Increased Oxygen Extraction Research Articles

Early oxygen-utilization and brain activity in preterm infants.

The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in μV (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants.

Multiple Hypointense Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke: Surrogate Marker of Oxygen Extraction Fraction in Penumbra?

Background: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) are frequently observed in patients with acute cerebral ischemia, but their implication has not been clearly established. To elucidate the clinical significance of MHV on SWI, we investigated the association of MHV on SWI with clinical data and other MR markers in patients with acute ischemic stroke. Methods: We enrolled acute stroke patients with internal carotid or proximal middle cerebral artery occlusion who underwent MRI including SWI within 3 days from stroke onset. Baseline clinical data were reviewed. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). We graded the degree of MHV on SWI as four groups of none, subtle, relative, or extensive by the modified Alberta Stroke Program Early CT Scan (ASPECTS) system. To evaluate the degree of collateral flow, distal hyperintense vessels (DHV) on FLAIR and vessels on post-contrast time-of-flight MR angiography (TOF MRA) source images were graded respectively as 3 groups: none/subtle/prominent and poor/moderate/good. Diffusion and perfusion lesion volume and diffusion-perfusion mismatch (DPM) ratio were measured in all patients. We analyzed the association of the degree of MHV on SWI with clinical data and MR markers. Results: Eighty patients were included in the study. The mean MR time from stroke onset was 12.4 h (range 0.5-63.0). There is no difference in MR time from stroke onset between groups of MHV on SWI. MHV were observed in 68 (85%) of 80 patients: none in 12, subtle in 11, relative in 13, and extensive in 44. There were no statistically significant associations between MHV on SWI and vascular risk factors. Patients with more extensive MHV on SWI had a smaller diffusion volume (p < 0.001), larger DPM (p < 0.001), and lower initial NIHSS scores (p = 0.022). Prominent DHV was presented in 29 of 44 patients with extensive MHV (p < 0.001). Good collateral flow on TOF MRA source images was presented in 37 of 44 patients with extensive MHV (p < 0.001). Conclusions: More extensive MHV on SWI in acute ischemic stroke is associated with lower initial NIHSS scores, smaller diffusion lesion volume, better collateral flow, and larger DPM. Our results show the possibility that MHV on SWI may be a useful surrogate marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemisphere.

Quantitative T2'-mapping in acute ischemic stroke.

Quantitative T2'-mapping detects regional changes in the relation of oxygenated and deoxygenated haemoglobine and might reflect areas with increased oxygen extraction. T2'-mapping in conjunction with an elaborate algorithm for motion correction was performed in patients with acute large-vessel stroke, and quantitative T2'-values were determined within the diffusion-weighted imaging lesion and perfusion-restricted tissue. Eleven patients (median age, 71 years) with acute middle cerebral or internal carotid artery occlusion underwent MRI before scheduled endovascular treatment. MR-examination included diffusion- and perfusion-weighted imaging and quantitative, motion-corrected mapping of T2'. Time-to-peak maps were thresholded for different degrees of perfusion delays (eg, ≥0 s, ≥ 2s) when compared with a reference time-to-peak value from healthy contralateral tissue. Mean T2'-values in areas with reduced apparent diffusion coefficient and in areas with impaired perfusion were compared with T2'-values in corresponding contralateral areas. Median time between symptom onset and MRI was 238 minutes. T2'-values were significantly reduced within the apparent diffusion coefficient -lesion when compared with contralateral healthy tissue (83 ms [67, 97] versus 97 ms [91, 111]; P<0.003). In perfusion-restricted tissue, T2'-values were also significantly lower when compared with contralateral healthy tissue (ie, for time to peak, ≥0 s 93 ms [86, 102] versus 104 [90, 110]; P=0.008) but were significantly higher than within the apparent diffusion coefficient lesion. The severity of the perfusion impairment had no influence on median T2'-values. Motion-corrected T2'-mapping reveals significant and gradually declining values from healthy to perfusion-disturbed to apparent diffusion coefficient-restricted tissue. Current T2'-mapping can differentiate between the ischemic core and the perfusion-impaired areas but not on its own between penumbral and oligemic tissue.

Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

ObjectivesOxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and methodsCOPD patients (n=40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler® 320/9μg or formoterol Turbuhaler®. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. ResultsOE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p<0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p<0.05) and increased oxygen extraction from the lung by 58% (p<0.01). Single-dose formoterol increased both lung wash-out time (+47%, p<0.05) and lung oxygenation time (+47%, p<0.05). FEV1 was improved by single-dose formoterol (+12%, p<0.001) and 8 weeks of budesonide/formoterol (+ 18%, p<0.001), consistent with published studies. ConclusionsIn COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with (15)O PET.

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF(b)), CBV, OEF, cerebral oxygen metabolic rate (CMRO2), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by (15)O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF(b) (> 47.6 mL/100 mL/min, n = 7) was associated with normal CBF(b)/CBV, increased CBV, decreased OEF, and normal CMRO2. Low CBF(b) (< 31.8 mL/100 mL/min, n = 9) was associated with decreased CBF(b)/CBV, increased CBV, increased OEF, and decreased CMRO2. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF(b) regions with normal CPP, which has not been described in previous studies.

Discussion: "The efficacy of the self-paced V̇O2max test to measure maximal oxygen uptake in treadmill running".

are extremely cautious in the strength placed behind these given that they have not been directly measured. We agree with Peter Wagner that the limitation to VO2max may arise from any of the in series resistances along the oxygen transport cascade (Wagner 1996), so while we have suggested that the more likely candidate for the higher VO2max in the SPV is an increased oxygen extraction at the working muscle, we recognise that this could be due to any one, or combination of, several mechanisms. Therefore, while Dr Poole presents an interesting argument for blood flow not being limiting, he also ignores a multitude of other potential candidates that could explain the VO2 response and consequently oversimpli-

Device for simultaneous positron emission tomography, laser speckle imaging and RGB reflectometry: Validation and application to cortical spreading depression and brain ischemia in rats

Brain function critically relies on the supply with energy substrates (oxygen and glucose) via blood flow. Alterations in energy demand as during neuronal activation induce dynamic changes in substrate fluxes and blood flow. To study the complex system that regulates cerebral metabolism requires the combination of methods for the simultaneous assessment of multiple parameters. We developed a multimodal imaging device to combine positron emission tomography (PET) with laser speckle imaging (LSI) and RGB reflectometry (RGBR). Depending on the radiotracer, PET provides 3-dimensional quantitative information of specific molecular processes, while LSI and RGBR measure cerebral blood flow (CBF) and hemoglobin oxygenation at high temporal and spatial resolution. We first tested the functional capability of each modality within our system and showed that interference between the modalities is negligible. We then cross-calibrated the system by simultaneously measuring absolute CBF using 15O-H2O PET (CBFPET) and the inverse correlation time (ICT), the LSI surrogate for CBF. ICT and CBFPET correlated in multiple measurements in individuals as well as across different animals (R2=0.87, n=44 measurements) indicating that ICT can be used for absolute quantitative assessment of CBF. To demonstrate the potential of the combined system, we applied it to cortical spreading depression (CSD), a wave of transient cellular depolarization that served here as a model system for neurovascular and neurometabolic coupling. We analyzed time courses of hemoglobin oxygenation and CBF alterations coupled to CSD, and simultaneously measured regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) used as a radiotracer for regional glucose metabolism, in response to a single CSD and to a cluster of CSD waves. With this unique combination, we characterized the changes in cerebral metabolic rate of oxygen (CMRO2) in real-time and showed a correlation between 18F-FDG uptake and the number of CSD waves that passed the local tissue. Finally, we examined CSD spontaneously occurring during focal ischemia also referred to as peri-infarct depolarization (PID). In the vicinity of the ischemic territory, we observed PIDs that were characterized by reduced CMRO2 and increased oxygen extraction fraction (OEF), indicating a limitation of oxygen supply. Simultaneously measured PET showed an increased 18F-FDG uptake in these regions. Our combined system proved to be a novel tool for the simultaneous study of dynamic spatiotemporal alterations of cortical blood flow, oxygen metabolism and glucose consumption under normal and pathologic conditions.

Lower stroke risk with lower blood pressure in hemodynamic cerebral ischemia

To determine whether strict blood pressure (BP) control is the best medical management for patients with symptomatic carotid artery occlusion and hemodynamic cerebral ischemia. In this prospective observational cohort study, we analyzed data from 91 participants in the nonsurgical group of the Carotid Occlusion Surgery Study (COSS) who had recent symptomatic internal carotid artery occlusion and hemodynamic cerebral ischemia manifested by ipsilateral increased oxygen extraction fraction. The target BP goal in COSS was ≤130/85 mm Hg. We compared the occurrence of ipsilateral ischemic stroke during follow-up in the 41 participants with mean BP ≤130/85 mm Hg to the remaining 50 with higher BP. Of 16 total ipsilateral ischemic strokes that occurred during follow-up, 3 occurred in the 41 participants with mean follow-up BP of ≤130/85 mm Hg, compared to 13 in the remaining 50 participants with mean follow-up BP >130/85 mm Hg (hazard ratio 3.742, 95% confidence interval 1.065-13.152, log-rank p = 0.027). BPs ≤130/85 mm Hg were associated with lower subsequent stroke risk in these patients. This study provides Class III evidence that control of hypertension ≤130/85 mm Hg is associated with a reduced risk of subsequent ipsilateral ischemic stroke in patients with recently symptomatic carotid occlusion and hemodynamic cerebral ischemia (increased oxygen extraction fraction).

Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) trial

To determine whether extracranial-intracranial (EC-IC) bypass can improve cognition over 2 years compared to best medical therapy alone in patients with symptomatic internal carotid artery (ICA) occlusion and increased oxygen extraction fraction (OEF) on PET. Patients underwent (15)O PET and were randomized if OEF ratio was >1.13 on the occluded side. Using blinded baseline and 2-year cognitive assessments, age-adjusted composite z scores were generated from subtests sensitive to right/left hemisphere plus global cognitive functioning. Multiple regression predicted 2-year cognitive change. Eighty-nine patients were enrolled; 41 had increased OEF and were randomized. Two died, 2 were lost to follow-up, and 2 refused 2-year testing. Of the 35 remaining, 6 had ipsilateral stroke or death, leaving 13 surgical and 16 medical patients. Controlling for age, education, and depression, there was no difference in 2-year cognitive change between the medical and surgical arms (95% confidence interval -0.5 to 0.5, p = 0.9). In post hoc analysis of 26 patients with no stroke in the follow-up period, cognitive improvement was associated with less impaired PET OEF at baseline (p = 0.045). Cognitive improvement following bypass surgery was not superior to medical therapy among patients with recently symptomatic carotid occlusion and increased OEF. Among those with no recurrent stroke, less hemodynamic impairment at baseline was associated with greater cognitive gain in both groups. Reversing cognitive impairment in hemodynamic failure remains an open challenge. This study provides Class II evidence that for patients with symptomatic ICA occlusion and increased OEF on PET, EC-IC bypass compared to no bypass does not improve cognitive function after 2 years.

Physiological mechanism of increase in deoxy-hemoglobin concentration during neuronal activation in patients with cerebral ischemia: a simulation study with the balloon model.

Patients with cerebral ischemia or brain tumor have been reported to exhibit an increase of deoxygenated hemoglobin (deoxy-Hb) together with an increase of oxygenated hemoglobin (oxy-Hb). However, the physiological mechanisms underlying this hemodynamic response pattern are unclear. In this study, we performed a simulation using the balloon model (Buxton et al., Magn Reson Med 39:855-864, 1998). We hypothesized that the oxygen extraction rate during the rest period (E 0) in the patients is larger than in normal subjects, because the cerebral blood flow and the speed at which the blood passes through the brain tissues are lower in the patients. The simulation result showed an increase of deoxy-Hb as well as oxy-Hb, especially when E 0 is extremely high. Thus, the results of our simulation suggest that the increase of deoxy-Hb during activation in patients with ischemia or brain tumor is caused by an increased oxygen extraction rate at rest, compared with that of healthy adults.

Transcranial Doppler Ultrasonography CO2 Reactivity Does Not Predict Recurrent Ischaemic Stroke in Patients with Symptomatic Carotid Artery Occlusion

Background: Patients with transient ischaemic attacks (TIAs) or minor disabling ischaemic stroke associated with an internal carotid artery (ICA) occlusion have a high risk of recurrent stroke in case of compromised cerebral blood flow. Recent studies showed that increased oxygen extraction fraction measured by positron emission tomography (PET) is still an independent predictor of subsequent stroke under current medical treatment, but PET facilities are not widely available. Transcranial Doppler (TCD) ultrasonography CO₂ reactivity is a cheap and non-invasive alternative to measure haemodynamic compromise. The aim of our study was to investigate whether TCD CO₂ reactivity is an independent predictor of recurrent ischaemic stroke in a large cohort of patients with symptomatic ICA occlusion in a time where rigorous control of vascular risk factors has been widely implemented in clinical practice. Methods: Between July 1995 and December 2009, we included consecutive patients with TIAs or minor disabling ischaemic stroke (modified Rankin Scale ≤3) associated with ICA occlusion who were referred to the University Medical Centre Utrecht, The Netherlands. All patients were treated with antiplatelet therapy and received rigorous control of vascular risk factors, including statins, treatment for diabetes and hypertension and lifestyle advices. CO₂ reactivity was measured with TCD within 3 months after presentation. We determined the predictive value of TCD CO₂ reactivity for recurrent ischaemic stroke using Cox proportional hazard analysis. Results: We included 201 patients with a median follow-up time of 7.1 years. Mean CO₂ reactivity was 15% (±20 standard deviation). The annual rate for ipsilateral ischaemic stroke was 2.2% [95% confidence interval (CI) 1.4-3.2] and for any recurrent stroke 3.2% (95% CI 2.3-4.4). We did not find a significant relationship between CO₂ reactivity and the risk of ipsilateral [hazard ratio (HR) for every increase in percentage point 1.01, 95% CI 0.99-1.02] or any recurrent ischaemic stroke (HR 1.01, 95% CI 0.998-1.02). Multivariable analysis showed a significant relationship with history of stroke (HR 4.0, 95% CI 1.8-9.0) for ipsilateral recurrent stroke, and age (HR for increase per year 1.05, 95% CI 1.01-1.09) and a history of stroke (HR 3.4, 95% CI 1.7-6.6) for any recurrent stroke. Conclusions: In patients with TIAs or non-disabling stroke associated with occlusion of the carotid artery, the long-term annual risk of stroke is generally low with careful control of vascular risk factors. Impaired CO₂ reactivity measured within 3 months after presentation does not identify the subgroup of patients at high risk of recurrent ischaemic stroke.

Early Predictive Value of Susceptibility Weighted Imaging (SWI) in Pediatric Hypoxic‐Ischemic Injury

Susceptibility weighted imaging (SWI) provides information about the intravascular cerebral blood oxygenation level. Deoxyhemoglobin is increased in tissue with increased oxygen extraction fraction. Accordingly, the draining veins in hypoxic-ischemic brain may reveal abnormally low SWI signal. We report on a boy with hypoxic-ischemic injury (HII) after cardiac arrest and the ability of SWI to depict areas of HII by focusing on the venous cerebral drainage.

Oxygen Extraction Fraction and Stroke Risk in Patients with Carotid Stenosis or Occlusion: A Systematic Review and Meta-Analysis

Increased oxygen extraction fraction on PET has been considered a risk factor for stroke in patients with carotid stenosis or occlusion, though the strength of this association has recently been questioned. We performed a systematic review and meta-analysis to summarize the association between increased oxygen extraction fraction and ipsilateral stroke risk. A comprehensive literature search was performed. We included studies with baseline PET oxygen extraction fraction testing, ipsilateral stroke as the primary outcome, and at least 1 year of follow-up. A meta-analysis was performed by use of a random-effects model. After screening 2158 studies, 7 studies with 430 total patients with mean 30-month follow-up met inclusion criteria. We found that 6 of 7 studies were amenable to meta-analysis. Although 4 of the 6 studies independently did not reach statistical significance, meta-analysis revealed a significant positive relationship between abnormal oxygen extraction fraction and future ipsilateral stroke, with a pooled OR of 6.04 (95% CI, 2.58-14.12). There was no statistically significant difference in OR in the subgroup analyses according to testing method or disease site. Abnormal oxygen extraction fraction remains a powerful predictor of stroke in carotid stenosis or occlusion and is a valuable reference standard to compare and validate MR imaging-based measures of brain oxygen metabolism. However, there is a need for further evaluation of oxygen extraction fraction testing in patients with high-grade but asymptomatic carotid disease.

