Changes In Oxygen Metabolism Research Articles

Retinal oximetry imaging in Alzheimer's disease.

Structural and physiological abnormalities have been reported in the retina in Alzheimer's disease (AD). Retinal oximetry detects changes in retinal oxygen metabolism in many eye diseases, where structural changes are seen. To compare oxygen saturation in retinal blood vessels in patients with AD and a healthy cohort. Oxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric noninvasive retinal oximeter. 18 individuals with mild to moderate dementia of the Alzheimer-type (stage 3-5 according to the Global Deterioration Scale) and 18 healthy subjects underwent retinal oximetry in a case control study. Retinal oxygen saturation in arterioles and venules in patients with moderate AD was significantly elevated compared to healthy individuals. Retinal arterioles have 94.2 ± 5.4% oxygen saturation in moderate AD compared with 90.5 ± 3.1% in healthy subjects (mean ± SD, n = 10, p = 0.028). Retinal venules were 51.9 ± 6.0% saturated in moderate AD compared with 49.7 ± 7.0% in healthy subjects (mean ± SD, n = 10, p = 0.02). This is the first study of retinal oxygen metabolism in any central nervous system disease. It discovers abnormalities in retinal oxygen metabolism in AD. The findings are similar to those seen in age-related macular degeneration and diabetic retinopathy. Noninvasive retinal oximetry may offer new insights into pathophysiology of AD. Further studies are needed to confirm and expand these findings.

Sources of systematic error in calibrated BOLD based mapping of baseline oxygen extraction fraction

Recently a new class of calibrated blood oxygen level dependent (BOLD) functional magnetic resonance imaging (MRI) methods were introduced to quantitatively measure the baseline oxygen extraction fraction (OEF). These methods rely on two respiratory challenges and a mathematical model of the resultant changes in the BOLD functional MRI signal to estimate the OEF. However, this mathematical model does not include all of the effects that contribute to the BOLD signal, it relies on several physiological assumptions and it may be affected by intersubject physiological variability. The aim of this study was to investigate these sources of systematic error and their effect on estimating the OEF. This was achieved through simulation using a detailed model of the BOLD signal. Large ranges for intersubject variability in baseline physiological parameters such as haematocrit and cerebral blood volume were considered. Despite this the uncertainty in the relationship between the measured BOLD signals and the OEF was relatively low. Investigations of the physiological assumptions that underlie the mathematical model revealed that OEF measurements are likely to be overestimated if oxygen metabolism changes during hypercapnia or cerebral blood flow changes under hyperoxia. Hypoxic hypoxia was predicted to result in an underestimation of the OEF, whilst anaemic hypoxia was found to have only a minimal effect.

Understanding the dynamic relationship between cerebral blood flow and the BOLD signal: Implications for quantitative functional MRI

Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool for untangling the physiological processes associated with neural stimulus-induced BOLD activation. However, to date this technique has largely been applied to the study of essentially steady-state physiological changes (baseline to activation) associated with block-design stimuli, and it is unclear whether this approach may be directly extended to the study of more dynamic, naturalistic experimental designs. In this study we tested an assumption underlying this technique whose validity is critical to the application of calibrated BOLD to the study of more dynamic stimuli, that information about fluctuations in venous cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations in CBF, making the independent measurement of CBVv unnecessary. To accomplish this, simultaneous arterial spin labeling and BOLD imaging were used to measure the CBF and BOLD responses to flickering checkerboards with contrasts that oscillated continuously with frequencies of ~0.02–0.16Hz. The measurements were then fit to a dynamic physiological model of the BOLD response in order to explore the range of consistent CMRO2 and CBVv responses. We found that the BOLD and CBF responses were most consistent with relatively tight dynamic coupling between CBF and CMRO2 and a CBVv response that was an order of magnitude slower than either CBF or CMRO2. This finding suggests that the assumption of tight flow–volume coupling may not be strictly valid, complicating the extension of calibrated BOLD to more naturalistic experimental designs.

