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Query: UMLS:C0020440 (hypercapnia)
7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association between recovery of brain function and behavior after transient cerebral ischemia in animals and humans is incompletely characterized. Quantitative diffusion- (DWI), perfusion- (PWI), T(2)-weighted (T(2)WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 1 day after 20-mins transient middle cerebral artery occlusion (tMCAO; n=6) or sham operation (n=6) in male Sprague-Dawley rats. Viability thresholds were employed to calculate diffusion, perfusion, and T(2) lesion volumes. Region of interest analysis was used to evaluate structural and functional MR signal changes within the sensorimotor network, which were then related to corresponding behavioral measures. Post-mortem 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 24 h after ischemia. Transient middle cerebral artery occlusion produced lesions on DWI and PWI, which fully recovered by 30 mins after reperfusion. Ipsilesional fMRI responses to hypercapnia and forepaw stimulation were significantly impaired after ischemia and did not fully normalize until 3 and 24 h after tMCAO, respectively. No abnormalities were observed on imaging or TTC at 24 h despite significant behavioral dysfunctions including contralesional forelimb impairment and ipsilesional neglect. No MRI, behavioral, or TTC anomalies were observed in sham-operated rats. There were no significant correlations between MRI parameters, behavior, and TTC in either group. Together, these results suggest that normal findings on diffusion, perfusion, and T(2) imaging shortly after transient ischemia may not indicate normal tissue status as indicated by fMRI and behavior, which may help explain the persistence of neurologic deficits in patients with normal conventional MRI after cerebral ischemia.
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PMID:Differential recovery of multimodal MRI and behavior after transient focal cerebral ischemia in rats. 1653 30

Using hypercapnia and carbogen as functional markers of vessel maturation and function, we compared blood oxygen level-dependent (BOLD) contrast with standard dynamic contrast-enhanced (DCE)-MRI quantitative parameters in murine fibrosarcoma. Our results show that there was no correlation between vessel maturity and contrast-agent uptake rate (K(in) (Trans)) or contrast agent efflux rate (k(ep)). In addition, DCE-MRI provided higher estimates of the fraction of functional tumor compared to BOLD-MRI. The two putative markers of regional vascular density, i.e., the magnitude of BOLD signal change during carbogen challenge (VF) and the fractional plasma volume found by DCE-MRI (V(p)), were only weakly correlated (r(2) = 0.02-0.14). Furthermore, VF showed no correlation with K(in) (Trans). A positive correlation was observed (r(2) = 0.75) between mean tumor VF and k(ep), but only when averaged over the whole tumor (which includes tumor regions completely unperfused by the gadolinium (Gd) contrast agent). This would merely reveal a relationship between perfusion status and the capacity to respond to carbogen breathing. In conclusion, characterizations of tumor microvasculature imaging using BOLD-MRI and DCE-MRI appear to be largely complementary, given the weak correlations between their corresponding derived parameters.
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PMID:Determination of the maturity and functionality of tumor vasculature by MRI: correlation between BOLD-MRI and DCE-MRI using P792 in experimental fibrosarcoma tumors. 1698 9

Changes in cerebral blood flow (CBF), volume (CBV), and oxygenation (blood-oxygenation level dependent (BOLD)) during functional activation are important for calculating changes in cerebral metabolic rate of oxygen consumption (CMRo2) from calibrated functional MRI (fMRI). An important part of this process is the CBF/CBV relationship, which is signified by a power-law parameter: gamma=ln (1+DeltaCBV/CBV)/ln (1+DeltaCBF/CBF). Because of difficulty in measuring CBF and CBV with MRI, the value of gamma is therefore assumed to be approximately 0.4 from a prior primate study under hypercapnia. For dynamic fMRI calibration, it is important to know if the value of gamma varies after stimulation onset. We measured transient relationships between DeltaCBF, DeltaCBV, and DeltaBOLD by multimodal MRI with temporal resolution of 500 ms (at 7.0 T) from the rat somatosensory cortex during forepaw stimulation, where the stimulus duration ranged from 4 to 32 secs. Changes in CBF and BOLD were measured before the administration of the contrast agent for CBV measurements in the same subjects. We observed that the relationship between DeltaCBF and DeltaCBV varied dynamically from stimulation onset for all stimulus durations. Typically after stimulation onset and at the peak or plateau of the DeltaCBF, the value of gamma ranged between 0.1 and 0.2. However, after stimulation offset, the value of gamma increased to 0.4 primarily because of rapid and slow decays in DeltaCBF and DeltaCBV, respectively. These results suggest caution in using dynamic measurements of DeltaCBF and DeltaBOLD required for calculating DeltaCMRo2 for functional stimulation, when either DeltaCBV has not been accurately measured or a fixed value of gamma during hypercapnia perturbation is used.
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PMID:Dynamics of changes in blood flow, volume, and oxygenation: implications for dynamic functional magnetic resonance imaging calibration. 1703 88

