Measurement Of Cerebral Metabolic Rate Research Articles

Multi-Tracer Studies of Brain Oxygen and Glucose Metabolism Using a Time-of-Flight Positron Emission Tomography - Computed Tomography Scanner.

The authors have developed a paradigm using positron emission tomography (PET) with multiple radiopharmaceutical tracers that combines measurements of cerebral metabolic rate of glucose (CMRGlc), cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral blood volume (CBV), culminating in estimates of brain aerobic glycolysis (AG). These in vivo estimates of oxidative and non-oxidative glucose metabolism are pertinent to the study of the human brain in health and disease. The latest positron emission tomography-computed tomography (PET-CT) scanners provide time-of-flight (TOF) imaging and critical improvements in spatial resolution and reduction of artifacts. This has led to significantly improved imaging with lower radiotracer doses. Optimized methods for the latest PET-CT scanners involve administering a sequence of inhaled 15O-labeled carbon monoxide (CO) and oxygen (O2), intravenous 15O-labeled water (H2O), and 18F-deoxyglucose (FDG)-all within 2-h or 3-h scan sessions that yield high-resolution, quantitative measurements of CMRGlc, CMRO2, CBF, CBV, and AG. This methods paper describes practical aspects of scanning designed for quantifying brain metabolism with tracer kinetic models and arterial blood samples and provides examples of imaging measurements of human brain metabolism.

Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.

Several studies have suggested that greater adiposity in older adults is associated with a lower risk of Alzheimer's disease (AD) related cognitive decline, some investigators have postulated that this association may be due to the protective effects of the adipose tissue-derived hormone leptin. In this study we sought to demonstrate that higher body mass indices (BMIs) are associated with greater baseline FDG PET measurements of the regional cerebral metabolic rate for glucose (rCMRgl), a marker of local neuronal activity, slower rCMRgl declines in research participants with amnestic mild cognitive impairment (aMCI). We then sought to clarify the extent to which those relationships are attributable to cerebrospinal fluid (CSF) or plasma leptin concentrations. We used baseline PET images from 716 73 ± 8 years-old aMCI participants from the AD Neuroimaging Initiative (ADNI) of whom 453 had follow up images (≥6 months; mean follow up time 3.3 years). For the leptin analyses, we used baseline CSF samples from 81 of the participants and plasma samples from 212 of the participants. As predicted, higher baseline BMI was associated with greater baseline CMRgl measurements and slower declines within brain regions preferentially affected by AD. In contrast and independently of BMI, CSF, and plasma leptin concentrations were mainly related to less baseline CMRgl within mesocorticolimbic brain regions implicated in energy homeostasis. While higher BMIs are associated with greater baseline CMRgl and slower declines in persons with aMCI, these associations appear not to be primarily attributable to leptin concentrations.

Hemodynamic and metabolic correspondence of resting-state voxel-based physiological metrics in healthy adults

Voxel-based physiological (VBP) variables derived from blood oxygen level dependent (BOLD) fMRI time-course variations include: amplitude of low frequency fluctuations (ALFF), fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity (ReHo). Although these BOLD-derived variables can detect between-group (e.g. disease vs control) spatial pattern differences, physiological interpretations are not well established. The primary objective of this study was to quantify spatial correspondences between BOLD VBP variables and PET measurements of cerebral metabolic rate and hemodynamics, being well-validated physiological standards. To this end, quantitative, whole-brain PET images of metabolic rate of glucose (MRGlu; 18FDG) and oxygen (MRO2; 15OO), blood flow (BF; H215O) and blood volume (BV; C15O) were obtained in 16 healthy controls. In the same subjects, BOLD time-courses were obtained for computation of ALFF, fALFF and ReHo images. PET variables were compared pair-wise with BOLD variables. In group-averaged, across-region analyses, ALFF corresponded significantly only with BV (R = 0.64; p < 0.0001). fALFF corresponded most strongly with MRGlu (R = 0.79; p < 0.0001), but also significantly (p < 0.0001) with MRO2 (R = 0.68), BF (R = 0.68) and BV (R=0.68). ReHo performed similarly to fALFF, with significant strong correspondence (p < 0.0001) with MRGlu (R = 0.78), MRO2 (R = 0.54), and, but less strongly with BF (R = 0.50) and BV (R=0.50). Mutual information analyses further clarified these physiological interpretations. When conditioned by BV, ALFF retained no significant MRGlu, MRO2 or BF information. When conditioned by MRGlu, fALFF and ReHo retained no significant MRO2, BF or BV information. Of concern, however, the strength of PET-BOLD correspondences varied markedly by brain region, which calls for future investigation on physiological interpretations at a regional and per-subject basis.

Non-invasive optical neuromonitoring of the temperature-dependence of cerebral oxygen metabolism during deep hypothermic cardiopulmonary bypass in neonatal swine

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 < 0.001) between cooling and rewarming periods in the NPT versus ICT and NPT versus CMRO2 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.

Longitudinal Changes in Serum Glucose Levels are Associated with Metabolic Changes in Alzheimer's Disease Related Brain Regions.

The association between longitudinal changes in serum glucose level and longitudinal changes in [18F] Fluorodeoxyglucose-PET (FDG PET) measurements of Alzheimer's disease (AD) risk are unknown. To investigate whether variation in serum glucose levels across time are associated with changes in FDG PET measurements of cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer's disease (AD). Participants are a subset of a prospective cohort study investigating FDG PET, apolipoprotein E (APOE) ɛ4, and risk for AD which includes data from baseline, interim, and follow up visits over 4.4±1.0-years. An automated brain-mapping algorithm was utilized to characterize and compare associations between longitudinal changes in serum glucose levels and longitudinal changes in rCMRgl. This study included 80 adults aged 61.5±5 years, including 38 carriers and 42 non-carriers of the APOE ɛ4 allele. Longitudinal increases in serum glucose levels were associated with longitudinal CMRgl decline in the vicinity of parietotemporal, precuneus/posterior cingulate, and prefrontal brain regions preferentially affected by AD (p < 0.05, corrected for multiple comparisons). Findings remained significant when controlled for APOE ɛ4 status and baseline and advancing age. Additional studies are needed to clarify and confirm the relationship between longitudinal changes in peripheral glucose and FDG PET measurements of AD risk. Future findings will set the stage on the use of FDG PET in the evaluation of possible interventions that target risk factors for the development of AD.

Assessing the repeatability of absolute CMRO2, OEF and haemodynamic measurements from calibrated fMRI

As energy metabolism in the brain is largely oxidative, the measurement of cerebral metabolic rate of oxygen consumption (CMRO2) is a desirable biomarker for quantifying brain activity and tissue viability. Currently, PET techniques based on oxygen isotopes are the gold standard for obtaining whole brain CMRO2 maps. Among MRI techniques that have been developed as an alternative are dual calibrated fMRI (dcFMRI) methods, which exploit simultaneous measurements of BOLD and ASL signals during a hypercapnic-hyperoxic experiment to modulate brain blood flow and oxygenation.In this study we quantified the repeatability of a dcFMRI approach developed in our lab, evaluating its limits and informing its application in studies aimed at characterising the metabolic state of human brain tissue over time. Our analysis focussed on the estimates of oxygen extraction fraction (OEF), cerebral blood flow (CBF), CBF-related cerebrovascular reactivity (CVR) and CMRO2 based on a forward model that describes analytically the acquired dual echo GRE signal.Indices of within- and between-session repeatability are calculated from two different datasets both at a bulk grey matter and at a voxel-wise resolution and finally compared with similar indices obtained from previous MRI and PET measurements. Within- and between-session values of intra-subject coefficient of variation (CVintra) calculated from bulk grey matter estimates 6.7 ± 6.6% (mean ± std.) and 10.5 ± 9.7% for OEF, 6.9 ± 6% and 5.5 ± 4.7% for CBF, 12 ± 9.7% and 12.3 ± 10% for CMRO2. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) maps showed the spatial distribution of the repeatability metrics, informing on the feasibility limits of the method.In conclusion, results show an overall consistency of the estimated physiological parameters with literature reports and a satisfactory level of repeatability considering the higher spatial sensitivity compared to other MRI methods, with varied performance depending on the specific parameter under analysis, on the spatial resolution considered and on the study design.

Two-photon microscopy measurement of cerebral metabolic rate of oxygen using periarteriolar oxygen concentration gradients

The cerebral metabolic rate of oxygen ([Formula: see text]) is an essential parameter for evaluating brain function and pathophysiology. However, the currently available approaches for quantifying [Formula: see text] rely on complex multimodal imaging and mathematical modeling. Here, we introduce a method that allows estimation of [Formula: see text] based on a single measurement modality-two-photon imaging of the partial pressure of oxygen ([Formula: see text]) in cortical tissue. We employed two-photon phosphorescence lifetime microscopy (2PLM) and the oxygen-sensitive nanoprobe PtP-C343 to map the tissue [Formula: see text] distribution around cortical penetrating arterioles. [Formula: see text] is subsequently estimated by fitting the changes of tissue [Formula: see text] around arterioles with the Krogh cylinder model of oxygen diffusion. We measured the baseline [Formula: see text] in anesthetized rats and modulated tissue [Formula: see text] levels by manipulating the depth of anesthesia. This method provides [Formula: see text] measurements localized within [Formula: see text] and it may provide oxygen consumption measurements in individual cortical layers or within confined cortical regions, such as in ischemic penumbra and the foci of functional activation.

Arterial Spin Labeling and Its Related Techniques

The arterial spin labeling(ASL) magnetic resonance imaging(MRI) is able to quantify regional cerebral blood flow using endogenous contrast agent.Many different ASL sequences had been developed.Related with ASL,MRI techniques for the measurements of cerebral metabolic rate of oxygen(CMRO2) were recently developed.In this paper,the principles of three typical ASL sequences and two related techniques for measuring CMRO2 were reviewed.

Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas

The quantitative measurement of cerebral metabolic rate of oxygen (CMRO(2)) for rats using positron emission tomography (PET) has been technically difficult. The present study was performed to provide a technique to measure CMRO(2) for rats using a dedicated animal PET technique. CMRO(2) in the rat brain was quantitatively measured under alpha-chloralose anaesthesia (30 mg . kg(-1) . h(-1), intravenous infusion) using a PET imaging technique. In our experiment, the (15)O-labelled gas tracer (O(15)O) was administered by a bolus insufflation into the lung through a surgically placed cannula in the trachea. The tracer distribution was then dynamically imaged using the microPET. Unlike other conventional PET methods in which a series of arterial blood samples need to be withdrawn for the measurement of an arterial input function, no arterial blood sampling was employed. Instead, the heart was scanned in dynamic mode at the same time of imaging the brain, and the region of interest drawn over the heart was analysed to obtain an arterial input function. The CMRO(2) value (micromol . 100 g(-1) . min(-1)) from 10 rats was 208 +/- 15 (mean +/- SD). Our results suggest that the microPET-based CMRO(2) measurement in the rat brain combined with a non-invasive measurement of arterial input function is promising, especially for many applications involving small animals in which repeated measurements of absolute CMRO(2) need to be performed.