Calibrating the BOLD response without administering gases: Comparison of hypercapnia calibration with calibration using an asymmetric spin echo

The calibrated BOLD (blood oxygen level dependent) technique was developed to quantify the BOLD signal in terms of changes in oxygen metabolism. In order to achieve this a calibration experiment must be performed, which typically requires a hypercapnic gas mixture to be administered to the participant. However, an emerging technique seeks to perform this calibration without administering gases using a refocussing based calibration. Whilst hypercapnia calibration seeks to emulate the physical removal of deoxyhaemoglobin from the blood, the aim of refocussing based calibration is to refocus the dephasing effect of deoxyhaemoglobin on the MR signal using a spin echo. However, it is not possible to refocus all of the effects that contribute to the BOLD signal and a scale factor is required to estimate the BOLD scaling parameter M. In this study the feasibility of a refocussing based calibration was investigated. The scale factor relating the refocussing calibration to M was predicted by simulations to be approximately linear and empirically measured to be 0.88±0.36 for the visual cortex and 0.93±0.32 for a grey matter region of interest (mean±standard deviation). Refocussing based calibration is a promising approach for greatly simplifying the calibrated BOLD methodology by eliminating the need for the subject to breathe special gas mixtures, and potentially provides the basis for a wider implementation of quantitative functional MRI.

PS-098 Haemodynamic And Metabolic Effects Of A New Paediatric Dobutamine Formulation In Hypoxic Newborn Piglets

Background Using an age-appropriate new dobutamine formulation, the aims of the study were: to validate superior vena cava flow (SVCF) as a marker of cardiac output (CO), and to study drug-related changes in haemodynamics and oxygen metabolism in response to escalating doses of dobutamine in hypoxic neonatal piglets. Methods 2–days-old-piglets were exposed to hypoxia (10–15% oxygen) for 2 h followed by reoxigenation with 21–30% oxygen for 6 h. After 60-min of reoxigenation, 18 piglets were randomised to: Control group, hypoxic animals without treatment, and 10–15 µg/kg/min or 15–20 µg/kg/min dose groups, each animal received two doses of dobutamine (Proveca Ltd.) during 30-min with 60-min washout period between doses. All animals were monitored for arterial blood pressure (MABP), heart-rate (HR), CO, stroke-volume-index (SVI), systemic-vascular-resistance-index (SVRI), oxygen-delivery (OD), systemic consumption (VO 2 ) and fractional-tissue-oxygen extraction (FTOE). In three animals an ultrasonic perivascular flow probe was placed around superior vena cava to continuously measure SVCF. Statistics: Mean ± SD, ANOVA, p Result A good positive correlation was observed between SVCF and CO. Hypoxia resulted in a significant decreased on CO, SVI, SVRI and MABP. All dobutamine doses improved significantly HR, CO and SVRI without changes in SVI and MABP. All doses increased OD but only 10–15 µg/kg/min increased VO 2 without changes in FTOE. Conclusion The new dobutamine formulation targeted to support neonatal cardiovascular function reveals a significant improvement of haemodynamic status, but dose-specific differences in metabolic response in hypoxic neonatal piglets. Further studies are needed to evaluate those drug effects in other vital organs. FP7-HEALTH-F5–2011 (no282533).

The apoplastic oxidative burst as a key factor of hyperhydricity in garlic plantlet in vitro

The phenomenon of hyperhydricity, a physiological disorder occurring frequently in tissue culture, causes ultrastructural modification and metabolic alteration of shoots. Reactive oxygen species (ROS) accumulation and oxidative stress induction are common features during the development of hyperhydricity, but the relationship between organelle redox homeostasis and hyperhydricity with ultrastructural abnormalities is unclear. To investigate the origin of oxidative stress-induced hyperhydricity, changes in oxygen metabolism in different subcellular compartments of garlic plantlets in vitro were studied. Under exogenous hydrogen peroxide (H2O2) stress, the chloroplastic and mitochondrial ultrastructure was disrupted, which was concomitant with aggravated frequency and severity of hyperhydricity. The addition of H2O2 to the growth medium enhanced superoxide anion generation and H2O2 content in the subcellular compartments. Accumulation of ROS was the highest in apoplasts. Compared with control shoots, in apoplasts exogenous H2O2 stimulated a sharp increase in superoxide dismutase activity within 4 days and a sharp increase in ascorbate peroxidase and glutathione reductase activities and in ascorbic acid and glutathione contents after 8 days of H2O2 treatment. In the other subcellular compartments, dramatic improvement of the antioxidant system occurred after 12 days. Thus, the apoplast was the most sensitive compartment among those investigated. Apoplastic ROS might play a signaling role to participate in the coordination of stress adaptation. The apoplastic oxidative burst in garlic plantlets in vitro is an early response to the development of hyperhydricity.