MRI is a noninvasive diagnostic modality that reveals anatomy, physiology, and function in vivo without depth limitation or optical interference. MRI application to the retina, however, remains challenging. We improved spatial resolution to resolve layer-specific structure and functional responses in the retina and confirmed the laminar resolution in an established animal model of retinal degeneration. Structural MRI of normal rat retinas revealed three bands corresponding histologically to (i) the combined ganglion cell layer/inner nuclear layer plus the embedded retinal vessels, (ii) the avascular outer nuclear (photoreceptor) layer and its photoreceptor segments, and (iii) the choroidal vascular layer. Imaging with an intravascular contrast agent (gadolinium-diethylene-tri-amine-pentaacetic acid) enhanced the retinal and choroidal vascular layers bounding the retina, but not the avascular outer nuclear layer and the vitreous. Similarly, blood-oxygen-level-dependent (BOLD) functional MRI revealed layer-specific responses to hyperoxia and hypercapnia. Importantly, layer-specific BOLD responses in the two vascular layers were divergent, suggesting the two vasculatures are differentially regulated. To corroborate sensitivity and specificity, we applied layer-specific MRI to document photoreceptor degeneration in Royal College of Surgeons rats. Consistent with histology, layer-specific MRI detected degeneration of the outer nuclear layer. Surprisingly, MRI revealed increased thickness in the choroidal vascular layer and diminished BOLD responses to hyperoxia and hypercapnia in the Royal College of Surgeons rat retinas, suggesting perturbation of vascular reactivity secondary to photoreceptor loss. We conclude that MRI is a powerful investigative tool capable of resolving lamina-specific structures and functional responses in the retina as well as probing lamina-specific changes in retinal diseases.
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PMID:Structural and functional MRI reveals multiple retinal layers. 1708 44

The magnitude and shape of blood oxygen level-dependent (BOLD) responses in functional MRI (fMRI) studies vary across brain regions, subjects, and populations. This variability may be secondary to neural activity or vasculature differences, thus complicating interpretations of BOLD signal changes in fMRI experiments. We compare the BOLD responses to neural activity and a vascular challenge and test a method to dissociate these influences in 26 younger subjects (ages 18-36) and 24 older subjects (ages 51-78). Each subject performed a visuomotor saccade task (a vascular response to neural activity) and a breathholding task (vascular dilation induced by hypercapnia) during separate runs in the same scanning session. For the saccade task, signal magnitude showed a significant decrease with aging in FEF, SEF, and V1, and a delayed time-to-peak with aging in V1. The signal magnitudes from the saccade and hypercapnia tasks showed significant linear regressions within subjects and across individuals and populations. These two tasks had weaker, but sometimes significant linear regressions for time-to-peak and coherence phase measures. The significant magnitude decrease with aging in V1 remained after dividing the saccade task magnitude by the hypercapnia task magnitude, implying that the signal decrease is neural in origin. These findings may lead to a method to identify vascular reactivity-induced differences in the BOLD response across populations and the development of methods to account for the influence of these vasculature differences in a simple, noninvasive manner.
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PMID:Reducing vascular variability of fMRI data across aging populations using a breathholding task. 1709 19

