High-resolution relaxometry-based calibrated fMRI in murine brain: Metabolic differences between awake and anesthetized states

2021 ◽  
pp. 0271678X2110622
Author(s):  
Mengyang Xu ◽  
Binshi Bo ◽  
Mengchao Pei ◽  
Yuyan Chen ◽  
Christina Y Shu ◽  
...  

Functional magnetic resonance imaging (fMRI) techniques using the blood-oxygen level-dependent (BOLD) signal have shown great potential as clinical biomarkers of disease. Thus, using these techniques in preclinical rodent models is an urgent need. Calibrated fMRI is a promising technique that can provide high-resolution mapping of cerebral oxygen metabolism (CMRO2). However, calibrated fMRI is difficult to use in rodent models for several reasons: rodents are anesthetized, stimulation-induced changes are small, and gas challenges induce noisy CMRO2 predictions. We used, in mice, a relaxometry-based calibrated fMRI method which uses cerebral blood flow (CBF) and the BOLD-sensitive magnetic relaxation component, R2′, the same parameter derived in the deoxyhemoglobin-dilution model of calibrated fMRI. This method does not use any gas challenges, which we tested on mice in both awake and anesthetized states. As anesthesia induces a whole-brain change, our protocol allowed us to overcome the former limitations of rodent studies using calibrated fMRI. We revealed 1.5-2 times higher CMRO2, dependent upon brain region, in the awake state versus the anesthetized state. Our results agree with alternative measurements of whole-brain CMRO2 in the same mice and previous human anesthesia studies. The use of calibrated fMRI in rodents has much potential for preclinical fMRI.

2009 ◽  
Vol 101 (6) ◽  
pp. 3270-3283 ◽  
Author(s):  
Michael D. Fox ◽  
Dongyang Zhang ◽  
Abraham Z. Snyder ◽  
Marcus E. Raichle

Resting state studies of spontaneous fluctuations in the functional MRI (fMRI) blood oxygen level dependent (BOLD) signal have shown great promise in mapping the brain's intrinsic, large-scale functional architecture. An important data preprocessing step used to enhance the quality of these observations has been removal of spontaneous BOLD fluctuations common to the whole brain (the so-called global signal). One reproducible consequence of global signal removal has been the finding that spontaneous BOLD fluctuations in the default mode network and an extended dorsal attention system are consistently anticorrelated, a relationship that these two systems exhibit during task performance. The dependence of these resting-state anticorrelations on global signal removal has raised important questions regarding the nature of the global signal, the validity of global signal removal, and the appropriate interpretation of observed anticorrelated brain networks. In this study, we investigate several properties of the global signal and find that it is, indeed, global, not residing preferentially in systems exhibiting anticorrelations. We detail the influence of global signal removal on resting state correlation maps both mathematically and empirically, showing an enhancement in detection of system-specific correlations and improvement in the correspondence between resting-state correlations and anatomy. Finally, we show that several characteristics of anticorrelated networks including their spatial distribution, cross-subject consistency, presence with modified whole brain masks, and existence before global regression are not attributable to global signal removal and therefore suggest a biological basis.


2019 ◽  
Author(s):  
Robyn L. Miller ◽  
Godfrey Pearlson ◽  
Vince D. Calhoun

AbstractFrom a large clinical blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) study, we report several interrelated findings involving transient supra-network brainwide states characterized by a saturation phenomenon we are referring to as “polarization.” These are whole-brain states in which the voxelwise-normalized BOLD (vnBOLD) activation of a large proportion of voxels is simultaneously either very high or very low. The presence of such states during a resting-state fMRI (rs-fMRI) scan is significantly anti-correlated with diagnosed schizophrenia, significantly anti-correlated with connectivity between subcortical networks and auditory, visual and sensorimotor networks and also significantly anti-correlated with contemporaneous occupancy of transient functional network connectivity states featuring broad disconnectivity or strong inhibitory connections between the default mode and other networks. Conversely, the presence of highly polarized vn-BOLD states is significantly correlated with connectivity strength between auditory, visual and sensorimotor networks and with contemporaneous occupancy of transient whole-brain patterns of strongly modularized network connectivity and diffuse hyperconnectivity. Despite their consistency with well-documented effects of schizophrenia on static and time-varying functional network connectivity, the observed relationships between polarization and network connectivity are with very few exceptions unmediated by schizophrenia diagnosis. We also find that the spatial distribution of voxels most likely to contribute to the highly polarized states (polarity participation maps (PPMs)) differs with a high degree of statistical significance between schizophrenia patients and healthy controls. Finally, we report evidence suggesting the process by which the most polarized states are achieved, i.e. the ways that strongly polarized voxel regions extend, merge and recede also differs significantly between patient and control populations. Many differences observed between patients and controls are echoed within the patient population itself in the effect patterns of positive symptomology (e.g. hallucinations, delusions, grandiosity and other positive symptoms of schizophrenia). Our findings highlight a particular whole-brain spatiotemporal BOLD activation phenomenon that differs markedly between healthy subjects and schizophrenia patients, one that also strongly informs time-resolved network connectivity patterns that are associated with this serious clinical disorder.


