Rate Of Cerebral Oxygen Consumption Research Articles

High-resolution dynamic oxygen-17 MR imaging of mouse brain with golden-ratio-based radial sampling and k-space-weighted image reconstruction.

The current study aimed to develop a three-dimensional (3D) dynamic oxygen-17 (17 O) MR imaging method with high temporal and spatial resolution to delineate the kinetics of 17 O water uptake and washout in the brains of mice with glioblastoma (GBM). A 3D imaging method with a stack-of-stars golden-ratio-based radial sampling scheme was employed to acquire 17 O signal in vivo. A k-space-weighted image reconstruction method was used to improve the temporal resolution while preserving spatial resolution. Simulation studies were performed to validate the method. Using this method, the kinetics of 17 O water uptake and washout in the brains of mice with GBM were delineated after an intravenous bolus injection of 17 O water. The proposed 17 O imaging method achieved an effective temporal resolution of 7.56 s with a nominal voxel size of 5.625 μL in the mouse brain at 9.4 T. Reduced uptake and prolonged washout of 17 O water were observed in tumor tissue, suggesting compromised cerebral perfusion. This study demonstrated a promising dynamic 17 O imaging approach that can delineate 17 O water kinetics in vivo with high temporal and spatial resolution. It can also be used to image cerebral oxygen consumption rate in oxygen-17 inhalation studies. Magn Reson Med 79:256-263, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

My starting point: The discovery of an NMR method for measuring blood oxygenation using the transverse relaxation time of blood water

This invited personal story, covering the period from 1979 to 2010, describes the discovery of the dependence of the transverse relaxation time of water in blood on the oxygenation state of hemoglobin in the erythrocytes. The underlying mechanism of the compartmentation of the different magnetic susceptibilities of hemoglobin in its different oxygenation states also explains the mechanism that underlies blood oxygenation level dependent contrast used in fMRI. The story begins with the initial observation of line broadening during ischemia in small rodents detected by in vivo 31P NMR spectroscopy at high field. This spectroscopic line broadening or T2* relaxation effect was demonstrated to be related to the oxygenation state of blood. The effect was quantified more accurately using T2 values measured by the Carr-Purcell-Meiboom-Gill method. The effect was dependent on the integrity of the erythrocytes to compartmentalize the different magnetic susceptibilities produced by the changing spin state of the ferrous iron of hemoglobin in its different oxygenation states between the erythrocytes and the suspending solution. The hematocrit and magnetic field dependence, the requirement for erythrocyte integrity and lack of T1 dependence confirmed that the magnetic susceptibility effect explained the oxygenation state dependence of T2* and T2. This T2/T2* effect was combined with T1 based measurements of blood flow to measure oxygen consumption in animals. This blood oxygenation assay and its underlying magnetic susceptibility gradient mechanism was published in the biochemistry literature in 1982 and largely forgotten. The observation was revived to explain evolving imaging features of cerebral hematoma as MR imaging of humans increased in field strength to 1.5 T by the mid 1980s. Although the imaging version of this assay was used to measure a global metabolic rate of cerebral oxygen consumption in humans at 1.5-T by 1991, the global measurement had little clinical value. By contrast, a decade after the spectroscopic observation, imaging experiments performed on rodents at 7 T by Ogawa and colleagues identified the extravascular T2* imaging characteristics of the blood oxygenation effect and, most importantly, associated that change with brain functional states. Ogawa appropriately branded this blood oxygenation level dependent mechanism as BOLD contrast. This mechanism was subsequently shown to be the basis of localized MR signal changes associated with local brain function. This connection led to the fMRI revolution in human brain mapping.

Cerebral oxygen metabolism in patients with early Parkinson's disease

Aim Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO 2). To test this hypothesis, we compared CMRO 2 and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. Materials and methods Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO 2 and CBF. Between-group differences were evaluated for absolute data and intensity-normalized values. Results No group differences were detected in regional magnitudes of CMRO 2 or CBF. Upon normalization using the reference cluster method, significant relative CMRO 2 decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical regions, brainstem, and the cerebellum were spared. A similar pattern was evident in normalized CBF data, as described previously. Conclusion While the data did not reveal substantially altered absolute CMRO 2 in brain of PD patients, employing data-driven intensity normalization revealed widespread relative CMRO 2 decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO 2, CBF, and CMRglc in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD.

Increased oxygen consumption in the somatosensory cortex of α-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla

The significance of changes in cerebral oxygen consumption in focally activated brain tissue is still controversial. Since the rate of cerebral oxygen consumption is tightly coupled to that of tricarboxylic acid cycle which can be measured from the turnover kinetics of [4- 13C]glutamate using in vivo 1H{ 13C} magnetic resonance spectroscopy, changes in tricarboxylic acid cycle flux rate were assessed in primary somatosensory cortex of α-chloralose anesthetized rats during electrical forepaw stimulation. With markedly improved 1H{ 13C} magnetic resonance spectroscopy technique and the use of high magnetic field strength of 11.7 T accessible to the current study, [4- 13C]glutamate at 2.35 ppm was spectrally resolved from overlapping resonances of [4- 13C]glutamine at 2.46 ppm and [2- 13C]GABA at 2.28 ppm as well as the more distal [3- 13C]glutamate and [3- 13C]glutamine. The results showed a significantly increased V TCA in focally activated primary somatosensory cortex during forepaw stimulation, corresponding to approximately 51 ± 27% ( n = 6, mean ± SD) increase in cerebral oxygen consumption rate. Considering the high efficiency in producing adenosine triphosphate by oxidative metabolism of glucose, the results demonstrate that aerobic oxidative metabolism provides the majority of energy required for cerebral focal activation in α-chloralose anesthetized rats subjected to forepaw stimulation.

Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging. Part 2. Determination of CMRO2 for the rat by 17O NMR, and CMRO2, rCBF and the partition coefficient for the cat by 17O MRI.

The rate of oxygen consumption (CMRO2) in intact rat and cat brains was calculated by novel data analysis methods from data obtained in in vivo 17O NMR spectroscopy and imaging inhalation studies. Data analysis methods of 17O inhalation measurements are applied to the calculation of CMRO2, regional cerebral blood flow (rCBF), the reflow (R), the arterial venous difference (AVD) and the partition coefficient (lambda). Several of the applied methods for the determination of CMRO2 do not require measurements of regional cerebral blood flow and H2 17O arterial concentration. The proposed methods have been tested, and the results obtained by the different methods are in very good agreement. It is shown that 17O NMR is unique in providing the rate of blood water flow, where the natural abundance 17O NMR signal consists of an internal reference and that lambda is essentially 1. The average values of CMRO2 for rats and cats were found to be 2.09 +/- 0.35 and 1.18 +/- 0.58 (mumol/O2/g tissue)/min, respectively. The average value for rCBF for the cat was found to be 0.38 +/- 0.12 [(mg/g)/min]. The average value for lambda was found to be 1.00 +/- 0.04. The ratio of AVD due to organs other than the brain to AVD due to the brain is smaller than 1 for the rat and the cat. The time and spatial resolution accuracy of the spectroscopic and imaging methods are compared, discussed and statistically analysed. It is concluded that the accuracy of determination of CMRO2 for the rat is higher than for the cat by a factor of 8.

Systemic hypotension in neurosurgery.

The authors review the intraoperative use of elective hypotension to reduce the probability of hemorrhage, to increase pliability of the aneurysmal sac for ease of clip application, and to control hemorrhage. The optimum agent and techniques for lowering systemic blood pressure remain controversial, but trimethaphan, sodium nitroprusside, and halothane have been found most useful. When cerebral blood flow falls below the brain's capacity to autoregulate, distinct time-related alterations occur biochemically and histologically. The profile of prolonged reduced adenosine triphosphate (ATP), low phosphocreatine, low glucose, and elevated lactate and lactate/pyruvate ratio is associated with swelling of perivascular astrocytes and "blebbing" of vascular endothelial cells with subsequent cerebral damage. To prevent permanent alteration it is desirable to observe time constraints and to employ other means of protection such as hypothermia, although the authors believe the latter unnecessary for short hypotensive periods. It has been proposed, but not substantiated, that anesthetics which depress rate of cerebral oxygen consumption but do not affect cerebral ATP level protect the brain from hypotension. Several investigations suggest that halothane, a vasodiltor, satisfies the safety requirement. The most prominent contraindication to halothane, however, is elevation of intracranial pressure. At present hypotensive surgery for aneurysmorrhapy is usually performed when intracranial pressure has returned to normal. Experimentally the electroencephalogram has been observed to show alterations prior to biochemical parameters for following brain vulnerability, so that it conceivably could be an effective monitoring technique during prolonged profound hypotension.

Effects of methoxyflurane on canine cerebral metabolism and blood flow.