Combined blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL) functional MRI (fMRI) was performed for simultaneous investigation of neurovascular coupling in the primary visual cortex (PVC), primary motor cortex (PMC), and supplementary motor area (SMA). The hypercapnia-calibrated method was employed to estimate the fractional change in cerebral metabolic rate of oxygen consumption (CMR(O2)) using both a group-average and a per-subject calibration. The group-averaged calibration showed significantly different CMR(O2)-CBF coupling ratios in the three regions (PVC: 0.34 +/- 0.03; PMC: 0.24 +/- 0.03; and SMA: 0.40 +/- 0.02). Part of this difference emerges from the calculated values of the hypercapnic calibration constant M in each region (M(PVC) = 6.6 +/- 3.4, M(PMC) = 4.3 +/- 3.5, and M(SMA) = 7.2 +/- 4.1), while a relatively minor part comes from the spread and shape of the sensorimotor BOLD-CBF responses. The averages of the per-subject calibrated CMR(O2)-CBF slopes were 0.40 +/- 0.04 (PVC), 0.31 +/- 0.03 (PMC), and 0.44 +/- 0.03 (SMA). These results are 10-30% higher than group-calibrated values, and are potentially more useful for quantifying individual differences in focal functional responses. The group-average calibrated motor coupling value is increased to 0.28 +/- 0.03 when stimulus-correlated increases in end-tidal CO(2) are included. Our results support the existence of regional differences in neurovascular coupling, and argue for the importance of achieving optimal accuracy in hypercapnia calibrations to resolve method-dependent variations in published results.
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PMID:Flow-metabolism coupling in human visual, motor, and supplementary motor areas assessed by magnetic resonance imaging. 1732 78

The effects of cocaine on cerebral blood flow and tissue oxygen levels in the rat brain were investigated with concurrent laser Doppler flowmetry and fluorescence quenching spectroscopy. Responses elicited by mild hypercapnia were used as calibration to assess the effects of cocaine on oxidative metabolism. Intravenous cocaine challenge of 0.5 mg/kg induced significant increases in tissular oxygenation and perfusion in all regions investigated (primary motor cortex, medial prefrontal cortex and dorsal striatum). Mild hypercapnia, a challenge that affects haemodynamics but not metabolism, elicited comparable changes in blood flow but substantially larger changes in tissue oxygen levels. These differences in tissue oxygen build-up suggest that increased oxidative metabolism is a significant component of the cerebral metabolic response to acute cocaine challenge. The implications for the interpretation of pharmacological MRI data are discussed.
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PMID:Effects of cocaine on blood flow and oxygen metabolism in the rat brain: implications for phMRI. 1744 19

The estimation of changes in CMR(O2) using functional MRI involves an essential calibration step using a vasoactive agent to induce an isometabolic change in CBF. This calibration procedure is performed most commonly using hypercapnia as the isometabolic stimulus. However, hypercapnia possesses a number of detrimental side effects. Here, a new method is presented using hyperoxia to perform the same calibration step. This procedure requires independent measurement of Pa(O2), the BOLD signal, and CBF. We demonstrate that this method yields results that are comparable to those derived using other methods. Further, the hyperoxia technique is able to provide an estimate of the calibration constant that has lower overall intersubject and intersession variability compared to the hypercapnia approach.
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PMID:A calibration method for quantitative BOLD fMRI based on hyperoxia. 1763 16

This study describes a novel MRI application to image basal blood flow, physiologically induced blood-flow changes, and the effects of isoflurane concentration on blood flow in the retina. Continuous arterial-spin-labeling technique with a separate neck coil for spin labeling was used to image blood flow of the rat retina at 90 x 90 x 1500-microm resolution. The average blood flow of the whole retina was 6.3+/-1.0 ml/g/min under 1% isoflurane, consistent with the high blood flow in the retina reported using other techniques. Blood flow is relatively constant along the length of the retina, except it dipped slightly around the optic nerve head and dropped significantly at the distal edges where the retina terminates. Hyperoxia (100% O(2)) decreased blood flow 25+/-6% relative to baseline (air) due to vasoconstriction. Hypercapnia (5% CO(2)+21% O(2)) increased blood flow 16+/-6% due to vasodilation. Increasing isoflurane (a potent vasodilator) concentration to 1.5% increased blood flow to 9.3+/-2.7 ml/g/min. Blood-flow signals were confirmed to be genuine by repeating measurements after the animals were sacrificed in the MRI scanner. This study demonstrates a proof of concept that quantitative blood flow of the retina can be measured using MRI without depth limitation. Blood-flow MRI has the potential to provide unique insights into retinal physiology, serve as an early biomarker for some retinal diseases, and could complement optically based imaging techniques.
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PMID:Blood-flow magnetic resonance imaging of the retina. 1806 88

Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). In this study, we implemented a quantitative R(2)* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO(2) responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, +/-11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, +/-2.9) and CMRO(2) (+20.7%, +/-1.4), and caffeine decreased CBF (-34.5%, +/-2.6) with a non-significant change in CMRO(2) (+5.2%, +/-6.4). The coupling between CBF and CMRO(2) was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R(2) * is a promising approach for evaluating CBF and CMRO(2) changes in response to pharmacological interventions.
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PMID:Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study. 1819 83


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