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This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.

Interpretation of Emergency Head CT is an invaluable quick reference to the key aspects of the head CT. It provides the clinician with an easy-to-use 'ABCs' system to analyse any head CT scan that may be encountered in the acute setting. Section 1 contains both a comprehensive section on radiological anatomy of the brain showing cranial anatomy overlaid onto CT images and technical details of CT imaging in a simplified form. Section 2 covers the wide gamut of conditions that are likely to be encountered in acute medical practice. Pitfalls are highlighted and tips are included to assist the recognition of important signs, along with ways to distinguish other pathologies with a similar appearance. This is an excellent practical resource for all clinicians who utilise CT scans of the head as part of their patient management.

BACKGROUND: Clear evidence of cerebral blood circulation has not been shown after axillo-axillary bypass surgery in patients with subclavian steal syndrome. METHODS: We investigated the cerebral circulation and blood flow in 3 patients receiving axillo-axillary bypass by RI angiography using 99mTc-dl hexamethyl propylene amine oxime (99mTc-HMPAO). Two patients had vertebral basilar cerebral symptoms which were related to decreased cerebral blood flow evidenced by 99mTc-HMPAO. RESULTS: After the correction, cerebral symptoms disappeared and improved cerebral blood circulation detected by 99mTc-HMPAO-SPECT. CONCLUSIONS: We concluded that axillo-axillary bypass was a fairly effective procedure to improve cerebral blood circulation evidenced by 99mTc-HMPAO-SPECT.

Background Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixation is compatible with the diagnosis of the vegetative state (i.e., represents \"automatic\" subcortical processing) or is a sufficient sign of consciousness and higher order cortical processing. Methods We here studied cerebral metabolism in ten patients with chronic post-anoxic encephalopathy and 39 age-matched healthy controls. Five patients were in a vegetative state (without fixation) and five presented visual fixation but otherwise showed all criteria typical of the vegetative state. Patients were matched for age, etiology and time since insult and were followed by repeated Coma Recovery Scale-Revised (CRS-R) assessments for at least 1 year. Sustained visual fixation was considered as present when the eyes refixated a moving target for more than 2 seconds as defined by CRS-R criteria. Results Patients without fixation showed metabolic dysfunction in a widespread fronto-parietal cortical network (with only sparing of the brainstem and cerebellum) which was not different from the brain function seen in patients with visual fixation. Cortico-cortical functional connectivity with visual cortex showed no difference between both patient groups. Recovery rates did not differ between patients without or with fixation (none of the patients showed good outcome). Conclusions Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function.

The concept of fatigue refers to a class of acute effects that can impair motor performance, and not to a single mechanism. A great deal is known about the peripheral mechanisms underlying the process of fatigue, but our knowledge of the roles of the central structures in that process is still very limited. During fatigue, it has been shown that peripheral apparatus is capable of generating adequate force while central structures become insufficient/sub-optimal in driving them. This is known as central fatigue, and it can vary between muscles and different tasks. Fatigue induced by submaximal isometric contraction may have a greater central component than fatigue induced by prolonged maximal efforts. We studied the changes in regional cerebral blood flow (rCBF) of brain structures after sustained isometric muscle contractions of different submaximal force levels and of different durations, and compared them with the conditions observed when the sustained muscle contraction becomes fatiguing. Changes in cortical activity, as indicated by changes in rCBF, were measured using positron emission tomography (PET). Twelve subjects were studied under four conditions: (1) rest condition; (2) contraction of the m. biceps brachii at 30% of MVC, sustained for 60 s; (3) contraction at 30% of MVC, sustained for 120 s, and; (4) contraction at 50% of MVC, sustained for 120 s. The level of rCBF in the activated cortical areas gradually increased with the level and duration of muscle contraction. The fatiguing condition was associated with predominantly contralateral activation of the primary motor (MI) and the primary and secondary somatosensory areas (SI and SII), the somatosensory association area (SAA), and the temporal areas AA and AI. The supplementary motor area (SMA) and the cingula were activated bilaterally. The results show increased cortical activation, confirming that increased effort aimed at maintaining force in muscle fatigue is associated with increased activation of cortical neurons. At the same time, the activation spread to several cortical areas and probably reflects changes in both excitatory and inhibitory cortical circuits. It is suggested that further studies aimed at controlling afferent input from the muscle during fatigue may allow a more precise examination of the roles of each particular region involved in the processing of muscle fatigue.

We aimed at characterizing the neural correlates of delta activity during Non Rapid Eye Movement (NREM) sleep in non-sleep-deprived normal young adults, based on the statistical analysis of a positron emission tomography (PET) sleep data set. One hundred fifteen PET scans were obtained using H215O under continuous polygraphic monitoring during stages 2–4 of NREM sleep. Correlations between regional cerebral blood flow (rCBF) and delta power (1.5–4 Hz) spectral density were analyzed using statistical parametric mapping (SPM2). Delta power values obtained at central scalp locations negatively correlated during NREM sleep with rCBF in the ventromedial prefrontal cortex, the basal forebrain, the striatum, the anterior insula, and the precuneus. These regions embrace the set of brain areas in which rCBF decreases during slow wave sleep (SWS) as compared to Rapid Eye Movement (REM) sleep and wakefulness (Maquet, P., Degueldre, C., Delfiore, G., Aerts, J., Peters, J.M., Luxen, A., Franck, G., 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17, 2807–S2812), supporting the notion that delta activity is a valuable prominent feature of NREM sleep. A strong association was observed between rCBF in the ventromedial prefrontal regions and delta power, in agreement with electrophysiological studies. In contrast to the results of a previous PET study investigating the brain correlates of delta activity (Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A.C., Jones, B.E., 1997. Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans. J. Neurosci. 17, 4800–4808), in which waking scans were mixed with NREM sleep scans, no correlation was found with thalamus activity. This latter result stresses the importance of an extra-thalamic delta rhythm among the synchronous NREM sleep oscillations. Consequently, this rCBF distribution might preferentially reflect a particular modulation of the cellular processes involved in the generation of cortical delta waves during NREM sleep.

Triptans are highly effective in the treatment of migraine. Both central and peripheral mechanisms of action have been suggested. Until now, firm data about the passage of triptans into the CNS in humans have been lacking. The aim of the current study was to evaluate, using positron emission tomography (PET), the uptake and distribution of zolmitriptan into the CNS after intranasal administration. Eight healthy volunteers, five males and three females (mean ages 23 and 26 years, respectively), were included. Radioactive [carbonyl-11C]zolmitriptan was infused intravenously for 5 minutes on two occasions: once alone, and once 30-40 minutes after intranasal administration of unlabelled zolmitriptan 5 mg. PET was used to measure the concentration of labelled zolmitriptan in the brain, from the start of the tracer infusion for 90 minutes. Regional cerebral blood volume was determined with [15O]carbon monoxide. In addition, an MRI scan was performed to obtain anatomical information. The PET images were analysed quantitatively for different areas of the brain, generating [11C]zolmitriptan time-activity data corrected for circulating tracer activity. The rate of uptake of intranasal zolmitriptan into the CNS was estimated by kinetic modelling using the PET data. PET data from this study demonstrate a rapid dose-proportional uptake of [11C]zolmitriptan into the brain. Significant concentrations of [11C]zolmitriptan were found in all brain regions studied. Calculated CNS concentrations after intranasal zolmitriptan administration showed a gradual increase, reaching about 2 nM (0.5 microg/L) 30 minutes after administration and 3.5 nM (1.0 microg/L), or one-fifth of the plasma concentration, 1 hour after administration. Five minutes after zolmitriptan administration, the mean CNS concentration had already reached 0.5 nM, which is higher than in vitro values for initiation of the agonistic action on 5-HT(1B/1D) receptors. This study demonstrates by direct measurements that zolmitriptan enters the brain parenchyma in humans, achieving an uptake rate and concentration compatible with a central mode of action.

An automated method for placement of 3D rat brain atlas-derived volumes of interest (VOIs) onto PET studies has been designed and evaluated. VOIs representing major structures of the rat brain were defined on a set of digitized cryosectioned images of the rat brain. For VOI placement, each PET study was registered with a synthetic PET target constructed from the VOI template. Registration was accomplished with an automated algorithm that maximized the mutual information content of the image volumes. The accuracy and precision of this method for VOI placement was determined using datasets from PET studies of the striatal dopamine and hippocampal serotonin systems. Each evaluated PET study could be registered to at least one synthetic PET target without obvious failure. Registration was critically dependent upon the initial position of the PET study relative to the synthetic PET target, but not dependent on the amount of synthetic PET target smoothing. An evaluation algorithm showed that resultant radioactivity concentration measurements of selected brain structures had errors = 2% due to misalignment with the corresponding VOI. Further, radioligand binding values calculated from these measurements were found to be more precise than those calculated from measurements obtained with manually drawn regions of interest (ROIs). Overall, evaluation results demonstrated that this atlas-derived VOI method can be used to obtain unbiased measurements of radioactivity concentration from PET studies. Its automated features, and applicability to different radioligands and brain regions, will facilitate quantitative rat brain PET assessment procedures.

