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Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO2 during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO2 responses were observed in premanifest and early manifest HD patients compared to controls ( P 2 = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO2 response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.

The relationship between the topological characteristics of the white matter (WM) network have been shown to be related to neural development, intelligence, and various diseases; however, few studies have been conducted to explore the relationship between topological characteristics of the WM network and cerebral metabolism. In a recent study we investigated the relationship between WM network topological and metabolic metrics of the cerebral parenchyma in healthy volunteers using the newly developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging technique and graph theory approaches. Ninety-six healthy adults (25.5 ± 1.8 years of age) were recruited as volunteers in the current study. The cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction, and the global topological metrics of the WM network (global efficiency [Eglob], local efficiency, and small-worldliness) were assessed. A stepwise multiple linear regression model was estimated. CMRO2 was entered as the dependent variable. The topological and demographic parameters (age, gender, FIQ, SBP, gray matter volume, and WM volume) were entered as independent variables in the model. The final performing models were comprised of predictors of Eglob, FIQ, and age (adjusted R2 values were 0.489 [L-AAL] and 0.424 [H-1024]). Our study initially revealed a relationship between Eglob and cerebral oxygen metabolism in healthy young adults.

Background: We aimed to explore the effect of comprehensive cerebral protection on cerebral oxygen metabolism and vascular endothelial function in elderly patients with acute cerebral infarction. Methods: A total of 168 elderly patients with acute cerebral infarction treated in The First Affiliated Hospital of Nanchang University, China from January 2016 to January 2018 were selected. The patients were divided into a control group and an observation group using random number method, n=84. Patients in the observation group were given comprehensive cerebral protection treatment, and patients in the control group were treated with conventional standardized treatments. The changes of cerebral oxygen metabolism, hemorheology and vascular endothelial function before and after treatment were compared between the two groups. Results: After treatment, oxygen content in arteries and internal jugular veins (Da-vO2), ofoxygen uptake fraction (OEF), Oxygen saturation (SpO2), nitric oxide (NO) were increased in both groups in comparison to before treatment, jugular venous oxygen saturation (SjvO2), brain oxygen uptake rate (ERO2), endothelin (ET), intracranial pressure (ICP), whole blood viscosity, plasma viscosity, reduced viscosity of whole blood, and hematocrit were decreased. However, the changes in the observation group were larger than those in the control group, the difference was statistically significant (P

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the rate of cerebral metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. Existing methods of mapping CMRO2, based on respiratory modulation of arterial spin labelling (ASL) and blood oxygen level dependent (BOLD) signals, require lengthy acquisitions and independent modulation of both arterial oxygen and carbon dioxide levels. Here, we present a new simplified method for mapping the rate of cerebral oxygen metabolism that can be performed using a simple breath-holding paradigm. The method incorporates flow-diffusion modelling of oxygen transport and physiological constraints to create a non-linear mapping between the maximum BOLD signal, M, baseline blood flow (CBF0), and CMRO2. A gradient boosted decision tree is used to learn this mapping directly from simulated MRI data. Modelling studies demonstrate that the proposed method is robust to variation in cerebral physiology and metabolism. This new gas-free methodology offers a rapid and pragmatic alternative to existing dual-calibrated methods, removing the need for specialist respiratory equipment and long acquisition times. In-vivo testing of the method, using an 8-minute 45 second protocol of repeated breath-holding, was performed on 15 healthy volunteers, producing quantitative maps of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and CMRO2.

Standard magnetic resonance imaging approaches offer high‐resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low‐frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual‐echo, pseudocontinuous arterial spin labeling, and blood‐oxygen‐level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain‐wide, CMRO2 low‐frequency fluctuations were subjected to graph‐based and voxel‐wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2 fluctuations exhibited complex, small‐world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel‐wise CMRO2 connectivity also exhibited spatial patterns consistent with four targeted resting‐state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital‐visual). These are the first findings to support the use of calibration‐derived CMRO2 low‐frequency fluctuations for detecting brain‐wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration‐derived oxygen metabolism signals for examining the intrinsic organization of the human brain., Calibrated imaging was used during the resting state to recover low‐frequency fluctuations of the cerebral metabolic rate of oxygen. Oxygen metabolism signals demonstrate complex, small‐world topologies and subnetwork profiles consistent with previous anatomical and functional connectivity studies

