Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe

Gagnon, Louise; Sakadžić, Sava; Lesage, Frédéric; Musacchia, Joseph J.; Fang, Qianqian; Yücel, Meryem A.; Evans, Karleyton C.; Mandeville, Emiri T.; Cohen‐Adad, Julien; Polimeni, Jon̈athan R.; Yaseen, Mohammad A.; Lo, Eng H.; Greve, Douglas N.; Buxton, Richard B.; Dale, Anders M.; Devor, Anna; Boas, David A.

doi:10.1523/jneurosci.3555-14.2015

Cited by 203 publications

(327 citation statements)

References 55 publications

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“…We then acquired a 600 × 600 × 660 μm 3 stack of the FITC-labeled vasculature using TPLSM (1.17 × 1.17 × 2.0 μm 3 voxel size) as described in Sakadžić et al 21 Although OCT can also be used to generate angiograms, the spatial resolution and contrast-to-noise ratio is generally higher with FITC TPLSM, which makes it easier to graph (i.e., vectorize) the vascular stack in the subsequent steps. This data was previously published in Sakadžić et al 21 and Gagnon et al 22 …”

Section: Experimental Measurementssupporting

confidence: 86%

“…4(a) where a maximum intensity projection is displayed over the first 300 μm of the mouse cortex. This vascular stack and the DOCT measurements were previously published in Sakadžić et al 21 and Gagnon et al 22 A high contrast-to-noise ratio can be appreciated and this feature allowed the vascular network to be graphed (see Sec. 3).…”

Section: Reconstruction Of μCbf From Experimental Measurements On a Mmentioning

confidence: 83%

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Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography

et al. 2015

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Abstract. Computing microvascular cerebral blood flow (μCBF) in real cortical angiograms is challenging. Here, we investigated whether the use of Doppler optical coherence tomography (DOCT) flow measurements in individual vessel segments can help in reconstructing μCBF across the entire vasculature of a truncated cortical angiogram. A μCBF computational framework integrating DOCT measurements is presented. Simulations performed on a synthetic angiogram showed that the addition of DOCT measurements, especially close to large inflowing or outflowing vessels, reduces the impact of pressure boundary conditions and estimated vessel resistances resulting in a more accurate reconstruction of μCBF. Our technique was then applied to reconstruct microvascular flow distributions in the mouse cortex down to 660 μm by combining two-photon laser scanning microscopy angiography with DOCT.

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Section: Experimental Measurementssupporting

confidence: 86%

Section: Reconstruction Of μCbf From Experimental Measurements On a Mmentioning

confidence: 83%

Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography

et al. 2015

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“…5), the recruitment of capillaries leads to higher antiphase contribution of Δα _ O2 and Δc to hPod. Previous studies have shown that a transient increase in oxygen consumption induced by neural activation is outpaced by increases in blood flow caused by the dilation of arteriole vessels in the mature brain (39)(40)(41). Thus, the mature form of neurovascular coupling is represented as an antiphase pattern consisting of increases in oxy-Hb and decreases in deoxy-Hb caused by blood flow increases in adults (16) and infants as young as 3 mo of age (17).…”

Section: Rapid Change Of Hpod From An In-phase To An Antiphase Pattermentioning

confidence: 99%

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

Watanabe

Shitara

Aoki

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an inphase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants.irth is a drastic event for the developing brain, because this is when the oxygen supply switches from the fetal-placental circulation to an autonomous system. In addition, the extrauterine environment begins to provide the neonate with a tremendous flow of stimuli. Earlier exposure to the extrauterine environment is thought to influence the developmental trajectory of the brain. It has long been known that preterm birth affects brain development and is associated with a higher rate of neurodevelopmental impairment (1). A growing number of MRI studies have shown that preterm-born neonates and infants have brain structures with aberrant volumes, morphologies, and networks at term equivalent (2, 3) and school age (4, 5). Studies of resting-state fMRI have also shown that the functional connectivity of the cortex is different in term and preterm infants (6). However, it is a matter of controversy whether neonatal MRI of the brain can predict long-term adverse outcomes, such as minor neurological dysfunction (7,8). Given the fact that preterm birth before 37 wk of gestation accounts for more than 10% of all live births (9), we need a practical and safe method to detect the status of brain development in newborns.The development of the brain involves underlying hemodynamic and metabolic changes (10). Near-infrared spectroscopy (NIRS) has been used to measure cerebral blood concentrations of oxygenated Hb (oxy-Hb) and deoxygenated Hb (deoxy-Hb) at the bedside and estimate cerebral blood volume, oxygen saturation (SO 2 ), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO 2 ) in neonates (11,12). Previous studies in pr...

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“…Functional magnetic resonance imaging (fMRI) is the result of the blood oxygenation level (BOLD). This technique has become a widely used tool for the exploration of brain function; nevertheless, the neuro-physiological bases are still ill-defined [2]. Functional magnetic resonance imaging (fMRI) indirectly measures the increase in blood flow resulting from the neuron activation using the property of oxygen-deprived hemoglobin (Deoxy-hemoglobin) which is to disrupt a magnetic field.…”

Section: Introductionmentioning

confidence: 99%

Functional magnetic resonance imaging: fuzzy inference analysis

Imane¹,

Khaoula²,

Saddek³

et al. 2017

Radiol Diagn Imaging

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Aim: Nowadays, functional MRI is widely used in the study of brain functions. If it has the advantage of being non-invasive and allows delimiting the zones that are activated at each stimulus in 3D, it presents several deficiencies. On the psychotic studies, the zones which activate induce the analyst in error in view of the complexity and the differences between individuals and their states of anxiety. Even minimal movements of the head influence the result; the response of the vascular system signal is delayed after the stimulus...etc. A heavy numerical processing in particular in statistical analyzes is necessary to refine the images. Despite this, difficulties persist. Method:In this study, a fuzzy logic system in this analysis is proposed. Viewing the complexity of the system, the variables that define the constructed image are considered as inaccurate variables and therefore fuzzy variable. The motor and emotional stimulus, the parasites movements, the anxiety state are considerate as inputs system. The quality of image constructed is the output system. The data base constructed permits adjusting input variables for optimal image. Conclusion:The proposed system allows defining the optimal interaction of the different factors for an optimal image. Considering the variables of input and output as fuzzy variables thus imprecise, this makes it possible to overcome the deficiencies of the system

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Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe

Cited by 203 publications

References 55 publications

Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography

Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

Functional magnetic resonance imaging: fuzzy inference analysis

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