Development of new optical imaging systems of oxygen metabolism and simultaneous measurement in hemodynamic changes using awake mice.

PET allows the measurement of CBF, CBV and CMRO2 in human and plays an important role in the diagnosis of pathologic conditions and clinical research. On the other hand, in animal studies, there is no optical imaging system for evaluating changes in CBF and CBV, and oxygen metabolism, from the same brain area under awake condition. In the present study, we developed a simultaneous measurement system of LSI and IOSI, which was verified by LDF. Moreover, to evaluate oxygen metabolism, FAI was performed from the same brain area as LSI and IOSI measurements. The change in CBF according to LSI was correlated with that by LDF. Similarly, the change in CBV obtained by IOSI was also correlated with RBC concentration change measured by LDF. The change in oxygen metabolism by FAI was associated with that in CBF obtained by LSI, although the change in CBF was greater than that in oxygen metabolism. We revealed that the relationship between oxygen metabolism and CBF as measured by our system was in good agreement with the relationship between CMRO2 and CBF in human PET studies. Our measurement system of CBF, CBV and oxygen metabolism is not only useful for studying neurovascular coupling, but also easily corroborates human PET studies.

Overproduction of reactive oxygen species involved in the pathogenicity of Fusarium in potato tubers

Differences in virulence between Fusarium sulphureum and Fusarium sambucinum were compared. Changes in reactive oxygen species production and metabolism in inoculated slices of potato tubers were also compared. The result showed that Fusarium infection induced significant production of ROS, lipid peroxidation and loss of cell membrane integrity, but low activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX). Compared to F. sambucinum, F. sulphureum led larger lesion diameters on potato tubers and slices. It resulted in more superoxide anion (O2-) and earlier peak of hydrogen peroxide (H2O2), but lower activity of catalase (CAT) and APX, and accompanied with higher malondialdehyde (MDA) content and lower cell membrane integrity. These findings suggested that overproduction of ROS involved in the pathogenicity of Fusarium in potato tubers.

The significance of changes in cerebral oxygen and glucose metabolism in patients with cerebral hemorrhage caused by acute hypertension

Objective To study the clinical significance of early changes in cerebral oxygen and glucose metabolism in patients with cerebral hemorrhage and with Glasgow coma score (GCS) of 5-8 caused by acute hypertension in order to find relationship between those changes and prognosis.Methods From January 1,2011 to June 30,2012,a cohort of 43 patients with cerebral hemorrhage caused by acute hypertension were enrolled for retrospective study.Radial artery and internal jugular vein were separately cannulated retrogradely for collecting blood for blood gas analysis and blood glucose tests carried out 24 hours after the onset of the cerebral hemorrhage and then every 6-8 hours and as any major changes in physical signs of patients occurred.And this monitoring kept for consecutive 3 days.The data of these laboratory findings were analyzed and calculated to determine internal jugular vein oxygen saturation (SjVO2),cerebral oxygen utilization rate (CEO2),cerebral arterio-venous oxygen difference (AVDO2),arterio-venous blood glucose difference (V-Aglu),arterio-venous lactic acid difference (V-Alac) and absolute value of carbon dioxide pressure difference between jugular vein and artery (V-APCO2).All patients met the diagnostic criteria of hypertensive cerebral hemorrhage revised by the 4th National Academic Conference on cerebrovascular disease in 1995 requiring diagnosis confirmed by brain CT,admitted within 24 hours of onset,Glasgow coma score (GCS) 5-8 and a history of hypertension.Exclusion criteria were:cerebral hemorrhage caused by traumatic intracranial hematoma,spontaneous subarachnoid hemorrhage,arteriovenous malformation and Moyamoya disease,intracranial tumor apoplexy,cerebral bleeding derived from the disturbance of blood coagulation system,and cerebral hemorrhagic infarction.According to the short-term prognosis,the patients were divided into the death group and the survival group.Then the differences in biomarkers mentioned above between two groups were compared to find the relationship between levels of those biomarkers and outcomes of patients.Thereafter,the results of this retrospective study inspired us to carry out a prospective and double blind study in another 23 patients from July 2012 to January 2013 for further confirming the validity of these biomarkers to predict the short-term outcomes of patients.The statistical analysis was performed with SPSS 16.0 software (SPSS,USA) and a P ＜ 0.05 was considered significant.Numerical values were given as means ± SD unless stated otherwise.For statistical analyses,normality was assessed before choosing the relevant comparative test and nonparametric tests was used in cases as the normality test failed.Results Of 43 patients with cerebral hemorrhage for retrospective analysis,there were 27 male and 16 female with M/F ratio =1.7:1,aged from 49 to 81 with mean 66.2 ± 15.3 years and their GCS scores were 5-8.of them,there were 28 patients suffered from basal ganglia hemorrhage,6 cerebella hemorrhage,5 pons cerebelli hemorrhage and 4 lobe hemorrhage.There were 25 patients with supratentorial hematoma in volume of no less than 30 mL and 10 infratentorial hematoma in volume of no less than 10 mL of them,11 patients were treated with craniotomy and evacuation of hematoma or decompression craniotomy and rest were treated with conservative strategy.Compared with the death group,the CEO2,AVDO2,V-AGlu,V-ALac in the survival group decreased significantly (P ＜ 0.05),while V-APCO2 and SjvO2 increased significantly (P ＜ 0.05).In the subsequent prospective study,the accuracy rate of the levels of SjvO2 ＜ 52％,AVDO2 ＞ 83％ for predicting prognosis was 78.3％.Conclusions The cerebral oxygen and glucose metabolism was obviously abnormal in hypertensive cerebral hemorrhagic patients with GCS score of 5-8 among the death group,and especially the anaerobic metabolism was apparently increased.It was also found that the risk threshold (SjvO2 ＜ 52％,AVDO2 ＞83％) was in close relationship with patients'death expectation. Key words: Hypertensive cerebral hemorrhage; Glucose metabolism; Cerebral oxygen metabolism; Glasgow coma score (GCS) ; Stroke; Secondary brain injury; Prognosis; Survival analysis

