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Current treatment protocols for flexor tendon injuries of the hand generally result in an acceptable function, which can be quantified by objective parameters such as range of motion. The latter does not always match the patients' subjective experiences of persisting dysfunction. This raises the question whether changes in the cerebral control of movement might contribute to the perceived deficit. The main objective of the present positron emission tomography (PET) study was to characterise the cerebral responses in movement-associated areas during simple finger flexion immediately after dynamic immobilisation and after a subsequent 6-week period of active training. Ten subjects with flexor tendon injury participated in the PET study. Electromyography (EMG) recordings were made during finger flexion and extension in an additional subject. The main finding was that the (ventral) putamen contralateral to flexor movement was not activated immediately after release from splinting, while such activation reappeared after a period of training. This indicates a temporary loss of efficient motor control of over-learnt movements. The increase of unwanted co-contractions during flexion in a first EMG session, and not during extension, supports a concept of lost skills., (Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aim: Tumor marker based recurrences of previously treated testicular cancer are generally detected with CT scan. They sometimes cannot be visualized with conventional morphologic imaging. FDG-PET has the ability to detect these recurrences. PET probe-guided surgery, may facilitate the extent of surgery and optimize the surgical resection., Methods: Three patients with resectable 2nd or 3rd recurrent testicular cancer based on elevated tumor markers after previous various chemotherapy schedules and resections of residual retroperitoneal tumor masses were included in this study. A diagnostic FDG-PET was performed and a hotspot in previously operated area of the retroperitoneal space in all three patients was visualized. PET probe-guided surgery was performed using a high-energy gamma probe 3 h post-injection of 500 MBq FDG., Results: All patients showed extended adhesions and scar tissue in the retroperitoneal area due to the previous surgeries. Pre-operative PET/CT scan showed a good correlation with intra-operative PET probe-guided detection of recurrent lesions. There was a high target to background ratio (TGB) of 5:1 during the procedure. In one patient, a 2 cm large lesion, which did not show on pre-operative FDG-PET scan, was detected with the PET probe. Histopathologic tissue evaluation demonstrated recurrent vital tumor in all PET probe positive lesions., Conclusions: PET probe-guided surgery seems to be a promising tool to localize FDG-PET positive lesion in recurrent testicular cancer in hardly accessible surgical locations. PET probe-guided surgery might be a useful technique in surgical oncology for recurrent testicular cancer and has the potential to be applied in surgery of other malignant diseases., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

After flexor tendon injury, most attention is given to the quality of the tendon repair and postoperative early passive dynamic mobilisation. Schemes for active mobilisation have been developed to prevent tendon adhesions and joint stiffness. This paper describes five patients to demonstrate the cerebral consequences of immobilisation allowing only passive movements, which implies a prolonged absence of actual motor commands. At the end of such immobilisation, PET imaging revealed reduced blood flow in specific motor areas, associated with temporary loss of efficient motor control. Effective motor control was regained after active flexion exercises which was reflected in normalised cerebral activations. This suggests that temporary, reversible cerebral dysfunction may affect the outcome of flexor tendon injuries.

In implant dentistry, there is continuing debate regarding whether a barrier membrane should be applied to cover autologous bone grafts in jaw augmentation. A membrane would prevent graft remodeling with resorption and enhance graft incorporation. We hypothesized that membrane coverage does not effect resorption and incorporation of autologous onlay bone grafts. We treated 192 male Sprague-Dawley rats. A 4.0-mm-diameter bone graft was harvested from the right mandibular angle and transplanted to the left. Poly(DL-lactide-epsilon-caprolactone), collagen, and expanded polytetrafluoroethylene membranes were used to cover the grafts. The controls were left uncovered. Graft resorption at 2, 4, and 12 weeks was evaluated by post mortem microradiography and microCT. Analysis of the data showed no significant differences among the 4 groups. This demonstrates that the indication of barrier membrane use, to prevent bone remodeling with resorption and to enhance incorporation of autologous onlay bone grafts, is at least disputable.

Background: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan., Methods: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation., Findings: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up., Conclusion: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.

