Cerebral Fractional Oxygen Extraction Research Articles

Intervention versus standard medical treatment in patients with symptomatic occlusion of the internal carotid artery: a randomised oxygen-15 PET study

BackgroundThe aim of this randomised pilot study was to investigate the haemodynamic effects measured by oxygen-15 positron emission tomography (PET) of interventional treatment consisting of either endarterectomy or endovascular treatment of stenosed cerebropetal arteries, or tapering of antihypertensive medication in comparison with standard medical treatment alone in patients with symptomatic internal carotid artery (ICA) occlusion.MethodsTwenty-three patients with symptomatic ICA occlusion underwent PET scanning at baseline and after 3 months. Twelve patients were randomised to intervention (either endarterectomy or endovascular treatment of stenosed cerebropetal arteries, or tapering of antihypertensive medication) and 11 to standard medical treatment alone. Primary outcome was a change in cerebral blood flow (CBF), cerebral blood volume (CBV) and/or oxygen extraction fraction (OEF) after 3 months measured by PET.ResultsThere were no differences in changes in CBF, CBV or OEF between the two groups. Only patients with compromised perfusion at presentation showed a borderline significant increase in CBF of 2.8 mL/min/100 mL (95% confidence interval 0.0 to 5.7) after intervention (n = 7).ConclusionThis pilot study shows that in patients with symptomatic ICA occlusion, oxygen-15 PET did not detect differences in improvement of CBF, CBV or OEF between interventional and standard treatment.

MR evaluation of cerebral oxygen metabolism and blood flow in stroke-like episodes of MELAS

Metabolic information is essential in the investigation of the pathophysiology of stroke-like episodes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Here, we used magnetic resonance imaging to evaluate the dynamic metabolic changes before and after a stroke-like episode in two patients with MELAS caused by the mitochondrial DNA mutation A3243G. We performed functional magnetic resonance imaging, including arterial spin labeling and oxygen extraction fraction imaging, and generated cerebral blood flow and oxygen extraction fraction maps. We recruited eight healthy volunteers to define the normal range of the oxygen extraction fraction. We detected a heterogeneous reduction in the oxygen extraction fraction in the brain in the interictal period as well as at the onset of a stroke-like attack. However, the oxygen extraction fraction in the stroke-like lesions normalized in the acute stage. The stroke-like lesions showed consistent hyperperfusion in the acute phase but hypoperfusion in the chronic phase. We have demonstrated the utility of using new magnetic resonance imaging techniques in the evaluation of the pathophysiology of stroke-like lesions. The increased utilization of oxygen in an acute lesion is a novel finding in our study, which might play a role in the oxidative stress.

Crossed Cerebellar Diaschisis: Insights into Oxygen Challenge MRI

Hyperoxia during T2*-weighted magnetic resonance imaging (oxygen challenge imaging (OCI)) causes T2*-weighted signal change that is dependent on cerebral blood volume (CBV) and oxygen extraction fraction (OEF). Crossed cerebellar diaschisis (CCD), where CBV is reduced but OEF is maintained, may be used to understand the relative contributions of OEF and CBV to OCI results. In subjects with large hemispheric strokes, OCI showed reduced signal change in the contralesional cerebellum (P=0.027, n=12). This was associated with reduced CBV in contralesional cerebellum (P=0.039, n=9). CCD may be a useful model to determine the relative contribution of CBV to signal change measured by OCI.

Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice.

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO(2) and CBF. This study employed the recently developed in vivo (17)O MR spectroscopic imaging to simultaneously assess CMRO(2), CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of (17)O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive (17)O-MR approach for rapidly imaging CMRO(2), CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO(2) and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising (17)O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This (17)O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy.

