygen Level ◽  
Oxygen Conditions ◽  
Health And Disease ◽  
The Brain ◽  
Mild Hypoxia

Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are physiological parameters that not only reflect brain health and disease but also jointly contribute to blood oxygen level-dependent (BOLD) signals. Nevertheless, unsolved issues remain concerning the CBF–CMRO2 relationship in the working brain under various oxygen conditions. In particular, the CMRO2 responses to functional tasks in hypoxia are less studied. We extended the calibrated BOLD model to incorporate CMRO2 measurements in hypoxia. The extended model, which was cross-validated with a multicompartment BOLD model, considers the influences of the reduced arterial saturation level and increased baseline cerebral blood volume (CBV) and deoxyhemoglobin concentration on the changes of BOLD signals in hypoxia. By implementing a pulse sequence to simultaneously acquire the CBV-, CBF- and BOLD-weighted signals, we investigated the effects of mild hypoxia on the CBF and CMRO2 responses to graded visual stimuli. Compared with normoxia, mild hypoxia caused significant alterations in both the amplitude and the trend of the CMRO2 responses but did not impact the corresponding CBF responses. Our observations suggested that the flow-metabolism coupling strategies in the brain during mild hypoxia were different from those during normoxia.

scholarly journals The effect of imatinib therapy on tumour cycling hypoxia, tissue oxygenation and vascular reactivity

2017 ◽  
Vol 2 ◽  
pp. 38
Author(s):  
Miguel R. Gonçalves ◽  
Sean Peter Johnson ◽  
Rajiv Ramasawmy ◽  
Mark F. Lythgoe ◽  
R. Barbara Pedley ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Tissue Oxygenation ◽  
Chronic Hypoxia ◽  
Imaging Techniques ◽  
Blood Oxygen Level Dependent ◽  
Imaging Biomarkers ◽  
Blood Oxygen Level ◽  
Bold Mri ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes

Background: Several biomedical imaging techniques have recently been developed to probe hypoxia in tumours, including oxygen-enhanced (OE) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). These techniques have strong potential for measuring both chronic and transient (cycling) changes in hypoxia, and to assess response to vascular-targeting therapies in the clinic. Methods: In this study, we investigated the use of BOLD and OE-MRI to assess changes in cycling hypoxia, tissue oxygenation and vascular reactivity to hyperoxic gas challenges, in mouse models of colorectal therapy, following treatment with the PDGF-receptor inhibitor, imatinib mesylate (Glivec). Results: Whilst no changes were observed in imaging biomarkers of cycling hypoxia (from BOLD) or chronic hypoxia (from OE-MRI), the BOLD response to carbogen-breathing became significantly more positive in some tumour regions and more negative in other regions, thereby increasing overall heterogeneity. Conclusions: Imatinib did not affect the magnitude of cycling hypoxia or OE-MRI signal, but increased the heterogeneity of the spatial distribution of BOLD MRI changes in response to gas challenges.

scholarly journals A Model of the Dynamic Relationship between Blood Flow and Volume Changes during Brain Activation

2004 ◽  
Vol 24 (12) ◽  
pp. 1382-1392 ◽  
Author(s):  
Yazhuo Kong ◽  
Ying Zheng ◽  
David Johnston ◽  
John Martindale ◽  
Myles Jones ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Volume ◽  
Temporal Dynamics ◽  
Blood Oxygen Level Dependent ◽  
Extended Model ◽  
Biophysical Modeling ◽  
Blood Oxygen Level ◽  
Windkessel Model ◽  
Dynamic Relationship ◽  
Dependent Signal

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level–dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBVαCBFΦ has been used extensively in the literature. Two similar models, the Balloon ( Buxton et al., 1998 ) and the Windkessel ( Mandeville et al., 1999 ), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

scholarly journals Cortical Depth-Dependent Temporal Dynamics of the BOLD Response in the Human Brain