Purpose: Standardised uptake values (SUVs) depend on acquisition, reconstruction and region of interest (ROI) parameters. SUV quantification in multi-centre trials therefore requires standardisation of acquisition and analysis protocols. However, standardisation is difficult owing to the use of different scanners, image reconstruction and data analysis software. In this study we evaluated whether SUVs, obtained at three different institutes, may be directly compared after calibration and correction for inter-institute differences., Methods: First, an anthropomorphic thorax phantom containing variously sized spheres and activities, simulating tumours, was scanned and processed in each institute to evaluate differences in scanner calibration. Secondly, effects of image reconstruction and ROI method on recovery coefficients were studied. Next, SUVs were derived for tumours in 23 subjects. Of these 23 patients, four and ten were scanned in two institutes on an HR+ PET scanner and nine were scanned in one institute on an ECAT EXACT PET scanner. All phantom and clinical data were reconstructed using iterative reconstruction with various iterations, with both measured (MAC) and segmented attenuation correction (SAC) and at various image resolutions. Activity concentrations (AC) or SUVs were derived using various ROI isocontours., Results: Phantom data revealed differences in SUV quantification of up to 30%. After application-specific calibration, recovery coefficients obtained in each institute were equal to within 15%. Varying the ROI isocontour value resulted in a predictable change in SUV (or AC) for both phantom and clinical data. Variation of image resolution resulted in a predictable change in SUV quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2 cc), differences of up to 40% were found between high (7 mm) and low (10 mm) resolution images. Similar differences occurred when data were reconstructed with a small number of iterations. Finally, no significant differences between MAC and SAC reconstructed data were observed, except for tumours near the diaphragm., Conclusion: Standardisation of acquisition, reconstruction and ROI methods is preferred for SUV quantification in multi-centre trials. Small unavoidable differences in methodology can be accommodated by performing a phantom study to assess inter-institute correction factors.

We aimed to test the hypothesis that the cerebral selection of movement includes active suppression of unwanted movements. To that end, a cerebral activation paradigm was used in which index finger flexion was compared with similar movement, made together with fingers 3, 4, 5. Cerebral activations were assessed by positron emission tomography (PET) measurements of cerebral perfusion in 10 healthy subjects, during the two motor tasks and rest. Statistical parametric mapping (SPM) revealed significant increase of (antero)medial prefrontal activity and subtle changes in pallidum and thalamus in the condition of less movement, i.e. isolated index finger flexion contrasted to full-hand flexion. These increases indicated a mechanism of selection mediated by active suppression of unwanted movements. Suppression of all motor responses was inferred from anterolateral prefrontal activation related to rest (with only auditory cues), contrasted to both motor conditions. This segregation of inhibitory functions specifies the complementary character of response selection and inhibitory control, in such a way, that towards the medial prefrontal surface, a transition from general to increasingly selective inhibition allows the internal ordering of action.

Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with Multiple Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory. Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.

Surgical treatment of a flexor tendon lesion of the hand is followed by a 6-week period of dynamic immobilisation. This is achieved by the elastic strings of a Kleinert splint, enabling only passive and no active flexor movements. After such immobilisation, the appearance of a temporary clumsy hand indicates decreased efficiency of cerebral motor control. Using PET we identified the recruitment of contralateral parietal and cingulate activations specifically related to the suboptimal character of these hand movements. After 6-8 weeks, normalised movement was related with contralateral putamen activation. Activations of the sensorimotor cortex and cerebellum were present during both scanning sessions. Changes in the pattern of cerebral activations reflect functional reorganisation. The shift from cortical to striatal involvement, observed in the group of four patients, generates the concept of unlearned movements being relearned.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

In PET activation studies, linear changes in regional cerebral blood flow may be caused by subject interscan displacements rather than by changes in cognitive state. The aim of this study was to investigate the impact of these artifacts and to assess whether they can be removed by applying a scan-specific calculated attenuation correction (CAC) instead of the default measured attenuation correction (MAC). Two independent data sets were analyzed, one with large (data I) and one with small (data II) interscan displacements. After attenuation correction (CAC or MAC), data were analyzed using SPM99. Interscan displacement parameters (IDP), obtained during scan realignment, were included as additional regressors in the General Linear Model and their impact was assessed by variance statistics revealing the affected brain volume. For data I, this volume reduced dramatically from 579 to 12 cm(3) (approximately 50-fold) at P(uncorr)