Optimization strategies for evaluation of brain hemodynamic parameters with qBOLD technique

Quantitative blood oxygenation level dependent technique provides an MRI-based method to measure tissue hemodynamic parameters such as oxygen extraction fraction and deoxyhemoglobin-containing (veins and prevenous part of capillaries) cerebral blood volume fraction. It is based on a theory of MR signal dephasing in the presence of blood vessel network and experimental method-gradient echo sampling of spin echo previously proposed and validated on phantoms and animals. In vivo human studies also demonstrated feasibility of this approach but also recognized that obtaining reliable results requires high signal-to-noise ratio in the data. In this paper, we analyze in detail the uncertainties of the quantitative blood oxygenation level dependent parameter estimates in the framework of the Bayesian probability theory, namely, we examine how the estimated parameters oxygen extraction fraction and deoxygenated cerebral blood volume fraction depend on their "true values," signal-to-noise ratio, and data sampling strategies. On the basis of this analysis, we develop strategies for optimization of the quantitative blood oxygenation level dependent technique for deoxygenated cerebral blood volume and oxygen extraction fraction evaluation. In particular, it is demonstrated that the use of gradient echo sampling of spin echo sequence allows substantial decrease of measurement errors as the data are acquired on both sides of spin echo. We test our theory on phantom mimicking the structure of blood vessel network. A 3D gradient echo sampling of spin echo pulse sequence is used for the acquisition of the MRI signal that was subsequently analyzed by Bayesian Application Software. The experimental results demonstrated a good agreement with theoretical predictions.

Relationship Between Angiographic Vasospasm and Regional Hypoperfusion in Aneurysmal Subarachnoid Hemorrhage

Angiographic vasospasm frequently complicates subarachnoid hemorrhage and has been implicated in the development of delayed cerebral ischemia. Whether large-vessel narrowing adequately accounts for the critical reductions in regional cerebral blood flow underlying ischemia is unclear. We sought to clarify the relationship between angiographic vasospasm and regional hypoperfusion. Twenty-five patients with aneurysmal subarachnoid hemorrhage underwent cerebral catheter angiography and 15O-positron emission tomographic imaging within 1 day of each other (median of 7 days after subarachnoid hemorrhage). Severity of vasospasm was assessed in each intracranial artery, whereas cerebral blood flow and oxygen extraction fraction were measured in 28 brain regions distributed across these vascular territories. We analyzed the association between vasospasm and perfusion and compared frequency of hypoperfusion (cerebral blood flow<25 mL/100 g/min) and oligemia (low oxygen delivery with oxygen extraction fraction≥0.5) in territories with versus without significant vasospasm. Twenty-four percent of 652 brain regions were supplied by vessels with significant vasospasm. Cerebral blood flow was lower in such regions (38.6±12 versus 48.7±16 mL/100 g/min), whereas oxygen extraction fraction was higher (0.48±0.19 versus 0.37±0.14, both P<0.001). Hypoperfusion was seen in 46 regions (7%), but 66% of these were supplied by vessels with no significant vasospasm; 24% occurred in patients without angiographic vasospasm. Similarly, oligemia occurred more frequently outside territories with vasospasm. Angiographic vasospasm is associated with reductions in cerebral perfusion. However, regional hypoperfusion and oligemia frequently occurred in territories and patients without vasospasm. Other factors in addition to large-vessel narrowing must contribute to critical reductions in perfusion.

Comparison of early and late images on 123I-iomazenil SPECT with cerebral blood flow and oxygen extraction fraction images on PET in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease

The aim of the present study was to determine whether early and late/early images on 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) correlate with cerebral blood flow (CBF) images and oxygen extraction fraction (OEF) images on PET, respectively, in the cerebral cortex of patients with chronic unilateral middle cerebral artery or internal carotid artery occlusive disease. In 20 normal individuals and in 68 patients, CBF and OEF were assessed using 15O-PET, and brain SPECT scans were initiated immediately after (early images) and 180 min after (late images) the administration of 123I-IMZ. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a three-dimensional stereotaxic region of interest template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. Among patients, a significant positive correlation was observed between PET-CBF ratios and the SPECT-early IMZ ratios (r=0.797, P<0.0001) as well as between the PET-OEF ratios and the SPECT-late/early IMZ ratios (r=0.679, P<0.0001). When an abnormally elevated PET-OEF ratio was defined as a value greater than the mean+2 SD obtained in normal participants, the SPECT-late/early IMZ ratios yielded 100% sensitivity and 93% specificity, with 76% positive-predictive and 100% negative-predictive values for detecting abnormally elevated PET-OEF ratios. Early and late/early images on 123I-IMZ SPECT correlate with CBF images and OEF images on PET, respectively, in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease.

Mapping of Cerebral Oxygen Extraction Fraction Changes with Susceptibility-weighted Phase Imaging

To develop a map to detect changes in oxygen extraction fraction (OEF) utilizing susceptibility-weighted (SW) phase images and to correlate such changes in OEF with those in cerebral blood flow (CBF). The study protocol was approved by the institutional review board, and written informed consent was obtained from all subjects. Eight healthy volunteers (mean age ± standard deviation, 29.8 years ± 4.6) were included in the study. Subjects were evaluated by using SW imaging, and the change in OEF was calculated by subtracting the image at baseline from one of the images obtained during six different conditions, including two at resting state, three different types of respiratory challenges, and one drug challenge with acetazolamide. Arterial spin labeling was carried out to measure CBF, while SW imaging was used to generate maps of change in OEF in response to a given condition. Statistical tests included one-way analysis of variance and Dunnett multiple comparisons to compare among the six conditions the magnitude of change from baseline for both OEF and CBF, by using the OEF change at resting state (resting 1) as the control. Hyperventilation caused a statistically significant decrease in CBF (-29.3%, P < .001) and an increase in OEF (+5.2%, P < .001) compared with the control, resting 1 (+2.2%, -0.7%, respectively). Acetazolamide caused a significant increase in CBF (+39.7%, P < .001) and a decrease in OEF (-3.4%, P = .040). Carbogen also induced a CBF increase (+16.2%); however, the change was not significant (P = .090), even though OEF decreased significantly (-4.2%, P = .003). Oxygen administration resulted in a significant CBF decrease (-27.2%, P < .001), whereas OEF showed no significant difference (-0.6%, P > .99). Maps of changes in OEF generated from SW phase images revealed changes in OEF corresponding to anticipated changes in CBF induced by various conditions; SW phase imaging might, in the future, be applied to evaluate cerebrovascular and other cerebral disorders in which changes in oxygen metabolism are important for planning therapeutic strategies.

634 Effect of Indomethacine Infusion Rate for Patent Ductus Arteriosus on Cerebral Oxygenation in Preterm Infants

Background: Indomethacine treatment for patent ductus arteriosus (PDA), might lead to vasoconstriction of cerebral blood vessels and under-perfusion of the brain. A lower infusion rate might prevent this. We aimed to determine the effect of two indomethacine infusion rates on fractional cerebral oxygen extraction (FTOE), which is indicative for cerebral blood flow. Methods: In preterms with PDA, we compared the effect of indomethacine infusion (0.2 mg/kg) in 30 versus 60 minutes, on cerebral oxygenation. Patients in both groups were matched for GA, BW, PDA closure, and postnatal age. Near-infrared spectroscopy was used to measure regional cerebral oxygen saturation (rcSO2). Transcutaneous arterial oxygen saturation (tcSaO2) was measured simultaneously. FTOE was calculated: (tcSaO2- rcSO2)/tcSaO2. We analyzed 6 episodes of 1-h measurements: before, 1h-4h, and 12 hours after treatment, using Mann-Whitney-U-test. Results: Twenty infants (13 girls, median GA 27.0 weeks (range 25.3-28.7), BW 1007 gram (615- 1300), age 3.0 days (2-11)) were included, 10 in each group. No significant differences existed between the groups regarding GA, BW, age, effectiveness of indomethacine, need of surgery, and gender. The first hour after the start of treatment, we found an increase in FTOE of 0.04 in the 30 minutes-infusiongroup, compared to no change in FTOE in the 60-minutes-infusion group (p=.03). No significant differences were found at all other time-points. Conclusion: Higher infusion rate of indomethacine for PDA seems to decrease cerebral blood flow the first hour, compared to lower infusion rate, possibly due to indomethacine induced vasoconstriction. The clinical relevance of this difference needs to be Investigated.

319 Effects of Blood Sampling on Cerebral Tissue Oxygenation Index (TOI) in VLBW Infants: Venepuncture Versus Heel Lance

Background and aims: In term neonates venepuncture is considered less painful than heel lance for blood sampling. Here, we compared the effects of venepuncture and heel lance blood sampling in preterm infants < 1500 g birth weight. Methods: Twenty infants (median [range] birth weight 855 [355 - 1470] g, gestational age 28 [24 - 32] weeks) were studied during sequentially performed venepuncture and heel lance blood sampling. Heart rate and arterial oxygen saturation were registered continuously. Cerebral tissue oxygenation index (TOI) was measured by near infrared spectroscopy. Cerebral fractional oxygen extraction (FOE) was calculated. Results: During both procedures, heart rate increased and TOI decreased significantly. The decrease in TOI was significantly larger during venepuncture (from 64 [45-99]% to 57 [47-95%]) than during heel lance blood sampling (from 68 [51-99]% to 63 [47-99] %, p=0.05). Arterial oxygen saturation decreased and FOE increased during venepuncture only. Conclusions: Our results indicate that - in contrast to term neonates - for preterm infants venepuncture is more stressful than heel lance blood sampling.

Cerebral Oxygenation and Oxygen Extraction in the Preterm Infant during Desaturation: Effects of Increasing FiO2 to Assist Recovery

Background: In the clinical setting, episodes of desaturation in newborn infants are often treated by increasing the fraction of inspired oxygen (FiO₂). Objectives: To study the effect of an increase in FiO₂ on cerebral oxygenation during recovery from desaturation, as measured by near-infrared spectroscopy (NIRS). Methods: Peripheral arterial saturation (SaO₂), NIRS-monitored cerebral saturation (rScO₂), and fractional cerebral oxygen extraction (cFTOE) were analyzed in the first 3 days of life during 6 episodes of desaturation (SaO₂ <75%, >30 s) in each of 24 otherwise stable spontaneously breathing preterm infants (gestational age 29.8 ± 1.5 weeks, birth weight 1,215 ± 280 g; mean ± SD), during 3 episodes without and 3 episodes with increased FiO₂ during recovery from desaturation. Results: Post-recovery SaO₂ with increased FiO₂ was significantly higher than post-recovery SaO₂ without increased FiO₂. Post-recovery SaO₂ and rScO₂ were significantly increased over baseline saturations when FiO₂ was increased. Post-recovery rScO₂ was very high for several minutes in some cases, while cFTOE was highly suggestive of oxygen delivery that exceeded consumption. Conclusions: Assuming that NIRS-measured rScO₂ is an indicator of cerebral oxygen content, an increase in FiO₂ to assist recovery from desaturation may cause hyperoxygenation of the brain in relatively stable preterm infants. This procedure may be particularly harmful in the sick very preterm infant with limited regulation of brain circulation and poorly developed antioxidant defenses.

Dopamine therapy promotes cerebral flow-metabolism coupling in preterm infants

Dopamine is widely used to maintain blood pressure in very preterm infants, but it may affect neurovascular regulation as it crosses the immature blood-brain barrier. We contrasted the relationship between cerebral perfusion and oxygen metabolism in preterm infants treated with dopamine because of hypotension with normotensive controls. Prospective observational study in a neonatal intensive care unit. Cerebral metabolic rate of oxygen consumption (CMRO2) was determined via measurements of cerebral blood flow (CBF) and cerebral venous saturation (CSvO2) using near infrared spectroscopy. Twenty-six infants (median gestation 26 weeks) were studied at a median postnatal age of 17 h. Infants were categorised as control (n = 16) or dopamine-treated (DOPA, n = 10). No relationship was found between CBF and CMRO2 in the control group, while a strong positive correlation was found in the DOPA group (R (2) = 0.62, P = 0.01). Cerebral fractional oxygen extraction (CFOE) and CBF showed strong negative correlation in the control infants (R2 = 0.65, P < 0.001), but not in the DOPA group. CSvO2 was lower at decreased CBF (R2 = 0.56, P < 0.001) in the control infants, but not in the DOPA group. Cerebral blood flow-metabolism coupling in the very preterm brain differs strikingly from that in the mature brain, where CBF is coupled to CMRO2. In the very preterm brain, variations of cerebral oxygen extraction, not CBF, sustain CMRO2. In contrast, preterm infants receiving dopamine exhibit flow-metabolism coupling similar to the mature brain. These findings suggest a previously unrecognised role for dopamine in the preterm brain in promoting flow-metabolism coupling.

Brain Temperature Measured Using Proton MR Spectroscopy Detects Cerebral Hemodynamic Impairment in Patients With Unilateral Chronic Major Cerebral Artery Steno-Occlusive Disease

Brain temperature is determined by the balance between heat produced by cerebral energy turnover and heat removed by cerebral blood flow. The purpose of the present study was to investigate whether brain temperature measured noninvasively using proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with unilateral chronic internal carotid or middle cerebral artery occlusive disease when compared with positron emission tomography. Brain temperature, cerebral blood flow, and metabolism were measured using proton MR spectroscopy and (15)O-positron emission tomography, respectively, in 21 normal subjects and 37 patients. Positron emission tomography images were coregistered with MR images and resliced automatically using image analysis software. Regions of interest placed in both cerebral hemispheres on MR images were automatically superimposed in these resliced positron emission tomography images. A significant correlation was observed between brain temperature difference (affected hemisphere-contralateral hemisphere) and both cerebral blood volume and oxygen extraction fraction ratio (affected hemisphere/contralateral hemisphere; r=0.607; P=0.0004 and r=0.631; P=0.0002). With abnormally elevated cerebral blood volume or oxygen extraction fraction ratio defined as higher than the mean +2 SDs obtained from normal subjects, brain temperature difference provided 86% or 92% sensitivity and 87% or 84% specificity with 80% or 73% positive and 91% or 95% negative predictive values for detecting abnormally elevated cerebral blood volume or oxygen extraction fraction ratios, respectively. Brain temperature measured using proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with unilateral chronic major cerebral artery steno-occlusive disease.

Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study

Few data exist regarding antegrade selective cerebral perfusion (ASCP) and its application in newborn and juvenile patients. Clinical data suggest ASCP alone to be superior to deep hypothermic circulatory arrest (DHCA); however, the effects of moderate hypothermia during ASCP on cerebral metabolism in this patient population are still unclear. After obtaining the approval from animal investigation committee, 16 piglets were randomly assigned to circulatory arrest combined with either ASCP at 27 degrees C or DHCA at 18 degrees C for 90 min. Cerebral oxygen extraction fraction (COEF) from blood as well as cerebral tissue glucose, glycerol, lactate, pyruvate, and the lactate/pyruvate ratio (L/P ratio) by microdialysis were obtained repeatedly. COEF was lower during cooling and rewarming, respectively, in the DHCA18 group compared to the ASCP27 group (30 +/- 8 vs 56 +/- 13% and 35 +/- 6 vs 58 +/- 7%, respectively). Glucose decreased in both the DHCA18 and ASCP27 groups during the course of cardiopulmonary bypass (CPB), but were higher in the ASCP27 group during ASCP, compared to the DHCA18 group during circulatory arrest (0.7 +/- 0.1 vs 0.2 +/- 0.1 mm.l(-1), P < 0.05). Pyruvate was higher (ASCP27 vs DHCA18: 53 +/- 17 vs 6 +/- 2 microm.l(-1), P < 0.05), and the L/P ratio increased during circulatory arrest in the DHCA18 group, compared to the selective perfusion phase of the ASCP27 group (DHCA18 vs ASCP27: 1891 +/- 1020 vs 70 +/- 28, P < 0.01). In this piglet model, both cerebral oxygenation and microdialysis findings suggested a depletion of cerebral energy stores during circulatory arrest in the DHCA18 group, compared to selective cerebral perfusion combined with circulatory arrest in the ASCP27 group.

MR Mismatch and Thrombolysis

Since the initial description of the ischemic penumbra 30 years ago, the concept of rapid restoration of blood flow to threatened brain tissue has been the “holy grail” of acute stroke therapy.1,2 Despite its drawbacks, MR imaging of perfusion diffusion mismatch remains the most widely used and practical means of in vivo assessment. There is accumulating evidence linking reperfusion with better clinical outcomes and attenuation of infarct growth in patients in patients with MR mismatch. However, validation that imaging effectively selects thrombolytic responders is still lacking. Both protagonists have highlighted areas of uncertainty …

Cerebral metabolic rate of oxygen (CMRO 2) in pig brain determined by PET after resuscitation from cardiac arrest

Aim To assess the regional vulnerability to ischemic damage and perfusion/metabolism mismatch of reperfused brain following restoration of spontaneous circulation (ROSC) after cardiac arrest. Method We used positron emission tomography (PET) to map cerebral metabolic rate of oxygen (CMRO 2), cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in brain of young pigs at intervals after resuscitation from cardiac arrest. After obtaining baseline PET recordings, ventricular fibrillation of 10 min duration was induced, followed by mechanical closed-chest cardiopulmonary resuscitation (CPR) in conjunction with i.v. administration of 0.4 U/kg of vasopressin. After CPR, external defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). CBF and CMRO 2 were mapped and voxelwise maps of OEF were calculated at times of 60, 180, and 300 min after ROSC. Results There was hypoperfusion throughout the telencephalon at 60 min, with a return towards baseline values at 300 min. In contrast, there was progressively increasing CBF in cerebellum throughout the observation period. The magnitude of CMRO 2 decreased globally after ROSC, especially in cerebral cortex. The magnitude of OEF in cerebral cortex was 60% at baseline, tended to increase at 60 min after ROSC, and declined to 50% thereafter, thus suggesting transition to an ischemic state. Conclusion The cortical regions tended most vulnerable to the ischemic insult with an oligaemic pattern and a low CMRO 2 whereas the cerebellum instead showed a pattern of luxury perfusion.

Influence of residual oxygen-15-labeled carbon monoxide radioactivity on cerebral blood flow and oxygen extraction fraction in a dual-tracer autoradiographic method

Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with (15)O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating (15)O(2) and C(15)O(2) gases. In this protocol, before the sequential PET scan with (15)O(2) and C(15)O(2) gases ((15)O(2)-C(15)O(2) PET scan), a PET scan with C(15)O should be preceded to obtain CBV image. C(15)O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C(15)O might exist during a (15)O(2)-C(15)O(2) PET scan. As the current DARG method assumes no residual C(15)O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C(15)O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C(15)O radioactivity. In the simulation, normal and ischemic conditions were considered. The (15)O(2) and C(15)O(2) PET count curves with the residual C(15)O PET counts were generated by the arterial input function with the residual C(15)O radioactivity. The amounts of residual C(15)O radioactivity were varied by changing the interval between the C(15)O PET scan and (15)O(2)-C(15)O(2) PET scan, and the absolute inhaled radioactivity of the C(15)O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C(15)O gas in the input function and PET counts. Our simulations revealed that the CBF and OEF values were underestimated by the residual C(15)O radioactivity. The magnitude of this underestimation depended on the amount of C(15)O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. This study showed the influence of C(15)O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C(15)O, and the physiological condition.

Cerebral hemodynamics as a predictor of stroke in adult patients with moyamoya disease: a prospective observational study

Moyamoya disease is an obliterative vasculopathy of the large arteries at the base of the brain. In the US, it most commonly affects women in their 3rd and 4th decades of life, frequently causing ischemic stroke. The natural history of this disorder is not well described. It is very likely that hemodynamic factors play an important role in the risk of future stroke, as has been established in atherosclerotic carotid occlusive disease. The authors describe an ongoing, prospective observational study designed to test the hypothesis that increased oxygen extraction in the cerebral hemisphere beyond the occlusive lesion is a predictor of subsequent risk of ipsilateral stroke in medically treated patients with moyamoya phenomenon. On enrollment, all patients undergo regional measurements of cerebral oxygen extraction fraction (OEF) with PET. Information on baseline clinical, laboratory, epidemiological, and angiographic risk factors are obtained at the time of the PET study. Decisions regarding surgery are made by the treating physicians based on clinical information while being blinded to PET data. Patients undergo follow-up at 6-month intervals to determine the subsequent risk of ipsilateral stroke. All patients will return at 1 and 3 years for repeat PET studies. Secondary, exploratory, aims of this longitudinal and blinded study are to determine other predictive factors for stroke in this population; to determine preliminary estimates of the effects of different medical treatment regimens in this population; to determine the temporal changes in hemodynamic impairment in medically treated patients; to determine the effects of surgery on hemodynamic impairment in the subset of patients who undergo surgical revascularization; and to obtain estimates of surgical complication rates for patients with and without hemodynamic impairment.

Early Metabolic Characteristics of Lesion and Nonlesion Tissue after Head Injury

We defined lesion and structurally normal regions using magnetic resonance imaging at follow-up in patients recovering from head injury. Early metabolic characteristics in these regions of interest (ROIs) were compared with physiology in healthy volunteers. Fourteen patients with severe head injury had positron emission tomography within 72 h, and magnetic resonance imaging at 3 to 18 months after injury. Cerebral blood flow (CBF), oxygen utilization (CMRO(2)), and oxygen extraction fraction (OEF) were all lower in lesion ROIs, compared with nonlesion and control ROIs (P<0.001); however, there was substantial overlap in physiology. Control ROIs showed close coupling among CBF, blood volume (CBV), and CMRO(2), whereas relationships within lesion and nonlesion ROIs were abnormal. The relationship between CBF and CMRO(2) generally remained coupled but the slope was reduced; that for CBF and OEF was variable; whereas that between CBF and CBV was highly variable. There was considerable heterogeneity between and within patients. Although irreversibly damaged tissue is characterized by marked derangements in physiology, a more detailed analysis shows acute changes in physiology and physiologic relationships within regions of the brain that appear structurally normal at follow-up. Such pathophysiological derangements may result in selective neuronal loss and impact on functional outcome.

Optimal scan time of oxygen-15-labeled gas inhalation autoradiographic method for measurement of cerebral oxygen extraction fraction and cerebral oxygen metabolic rate

Regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) can be estimated from C15O, H(2)15O, and 15O2 tracers and positron emission tomography (PET) using an autoradiographic (ARG) method. Our objective in this study was to optimize the scan time for 15O2 gas study for accurate estimation of OEF and CMRO2. We evaluated statistical noise in OEF by varying the scan time and error caused by the tissue heterogeneity in estimated OEF and CMRO2 using computer simulations. The characteristics of statistical noise were investigated by signal-to-noise (S/N) ratio from repeated tissue time activity curves with noise, which were generated using measured averaged arterial input function and assuming CBF=20, 50, and 80 (ml/100 g per minute). Error caused by tissue heterogeneity was also investigated by estimated OEF and CMRO2 from tissue time activity curve with mixture of gray and white matter varying fraction of mixture. In the simulations, three conditions were assumed (i) CBF in gray and white matter (CBFg and CBFw) was 80 and 20, OEF in gray and white matter (Eg and Ew) was 0.4 and 0.3, (ii) CBFg and CBFw decreased by 50%, and Eg and Ew increased by 50% when compared with conditions (i) and (iii). CBFg and CBFw decreased by 80%, and Eg and Ew increased by 50% when compared with condition (i). The longer scan time produced the better S/N ratio of estimated OEF value from three CBF values (20, 50, and 80). Errors of estimated OEF for three conditions owing to tissue heterogeneity decreased, as scan time took longer. Meanwhile in the case of CMRO2, 3 min of scan time was desirable. The optimal scan time of 15O2 inhalation study with the ARG method was concluded to be 3 min from taking into account for maintaining the S/N ratio and the quantification of accurate OEF and CMRO2.