2011 ◽  
Vol 31 (10) ◽  
pp. 1999-2008 ◽  
Author(s):  
Jeroen CW Siero ◽  
Natalia Petridou ◽  
Hans Hoogduin ◽  
Peter R Luijten ◽  
Nick F Ramsey
Keyword(s):  
Human Brain ◽  
Gray Matter ◽  
Animal Studies ◽  
Temporal Dynamics ◽  
Onset Time ◽  
Neurovascular Coupling ◽  
Blood Oxygen Level Dependent ◽  
Peak Time ◽  
Blood Oxygen Level ◽  
Coupling Mechanisms

Recent animal studies at high field have shown that blood oxygen level-dependent (BOLD) contrast can be specific to the laminar vascular architecture of the cortex, by differences in its temporal dynamics in reference to cortical depth. In this study, we characterize the temporal dynamics of the hemodynamic response (HDR) across cortical depth in the human primary motor and visual cortex, at 7T and using very short stimuli and with high spatial and temporal resolution. We find that the shape and temporal dynamics of the HDR changed in an orderly manner across cortical depth. Compared with the pial vasculature, HDRs in deeper gray matter are significantly faster in onset time (by ∼ 0.5 second) and peak time (∼2 seconds), and are narrower (by ∼1 second) and with smaller amplitude, in line with the known vascular organization across cortical depth and the transit of deoxygenated blood through the vasculature. The width of the HDR in deeper gray matter was as short as 2.1 seconds, indicating that neurovascular coupling takes place at a shorter timescale than previously reported in the human brain. These findings open the possibility to probe layer-specific hemodynamics and neurovascular coupling mechanisms in human gray matter.

scholarly journals Neurovascular Coupling in Development and Disease: Focus on Astrocytes

2021 ◽  
Vol 9 ◽  
Author(s):  
Teresa L. Stackhouse ◽  
Anusha Mishra
Keyword(s):  
Blood Flow ◽  
Energy Demand ◽  
Neurovascular Unit ◽  
Neurovascular Coupling ◽  
Time Frame ◽  
Blood Oxygen Level Dependent ◽  
High Energy ◽  
Neural Activation ◽  
Blood Oxygen Level ◽  
Similar Time

Neurovascular coupling is a crucial mechanism that matches the high energy demand of the brain with a supply of energy substrates from the blood. Signaling within the neurovascular unit is responsible for activity-dependent changes in cerebral blood flow. The strength and reliability of neurovascular coupling form the basis of non-invasive human neuroimaging techniques, including blood oxygen level dependent (BOLD) functional magnetic resonance imaging. Interestingly, BOLD signals are negative in infants, indicating a mismatch between metabolism and blood flow upon neural activation; this response is the opposite of that observed in healthy adults where activity evokes a large oversupply of blood flow. Negative neurovascular coupling has also been observed in rodents at early postnatal stages, further implying that this is a process that matures during development. This rationale is consistent with the morphological maturation of the neurovascular unit, which occurs over a similar time frame. While neurons differentiate before birth, astrocytes differentiate postnatally in rodents and the maturation of their complex morphology during the first few weeks of life links them with synapses and the vasculature. The vascular network is also incomplete in neonates and matures in parallel with astrocytes. Here, we review the timeline of the structural maturation of the neurovascular unit with special emphasis on astrocytes and the vascular tree and what it implies for functional maturation of neurovascular coupling. We also discuss similarities between immature astrocytes during development and reactive astrocytes in disease, which are relevant to neurovascular coupling. Finally, we close by pointing out current gaps in knowledge that must be addressed to fully elucidate the mechanisms underlying neurovascular coupling maturation, with the expectation that this may also clarify astrocyte-dependent mechanisms of cerebrovascular impairment in neurodegenerative conditions in which reduced or negative neurovascular coupling is noted, such as stroke and Alzheimer’s disease.

scholarly journals Simultaneous mesoscopic Ca2+ imaging and fMRI: Neuroimaging spanning spatiotemporal scales