In both quadrupedal and bipedal walking, cyclic movements of opposite limbs are made in antiphase, with identical frequency of all four limbs. These kinematical characteristics generated the hypothesis that, in humans, the cerebral control of this stereotypic movement pattern is associated with a common circuitry involved in antiphase movement, independent from execution by either the two upper or the two lower limbs. By means of positron emission tomography (PET), we identified cerebral activations related to limb-independent antiphase movement, distributed over the right anterior parietal and the right dorsal premotor cortex. Particularly, involvement of the right parietal cortex demonstrates a lateralized brain function for higher-order somatosensory processing, enabling the sensorimotor anchoring of stereotypic multilimb movement.

The significance of task-induced cerebral blood flow responses, assessed using statistical parametric mapping, depends, among other things, on the signal-to-noise ratio (SNR) of these responses. Generally, positron emission tomography sinograms of H(2)(15)O activation studies are reconstructed using filtered backprojection (FBP). Alternatively, the acquired data can be reconstructed using an iterative reconstruction procedure. It has been demonstrated that the application of iterative reconstruction methods improves image SNR as compared with FBP. The aim of this study was to compare FBP with iterative reconstruction, to assess the statistical power of H(2)(15)O-PET activation studies using statistical parametric mapping. For this case study, PET data originating from a bimanual motor task were reconstructed using both FBP and maximum likelihood expectation maximization (ML-EM), an iterative algorithm. Both resulting data sets were statistically analyzed using statistical parametric mapping. It was found, with this dataset, that the statistical analysis of the iteratively reconstructed data confirm the a priori expected physiological response. In addition, increased Z scores were obtained in the iteratively reconstructed data. In particular, for the expected task-related response, activation of the posterior border of the left angular gyrus, the Z score increased from 3.00 to 3.96. Furthermore, the number of statistically significant clusters doubled while their volume increased by more than 50%. In conclusion, iterative reconstruction has the potential to increase the statistical power in H(2)(15)O-PET activation studies as compared with FBP reconstruction.

Regional cerebral blood flow was assessed during reaching movements with either target or finger selection. Measurements were performed with positron emission tomography in normal subjects. We thus identified two patterns of cerebral activation representing parietal command functions based on either external space or body scheme information. Directing the right-hand index finger toward one target dot in an array of five was related to activations distributed over dorsal extrastriate visual cortex (putative area V3A), along the parieto-occipital sulcus (putative V6/V6A) and the posterior intraparietal sulcus (IPS). Right-hemisphere dominance was present at the occipital extension of posterior IPS. Positioning one right-hand finger of five on the middle target dot was related with anterior IPS activation, extending over the marginal gyrus of the left inferior parietal lobe. The latter indicated a parietal role in prehension, independent of the shape of the target reached for. In both conditions of the reaching task, instructions for movement were auditorily given by random numbers 1 to 5, thus excluding visual cueing. The observed lateralization of movement-related parietal functions helps to explain neurological symptoms such as ideomotor apraxia and spatial hemineglect., (Copyright 2001 Academic Press.)

We investigated whether left-hemisphere arachnoid cysts lead to reorganization of the language function using PET. A group analysis demonstrated that patients showed no more right-hemisphere activation than a matched control group. Several patients had clear language localizations in the left hemisphere during language comprehension; none of the patients showed right-hemisphere activation. We conclude that left-hemisphere tissue must suffer considerable compromise before reorganization of language into the right hemisphere becomes necessary. Language activations within the left hemisphere are clearly displaced. This is consistent with mere physical displacement in some patients rather than reorganization within the left hemisphere; in others intrahemispheric reorganization cannot be excluded.