FoxO3a-mediated activation of stress responsive genes during early torpor in a mammalian hibernator

The torpor-arousal cycle of mammalian hibernation is characterized by drastic changes in physiological state that are supported by reprogramming of metabolic functions. The entrance and arousal phases of the cycle function as transitional stages, where major changes in oxygen metabolism take place. Acute changes in oxygen delivery can lead to either ischemia-related injuries during torpor induction or reperfusion damage during arousal. This study examines the regulation of the forkhead box O3 (FoxO3) transcription factor, which functions to increase cellular cytoprotection in response to oxidative stress stimuli. Immunoblots show that total expression of FoxO3a was elevated during early torpor (ET) and late torpor by 3.6- and 4.5-fold, respectively, compared to euthermic control. However, enhanced phosphorylation of FoxO3a at Thr-32 was only evident during ET by 1.5-fold, accompanied by increased phosphorylation of c-Jun N-terminal kinases by 1.2-fold. During ET, increased nuclear inclusion of FoxO3a was evident along with its transcriptional co-activator β-catenin by 1.9- and 2.7-fold, respectively. As well, FoxO3a DNA binding was elevated by 1.8-fold during ET, along with increased expression of FoxO3a downstream genes catalase, p27, and cyclin G 2 , by 1.4-, 1.6-, and 1.3-fold, respectively. Overall, the results indicate activation of FoxO3a during ET, suggesting a role of FoxO3a in response to cellular stress during hibernation.

Changes of cerebral tissue oxygen saturation at sleep transitions in adolescents.

In adults, cerebral oxy-([O₂Hb]) and deoxyhemoglobin concentrations ([HHb]) change characteristically at transitions of sleep stages. The aims were to assess these changes in adolescents and additionally to measure tissue oxygen saturation (StO₂) by near infrared spectroscopy (NIRS). Previously it was reported that in adults [O₂Hb] increased and [HHb] decreased at the transition from non-rapid eye movement sleep (NREMS) to REMS and wakefulness. Transitions to NREMS from REMS/wakefulness led to a decrease in [O₂Hb] and an increase in [HHb]. We measured [O₂Hb], [HHb] and tissue oxygenation (StO₂) with NIRS approximately above the left prefrontal cortex in 12 healthy adolescent males (aged 10-16 years). We found comparable signs and magnitudes of changes in [O₂Hb] and [HHb] as observed in adults. StO₂ increased at the transitions from NREMS to REMS and decreased from REMS to NREMS and at sleep onset (all p < 0.01, linear mixed effects model). Changes in oxygen metabolism during sleep transitions are similar in adolescents and adults. In addition, we show for the first time temporal changes of StO₂ at sleep transitions.