2018 ◽  
Author(s):  
Evelyn MR Lake ◽  
Xinxin Ge ◽  
Xilin Shen ◽  
Peter Herman ◽  
Fahmeed Hyder ◽  
...  
Keyword(s):  
Brain Function ◽  
Brain Activity ◽  
Blood Oxygen Level Dependent ◽  
Optical Measurements ◽  
Wide Field ◽  
Blood Oxygen Level ◽  
Neural Basis ◽  
Novel Approach ◽  
Transgenic Murine Model ◽  
Spatiotemporal Scales

ABSTRACTTo achieve a more comprehensive understanding of brain function requires simultaneous measurement of activity across a range of spatiotemporal scales. However, the appropriate tools to perform such studies are largely unavailable. Here, we present a novel approach for concurrent wide-field optical and functional magnetic resonance imaging (fMRI). By merging these two modalities, we are for the first time able to simultaneously acquire whole-brain blood-oxygen-level-dependent and whole-cortex calcium-sensitive fluorescent measures of brain activity. We describe the developments that allow us to combine these modalities without compromising the fidelity of either technique. In a transgenic murine model, we examine correspondences between activity measured using these modalities and identify unique and complementary features of each. Our approach links cell-type specific optical measurements of neural activity to the most widely used method for assessing human brain function. These data and approach directly establish the neural basis for the macroscopic connectivity patterns observed with fMRI.

scholarly journals Non-linear frequency-dependence of neurovascular coupling in the cerebellar cortex implies vasodilation-vasoconstriction competition

2021 ◽  
Author(s):  
Giuseppe Gagliano ◽  
Anita Monteverdi ◽  
Stefano Casali ◽  
Umberto Laforenza ◽  
Claudia A.M. Gandini Wheeler-Kingshott ◽  
...  
Keyword(s):  
Frequency Dependence ◽  
Time Course ◽  
Mossy Fiber ◽  
Neurovascular Coupling ◽  
Blood Oxygen Level Dependent ◽  
Electrode Arrays ◽  
Blood Oxygen Level ◽  
Linear Frequency ◽  
Non Linear ◽  
Capillary Dynamics

Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood-oxygen-level-dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6-300Hz range, with a marked inflection around 50Hz (vermis) and 100Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time-course of the capillary dilation but not its non-linear frequency-dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation-vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation.

scholarly journals Mapping optogenetically-driven single-vessel fMRI with concurrent neuronal calcium recordings in the rat hippocampus

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xuming Chen ◽  
Filip Sobczak ◽  
Yi Chen ◽  
Yuanyuan Jiang ◽  
Chunqi Qian ◽  
...  
Keyword(s):  
Spreading Depression ◽  
Cerebral Blood Volume ◽  
Blood Oxygen Level Dependent ◽  
Electrophysiological Recording ◽  
Blood Oxygen Level ◽  
Hemodynamic Responses ◽  
Network Function ◽  
Single Vessel ◽  
Ca1 Region

AbstractExtensive in vivo imaging studies investigate the hippocampal neural network function, mainly focusing on the dorsal CA1 region given its optical accessibility. Multi-modality fMRI with simultaneous hippocampal electrophysiological recording reveal broad cortical correlation patterns, but the detailed spatial hippocampal functional map remains lacking given the limited fMRI resolution. In particular, hemodynamic responses linked to specific neural activity are unclear at the single-vessel level across hippocampal vasculature, which hinders the deciphering of the hippocampal malfunction in animal models and the translation to critical neurovascular coupling (NVC) patterns for human fMRI. We simultaneously acquired optogenetically-driven neuronal Ca2+ signals with single-vessel blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-fMRI from individual venules and arterioles. Distinct spatiotemporal patterns of hippocampal hemodynamic responses were correlated to optogenetically evoked and spreading depression-like calcium events. The calcium event-related single-vessel hemodynamic modeling revealed significantly reduced NVC efficiency upon spreading depression-like (SDL) events, providing a direct measure of the NVC function at various hippocampal states.

scholarly journals Simultaneous EEG-fMRI: A novel approach to localize the Seizure Onset Zone