Positron Emission Tomography (PET) is an imaging modality which can determine biochemical and physiological processes in vivo in a quantitative way by using radiopharmaceuticals labeled with positron emitting radionuclides as (11)C, (13)N, (15)O and (18)F and by measuring the annihilation radiation using a coincidence technique. This includes also measurement of the pharmacokinetics of labeled drugs and the assessment of the effects of drugs on metabolism. Because only very low amounts of the radiolabeled drug have to be administered, far below toxicity levels, human studies can be carried out even before the drug is entered in Phase I. Such studies can provide cost-effective predictive toxicology data and information on the metabolism and mode of action of drugs. PET is also very useful to study the metabolic consequences of gene expression or gene defects. In the last decade many genetically engineered small animal models have been developed. The study of these animals with high resolution small animal PET cameras provides new opportunities in drug development. Especially valuable is the contribution of PET to bridge the gap between molecular biology, understanding of pathology and to the design of a new generation of drugs.

In previous EEG experiments we have presented a time estimation task to our subjects, who had to press a button with either the left or right index finger 3 s after an auditory warning stimulus (WS). Two seconds later a visual Knowledge of Results (KR) stimulus was presented on a screen in front, informing them about whether the movement had been made in the correct time window (a vertical line), whether it was too early (a minus sign) or too late (a plus sign). The potential distribution underlying the anticipatory attention for the KR stimulus suggested a right hemisphere network in which the prefrontal cortex, the insula Reili and the parietal cortex were involved. In the present positron emission tomography (PET) activation study we aimed to further localize the exact positions of these regions, using the same paradigm. Two conditions were compared in which the WS had to be followed by a button press with the left index finger. In experimental condition A, subjects received true information about their performance, while in condition B false information was given, utilizing the same stimuli, but randomly, thus without any relation to the actual performance. In both conditions identical stimuli were presented and identical movements were made. Therefore we applied statistical parameter mapping (SPM) for comparison of condition A with B in order to identify regional increases in perfusion related to the anticipation and use of the KR. We found in line with our predictions a right hemisphere activation of (1) BA45, (2) the junction of the posterior insula with the temporal transverse gyrus and (3) the posterior part of the parietal cortex. This activation pattern was accompanied by a better performance due to KR. A second, though not predicted, effect was the increase in correct responses during the last two sessions compared to the first two sessions, independent of KR. This learning effect was accompanied by an activation of BA46 and the supplementary motor area (SMA), again in the right hemisphere. Summarizing, two different prefrontal areas in the right hemisphere were activated: a more ventral area, related to the use of external stimuli providing feedback about a past performance, in order to produce movements in time, and another mid-dorsal one, related to temporal programming on the basis of internal cues.

Using positron emission tomography, visual presentation of sentences was shown to cause increased regional cerebral blood flow relative to word lists in the left lateral anterior superior and middle temporal gyri, attributable to cognitive processes that occur during sentence comprehension in addition to those carried out during word comprehension. Additional comparisons showed that repeating words (in a different context, when subjects did not attempt to learn the initial lists) led to significant patterns of both increased blood flow (left putamen and right caudate) and decreased blood flow (left posterior temporal lobe). Increases are argued to reflect retrieval of memory traces, whereas decreases reflect diminished necessity for processing of input. A decrease in the left inferior parietal lobe was attributable to other factors.

Background: The aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography (PET) scans., Methods: We retrospectively analyzed the data of 20 patients who underwent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA). Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard., Results: Both QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y = 0.90 x x-5.9, r = 0.86, P < .0001; y = 0.80 x x+3.3, r = 0.84, P < .0001, respectively). The correlation between FPM and QGS left ventricular ejection fraction results was even higher (y = 0.89 x x+8.6, r = 0.97, P < .0001). Bland-Altman plots showed systematic differences in the left ventricular ejection fraction of -9.6% +/- 7.5% (QGS vs ERNA), -3.8% +/- 7.8% (FPM vs ERNA), and -5.8% +/- 3.5% (QGS vs FPM). Further comparison of the left ventricular volumes revealed systematic difference between QGS and FPM. Our results indicate that the correlation between the different left ventricular ejection fractions shows little sensitivity to errors in the left ventricular volumes; however, the exact relationship is influenced by these errors., Conclusion: It is concluded that the automated determination of the left ventricular ejection fraction from gated PET data has significant potential; its results are highly and significantly correlated with ERNA. However, the methods presented here require additional calibration before final accuracy and clinical applicability can be determined.

The distribution of increased regional cerebral blood flow (rCBF) related to visuomotor coordination was studied by means of positron emission tomography (PET) in normal subjects. An experimental condition, in which a vertically presented zigzag figure had to be copied in a horizontal orientation, was compared with a control condition in which the same horizontal drawing was made, guided by a horizontally presented example. Cognitive components dealing with the mismatch in visual orientation resulted in activation of (i) right dorsal premotor cortex, (ii) right posterior parietal cortex, (iii) visual cortex (area V1) and (iv) left fusiform gyrus. In a second experiment, conditions were compared in which the same horizontal zigzag figure was copied in either a vertical or a horizontal orientation. Now, the motor components of the transformation of orientation appeared to be associated only with left premotor cortex activation. The differential distribution of activations is regarded to reflect the selective effort to cope with either the visual or the motor component of spatial incongruity, and indicates specialization for perceptual and executive components in visuomotor control. We propose that the perceptual component of visuomotor transformation in our experiment relates to a realignment of the coordinates of a percept to an internally defined coordinate system. The executive component relates to guidance of movement within an internal representation of space. In a preceding behavioural experiment, a majority of patients with Parkinson's disease (PD) failed on the task in which they had to make a horizontal copy of a vertically presented picture. This finding may suggest a deficit in the maintenance of an internal spatial representation to guide movement., (Copyright 1999 Elsevier Science B. V.)

By using positron emission tomography, we aimed to identify cerebral foci of neuronal activation associated with the initiation of a specific motor program. To that end, a state of repeatedly alternating in- and antiphase of bimanual flexion and extension movements was compared with similar movement responses except phase changing. This comparison provided the opportunity to eliminate confounding effects of attention and simple movements. Change between the two bimanual motor programs was related with activation at the posterior border of the left angular gyrus, the right precuneus, and the right premotor and right medial prefrontal cortex. In a subsequent experiment, with attention and random movements as additional variables, activation at the posterior border of the left angular gyrus was found at the same significance level. This posterior parietal activation may indicate an equivalence with the coding of intention in monkey posterior parietal cortex. Lesion of the left posterior parietal cortex in human gives rise to left-right disorientation and ideomotor apraxia. Our results may support the view that these symptoms reflect the inability to transpose a motor plan to the representation of a personal body scheme. Activation of the right premotor and right medial prefrontal cortex was related both to the change between motor programs and to the condition with strictly regular movement in which no additional responses were made to randomly presented signals. This is consistent with the concept that motor preparation is associated with both the selection of internally instructed movements and the suppression of irrelevant environmental stimuli., (Copyright 1999 Academic Press.)

In the course of pregnancy maternal tissues become increasingly more insensitive to insulin. As 6 days of euglycaemic hyperinsulinaemic clamping, from day 8 until 14 of gestation, ameliorates total glucose consumption, we analysed the contribution of individual tissues in this phenomenon. We measured not only glucose consumption, but also concentrations of the glucose transporter protein GLUT4 in selected tissues. On day 15 of pregnancy in saline-infused (pregnant control) rats, 18F-fluoro-2-deoxy-D-glucose (FDG) consumption, as measured by positron emission tomography, as well as GLUT4 content were diminished in heart (P < 0.05), and in brown (P < 0.05) and white adipose tissues (P < 0.05) when compared with non-pregnant controls. During clamping, on day 13 of the experiments, both in pregnant and non-pregnant rats FDG consumption was increased in liver (P < 0.05), skeletal muscle (P < 0.05), brown (P < 0.05) and white adipose tissues (P < 0.05) when compared with saline-infused controls. In both the reproductive conditions, only in white adipose tissue was this increased FDG consumption associated with increased GLUT4 levels (P < 0.05); GLUT4 content of m. gastrocnemius, m. soleus, heart and brown adipose tissue was unaffected by clamping. In non-pregnant rats, 24 h after clamping ceased, FDG consumption was diminished in heart compared with control non-pregnant rats (P < 0.05). In pregnant rats, however, 24 h after clamping (i.e. day 15 of pregnancy) both FDG consumption (P < 0.05) and GLUT4 content (P < 0.05) were still increased in white adipose tissue only, when compared with saline-infused pregnant rats on the same day of gestation. It is suggested that hyperinsulinaemic euglycaemic clamping ameliorates insulin action halfway pregnancy, in particular by stimulation of glucose consumption and GLUT4 protein content in white adipose tissue.

The applicability of H215O-positron emission tomographic (PET) imaging for the assessment of skeletal muscle perfusion during exercise was investigated in five healthy subjects performing intermittent isometric contractions on a calf ergometer. The workload of the left calf muscles was kept constant in all exercises, while that of the right calf muscles was varied. During exercise H215O distribution in the calf muscles was measured by PET. Radioactivity measured in the left calf muscles was used as a reference for the radioactivity measured in the right calf muscles. In all studies, muscles were delineated by uptake of radioactivity. Four subjects demonstrated high radioactivity in the gastrocnemius medialis muscle, in one subject high radioactivity was distributed over the triceps surae muscles. The observed muscles demonstrated also local foci of radioactivity indicating regionally enhanced tissue perfusion. The right-left ratio of radioactivity in the active muscles increased as a function of the load. We conclude that inter- and intramuscle perfusion differences can be measured during exercise by H215O-PET imaging.

Three areas of the left hemisphere play different roles in sentence comprehension. An area of posterior middle and superior temporal gyrus shows activation correlated with the structural complexity of a sentence, suggesting that this area supports processing of sentence structure. The lateral anterior temporal gyrus is more activated bilaterally by all sentence conditions than by word lists; thus the function of the area probably does not directly support processing of structure but rather processing of words specific to a sentence context. Left inferior frontal cortex also shows activation related to sentence complexity but is also more activated in word list processing than in simple sentences; this region may thus support a form of verbal working memory which maintains sentence structural information as well as lexical items.

We monitored 10 patients with unresected (9) or partially resected (1) supratentorial gliomas with 11C-tyrosine position emission tomography (TYR-PET) before and after radiotherapy. TYR-PET tumour volumes were measured using a threshold technique. In seven patients the tumour volume decreased after radiotherapy, although all gliomas persisted on TYR-PET images. In eight patients the tumour protein synthesis rate (PSR) was calculated using a dynamic study protocol in combination with a PATLAK analysis. There were no changes in PSR after radiotherapy, but the PSR was calculated on the remaining tumour volume using the same threshold technique as before therapy, i.e. the decrease in tumour volume was not taken into account. In eight patients the PET data were compared with magnetic resonance spectroscopic imaging (1H-MRSI) performed simultaneously. Although there was no statistically significant correlation between TYR-PET volume changes and 1H-MRSI choline level we observed a simultaneous decrease in volume and choline in four patients.

Positron Emission Tomography (PET) is a method for determining biochemical and physiological processes in vivo in a quantitative way. This includes the measurement of the pharmacokinetics of labeled drugs and the measurement of the effects of drugs and/or therapy on metabolism. Also deviations of normal metabolism can be measured and insight in biological processes responsible for diseases can be obtained. To accomplish these measurements a multi-disciplinary team is necessary for the expertise in the fields of radionuclide production, radiochemistry, pharmacy, medicine, nuclear imaging and data analysis.

Primary brain tumours are usually assessed by computed tomography (CT) and magnetic resonance imaging (MRI), sometimes in conjunction with positron emission tomography (PET). We used cobalt-55 (55Co) as a calcium (Ca) tracer to visualize decaying tumour tissue, based on the fact that Ca-influx is essential in both cell death and leukocyte activation. Net 55Co uptake may be the result of cell decay, leukocyte infiltration, (re)perfusion and the pharmacological profile of 55Co. Three patients with primary malignant brain tumours (first presentation) were studied with CT, MRI and Co-PET after the intravenous administration of 0.5 mCi 55Co. Histopathological diagnosis was obtained by biopsy or resection. Co-PET demonstrated each of the brain tumours and showed good topographical agreement with CT and MRI. Co-PET provided additional detail as to the site and size of the necrotic core and the perinecrotic rim of decaying tumour. The 55Co uptake indices varied between 2.6 and 5.3. 55Co demonstrated uptake in decaying tissue, irrespective of the integrity of the blood-brain barrier. Neither necrotic nor viable tumour tissue showed affinity for 55Co. Since 55Co is readily applicable to both PET and single photon emission tomography (SPET), differences in the uptake mechanism and functional significance of the 55Co tracer are discussed in relation to 201Tl SPET. We present a (limited) pilot series of three patients to forward the claim of this new functional technique in nuclear neurology.

A story told by his mother was presented on tape to a trauma patient in persistent vegetative state (PVS). During auditory presentation, measurements of regional cerebral blood flow (rCBF) were performed by means of positron emission tomography (PET). Changes in rCBF related to this stimulus condition, as compared to presenting non-word sound, were evaluated by means of statistical parametric mapping (SPM). This analysis indicated activation of rostral anterior cingulate, right middle temporal and right premotor cortices, which may reflect appropriate cortical involvement in processing emotional attributes of sound or speech.

Unlabelled: We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier., Methods: The (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk. The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode., Results: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum. Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain. The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals., Conclusion: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease.

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H(2)(15)O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at T1 modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.

Unlabelled: The aims of the study were to compare the value of L-[1-11C]tyrosine (TYR) and [IBF]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy., Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels., Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG. Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94)., Conclusion: In this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease. SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.

After acute cerebral stroke, the (peri-) infarct tissue is characterized by calcium (Ca)-mediated neuronal damage and inflammatory processes. Monitoring Ca-mediated damage using the isotope cobalt-55 (Co) as a Ca-tracer may enable PET-imaging of this tissue. Since the fate of (peri-) infarct tissue determines clinical outcome, Co-PET may have prognostic value in stroke. Six stroke patients were examined with Co-PET, MRI and a middle cerebral artery (mca) stroke scale (Orgogozo). In every patient, specific Co-accumulation in the appropriate brain region was seen, irrespective of the integrity of the blood-brain barrier. This pilot study suggests Co-PET as a diagnostic tool in stroke, which may provide additional information on the clinical outcome. Validation of method in larger patient series is necessary.

Unlabelled: S-1'-[18F]fluorocarazolol was administered to healthy volunteers to assess its potential for noninvasive measurement of regional pulmonary and myocardial beta-adrenoceptor densities., Methods: High-specific activity fluorocarazolol was intravenously injected on two separate occasions within a 1-wk interval. The initial injection was without pretreatment, but before the second injection, the volunteers either inhaled salbutamol (2 x 200 micrograms aerosol) or they ingested pindolol (3 x 5 mg during a 12-hr interval). Twenty-eight PET time frames of 31 planes were acquired over a period of 60 min after each injection. Blood samples were drawn and analyzed for the presence of fluorocarazolol and radioactive metabolites., Results: Uptake of fluorocarazolol in the target tissues was hardly affected by salbutamol but was strongly depressed by pindolol. Pulmonary and myocardial tissue-to-plasma concentration ratios of fluorocarazolol reached plateau values of 11.6 +/- 0.6 (lungs) and 18.1 +/- 1.0 (heart) at 45-50 min postinjection. These values were reduced to 2.0 +/- 0.4 and 2.0 +/- 0.6 after treatment with pindolol., Conclusion: These data indicate that: 1. Pulmonary and myocardial uptake of radioactivity after intravenous administration of S-1'-[18F]fluorocarazolol represents radioligand binding to beta-adrenoceptors. 2. Pulmonary binding occurs mainly in alveoli rather than in airway smooth muscle under these conditions. 3. Binding kinetics do not preclude quantification of receptors with compartment models.

Background: It is often difficult to detect a local recurrence of soft-tissue sarcomas due to disturbance of the normal anatomy by previous surgery and radiotherapy. The aim of this study was to assess the value of positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) for detecting local recurrences., Methods: In the period 1992-1995, 17 patients with proven or suspected local recurrence of soft-tissue sarcoma were examined using FDG-PET. Fifteen of these patients were ultimately proven to have a recurrence., Results: Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter 0.5 cm) were as easily visible as large lesions (maximum diameter 20 cm). In one patient the PET scan was positive, but the recurrence could not be proven histologically. Recurrence was proven 1 year later. A recurrent low-grade liposarcoma was not visualized. The two patients with benign lesions had a negative PET scan. The mean glucose metabolic rate was calculated to be 13.2 mumol/100 g/min (range 1.9-28.4). A correlation was found between the histological malignancy grade and the metabolic rate (p < 0.05; Kruskal-Wallis)., Conclusion: PET with FDG is a useful addition to the diagnostic armamentarium for detecting local recurrence of soft-tissue sarcomas and provides an indication of the malignancy grade of the recurrent lesion.