NeuroImage ◽  
2018 ◽  
Vol 176 ◽  
pp. 259-267 ◽  
Author(s):  
Gregor Gryglewski ◽  
René Seiger ◽  
Gregory Miles James ◽  
Godber Mathis Godbersen ◽  
Arkadiusz Komorowski ◽  
...  

2018 ◽  
Vol 115 (9) ◽  
pp. E2105-E2114 ◽  
Author(s):  
Jonathan D. Power ◽  
Mark Plitt ◽  
Stephen J. Gotts ◽  
Prantik Kundu ◽  
Valerie Voon ◽  
...  

“Functional connectivity” techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO2) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.


PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e103154 ◽  
Author(s):  
Mohammad Haris ◽  
Anup Singh ◽  
Kejia Cai ◽  
Kavindra Nath ◽  
Gaurav Verma ◽  
...  

2018 ◽  
Vol 39 (11) ◽  
pp. 2210-2222 ◽  
Author(s):  
Mark P McAvoy ◽  
Enzo Tagliazucchi ◽  
Helmut Laufs ◽  
Marcus E Raichle

A hallmark of non-rapid eye movement (REM) sleep is the decreased brain activity as measured by global reductions in cerebral blood flow, oxygen metabolism, and glucose metabolism. It is unknown whether the blood oxygen level dependent (BOLD) signal undergoes similar changes. Here we show that, in contrast to the decreases in blood flow and metabolism, the mean global BOLD signal increases with sleep depth in a regionally non-uniform manner throughout gray matter. We relate our findings to the circulatory and metabolic processes influencing the BOLD signal and conclude that because oxygen consumption decreases proportionately more than blood flow in sleep, the resulting decrease in paramagnetic deoxyhemoglobin accounts for the increase in mean global BOLD signal.


NeuroImage ◽  
2019 ◽  
Vol 188 ◽  
pp. 845
Author(s):  
Gregor Gryglewski ◽  
René Seiger ◽  
Gregory Miles James ◽  
Godber Mathis Godbersen ◽  
Arkadiusz Komorowski ◽  
...  

2001 ◽  
Vol 43 (5) ◽  
pp. 364-369 ◽  
Author(s):  
J. R. Reichenbach ◽  
L. Jonetz-Mentzel ◽  
C. Fitzek ◽  
E. M. Haacke ◽  
D. K. Kido ◽  
...  

2004 ◽  
Vol 24 (7) ◽  
pp. 764-770 ◽  
Author(s):  
Hanzhang Lu ◽  
Xavier Golay ◽  
James J. Pekar ◽  
Peter C. M. van Zijl

The brain's response to functional activation is characterized by focal increases in cerebral blood flow. It is generally assumed that this hyperemia is a direct response to the energy demands of activation, the so-called flow-metabolism coupling. Here we report experimental evidence that increases in oxygen metabolism can occur after activation without increases in flow. When using multimodality functional MRI (fMRI) to study visual activation in human brain, we observed a postactivation period of about 30 seconds during which oxygen consumption remained elevated, while blood flow and volume had already returned to baseline levels. The finding of such a prolonged and complete dissociation of vascular response and energy metabolism during the poststimulus period indicates that increased metabolic demand needs not per se cause a concomitant increase in blood flow. The results also show that the postactivation undershoot after the positive blood-oxygen-level-dependent hemodynamic response in fMRI should be reinterpreted as a continued elevation of oxygen metabolism, rather than a delayed blood volume compliance.


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