The rate of cerebral oxygen consumption (CMRo2) and the cerebral blood flow (CBF) were determined in eight dogs at three end-expired concentrations of methoxyflurane (means >0.1, 0.25, and 0.44 per cent). With each increase in concentration above >0.1 per cent, a significant decrease in CMRo2 was observed (approximately 10 and 25 per cent less than the >0.1 per cent value, respectively). The cerebrovascular effects of methoxyflurane were less striking. At 0.25 per cent, a small but significant increase in CBF and a decrease in (cerebral vascular resistance) CVR were observed, compared with the >0.1 per cent values. No further significant change was observed at higher concentrations. The cerebrovascular responses to changes in Paco2 were tested at 0.25 per cent end-expired methoxyflurane. Over a range of Paco2 of approximately 20 mm Hg (30 to 50 mm Hg), the expected responses of CBF and CVR were observed. The authors conclude that methoxyflurane resembles halothane in its overall cerebral metabolic effects but, unlike halothane, produces only modest changes in CVR and CBF.

EFFECTS OF FENTANYL, DROPERIDOL, AND INNOVAR ON CANINE CEREBRAL METABOLISM AND BLOOD FLOW

The effects of droperidol and fentanyl given individually and in combination (Innovar) on the rate of cerebral oxygen consumption (CMRo,) and cerebral blood flow (c.b.f.) were studied in dogs anaesthetized with nitrous oxide (70 percent) and oxygen. Fentanyl (0.006 mg/kg) decreased both the CMRo, and the c.b.f. (mean decreases at 15 minutes were 18 per cent and 47 percent, respectively). The duration of effect was approximately 30 minutes. Droperidol (0.3 mg/kg) produced a decrease of 40 per cent in c.b.f. due primarily to a 30-40 per cent increase in cerebrovascular resistance, and this effect persisted for the period of observation (60 minutes). No significant change in CMRo, occurred after droperidol was administered. With the combination drug (Innovar), the effects were partially additive. After 15 minutes, CMRo, had decreased 23 per cent; c.b.f. had decreased 50 per cent; and cerebral vascular resistance had increased 85 per cent. After 30 minutes, the effects of Innovar were indistinguishable from those of droperidol alone. No significant changes occurred in the rate of cerebral glucose consumption or the oxygen-glucose index. The effect of increased and decreased Paooj on c.bi. after Innovar was compared widi that observed during halothane anaesthesia. With halothane, hypercapnia (Pacoi=60 tnm Hg) increased c.b.f. 40 per cent and hypocapnia (Pace = 20 mm Hg) decreased c.b.f. 40 per cent. Innovar at normocapnia reduced the c.b.f. 65 per cent. With hypercapnia, the c.bi. doubled, but with hypocapnia, little further reduction in c.b.f. occurred. It is concluded that droperidol is a potent cerebral vasoconstrictor, that this effect dominates when it is given in combination with fentanyl, that hypocapnia causes little further reduction in c.b.f., and that the reduction in c.bi. produced by Innovar is not accompanied by alterations in normal cerebral metabolic pathways

Respiratory and cerebral circulatory control during exercise at .21 and 2.0 atmospheres inspired p02.

Respiratory and cerebral hemodynamic responses to leg exercise during respiration of air at 1.0 atm. and O2 at 2.0 atm. were studied in relation to changes in arterial and internal jugular venous blood oxygen composition, pH, pCO2 and bicarbonate concentration. The hyperpnea of exercise at 1.0 atm. was accompanied by arterial and venous acidemia and hypocapnia. Oxygen administration during exercise at 2.0 atm. lowered ventilation, restored arterial pH and pCO2 toward resting levels and caused venous pCO2 to rise above the resting level; cerebral venous cH remained elevated in spite of reduction of blood fixed acid concentration. The ventilatory response to exercise showed positive correlations with work load, oxygen consumption, and with changes in arterial and internal jugular venous cH and fixed acid. The observed negative correlations of changes in respiratory minute volume with changes in arterial and internal jugular venous pCO2 and bicarbonate concentration suggest that these factors are functions, rather than primary determinants, of ventilation in exercise. Cerebral hemodynamics and oxygen consumption were not significantly altered by exercise at 1.0 atm. The data suggest either a slight elevation of cerebral blood flow or reduction in the rate of cerebral oxygen consumption during exercise breathing O2 at 2.0 atm., without gross elevation of cerebral venous pO2. Observed changes in cerebral vascular resistance during exercise at .21 and 2.0 atm. inspired pO2 appear related to concomitant alterations in arterial pCO2, with no detectable relationship either to brain oxygen requirement of cerebral venous acid-base composition. Submitted on November 25, 1958