Background: Brain growth differences are apparent between different types of cyanotic congenital heart disease, but the underlying mechanism remains unclear. Here, we explored and characterized longitudinal cerebral hemodynamic and oxygen metabolism profiles and their relationships to brain growth patterns in infants with single ventricle physiologies (SV) and transposition of the great arteries (TGA). We hypothesized that there are marked differences in cerebral oxygen metabolism in those with SV compared with TGA. Methods: Cerebral blood flow (CBF), oxygen delivery (CDO2) and consumption (CVO2) and brain growth were measured in 103 term newborns with SV and TGA using MRI at pre- and post-surgery and at follow-up. We measured whole brain size by segmenting a 3D steady state free precession acquisition. Cerebral blood flow was measured using phase contrast imaging of the neck vessels and cerebral venous blood oxygen saturation was derived from T2 oximetry of the superior sagittal sinus. TGAs were divided into those with and without ventricular septums. Results: CBF profiles were similar between the 3 lesion groups. Cerebral oxygen delivery trends increased but were not significantly different between cardiac groups. We observed that this may be mediated by different mechanisms: an increase in arterial saturation in TGAs, and an increase in hemoglobin concentration in SVs. Cerebral oxygen consumption in SV infants remained low (p = 0.54) while that of TGA increased over time (TGA IVS p < 0.001; TGA VSD p Conclusions: In conclusion, there are characteristic differences in hemodynamic adaptations between SVs and TGAs. Changes in oxygen metabolism may be facilitating brain growth trajectories. This informs us of possible mechanisms involved during a time of critical brain development.

Non-invasive, frequency-domain diffuse optical spectroscopy and diffuse correlation spectroscopy were combined to quantify cerebral oxygen metabolism in a neonatal swine model of deep hypothermic cardiopulmonary bypass, circulatory arrest, and selective cerebral perfusion.

Objective To investigate the effect of supplemental dexmedetomidine in interventional embolism on cerebral oxygen metabolism in patients with intracranial aneurysms. Methods Ninety patients who underwent interventional embolism of intracranial aneurysms were equally divided into Group A and Group B. In Group A, dexmedetomidine was injected intravenously 10 minutes before inducing anesthesia, with a loading dose of 0.6 µg/kg followed by 0.4 µg/kg/hour. Group B received the same amount of normal saline by the same injection method. Heart rate (HR), mean arterial pressure (MAP), arterial–jugular venous oxygen difference [D(a-jv) (O2)], cerebral oxygen extraction [CE (O2)], and intraoperative propofol use were recorded before inducing anesthesia (T0) and at five time points thereafter. Results The amount of propofol in Group A was lower vs Group B. At all five time points after T0, HR, MAP, D(a-jv) (O2), and CE (O2) in Group A were significantly lower vs Group B, with significant differences for jugular venous oxygen saturation (SjvO2) and the oxygen content of the internal jugular vein (CjvO2) between the groups. Conclusion Dexmedetomidine resulted in less intraoperative propofol, lower D(a-jv) (O2) and CE (O2), and improved cerebral oxygen metabolism.

Background: To investigate the effect of edaravone on the postoperative cognitive function and cerebral oxygen metabolism in elderly patients with spinal surgery. Methods: One hundred and twenty patients undergoing elective thoracolumbar surgery, aged 65–75 years, were randomly divided into two groups: edaravone group (Group E, n=60) and control group (Group C, n=60). At 30 minutes before anesthesia, the patients in Group E received 0.5 mg/kg edaravone, while the patients in Group C received the same volume of normal saline. Mini-mental state examination (MMSE) was performed at 1 day before the operation, and 1 day and 4 days after the operation. Results: A total of 26 patients in both groups had postoperative cognitive dysfunction. Compared with the preoperative MMSE scores, postoperative MMSE scores decreased significantly in both groups (p

Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen ( CMRO2). During CPB, n = 8 neonatal swine underwent cooling from normothermia to 18℃, sustained DH perfusion for 40 min, and then rewarming to simulate cardiac surgery. Continuous non-invasive and invasive measurements of intracranial temperature (ICT) and CMRO2 were acquired. Significant hysteresis ( p 2 relationships were found. Resolution of this hysteresis in the ICT versus CMRO2 relationship identified a crucial insufficiency of conventional NPT guidance. Non-invasive CMRO2 temperature coefficients with respect to NPT ( Q10 = 2.0) and ICT ( Q10 = 2.5) are consistent with previous reports and provide further validation of FD-DOS/DCS CMRO2 monitoring during DH CPB to optimize management.

This paper aims to study the effect of sevoflurane and propofol on cerebral oxygen metabolism during the maintenance of paediatric anaesthesia. To this end, the children who had undergone surgical treatment in General Surgery Department were selected as study subjects, and they were divided into experimental group and control group. Patients in the control group received propofol to maintain anesthesia, while patients in the experimental group maintained anaesthesia with sevoflurane. Then, the hemodynamic changes at different time points and the depth of anesthesia were compared between the two groups of patients during anesthesia maintenance. The results show that there was no significant difference in cerebral oxygen metabolism between these two groups; the content detected in the experimental group was significantly higher than that in the control group. Therefore, it is concluded that both the sevoflurane and propofol in the pediatric anesthesia maintenance process has a good effect value, which can reduce cerebral oxygen metabolism in children and have a minor impact on hemodynamics, but the sevoflurane is significantly superior to propofol in reducing cerebral oxygen metabolism.

Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures.In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction.For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002).Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

Background: While imaging biomarkers guide stroke prevention strategies in children with sickle cell (SC) disease, none have been adequately studied in adults. High oxygen extraction (OEF) predicts stroke in non-SC adults with carotid occlusion, while low oxygen metabolism (CMRO 2 ) predicts tissue at imminent risk in acute ischemic stroke. We hypothesized that metrics of cerebral metabolism: (1) differ between SC adults with and without stroke and (2) correlate with infarct burden. Methods: A prospective MRI study enrolled 37 adults (28 ± 8 yr) from SC clinic into 4 groups: (1) 9 age/race matched healthy controls, (2) 6 SC adults without infarcts, (3) 15 SC adults with infarcts (infarct volume 7.4 ± 17.5 ml), and (4) 7 SC adults on chronic transfusions (Tx) (infarct volume 3.6 ± 6.6 ml). Arterial spin labelling and asymmetric spin echo measured voxel-wise cerebral blood flow (CBF) and OEF. CMRO 2 = CBF x OEF x blood oxygen content. Infarcts were delineated on FLAIR. OEF, CBF, and CMRO 2 (excluding infarcted tissue) were compared: between groups 1-3 (Kruskal-Wallis) and in group 4 between pre- and post-tx scans (Signed Rank). An ROI defined by high OEF within the deep white matter (a region at high stroke risk in SC) was applied to group 3. OEF, CBF, and CMRO 2 within the ROI were correlated with hemispheric infarct volume (IV) (Spearman’s ρ ). Results: Whole brain OEF showed a stepwise increase from controls, to SC adults without stroke, to SC adults with stroke (P2 were similar for SC adults with and without stroke (Fig B, C). High OEF and low CBF/CMRO 2 in the ROI correlated with hemispheric infarct burden: IV vs. OEF ( ρ =.40, P=.043); IV vs. CBF ( ρ =-.61, P=.002); and IV vs. CMRO 2 ( ρ =-.50, P=.016). Conclusion: Global OEF holds promise to stratify stroke risk in SC disease. Regional metrics of cerebral oxygen metabolism may indicate tissue-specific metabolic stress at imminent risk of infarction.

Circulatory stability of patients with cerebrovascular malformations during the surgery is critical to their prognosis. Anesthesia-induced intubation, tumor separation, clamping and other operations may cause severe fluctuations in blood pressure and even result in aneurysm rupture. As a highly efficient and selective adrenergic α2 receptor agonists, dexmedetomidine hydrochloride is able to regulate the release of catecholamine by means of negative feedback so as to control blood pressure. This study aims to assess the effects of dexmedetomidine hydrochloride on hemodynamics and cerebral oxygen metabolism of intraoperative patients with cerebrovascular malformations.

Long-term cocaine use is known to negatively impact neural and cerebrovascular systems. However, the use of imaging markers to separately assess these parameters remains challenging. The primary reason is that most functional imaging markers, such as cerebral blood flow, functional connectivity, and task-evoked functional MRI, are known to reflect a complex interplay between neural and vascular components, thus the interpretation of the results is not straightforward. The goal of the present study is to examine neural-activity-specific changes in cocaine addiction, using cerebral metabolic rate of oxygen (CMRO2) as a surrogate marker of aggregated neural activity. We applied a recently developed CMRO2 technique in 13 cocaine-addicted subjects and 13 age- and gender-matched control subjects, and examined the impact of long-term cocaine use on CMRO2. Our results showed that CMRO2 in cocaine-addicted subjects (152 ± 16 µmol/100 g/min) is significantly lower (p = 0.031) than that in controls (169 ± 20 µmol/100 g/min). Furthermore, the severity of this decreased metabolism is associated with lifetime cocaine use (p = 0.05). Additionally, the CMRO2 reduction was accompanied by a trend of decrease in cerebral blood flow (p = 0.058), but venous oxygenation was unaffected (p = 0.96), which suggested that the CMRO2 change may be attributed to a vascular deficiency in chronic cocaine users. To our knowledge, this is the first study to measure CMRO2 in cocaine-addicted individuals. Our findings suggest that CMRO2 may be a promising approach for assessing the long-term effects of cocaine use on the brain.

The aim of the present study was to investigate the effects of ulinastatin on cerebral oxygen metabolism and C-reactive protein (CRP) levels in patients with severe traumatic brain injury (sTBI). A total of 92 patients with sTBI, admitted to the First Affiliated Hospital of Xinxiang Medical University (Xinxiang, China), were randomly divided into control and observation groups. The control group received conventional therapy plus a placebo (0.9% sodium chloride), while the observation group were administered conventional therapy plus 200,000 units ulinastatin via intravenous injection twice a day for seven days. Arterial and jugular venous blood was collected for blood gas analysis. The jugular venous blood lactate (JVBL), jugular venous bulb oxygen saturation (SjvO2), arteriovenous oxygen content difference (AVDO2) and cerebral extraction of oxygen (CEO2) levels were measured on day 1, 3, 5 and 7, as well as the level of CRP in the peripheral blood. In the control group, the level of JVBL decreased as compared with the level at day 1, however, no statistically significant differences were observed (P>0.05). By contrast, the observation group exhibited a significant reduction in the level of JVBL (P

Understanding cerebral oxygen metabolism is of great importance in both clinical diagnosis and animal experiments because oxygen is a fundamental source of brain energy and supports brain functional activities. Since small animals such as rats are widely used to study various diseases including cerebral ischemia, cerebrovascular diseases, and neurodegenerative diseases, the development of a noninvasivein vivomeasurement method of cerebral oxygen metabolic parameters such as oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as cerebral blood flow (CBF) and cerebral blood volume (CBV) has been a priority. Although positron emission tomography (PET) with15O labeled gas tracers has been recognized as a powerful way to evaluate cerebral oxygen metabolism in humans, this method could not be applied to rats due to technical problems and there were no reports of PET measurement of cerebral oxygen metabolism in rats until an15O-O2injection method was developed a decade ago. Herein, we introduce an intravenous administration method using two types of injectable15O-O2and an15O-O2gas inhalation method through an airway placed in the trachea, which enables oxygen metabolism measurements in rats.

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow ( CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism ( CMRO2i) and CBF indices ( CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume ( CBV) and hemoglobin oxygen saturation ( SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2remained unchanged after the therapy. Thus, FDNIRS–DCS can provide information complimentary to SO2and can assess individual cerebral metabolic responses to TH. Combined FDNIRS–DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization.

The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200 mL/kg/min. After cooling to 18°C (n = 6) or 25°C (n = 7), flow was reduced to 100 mL/kg/min (half-flow, HF) for 15 min and ACP was initiated at 40 mL/kg/min for 45 min. Following rewarming, animals were weaned from bypass and survived for 4 h. At baseline, HF, ACP, and 4 h post-CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO2) and cerebral metabolic rate of oxygen (CMRO2) were monitored. Regional cranial oxygen saturation (rSO2) was continuously recorded throughout the procedure using near-infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO2 trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO2 at ACP matched that at HF. Cranial rSO2 was significantly greater at HF and ACP (P

MRI may be used to measure fractional changes in cerebral oxygen metabolism via a metabolic model. One step commonly used in this measurement is calibration with image data acquired during hypercapnia, which is a state of increased CO2 content of the blood. In this study some commonly used hypercapnia-inducing stimuli were compared to assess their suitability for the calibration step. The following stimuli were investigated: (a) inspiration of a mixture of 4% CO2, 21% O2 and balance N2; (b) 30-s breath holding; and (c) inspiration of a mixture of 4% CO2 and 96% O2 (i.e., carbogen). Measurements of BOLD and cerebral blood flow made on nine subjects during the different hypercapnia-inducing stimuli showed that each stimulus leads to a different calibration of the model. We argue that of the aforementioned stimuli, inspiration of 4% CO2, 21% O2 and balance N2 should be preferred for the calibration as the other stimuli produce responses that violate assumptions of the metabolic model.

It is unknown whether barbiturates suppress cerebral oxygen metabolism after cerebral trauma as they do in normal individuals. We evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-hemorrhagic closed head injury (CHI). Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidized cytochrome oxidase concentration. CHI caused changes in both systemic and cerebral hemodynamics. Cerebral blood flow was reduced to 66% of its control value, but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a further decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function in traumatized rats, whereas it exerted this effect in all control animals. We therefore conclude that, in rats subjected to CHI, pentobarbital is unable to perform its beneficial effects on the cerebral metabolism.

Summary Acute normovolemic haemodilution (ANH) may cause an imbalance in cerebral oxygen metabolism because it decreases the arterial oxygen content. This study was designed to investigate the effect of ANH on cerebral oxygenation. By using cerebral oximetry, the regional cerebral oxygen saturation (rSO2) was monitored during ANH in 26 patients without systemic illness (initial haematocrit = 42 ± 1%). The rSO2 did not show a significant change until the Hct reached >30%. However, it decreased significantly thereafter to reach 88% of the baseline value when the ANH was completed with a Hct value of 24 ± 1% (before ANH; 71 ± 6% vs. after ANH; 62 ± 4%, p

Haemodynamic and metabolic disturbances in the acute stage of subarachnoid haemorrhage demonstrated by PET.

Frequency domain near infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) can provide noninvasive means to study cerebral hemodynamics in neonates with congenital heart disease (CHD). Using these advanced optical technologies, our preliminary data shows that neonates with CHD have lower cerebral oxygen metabolism than healthy neonates.

A quantitative estimate of cerebral blood oxygen saturation is of critical importance in the investigation of cerebrovascular disease because of the fact that it could potentially provide information on tissue viability in vivo. In the current study, a multi-echo gradient and spin echo magnetic resonance imaging sequence was used to acquire images from eight normal volunteer subjects. All images were acquired on a Siemens 1.5T Symphony whole-body scanner (Siemens, Erlangen, Germany). A theoretical signal model, which describes the signal dephasing phenomena in the presence of deoxyhemoglobin, was used for postprocessing of the acquired images and obtaining a quantitative measurement of cerebral blood oxygen saturation in vivo. With a region-of-interest analysis, a mean cerebral blood oxygen saturation of 58.4% ± 1.8% was obtained in the brain parenchyma from all volunteers. It is in excellent agreement with the known cerebral blood oxygen saturation under normal physiologic conditions in humans. Although further studies are needed to overcome some of the confounding factors affecting the estimates of cerebral blood oxygen saturation, these preliminary results are encouraging and should open a new avenue for the noninvasive investigation of cerebral oxygen metabolism under different pathophysiologic conditions using a magnetic resonance imaging approach.

Through the years, the clinical application of mild hypothermia has been carried out worldwide and is built from the exploration and cognition of neuroprotection mechanisms by hypothermia. However, within the last decade, extensive and fundamental researches in this area have been conducted. In addition to aspects of the previous findings, scholars have discovered several new contents and uncertain results. This article reviews and summarizes this decade’s progression of mild hypothermia in lowering the cerebral oxygen metabolism, protecting the blood–brain-barrier, regulating the inflammatory response, regulating the excessive release of neurotransmitters, inhibiting calcium overload, and reducing neuronal apoptosis. In many aspects, particularly in regulating inflammatory reverse reaction, various results have been reported and therefore guide scholars to conduct more detailed analysis and investigation in order to discover the inherent theories surrounding the effect of mild hypothermia, and for better clinical services.