2019 ◽  
pp. 130-139
Author(s):  
Elias Ebrahimzadeh ◽  
Mehran Nikravan ◽  
Maedeh Nikravan ◽  
Mohammad Sajad Manuchehri ◽  
Sana Amoozegar ◽  
...  
Keyword(s):  
Spatial Information ◽  
Cell Activity ◽  
Blood Oxygen Level Dependent ◽  
Temporal Information ◽  
Epileptic Focus ◽  
Blood Oxygen Level ◽  
Daily Lives ◽  
Localization Accuracy ◽  
Novel Approach ◽  
The Brain

Affecting daily lives of millions of people, Epilepsy is a common central nervous system (neurological) disorder where cell activity in brain is disturbed, causing recurrent seizures. Epilepsy can be treated commonly by medications. Be that as it may, medications do not always work as well as one may have hoped, and thus, some patients tend to resort to surgeries. The primary challenge in such surgeries, and by extension any other surgery where some part of brain may need to be disabled, disconnected or removed, is managing to pose no threat to the critical healthy textures adjacent or close to the part being operated on. Therefore, the precise localization of epileptic focus is a matter of vital importance in treating this condition. Various algorithms have been proposed to localize the brain sources and thus to determine the epileptic focus, however, none has yet been able to offer a solution to effectively address this issue. With EEG signal containing temporal information and fMRI carrying spatial information, it is hoped that the combination of the two can yield optimal results. In this case study, we first remove the artifacts caused by EEG gradients, and proceed to study the signal in and outside the scanner by localizing the brain sources. The simultaneous processing of EEG-fMRI enables us to make use of the temporal information in EEG to analyze fMRI. Epileptic foci are finally localized based on GLM method. This study has been conducted on 2 medication-resistant patients with epilepsy whose data was recorded in Iran National Brain Mapping Centre. The results suggest a significant improvement in localization accuracy compared to existing methods in the literature. Keywords: Simultaneous EEG-fMRI; Epilepsy; Independent Component Analysis (ICA); Blood-oxygen-level dependent imaging (BOLD); Generalized Linear Model (GLM)

scholarly journals Wide-field retinotopy reveals a new visuotopic cluster in macaque posterior parietal cortex

2020 ◽  
Vol 225 (8) ◽  
pp. 2447-2461
Author(s):  
Samy Rima ◽  
Benoit R. Cottereau ◽  
Yseut Héjja-Brichard ◽  
Yves Trotter ◽  
Jean-Baptiste Durand
Keyword(s):  
Parietal Cortex ◽  
Posterior Parietal Cortex ◽  
Blood Oxygen Level Dependent ◽  
Wide Field ◽  
Blood Oxygen Level ◽  
Retinotopic Mapping ◽  
Human Counterpart ◽  
Posterior Parietal ◽  
Dense Set ◽  
New Framework

Abstract We investigated the visuotopic organization of macaque posterior parietal cortex (PPC) by combining functional imaging (fMRI) and wide-field retinotopic mapping in two macaque monkeys. Whole brain blood-oxygen-level-dependent (BOLD) signal was recorded while monkeys maintained central fixation during the presentation of large rotating wedges and expending/contracting annulus of a “shaking” fruit basket, designed to maximize the recruitment of PPC neurons. Results of the surface-based population receptive field (pRF) analysis reveal a new cluster of four visuotopic areas at the confluence of the parieto-occipital and intra-parietal sulci, in a location previously defined histologically and anatomically as the posterior intra-parietal (PIP) region. This PIP cluster groups together two recently described areas (CIP1/2) laterally and two newly identified ones (PIP1/2) medially, whose foveal representations merge in the fundus of the intra-parietal sulcus. The cluster shares borders with other visuotopic areas: V3d posteriorly, V3A/DP laterally, V6/V6A medially and LIP anteriorly. Together, these results show that monkey PPC is endowed with a dense set of visuotopic areas, as its human counterpart. The fact that fMRI and wide-field stimulation allows a functional parsing of monkey PPC offers a new framework for studying functional homologies with human PPC.

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