Using carbogen for calibrated fMRI at 7 Tesla: Comparison of direct and modelled estimation of the M parameter

Task-evoked changes in cerebral oxygen metabolism can be measured using calibrated functional Magnetic Resonance Imaging (fMRI). This technique requires the use of breathing manipulations such as hypercapnia, hyperoxia or a combination of both to determine a calibration factor M. The M-value is usually obtained by extrapolating the BOLD signal measured during the gas manipulation to its upper theoretical physiological limit using a biophysical model. However, a recently introduced technique uses a combination of increased inspired concentrations of O2 and CO2 to saturate the BOLD signal completely. In this study, we used this BOLD saturation technique to measure M directly at 7Tesla (T). Simultaneous carbogen-7 (7% CO2 in 93% O2) inhalation and visuo-motor task performance were used to elevate venous oxygen saturation in visual and motor areas close to their maximum, and the BOLD signal measured during this manipulation was used as an estimate of M. As accurate estimation of M is crucial for estimation of valid oxidative metabolism values, these directly estimated M-values were assessed and compared with M-values obtained via extrapolation modelling using the generalized calibration model (GCM) on the same dataset. Average M-values measured using both methods were 10.4±3.9% (modelled) and 7.5±2.2% (direct) for a visual-related ROI, and 11.3±5.2% (modelled) and 8.1±2.6% (direct) for a motor-related ROI. Results from this study suggest that, for the CO2 concentration used here, modelling is necessary for the accurate estimation of the M parameter. Neither gas inhalation alone, nor gas inhalation combined with a visuo-motor task, was sufficient to completely saturate venous blood in most subjects. Calibrated fMRI studies should therefore rely on existing models for gas inhalation-based calibration of the BOLD signal.

A New Functional MRI Approach for Investigating Modulations of Brain Oxygen Metabolism

Functional MRI (fMRI) using the blood oxygenation level dependent (BOLD) signal is a common technique in the study of brain function. The BOLD signal is sensitive to the complex interaction of physiological changes including cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral oxygen metabolism (CMRO2). A primary goal of quantitative fMRI methods is to combine BOLD imaging with other measurements (such as CBF measured with arterial spin labeling) to derive information about CMRO2. This requires an accurate mathematical model to relate the BOLD signal to the physiological and hemodynamic changes; the most commonly used of these is the Davis model. Here, we propose a new nonlinear model that is straightforward and shows heuristic value in clearly relating the BOLD signal to blood flow, blood volume and the blood flow-oxygen metabolism coupling ratio. The model was tested for accuracy against a more detailed model adapted for magnetic fields of 1.5, 3 and 7T. The mathematical form of the heuristic model suggests a new ratio method for comparing combined BOLD and CBF data from two different stimulus responses to determine whether CBF and CMRO2 coupling differs. The method does not require a calibration experiment or knowledge of parameter values as long as the exponential parameter describing the CBF-CBV relationship remains constant between stimuli. The method was found to work well for 1.5 and 3T but is prone to systematic error at 7T. If more specific information regarding changes in CMRO2 is required, then with accuracy similar to that of the Davis model, the heuristic model can be applied to calibrated BOLD data at 1.5T, 3T and 7T. Both models work well over a reasonable range of blood flow and oxygen metabolism changes but are less accurate when applied to a simulated caffeine experiment in which CBF decreases and CMRO2 increases.

Binocular activation elicits differences in neurometabolic coupling in visual cortex