The aim of this study was to evaluate the usefulness of measuring the standardized uptake value (SUV) in primary brain tumors on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. Two groups of patients were studied. Whole-brain glucose cerebral metabolic rates (wCMRs) and SUVs were obtained in 20 normal subjects. Twenty-seven patients with histology-proven malignant primary CNS tumors (high-grade gliomas n=22, primitive neuroectodermal tumors n=3, ependymomas n=2) were also studied. The degree of FDG uptake was assessed by visual inspection and thereafter regions of interest were placed over the lesion, the contralateral cortex and white matter and the whole brain. Average (avg) and maximum (max) pixel values were determined in each site. Based on these measurements, SUV, tumor to cortex (T/C) and tumor to white matter (T/WM) activity ratios were calculated. There was no correlation between wCMRs (4.55±0.36 mg min^sup -1^ 100 g^sup -1^) and wSUVs (5.41±0.43) in the normal subjects (r=0.18, P=0.45). In the second group,17 lesions were described as definitely and seven as probably malignant. However, SUVs in these tumors and in the contralateral cortex were not significantly different. Although the SUVs were generally higher in the tumor than in the contralateral white matter, there was a significant overlap between the values. The range of the SUVs was wide: 2.54-11.8 for the tumors, 2.98-9.96 for the cortex and 1.87-6.76 for the white matter. SUVs in the normal cortex were negatively correlated with blood glucose level at the time of the injection. SUVs in the whole brain and in the cortex were lower in patients previously treated by irradiation, even months after completion of the treatment. No correlation was detectable between any of the SUVs and the age of the patients, tumor type, time post injection, use of dexamethasone, patient weight, dose injected and visual score. With cutoff levels of 1.5 for T max/WM and 0.6 for T max/C, the sensitivity of the activity ratios was 74% and 96% respectively. In conclusion, SUVs do not correlate with CMRs across subjects and appear to be of limited value in characterizing brain tumors. Visual assessment and measurement of the activity ratios currently remain the most reliable methods of analysis.[PUBLICATION ABSTRACT]

Positron emission tomography (PET) with the drug radiolabelled allows a direct measurement of brain or other organ kinetics, information which can be essential in drug development. Usually, however, a PET-tracer is administered intravenously (i.v.), whereas the therapeutic drug is mostly given orally or by a different route to the PET-tracer. In such cases, a recalculation is needed to make the PET data representative for the alternative administration route. To investigate the blood-brain barrier penetration of a drug (zolmitriptan) using dynamic PET and by PK modelling quantify the brain concentration of the drug after the nasal administration of a therapeutic dose. [11C]Zolmitriptan at tracer dose was administered as a short i.v. infusion and the brain tissue and venous blood kinetics of [11C]zolmitriptan was measured by PET in 7 healthy volunteers. One PET study was performed before and one 30 min after the administration of 5 mg zolmitriptan as nasal spray. At each of the instances, the brain radioactivity concentration after subtraction of the vascular component was determined up to 90 min after administration and compared to venous plasma radioactivity concentration after correction for radiolabelled metabolites. Convolution methods were used to describe the relationship between arterial and venous tracer concentrations, respectively between brain and arterial tracer concentration. Finally, the impulse response functions derived from the PET studies were applied on plasma PK data to estimate the brain zolmitriptan concentration after a nasal administration of a therapeutic dose. The studies shows that the PET data on brain kinetics could well be described as the convolution of venous tracer kinetics with an impulse response including terms for arterial-to-venous plasma and arterial-to-brain impulse responses. Application of the PET derived impulse responses on the plasma PK from nasal administration demonstrated that brain PK of zolmitriptan increased with time, achieving about 0.5 mg/ml at 30 min and close to a maximum of 1.5 mg/ml after 2 hr. A significant brain concentration was observed already after 5 min. The data support the notation of a rapid brain availability of zolmitriptan after nasal administration.