Among adults, wakefulness and rapid eye movement (REM) sleep, compared to non-REM sleep, require higher overall brain metabolism, but in neonates analogous data are not available. Behavioral states with higher metabolic demand could increase vulnerability to hypoperfusion or hypoxia in the compromised neonatal brain. Using cerebral oximetry (near-infrared spectroscopy), and simultaneous polysomnography, we evaluated whether brain oxygen metabolism varies by sleep-wake state among critically ill newborns. For each of 10 infants, sleep-wake cycling was detectable and cerebral oximetry varied ( P < .0001) across behavioral states, but the patterns differed among subjects. We conclude that cerebral oxygen metabolism varies with sleep-wake states in high-risk newborns. The direction and degree of these changes are variable and subject-specific in this initial sample, but could reflect or affect brain injury and vulnerability.

Acute mountain sickness (AMS) is a common condition occurring within hours of rapid exposure to high altitude. Despite its frequent occurrence, the pathophysiological mechanisms that underlie the condition remain poorly understood. We investigated the role of cerebral oxygen metabolism (CMRO2) in AMS. The purpose of this study was to test 1) if CMRO2 changes in response to hypoxia, and 2) if there is a difference in how individuals adapt to oxygen metabolic changes that may determine who develops AMS and who does not. Twenty-six normal human subjects were recruited into two groups based on Lake Louise AMS score (LLS): those with no AMS (LLS ≤ 2), and those with unambiguous AMS (LLS ≥ 5). [Subjects with intermediate scores (LLS 3–4) were not included.] CMRO2 was calculated from cerebral blood flow and arterial-venous difference in O2 content. Cerebral blood flow was measured using arterial spin labeling MRI; venous O2 saturation was calculated from the MRI of transverse relaxation in the superior sagittal sinus. Arterial O2 saturation was measured via pulse oximeter. Measurements were made during normoxia and after 2-day high-altitude exposure at 3,800 m. In all subjects, CMRO2 increased with sustained high-altitude hypoxia [1.54 (0.37) to 1.82 (0.49) μmol·g−1·min−1, n = 26, P = 0.045]. There was no significant difference in CMRO2 between AMS and no-AMS groups. End-tidal Pco2 was significantly reduced during hypoxia. Low arterial Pco2 is known to increase neural excitability, and we hypothesize that the low arterial Pco2 resulting from ventilatory acclimatization causes the observed increase in CMRO2.

Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO2) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BFix) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO2 and CBV, relative values of BFix, and relative cerebral metabolic rate of oxygen (rCMRO2) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO2 correlates with chronological age ( r=−0.54, P value 0.001) but not with PMA ( r=−0.07), whereas BFix and rCMRO2 correlate better with PMA ( r=0.37 and 0.43, respectively, P value 0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO2 are more accurate biomarkers of the brain development than SO2 in the premature newborns.

Oxidative stress during fetal development, delivery, or early postnatal life is a major cause of neuropathology, as both hypoxic and hyperoxic insults can significantly damage the developing brain. Despite the obvious need for reliable cerebral oxygenation monitoring, no technology currently exists to monitor cerebral oxygen metabolism continuously and noninvasively in infants at high risk for developing brain injury. Consequently, a rational approach to titrating oxygen supply to cerebral oxygen demand – and thus avoiding hyperoxic or hypoxic insults – is currently lacking. We present a promising method to close this crucial technology gap in the important case of neonates on conventional ventilators. By using cerebral near-infrared spectroscopy and signals from conventional ventilators, along with arterial oxygen saturation, we derive continuous (breath-by-breath) estimates of cerebral venous oxygen saturation, cerebral oxygen extraction fraction, cerebral blood flow, and cerebral metabolic rate of oxygen. The resultant estimates compare very favorably to previously reported data obtained by non-continuous and invasive means from preterm infants in neonatal critical care., National Institutes of Health (U.S.) (Grant R01EB001659), National Institutes of Health (U.S.) (Grant K24NS057568), National Institutes of Health (U.S.) (Grant R21HD056009)

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study is a sensitive test for predicting the outcome of permanent ICA occlusion. However, false negative results sometimes occur using single photon emission tomography (SPECT). We have recently developed a rapid positron emission tomography (PET) protocol that measures not only the CBF but also the cerebral oxygen metabolism before and during BTO in succession. We measured acute changes in regional CBF and OEF/CMRO2 before and during BTO in three cases with large or giant cerebral aneurysms using the rapid PET protocol. Although no patients showed ischemic symptoms during BTO, PET studies exhibited mildly to moderately decreased CBF (9∼34%) compared to the values obtained before BTO in all cases. The average OEF during BTO was significantly increased (21% and 43%) than that of before BTO in two cases. The two cases were considered to be non-tolerant for permanent ICA occlusion and treated without ICA sacrifice. Measurement of the CBF and OEF/CMRO2 using a rapid PET protocol before and during BTO is feasible and can be used for accurate assessment of tolerance prediction in ICA occlusion.