Non-invasive brain imaging requires comprehensive interpretation of hemodynamic signals. In functional magnetic resonance imaging, blood oxygen level dependent (BOLD) signals are used to infer neural processes. This necessitates a clear understanding of how BOLD signals and neural activity are related. One fundamental question concerns the relative importance of synaptic activity and spiking discharge. Although these two components are related, most previous work shows that synaptic activity is better reflected in the BOLD signal. However, the mechanisms of this relationship are not clear. The BOLD signal depends on relative changes in cerebral blood flow and cerebral metabolic rate of oxygen. Oxygen metabolism changes are difficult to measure with current imaging techniques, but it is possible to obtain direct quantitative simultaneous in vivo measurement of tissue oxygen and co-localized underlying neural activity. Here, we use this approach with a specific binocular stimulus protocol in order to activate inhibitory and excitatory neuronal pathways in the visual cortex. During excitatory binocular interaction, we find that metabolic, spiking, and local field potential responses are correlated. However, during suppressive binocular interaction, spiking activity and local field potentials (LFP) are dissociated while only the latter is coupled with metabolic response. These results suggest that inhibitory connections may be a key factor in the dissociation between LFP and spiking activity, which may contribute substantially to the close coupling between the BOLD signal and synchronized synaptic activity in the brain.

Adaptation of cerebral oxygen metabolism and blood flow and modulation of neurovascular coupling with prolonged stimulation in human visual cortex

Prolonged visual stimulation results in neurophysiologic and hemodynamic adaptation. However, the hemodynamic adaptation appears to be small compared to neural adaptation. It is not clear how the cerebral metabolic rate of oxygen (CMRO2) is affected by adaptation. We measured cerebral blood flow (CBF) and CMRO2 change in responses to peripheral stimulation either continuously, or intermittently (on/off cycles). A linear system's response to the continuous input should be equal to the sum of the original response to the intermittent input and a version of that response shifted by half a cycle. The CMRO2 response showed a large non-linearity consistent with adaptation, the CBF response adapted to a lesser degree, and the blood oxygenation level dependent (BOLD) response was nearly linear. The metabolic response was coupled with a larger flow in the continuous condition than in the intermittent condition. Our results suggest that contrast adaptation improves energy economy of visual processing. However BOLD modulations may not accurately represent the underlying metabolic nonlinearity due to modulation of the coupling of blood flow and oxygen metabolism changes.

Comparison between dexmedetomidine and nitroglycerin for controlled hypotension during intracranial aneurysm surgery

Objective To compare the effect of dexmedetomidine and nitroglycerin for controlled hypotension and the changes in cerebral oxygen metabolism during intracranial aneurysm surgery.Methods 60 patients with intracranial aneurysm surgery were randomly divided into 2 groups(n=30 each group):dexmedetomidine group (group D) and nitroglycerin group (group N).Group D:Continuous infusion of dexmedetomidine was start at 1 μg/kg 10 min later,adjust infusion rate to 0.4 μg·kg-1·h-1-0.8 μg·kg1 ·h-1 according the changes of mean arterial pressure (MAP).Group N:continuous infusion of nitroglycerin was start at 3 μg·kg1·min-1 10 min later,adjust infusion rate to 3 μg·kg-1 ·h-1-9 μg·kg-1 ·min-1 according the changes of MAP.MAP and heart rate (HR) were recorded at before induction,at controlled hypotension,10,20 min and 30 min after controlled hypotension and 30 min end of controlled hypotension (T,T0,T1,T2,T3,T4).Simultaneous acquisition radial artery and jugular venous bulb blood line blood gas analysis,calculation of cerebral oxygen uptake rate (CERO2).Results MAP in the two groups reached the target blood pressure within 30 min of controlled hypotension started.During controlled hypotension,HR and CERO2 in group D:T3 [(66± 10) bpm,(27±6)％) was lower than T0 (76±9) bpm,(35±6)％] (P＜0.05).HR in group N:T3 (86±8) bpm was higher than T0 (77±8) bpm(P＜0.05).There were no significant of CERO2 between T3 (32±6)％ and T0 (34±5)％ in group N (P＞0.05).CERO2 and MAP was positively correlated in group D (r=0.83).Conclusions Dexmedetomidine for controlled hypotension in intracranial aneurysm surgery is safe and reliable.Compared with nitroglycerin,dexmedetomidine can reduce HR and cerebral oxygen metabolism. Key words: Dexmedetomidine; Hypotension controlled; Nitroglycerin; Cerebral oxygen metabolism; Intracranial aneurysm

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5. With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

A Novel Method of Combining Blood Oxygenation and Blood Flow Sensitive Magnetic Resonance Imaging Techniques to Measure the Cerebral Blood Flow and Oxygen Metabolism Responses to an Unknown Neural Stimulus

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged.

Pain response measured with arterial spin labeling

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level-dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed-continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised.