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

The hypercapnia induced by carbogen (95% O(2)/5% CO(2)) breathing, which is being re-evaluated as a clinical radiosensitiser, causes patient discomfort and hence poor compliance. Recent preclinical and clinical studies have indicated that the CO(2) content might be lowered without compromising increased tumour oxygenation and radiosensitisation. This preclinical study was designed to see if lower levels of hypercapnia could evoke similar decreases in the transverse relaxation rate R(2)* of rodent tumours to those seen with carbogen breathing. The response of rat GH3 prolactinomas to 1%, 212% and 5% CO(2) in oxygen, and 100% O(2) breathing, was monitored by non-invasive multi-gradient echo MRI to quantify R(2)*. As the oxygenation of haemoglobin is proportional to the blood p(a)O(2) and therefore in equilibrium with tissue pO(2), R(2)* is a sensitive indicator of tissue oxygenation. Hyperoxia alone decreased R(2)* by 13%, whilst all three hypercapnic hyperoxic gases decreased R(2)* by 29%. Breathing 1% CO(2) in oxygen evoked the same decrease in R(2)* as carbogen. The DeltaR(2)* response is primarily consistent with an increase in blood oxygenation, though localised increases in tumour blood flow were also identified in response to hypercapnia. The data support the concept that levels of hypercapnia can be reduced without loss of enhanced oxygenation and hence potential radiotherapeutic benefit.
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PMID:Effects of different levels of hypercapnic hyperoxia on tumour R(2)* and arterial blood gases. 1135 53

The cerebrospinal fluid (CSF) secretion of rat was monitored by longitudinal relaxation time-weighted magnetic resonance imaging (T(1)-weighted MRI) in combination with a ventricular injection of a T(1)-relaxation reagent: gadolinium-diethylene triamine-N,N,N',N",N"-pentaacetic acid (Gd-DTPA). A cannula was inserted in the left lateral ventricle, and 5 microl of 8.5 mM Gd-DTPA was injected as a CSF marker. Changes in the image intensity of the CSF were measured every 30 s, and the turnover rate of CSF (k) in the left lateral ventricle was obtained from the dilution of Gd-DTPA, based on the assumption of a single compartment model. In the control conditions, k was 0.158 +/- 0.009 min(-1) at an arterial blood CO(2) tension (pCO(2)) of 38.6 +/- 2.2 mmHg (n = 10), which corresponds to the CSF secretion rate of 3.6 microl min(-1). The k value was decreased (0.078 +/- 0.010 min(-1), n = 4) by a carbonic-anhydrase inhibitor (acetazolamide). The turnover rate was decreased by hypocapnia (0.094 +/- 0.019 min(-1), pCO(2) = 24.7 +/- 2.9 mmHg, n = 4), and it increased gradually and reached a plateau level as a result of hypercapnia (0.194 +/- 0.011 min(-1), pCO(2) = 104.5 +/- 7.1 mmHg, n = 10). These results suggested that CO(2) upregulates the secretion of CSF in the rat.
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PMID:Effects of pCO(2) on the CSF turnover rate in T(1)-weighted magnetic resonance imaging. 1173 75

The effect of hypercapnia on the cerebral metabolic rate of oxygen consumption (CMRO(2)) remains incompletely understood. This study examined the relationship between susceptibility (blood oxygenation level dependent (BOLD)) and perfusion-weighted (flow-sensitive alternating inversion recovery (FAIR)) MRI techniques both during induction of repeated transient hypercapnia (THC) and after return to normocapnia during whisker barrel functional activation. During induction of THC the FAIR signal became significantly elevated over control after 100 s of hypercapnia (P = 0.039), with a trend of increasing significance to 5 min (P = 0.000008). The FAIR signal in the activated cortex during subsequent normocapnia was significantly increased compared to pre-THC control after each successive period of THC. The mean grouped FAIR signal increased by 81% +/- 63% after one exposure (P = 0.021), by 163% +/- 55% after the second exposure (P = 0.0002), and by 240% +/- 54% after the third exposure (P = 0.000002). The mean grouped BOLD signal trended upward, but did not increase significantly during or after exposure 1, 2, or 3. These data demonstrate increased uncoupling of perfusion-weighted from susceptibility imaging techniques, both in nonactivated cortex during hypercapnia, and with activation after multiple exposures to THC. These results are consistent with saturation of BOLD contrast as well as with increases in CMRO(2) with stimulation after multiple exposures to THC.
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PMID:Changes in CBF-BOLD coupling detected by MRI during and after repeated transient hypercapnia in rat. 1221 Sep 34

Near-infrared spectroscopy (NIRS) enables continuous non-invasive quantification of blood and tissue oxygenation, and may be useful for quantification of cerebral blood volume (CBV) changes. In this study, changes in cerebral oxy- and deoxyhemoglobin were compared to corresponding changes in CBF and CBV as measured by positron emission tomography (PET). Furthermore, the results were compared using a physiological model of cerebral oxygenation. In five healthy volunteers changes in CBF were induced in a randomized order by hyperventilation or inhalation of 6% CO(2). Arterial content of O(2) and CO(2) was measured several times during each scanning. Changes in deoxyhemoglobin (deltaHb), oxyhemoglobin (deltaHbO(2)) and total hemoglobin (deltaHb(tot)) were continuously recorded with NIRS equipment. CBF and CBV was also determined in MRI-coregistered PET-slices in regions determined by the placement of the two optodes, as localized from the transmission scan. The PET-measurements showed an average CBV of 5.5+/-0.74 ml 100 g(-1) in normoventilation, with an increase of 29% during hypercapnia, whereas no significant changes were seen during hyperventilation. CBF was 51+/-10 in normoventilation, increased by 37% during 6% CO(2) and decreased by 25% during hyperventilation. NIRS showed significant increases in oxygenation during hypercapnia, and a trend towards decreases during hyperventilation. Changes in CBV measured with both techniques were significantly correlated to CO(2) levels. However, deltaCBV(NIRS) was much smaller than deltaCBV(PET), and measured NIRS parameters smaller than those predicted from the model. It is concluded that while qualitatively correct, NIRS measurements of CBV should be used with caution when quantitative results are needed.
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PMID:Cerebral hemodynamics measured with simultaneous PET and near-infrared spectroscopy in humans. 1241 1

The pattern and role of brain plasticity in stroke recovery has been incompletely characterized. Both ipsilesional and contralesional changes have been described, but it remains unclear how these relate to functional recovery. Our goal was to correlate brain activation patterns with tissue damage, hemodynamics, and neurologic status after temporary stroke, using functional magnetic resonance imaging (fMRI). Transverse relaxation time (T2)-weighted, diffusion-weighted, and perfusion MRI were performed at days 1 (n = 7), 3 (n = 7), and 14 (n = 7) after 2 hr unilateral middle cerebral artery occlusion in rats. Functional activation and cerebrovascular reactivity maps were generated from contrast-enhanced fMRI during forelimb stimulation and hypercapnia, respectively. Before MRI, rats were examined neurologically. We detected loss of activation responses in the ipsilesional sensorimotor cortex, which was related to T2 lesion size (r = -0.858 on day 3, r = -0.979 on day 14; p < 0.05). Significant activation responses in the contralesional hemisphere were detected at days 1 and 3. The degree of shift in balance of activation between the ipsilesional and contralesional hemispheres, characterized by the laterality index, was linked to the T2 and apparent diffusion coefficient in the ipsilesional contralesional forelimb region of the primary somatosensory cortex and primary motor cortex at day 1 (r = -0.807 and 0.782, respectively; p < 0.05) and day 14 (r = -0.898 and -0.970, respectively; p < 0.05). There was no correlation between activation parameters and perfusion status or cerebrovascular reactivity. Finally, we found that the laterality index and neurologic status changed in parallel over time after stroke, so that when all time points were grouped together, neurologic status was inversely correlated with the laterality index (r = -0.571; p = 0.016). This study suggests that the degree of shift of activation balance toward the contralesional hemisphere early after stroke increases with the extent of tissue injury and that functional recovery is associated mainly with preservation or restoration of activation in the ipsilesional hemisphere.
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PMID:Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: a functional magnetic resonance imaging study. 1253 11

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.
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PMID:Functional magnetic resonance imaging based on changes in vascular space occupancy. 1287 2

