The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal

Toronov, Vladislav; Walker, Scott A.; Gupta, Rajarsi; Choi, Jee Hyun; Gratton, Enrico; Hueber, Dennis M.; Webb, Andrew

doi:10.1016/s1053-8119(03)00152-6

Cited by 135 publications

(114 citation statements)

References 33 publications

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“…Our data agree well with Ogawa et al (1993) and Buxton et al (1998), which assume that the BOLD signal arises mainly from magnetic disturbances caused by the paramagnetic deoxy-Hb. Our data are also consistent with simultaneous fMRI and fNIRS experiments showing a high correlation between the BOLD signal and deoxy-Hb (Kida et al, 1996;Mehagnoul-Schipper et al, 2002;Punwani et al, 1997Punwani et al, , 1998Toronov et al, 2003) and with Pouratian et al (2002) who showed a high temporal and spatial correlation between the BOLD signal and optical intrinsic signals measured at 610 nm (particularly sensitive to deoxy-Hb) in humans. Differences to Strangman et al (2002), who found a lower correlation of the BOLD signal with deoxy-compared with oxy-Hb during finger flexion/ extension motor activation, may be explained by their less (three) subjects, different (block) design, their shorter emitter -detector separation (Germon et al, 1999), and non-linear changes of oxyHb in relation to deoxy-Hb in the motor cortex (Wolf et al, 2002).…”

Section: Discussionsupporting

confidence: 91%

Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study

et al. 2006

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Measuring the hemodynamic response with functional magnetic resonance imaging (fMRI) together with functional near-infrared spectroscopy (fNIRS) may overcome limitations of single-method approaches. Accordingly, we measured the event-related hemodynamic response with both imaging methods simultaneously in young subjects during visual stimulation. An intertrial interval of 60 s was chosen to include the prolonged post-stimulus undershoot of the blood oxygenation level dependent (BOLD) signal. During visual stimulation, the BOLD signal, oxy-, and total hemoglobin (Hb) increased, whereas deoxy-Hb decreased. The post-stimulus period was characterized by an undershoot of the BOLD signal, oxy-Hb, and an overshoot of deoxy-Hb. Total Hb as measured by fNIRS returned to baseline immediately after the end of stimulation. Results suggest that the post-stimulus events as measured by fNIRS are dominated by a prolonged high-level oxygen consumption in the microvasculature. The contribution of a delayed return of blood volume to the BOLD post-stimulus undershoot in post-capillary veins as suggested by the Balloon and Windkessel models remains ambiguous. Temporal changes in the BOLD signal were highly correlated with deoxy-Hb, with lower correlation values for oxy-and total Hb. Furthermore, data show that fNIRS covers the outer 1 cm of the brain cortex. These results were confirmed by simultaneous fMRI/fNIRS measurements during rest. In conclusion, multimodal imaging approaches may contribute to the understanding of neurovascular coupling. D

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Section: Discussionsupporting

confidence: 91%

Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study

et al. 2006

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“…The optical probes were inserted in soft, flexible polyurethane with a dimension of 3 cm × 5 cm. The amount of hemoglobin in the skin and skull was separated and not considered in the brain tissue oxygenation measurements (Toronov et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

Effect of age on brain oxygenation regulation during changes in position

Gatto

Hoffman

Paisansathan

et al. 2007

Journal of Neuroscience Methods

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Introduction: Reports indicate that brain regulation of oxygenation is inhibited in patients with low baseline oxyhemoglobin concentrations and that brain oxyhemoglobin concentrations are decreased with aging. The purpose of this study was to determine if regulation of brain oxygenation to changes in blood pressure is inhibited by normal aging. Methods: Brain oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations were determined from the forehead using a frequency domain near infrared spectroscopy in 27 healthy volunteers. Subjects were separated into two groups by age (20-39, n = 16; 40-60, n = 11). Brain hemoglobin and non-invasive blood pressure were measured in (1) supine, (2) sitting, (3) supine and (4) sitting positions with 10-min equilibration intervals between each determination. Statistical differences were determined by two way repeated measures analysis of variance. Results: Young subjects were 28 ± 5 years (mean ± S.D.) and older subjects were 48 ± 6 years. In supine position, OHb and HHb were 28.4 ± 8.3 and 15.4 ± 2.4 mol/L, respectively, in young; 22.4 ± 5.7 and 13.4 ± 2.9 mol/L, respectively, in older subjects, both P < 0.05 between groups. Changing position from supine to sitting decreased OHb 5% and increased HHb 5% with no difference between groups. Conclusions: There was a small but significant decrease in OHb and an increase in HHb from supine to sitting position, and this effect was similar between young and older subjects. Regulation of brain oxygenation during modest decreases in blood pressure did not change in normal aging to 60 years compared to young adults.

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“…A similar windkessel model was proposed by Mandeville et al (1999b) to embody the same concept and provide a biomechanical mechanism for a delayed CBV return to baseline. The balloon model has been refined and compared with experimental data (Feng et al, 2001;Friston, 2002;Friston et al, 2000;Mildner et al, 2001;Obata et al, 2004;Toronov et al, 2003), and some errors in the original parameter estimates were recently corrected (Obata et al, 2004). The model is capable of producing BOLD poststimulus undershoots that match well with experimental data.…”

Section: The Balloon Modelmentioning

confidence: 99%

“…The model is capable of producing BOLD poststimulus undershoots that match well with experimental data. However, the central premise of the model, that the undershoot occurs when CBV returns slowly to baseline, has not been definitively established and focused experimental tests of this question are needed (e.g., Mandeville et al, 1999a;Toronov et al, 2003).…”

Section: The Balloon Modelmentioning

confidence: 99%

Modeling the hemodynamic response to brain activation

et al. 2004

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Neural activity in the brain is accompanied by changes in cerebral blood flow (CBF) and blood oxygenation that are detectable with functional magnetic resonance imaging (fMRI) techniques. In this paper, recent mathematical models of this hemodynamic response are reviewed and integrated. Models are described for: (1) the blood oxygenation level dependent (BOLD) signal as a function of changes in cerebral oxygen extraction fraction (E) and cerebral blood volume (CBV); (2) the balloon model, proposed to describe the transient dynamics of CBV and deoxyhemoglobin (Hb) and how they affect the BOLD signal; (3) neurovascular coupling, relating the responses in CBF and cerebral metabolic rate of oxygen (CMRO 2 ) to the neural activity response; and (4) a simple model for the temporal nonlinearity of the neural response itself. These models are integrated into a mathematical framework describing the steps linking a stimulus to the measured BOLD and CBF responses. Experimental results examining transient features of the BOLD response (post-stimulus undershoot and initial dip), nonlinearities of the hemodynamic response, and the role of the physiologic baseline state in altering the BOLD signal are discussed in the context of the proposed models. Quantitative modeling of the hemodynamic response, when combined with experimental data measuring both the BOLD and CBF responses, makes possible a more specific and quantitative assessment of brain physiology than is possible with standard BOLD imaging alone. This approach has the potential to enhance numerous studies of brain function in development, health, and disease. D

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The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal

Cited by 135 publications

References 33 publications

Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study

Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study

Effect of age on brain oxygenation regulation during changes in position

Modeling the hemodynamic response to brain activation

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