Objective. A better understanding of the developmental changes in brain energy metabolism that occur in human neonates is critically important for designing rational treatment strategies that ensure an adequate supply of nutrients to the brain and minimize deleterious side effects of therapeutic interventions in sick newborns. Methods. Cerebral metabolic rate for oxygen (CMRO2) was measured with positron emission tomography in 11 sick newborns of different gestational ages. Results. In five preterm infants, mean hemispheric CMRO2 was 0.06 to 0.54 mL 100 g-1 min-1. Two of these preterm infants with virtually absent CMRO2 (0.06 mL 100 g-1 min-1) had minimal or no evidence of parenchymal brain injury detected in the newborn period. In six term infants, mean hemispheric CMRO2 was 0.0 to 1.3 mL 100 g-1 min-1. Two with no neurological disease had mean hemispheric CMRO2 of 0.4 and 0.7 mL 100 g-1 min-1 and were normal at 6 and 7 months, respectively. Conclusions. CMRO2 in four newborns who had minimal or no detectable brain injury was considerably below the threshold for brain viability in adults of 1.3 mL 100 g-1 min-1. This indicates that energy requirements in fetal and newborn brain are minimal or can be met by nonoxidative metabolism.

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMR02) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal\ left infrafrontal and left parietal cortices, CMR02 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMR02 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMR02 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

Previous studies of cerebral oxygen metabolism and extraction in patients with subarachnoid hemorrhage (SAH) have yielded conflicting results. We used positron emission tomography (PET) to measure the regional cerebral metabolic rate for oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood flow (rCBF) 16 times in 11 patients with aneurysmal SAH. All studies were performed preoperatively; no patient had hydrocephalus or intracerebral hematoma on brain CT. Eight patients with no arteriographic vasospasm who were studied on days 1–4 post-SAH had a significant 25% reduction in global CMRO2 compared to age-matched controls, and no significant change in global OEF, suggesting a primary reduction in CMRO2 caused by SAH. Four patients studied seven times during arteriographic vasospasm had significantly increased rOEF with unchanged CMRO2 in arterial territories affected by arteriographic vasospasm compared to territories without vasospasm, indicative of cerebral ischemia without infarction. No brain regions studied with PET were infarcted on follow-up CT. We conclude that the initial aneurysm rupture produces a primary reduction in CMRO2, and that subsequent vasospasm causes ischemia.

The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO2 reactivity, and CMRO2. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO2 reactivity tests changes in CBF were estimated by the arterio-venous-oxygen-difference method. Median CBF was 52 ml/100 g/min (48-53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92-99). MABP was slightly reduced, by 8 mmHg (7-9), and 9 mmHg (4-11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO2, revealed a slight increase after 4 hours (p = 0.08). CMRO2 was 3.5 ml/100g/min (3.2-3.5) and was not changed by the infusion of NIM. At arterial CO2 tensions ranging from 4.0 to 6.5 Kpa the CO2 reactivity was 3.0% CBF/0.1 kPa (2.6-3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8-3.2) after the infusion of NIM for 3 hours (p = 0.02). The median slope of the LnCBFsat/PaCO2 relationship was 1.5 at baseline compared to 1.3 after NIM (p less than 0.01). No side effects were observed. The present study shows a decreased CO2 of the cerebral vessels and a maintained coupling of CBF and CMRO2 during the infusion of nimodipine.

各種脳神経疾患61例を対象として, ガス状標識化合物合成装置により製造した3種類の15O標識ガス (酸素, 一酸化炭素, 二酸化炭素) を用いて, 陽電子放出断層法 (PET) による局所脳循環代謝測定検査を施行した。本装置により標識ガスが安定して供給され, 検査によると考えられる副作用は認められなかった。脳血管障害や痴呆などの神経疾患で高頻度に脳血流や酸素代謝の異常を認め, 本検査法の臨床的有用性が確認された。