Coupling blood flow and neural function in the retina: a model for homeostatic responses to ocular perfusion pressure challenge

Retinal function is known to be more resistant than blood flow to acute reduction of ocular perfusion pressure (OPP). To understand the mechanisms underlying the disconnect between blood flow and neural function, a mathematical model is developed in this study, which proposes that increased oxygen extraction ratio compensates for relative ischemia to sustain retinal function. In addition, the model incorporates a term to account for a pressure-related mechanical stress on neurons when OPP reduction is achieved by intraocular pressure (IOP) elevation. We show that this model, combining ocular blood flow, oxygen extraction ratio, and IOP mechanical stress on neurons, accounts for retinal function over a wide range of OPP manipulations. The robustness of the model is tested against experimental data where ocular blood flow, oxygen tension, and retinal function were simultaneously measured during acute OPP manipulation. The model provides a basis for understanding the retinal hemodynamic responses to short-term OPP challenge.

Cerebral Ischemia and Reperfusion Increases the Heterogeneity of Local Oxygen Supply/Consumption Balance

After cerebral vessel blockage, local blood flow and O2 consumption becomes lower and oxygen extraction increases. With reperfusion, blood flow is partially restored. We examined the effects of ischemia-reperfusion on the heterogeneity of local venous oxygen saturation in rats in order to determine the pattern of microregional O2 supply/consumption balance in reperfusion. The middle cerebral artery was blocked for 1 hour using the internal carotid approach in 1 group (n=9) and was then reperfused for 2 hours in another group (n=9) of isoflurane-anesthetized rats. Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small vessel arterial and venous oxygen saturations were determined microspectrophotometrically. After 1 hour of ischemia, local cerebral blood flow (92±10 versus 50±10 mL/min per 100 g) and O2 consumption (4.5±0.6 versus 2.7±0.5 mL O2/min per 100 g) decreased compared with the contralateral cortex. Oxygen extraction increased (4.7±0.2 versus 5.4±0.3 mL O2/100 mL) and the variation in small vein (20-60 μm) O2 saturation as determined by its coefficient of variation (=100×SD/mean) increased (5.5 versus 10.5). With 2 hours of reperfusion, the blood flow decrement was reduced and O2 consumption returned to the value in the contralateral cortex. Oxygen extraction remained elevated in the ischemic-reperfused area and the coefficient of variation of small vein O2 saturation increased further (17.3). These data indicated continued reduction of O2 supply/consumption balance with reperfusion. They also demonstrated many small regions of low oxygenation within the reperfused cortical region.

Increased oxygen extraction capacity in the basal ganglia and thalamus of people with Alzheimer's disease

IC-P-176 INCREASED OXYGEN EXTRACTION CAPACITY IN THE BASAL GANGLIA AND THALAMUS OF PEOPLE WITH ALZHEIMER’S DISEASE Simon Eskildsen, Louise Gyldensted, Kartheeban Nagenthiraja, Jesper Frandsen, Anders Rodell, Carsten Gyldensted, Sune Norhoj Jespersen, Kim Mouridsen, Hans Braendgaard, Leif Ostergaard, Aarhus University, Aarhus, Denmark; Aarhus University Hospital, Aarhus, Denmark. Contact e-mail: eskild@gmail.com

Increased oxygen extraction capacity in the basal ganglia and thalamus of patients with Alzheimer's disease

Increased oxygen extraction capacity in the basal ganglia and thalamus of patients with Alzheimer's disease

Chronic Neurovascular Uncoupling Syndrome

Our current understanding of the blood supply to the human brain has advanced considerably but is far from complete. Although great progress has been made in determining the relationship between neuroglial activity and blood flow, especially in animal models, this relationship is not as well defined in humans, in particular for diseases that cause chronic compromise of the cervicocerebral vasculature. There is no mystery concerning the ischemic consequences to the brain when there is an acute loss in blood flow. However, there is a major gap in our knowledge concerning the effect of chronic vascular insufficiency on the integrity of the brain and the associated functional consequences. C. Miller Fisher in 1954 was the first to report an association between unilateral/bilateral carotid occlusion and senile dementia.1 Interestingly, the report references a study from Freyhan et al,2 in which a decrease in cerebral blood flow observed in patients with arteriosclerotic dementia and senile psychosis was thought to be attributable to increased vascular resistance with vascular changes preventing a compensatory increase in blood form. More recently, a study that compared the effect of increased oxygen extraction fraction and cognition in patients who were enrolled in the National Institute of Neurological Disorders and Stroke sponsored Carotid Occlusion Surgery Study3 found a significant association between increased oxygen extraction fraction and diminished mental function once covariates, including age, education, side of occlusion, depression, and previous stroke, were controlled.4 Therefore, it seems that a relationship between hemodynamic insufficiency and diminished brain function in the absence of clinically expressed ischemic events can occur. This raises important questions concerning the cause of the brain dysfunction in these patients. Is it secondary to inadequate delivery of metabolic substrates with functional impairment alone, or does inadequate blood flow actually result in a physical degradation in the …

Redefining the Pericontusional Penumbra following Traumatic Brain Injury: Evidence of Deteriorating Metabolic Derangements Based on Positron Emission Tomography

Abstract The pathophysiological changes in the pericontusional region after traumatic brain injury (TBI) have classically been considered to be ischemic. Using [F-18]fluorodeoxyglucose (FDG) and triple-oxygen PET studies, we examined the pericontusional "penumbra" to assess for increased oxygen extraction fraction (OEF), anaerobic metabolism, and tissue viability. Acute (≤4 days) CT, MRI, and PET studies were performed in eight patients with TBI who had contusions. Four regions-of-interest (ROI) containing the contusion core, pericontusional hypodense gray matter (GM), pericontusional normal-appearing GM, and remote normal-appearing GM, were defined using a semi-automatic method. The correlations of cerebral blood flow (CBF) with OEF, cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRglc) were examined. The oxygen-glucose ratio (OGR) in each brain region was evaluated for anaerobic metabolism. The results show that pericontusional tissue had progressively diminishing OEF, CBF, CMRO2, or CMRglc approaching the contusion core. In general, there was a preserved ratio of CBF to CMRO2 in pericontusional hypodense GM. The OGR of the pericontusional hypodense GM was low (<4.0) and was inversely correlated (r=-0.68) with time after injury. A large proportion (%area: 22-76%) of pericontusional hypodense GM tissue had CMRO2 values less than 35 μmol/100 g/min, with this percentage increased with time after injury.

Abstract 155: No Increased Stroke Risk with Lower Blood Pressures in Hemodynamic Cerebral Ischemia

Patients with symptomatic carotid artery occlusion and hemodynamic cerebral ischemia manifested by increased oxygen extraction fraction (OEF) are at 20-25% risk for ipsilateral stroke within 2 years. Disagreement exists whether strict blood pressure control is the best medical management for these patients or if higher blood pressures are needed to preserve cerebral perfusion. To address this issue, we analyzed data from the non-surgical group of the Carotid Occlusion Surgery Study (COSS), a randomized, controlled trial performed to determine whether EC-IC bypass could reduce subsequent ipsilateral ischemic stroke at two years in participants with recently symptomatic internal carotid artery occlusion and increased OEF. Of the 98 patients in the non-surgical group, 95 had 1-19 blood pressures recorded at follow-up visits. Average systolic and diastolic blood pressures were calculated from these data. Cox regression analyses were used to estimate the relative hazard of a post-randomization ipsilateral stroke in the tercile of subjects with the lowest average blood pressures ( &lt;/= 124 mm Hg systolic or 73 mm Hg diastolic) compared to the remainder. Lower blood pressures were associated with reduced, not increased, stroke risk. If the samples analyzed were from populations in which the true hazards were the same, hazard ratios of this magnitude or less would be expected less than 10% of the time. We cannot conclude from these data that strict blood pressure control is beneficial in patients with symptomatic carotid occlusion and increased OEF. However, since we found no evidence that that blood pressures below 124/73 were associated with increased stroke risk, we recommend treatment of blood pressure in these patients according to JNC VII guidelines to targets of &lt; 140/90 or &lt;130/80 for those with concomitant diabetes mellitus or kidney disease.