Reduced thalamic and cerebellar rest metabolism in relapsing–remitting multiple sclerosis, a positron emission tomography study: Correlations to lesion load

Magnetic resonance imaging (MRI) is the main tool for detecting central nervous system lesions in MS. However, classical anatomical MRI is unable to assess exactly disease related injury in normal-appearing brain tissue and to give information about the functional consequences of the disease, explaining weak correlation frequently observed between lesion load and clinical data. Recently, functional brain imaging techniques have provided new insights concerning pathophysiological processes of the disease. Among them Positron Emission Tomography (PET), a sensitive technique to evaluate functional consequences of tissue injury in other neurological diseases, has rarely been used in MS. Seventeen Relapsing–Remitting (RR-) MS patients with low disability at the early stage of the disease underwent measurements of cerebral metabolic rate of glucose (rCMRglu) in resting state by PET using [ 18F] fluorodeoxyglucose (FDG) and assessment of regional cortical and white matter lesion volume (LV), using an in-house-developed semi-automatic method, was done at the same time on MRI. rCMRglu of MS patients was compared with rCMRglu of 18 normal control subjects using univariate SPM99 analysis through Matlab 5 and correlations between rCMRglu and LV were tested using multivariate linear regression using SPM99. Statistical threshold was set at p < 0.05 corrected for multiple comparisons and correlations. Compared to controls, reduced rCMRglu was found in the right thalamus ( p < 0.001), in bilateral cerebellum ( p < 0.05 for right and p < 0.01 for left) and the posterior part of left inferior parietal cortex ( p < 0.05). In addition, higher rCMRglu in patients compared to controls was observed in left inferior frontal cortex, left (anterior part) and right inferior parietal cortex ( p < 0.001). rCMRglu in right thalamus correlates negatively with different LV: total LV, total juxtacortical and/or overlapping cortico-subcortical LV, total and frontal deep white matter LV. rCMRglu of the right superior frontal cortex negatively correlated with total and parieto-occipital deep white matter LV. The results of this study, performed in a group of recent RR-MS patients with low disability, suggest that demyelinating lesions in MS mainly have a remote effect on cortical, basal ganglia and cerebellum metabolism and that regional cortical compensatory mechanisms may be observed concurrently.

Quantitative measurement of cerebral metabolic rate of glucose by means of dual-head coincidence gamma camera and 2-deoxy-2- [18F] fluoro-D-glucose

Quantitative measurement of cerebral metabolic rate of glucose by means of dual-head coincidence gamma camera and 2-deoxy-2- [¹⁸F] fluoro-D-glucose

Diffuse optical measurement of cerebral metabolic rate of oxygen in adult brain

We combined diffuse optical (DOS) and correlation (DCS) spectroscopies to simultaneously measure the oxyhemoglobin (rHbO2), deoxyhemoglobin (rHb), total hemoglobin (rTHC) concentration and blood flow (rCBF) in adult human brain during a hypercapnic episode and sensorimotor stimulation. These measurements allowed calculation of the relative cerebral metabolic rate of oxygen (rCMRO2) in the human brain for the first time, to our knowledge, by use of all-optical methods. Briefly, 3 mW of light from three amplitude modulated lasers at 690, 785, and 830 nm were fiber-coupled to the head. Photons transmitted were detected in reflection mode. Spectroscopic analysis was carried to calculate rHb, rHbO2 and rTHC. A narrowband laser (5 mW at 800 nm), photon-counting, avalanche photo-diodes and a custom-build autocorrelator board was used for blood flow by fitting the obtained autocorrelation functions. The maximum penetration depth was about 2 cm from the top of the scalp and we report averaged values from the probed tissue volume after a partial volume correction1. As a first step towards validation in human brain, measurements were made in five subjects at a resting cerebral pCO2 and during 4-6 minute periods of increased pCO2 induced by respiration of a 6% CO2 gas mixture. The end tidal CO2, heart rate, blood pressure and arterial oxygenation were monitored continuously. A typical response is shown in Figure 1 (right panel). Over the five subjects a sustained mean CBF increase of 35.49.6% corresponding to 14.74.7 mmHg increase in pCO2 was observed. This corresponds to a 2.40.4 %/mmHg rise in CBF, well within the values reported in the literature (2-3.6%/mmHg). Seven male volunteers participated in the sensorimotor cortical activation studies. One subject further participated in a 3-T fMRI study in which BOLD and arterial spin-labeled (ASL) perfusion data were obtained sequentially to compare to optical results from the same subject. Figure 1 (left panel) shows group averaged results which indicate mean changes for rCBF rHBO2, rHB, rTHC, rCMRO2 of 3910%, 12.52.8 uM, -3.80.8 uM, 8.32.3 uM and 10.14.4% respectively in agreement with the literature. When the probe was placed away from the activation area, no significant, correlated changes were observed in the optical signals, demonstrating the local nature of the response. The feasibility of noninvasive optical measurement of blood flow and oxygen metabolism through the skull of the adult human is thus feasible, and the clinical potential of this hybrid, all-optical noninvasive, methodology is now being explored in patients suffering from severe head trauma. The optical technique offers a great deal of promise as a portable, non-invasive and relatively cheap modality, capable of doing longitudinal measurements of multiple important parameters.

Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects.

The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc(real)). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc(sim)) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC(real)) and simulated input function (AUC(IFsim)) and percent error between CMRGlc(real) and CMRGlc(sim) were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165+/-69 vs 100+/-9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%+/-1.3% vs 3.5%+/-2.2% in AUC, P=0.0015; 18.2%+/-2.2% vs 2.9%+/-1.9% in CMRGlc in grey matter, P=0.0028; 24.0%+/-4.6% vs 3.4%+/-2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions.

Quantitative measurements of cerebral metabolic rate of oxygen utilization using MRI: a volunteer study.

Quantitative estimates of cerebral metabolic rate of oxygen utilization using magnetic resonance imaging can have profound implications for the understanding of brain metabolic activity as well as the investigation of cerebrovascular disease. In this study, five normal volunteers were studied. All images were acquired on a Siemens 1.5 T scanner (Siemens Medical Systems Inc, Erlangen, Germany). Cerebral blood flow (CBF) was obtained in vivo with a dynamic imaging approach and the acquired images were post-processed with the singular value decomposition method (SVD). In addition, a multi-echo gradient echo/spin echo sequence was employed to provide MR estimates of oxygen extraction fraction (MR_OEF) in vivo. Subsequently, an absolute measure of MR cerebral metabolic rate of oxygen utilization (MR_CMRO(2)) was obtained in all subjects by taking the product of CBF and MR_OEF. A mean MR_CMRO(2) of 28.94 +/- 3.26 ml/min/100 g and 12.57 +/- 3.11 ml/min/100 g was obtained for gray matter and white matter, respectively, suggesting that the gray matter utilizes more oxygen than white matter under normal physiological conditions. These results yield a gray matter to white matter CMRO(2) ratio of 2.37 +/- 0.37, which is comparable to the reported values in the literature. More studies are needed to further improve on the accuracy as well as shortening the required data acquisition time so that the proposed approaches can be utilized in a routine clinical setting.

Arterial fraction of cerebral blood volume in humans measured by positron emission tomography.

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.

Quantitative measurements of cerebral metabolic rate of oxygen utilization using MRI: a volunteer study

Quantitative measurements of cerebral metabolic rate of oxygen utilization using MRI: a volunteer study

Issues in measuring glucose metabolism of rat brain using PET: the effect of Harderian glands on the frontal lobe

We estimated the effect of the Harderian gland (an orbital gland of land vertebrates) on the measurement of cerebral metabolic rate of glucose (CMRGlc) of the rat brain using positron emission tomography (PET) for animal use. The Harderian gland had the high accumulation of 18-F labeled deoxyglucose (FDG) after intravenous injection. By placing the large regions of interest (ROI) (twice the full width at half maximum in diameter), the CMRGlc in the frontal region was slightly higher compared with the CMRGlc after Harderian gland resection, but the parietal and occipital regions and the cerebellum had the similar level of CMRGlc before and after Harderian gland resection. Therefore the Harderian gland has a slight effect on the frontal lobe CMRGlc, but such overestimation can be within the permissible range for PET study of rat brains.