The possible role of oxygen metabolism in supporting brain activation remains elusive. We have used a newly developed neuroimaging approach based on high-field in vivo17O magnetic resonance spectroscopic (MRS) imaging to noninvasively image cerebral metabolic rate of oxygen (CMRO2) consumption in cats at rest and during visual stimulation. It was found that CMRO2 increases significantly (32.3% ± 10.8%, n = 6) in the activated visual cortical region as depicted in blood oxygenation level dependence functional maps; this increase is also accompanied by a CMRO2 decrease in surrounding cortical regions, resulting a smaller increase (9.7% ± 1.9%) of total CMRO2 change over a larger cortical region displaying either a positive or negative CMRO2 alteration. Moreover, a negative correlation between stimulus-evoked percent CMRO2 increase and resting CMRO2 was observed, indicating an essential impact of resting brain metabolic activity level on stimulus-evoked percent CMRO2 change and neuroimaging signals. These findings provide new insights into the critical roles of oxidative metabolism in supporting brain activation and function. They also suggest that in vivo17O MRS imaging should provide a sensitive neuroimaging modality for mapping CMRO2 and its change induced by brain physiology and/or pathologic alteration.

The development and validation of hybrid near-infrared spectroscopy and diffuse correlation/wave spectroscopy for non-invasive measurement of cerebral blood oxygenation, blood flow and metabolism at bedside in cerebrovascular disorders is described in adult and pediatric populations.

The authors report on a computed tomography (CT) scan which was used to measure and demonstrate cerebral oxygen metabolism indices such as oxygen concentration of brain tissue (OCBT), cerebral metabolic rate of oxygen (CMRO/sub 2/), and oxygen extraction fraction (OEF), simultaneously with cerebral blood flow (CBF), in animal brains. The animals were immobilized and inhaled xenon gas mixed with oxygen or a mixture of xenon, helium and oxygen, and diffusion constants were obtained. OCBT was calculated from the ratio between two diffusion constants. CMRO/sub 2/, OEF and CBF were simultaneously calculated and demonstrated by reconstructing the CT scan brain image with these data at each pixel. >

Multiple sclerosis (MS) is a progressive autoimmune disease with multifactorial etiology involving both environmental and genetic factors (Kemppinen et al, 2011). Due to complex etiology, clinical presentation of MS is also diverse. Conventional magnetic resonance imaging (MRI), including T1 and T2-weigthed and fluid attenuated inversion recovery T2 scans form the backbone of imaging MS patients for diagnosis and treatment monitoring. It has become evident, however, that alternative imaging techniques are needed to reveal subclinical disease (Filippi and Agosta, 2010) for stratification of patients to novel treatment strategies (Menge et al, 2008). At the same token, advanced imaging is expected to gain understanding from MS pathophysiology (Filippi and Agosta, 2010; Paling et al, 2011).

To investigate the accuracy of unilateral jugularvenous monitoring, we performed bilateral jugularvenous monitoring in 22 comatose head injured patients. Fiberoptic catheters were placed upstream in both internal jugular veins and advanced into the jugular bulbs. Arterial and bilateral jugularvenous blood samples were obtained simultaneously for in vitro determination of jugularvenous oxygen saturation (SJO2), arterial minus jugularvenous lactate content difference (AJDL) and modified lactate-oxygen-index (mLOI). Ischemia was assumed, if one of the following pathologies occured at least unilaterally: SJO2 0.08. The mean and maximum bilateral SJO2 differences varied between 1.4% to 21.0%, and 8.1% to 44.3% respectively. The bias and limits of agreement (mean differences ±2SD) between paired samples were -0.4% ± 12.8%. Regarding AJDL bias and limits of agreement were 0.01mmol/L ± 0.18mmol/L. At best 87% of defined ischemic events could be evaluated by monitoring at the side of predominant lesion or, in diffuse injuries, at the side of the larger jugular foramen in CT scan (CT approach). We conclude, due to the wide limits of agreement in bilateral SJO2 and AJDL the reliability of unilateral jugularvenous monitoring in patients with intracranial pathology is questionable. For diagnosing ischemia the CT approach has the highest sensitivity and is therefore recommended.

In order to select the optimal neurointensive treatment for patients with severe head injury and intracranial hypertension, the effects of hypothermia (HT), barbiturates (BT), and osmotic agents (OT) on focal and diffuse cerebral oxygen metabolism were evaluated by means of continuous monitoring of bifrontal regional oxygen saturation (rSO2), jugular bulb oxygen saturation (SjO2), jugular bulb temperature (Tjb), intracranial pressure (ICP), and cerebral perfusion pressure (CPP).