Most functional magnetic resonance imaging (fMRI) studies in animals are conducted under anesthesia to minimize motion artifacts. However, methods and techniques have been developed recently for imaging fully conscious rats. Functional MRI studies on conscious animals report enhanced BOLD signal changes as compared to the anesthetized condition. In this study, rats were exposed to different concentrations of carbon dioxide (CO(2)) while conscious and anesthetized to test whether cerebrovascular reactivity may be contributing to these enhanced BOLD signal changes. Hypercapnia produced significantly greater increases in MRI signal intensity in fully conscious animals (6.7-13.3% changes) as when anesthetized with 1% isoflurane (3.2-4.9% changes). In addition, the response to hypercapnia was more immediate in the conscious condition (< 30s) with signal risetimes twice as fast as in the anesthetized state (60s). Both cortical and subcortical brain regions showed a robust, dose- dependent increase in MRI signal intensity with hypercapnic challenge while the animals were conscious but little or no change when anesthetized. Baseline variations in MRI signal were higher while animals were conscious but this was off set by greater signal intensity changes leading to a greater contrast-to-noise ratio, 13.1 in conscious animals, as compared to 8.0 in the anesthetized condition. In summary, cerebral vasculature appears to be more sensitive to hypercapnic challenge in the conscious condition resulting in enhanced T2* MRI signal intensity and the potential for better BOLD signal changes during functional imaging.
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PMID:Changes in MRI signal intensity during hypercapnic challenge under conscious and anesthetized conditions. 1468 2

Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.
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PMID:Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis. 1588 Apr 97

A 32-year-old woman was transported to our hospital by ambulance because of loss of consciousness and breathing induced by drug intoxication. After general status was recovered, her arterial blood gas analysis under breathing room air revealed hypercapnia and hypoxemia which were caused by hypoventilation. After exclusion of apparent pulmonary, neuromuscular and central nerve diseases, she was diagnosed with primary alveolar hypoventilation syndrome. She had the complication of antiphospholipid syndrome (APS), suggesting the possibility of small lesions of the brainstem due to APS, which were too small to be detected on CT or MRI; these small lesions could cause injuries to the respiratory center.
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PMID:Primary alveolar hypoventilation syndrome complicated with antiphospholipid syndrome. 1625 18

Acute hypoxia (transient cycles of hypoxia-reoxygenation) is known to occur in solid tumors and is generally believed to be caused by tumor blood flow instabilities. It was recently demonstrated that T2*-weighted (T2*w) gradient echo (GRE) MRI is a powerful non-invasive method for investigating periodic changes in tumor pO2 and blood flow associated with acute hypoxia. Here, the possible correlation between tumor vessel immaturity, vessel functionality and T2*w GRE signal fluctuations was investigated. Intramuscularly implanted FSa II fibrosarcoma-bearing mice were imaged at 4.7 T. Maps of spontaneous fluctuations of MR signal intensity in tumor tissue during air breathing were obtained using a T2*w GRE sequence. This same sequence was also employed during air-5% CO2 breathing (hypercapnia) and carbogen breathing (hypercapnic hyperoxia) to obtain parametric maps representing vessel maturation and vessel function, respectively. Vascular density, vessel maturation and vessel perfusion were also assessed histologically by using CD31 labeling, alpha-smooth muscle actin immunoreactivity and Hoechst 33242 labeling, respectively. About 50% of the tumor fluctuations occurred in functional tumor regions (responsive to carbogen) and 80% occurred in tumor regions with immature vessels (lack of response to hypercapnia). The proportion of hypercapnia-responsive voxels were found to be twice as great in fluctuating than in non-fluctuating tumor areas (P: 0.22 vs 0.13). Similarly, the proportion of functional voxels was somewhat greater in fluctuating tumor areas (P: 0.54 vs 0.43). The mean values of MR signal changes during hypercapnia (VD) and during carbogen breathing (VF) (significant voxels only) were also larger in fluctuating than in non-fluctuating tumor areas (P < 0.05). This study demonstrated that adequate vessel functionality and advanced vessel maturation could explain at least in part the occurrence of spontaneous T2*w GRE signal fluctuations. Functionality and maturation are not required for signal fluctuations, however, because a large fraction of fluctuations could still occur in non-perfused and/or immature vessels.
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PMID:The role of vessel maturation and vessel functionality in spontaneous fluctuations of T2*-weighted GRE signal within tumors. 1641 Nov 70


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