Cerebral normoxia in the rhesus monkey during isoflurane- or propofol-induced hypotension and hypocapnia, despite disparate blood-flow patterns. A positron emission tomography study.

Due to a few reports of cerebral dysfunction in connection with isoflurane-induced hypotension and concomitant hypocapnia, positron emission tomography (PET) was used to measure cerebral oxygenation and blood flow during similar conditions with isoflurane or propofol. The short-lived radionuclide 15O was used for measurement of cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF) and oxygen extraction ratio (OER) regionally in rhesus monkeys during normotensive/normocapnic and hypotensive/hypocapnic conditions, mean arterial pressure 100-110 and 50-65 mmHg and PaCO2 4.4-5.4 and 3.4-4.4 kPa, respectively. Isoflurane or propofol anaesthesia was given (n = 4 in both groups), supported with 70% nitrous oxide and preceded by ketamine anaesthesia (baseline). PET revealed wide variations in CBF between regions during isoflurane anaesthesia, particularly in comparison with propofol anaesthesia, while rCMRO2 decreased globally in a dose-dependent manner during both isoflurane and propofol anaesthesia. The metabolism-flow coupling was intact during propofol but not during isoflurane anaesthesia. Hypotension reduced rCBF, and rOER increased globally with both study drugs when changing from normo- to hypotension. However, this rOER increase was not significant when using PaCO2 as a covariate, and rOER was never above an arbitrary limit for hypoxia of 70%. Thus, hypocapnia, rather than hypotension, was responsible for the somewhat higher rOER measured. PET indicated adequate cerebral oxygenation during isoflurane and propofol anaesthesia, despite disparate blood-flow patterns. Hypotension and concomitant moderate hyperventilation reduced rCBF, but did not result in hypoxia.

Brain imaging to determine the effects of sertindole in a double-blind, placebo-controlled trial in schizophrenic patients

We estimated the effect of the Harderian gland (an orbital gland of land vertebrates) on the measurement of cerebral metabolic rate of glucose (CMRGlc) of the rat brain using positron emission tomography (PET) for animal use. The Harderian gland had the high accumulation of 18-F labeled deoxyglucose (FDG) after intravenous injection. By placing the large regions of interest (ROI) (twice the full width at half maximum in diameter), the CMRGlc in the frontal region was slightly higher compared with the CMRGlc after Harderian gland resection, but the parietal and occipital regions and the cerebellum had the similar level of CMRGlc before and after Harderian gland resection. Therefore the Harderian gland has a slight effect on the frontal lobe CMRGlc, but such overestimation can be within the permissible range for PET study of rat brains.

Progressive Apraxia in Clinically Discordant Monozygotic Twins

To determine disease concordancy in the first identical twin with corticobasal degeneration. The patients were 63-year-old, erythrocyte antigen-confirmed monozygotic male twins who were clinically discordant for progressive apraxia caused by corticobasal degeneration. Neuropsychologic and kinesiologic testing, magnetic resonance imaging, and positron emission tomographic measurements of cerebral metabolic rate for glucose. The affected twin had lower neuropsychologic and kinesiologic test scores than did his brother, particularly on tests sensitive to right-compared with left-hemisphere function; widespread cerebral atrophy, worst in right parietotemporal cortices; and reduced whole-brain cerebral metabolic rate for glucose, worst in right posterior cortices. The clinically asymptomatic twin had normal neuropsychologic and kinesiologic test scores but performed more poorly on tests sensitive to left- compared with right-hemisphere function; had no abnormalities on magnetic resonance imaging; and had left temporoparietal as well as mild whole-brain hypometabolism. Corticobasal degeneration may remain clinically discordant in identical twins after 7 years. Positron emission tomography and neuropsychologic findings suggest the possibility of a preclinical stage of corticobasal degeneration. There is generalized cortical atrophy in patients with corticobasal degeneration in addition to focal atrophy.