Unlabelled: The isotopes 55Co and 57Co have been evaluated for PET and SPECT imaging in several clinical brain studies. For clinical application of cobalt, it is important to know the delivered radiation dose. The biodistribution of 55Co in both rat and humans after intravenous (bolus)-administration was studied. Based on pharmacokinetic data, radiation dose calculations according to the MIRD system are presented. By combining present measurements with literature data on 60CoCl2, the radiation dose delivered by 56CoCl2 (T1/2 78.8 days) and 57CoCl2 (T1/2 = 270 days) could be assessed., Methods: Whole-body Co-PET was performed in two healthy volunteers and one rat after intravenous injection of 37 and 3.7 MBq (1 resp. 0.1 mCi) 55Co, respectively. Blood samples were withdrawn during 300 min in humans. In seven rats the 55Co-biodistribution was determined by postmortem analysis. The residence time of the liver (critical organ) was determined in rats and humans. Blood partition-data of 55Co were assessed resulting in basic pharmacokinetic data in humans. Based on these kinetic data, radiation dose was calculated using the MIRD protocol., Results: In both the humans and the rat, the liver and bladder retained the highest fractions of 55Co (about 50% resp. 40% of the administered dose). The liver residence time in humans was 8.6 hr. The free fraction 55Co in the human plasma was at maximum 12%. The total-body mean transit time was 152 min. The volume of the central compartment = 2.8 liter and the steady-state distribution volume = 48 liter., Conclusion: From these results, according to the WHO recommendations for class II studies, 22.2 MBq (0.6 mCi) 55Co and 14.8 MBq (0.4 mCi) 57Co (excluding any radionuclide contamination) can be used.

The amino acid incorporation rate, generally described as protein synthesis rate or PSR, can be assessed in vivo using carboxylic-labelled amino acids such as L-[1-11C]tyrosine and PET. In animals, labelled tissue metabolites are below 4% of total tissue radioactivity and are therefore neglected in the model. Labelled plasma metabolites on the other hand rise continuously to 50% of total plasma radioactivity at 40 minutes. After correction of the total plasma radioactivity for the metabolite fraction, a Patlak analysis may be performed to calculate the PSR. A number of applications in the field of oncology were presented. The use of L-[1-11C]tyrosine in the study of metabolic disease was also discussed. It is concluded that the application of [11C]tyrosine-PET in a clinical setting is of interest for an increasing number of diseases.

Patients with phenylketonuria (PKU) may suffer from cognitive and neurological deficits which are related to reduced intracerebral concentrations of catecholamines. The function of phenylalanine (Phe) as an inhibitor of the uptake of the precursor amino acid tyrosine (Tyr) through the blood-brain barrier as well as an inhibitor of the expression of dopamine receptors in the brain is under investigation. Positron emission tomography (PET) is a method for quantitatively determining biochemical and physiological processes in vivo. In the current pilot study, L-[1-11C]-Tyr and 18F-fluoro-ethyl-spiperone (FESP) have been used. The metabolic pathway of carboxylic labelled Tyr is mainly incorporation into protein. From the measured tissue and plasma activity as a function of time in combination with a compartimental model the Protein Synthesis Rate (PSR) for Tyr can be calculated. FESP is a ligand which binds irreversibly to the dopamine D2-receptor and has also a low non specific binding, although affinity to the serotonin receptor has been described. The ratio of FESP concentration in striatum and in cerebellum is a measure of the receptor status in vivo. In patients with plasma Phe levels above the maximum therapeutic concentration (> 700 mumol/l) the PSR for Tyr was decreased as compared to controls and patients with plasma Phe concentrations within the therapeutic range, indicating a decreased availability of Tyr for neurotransmitter synthesis, and hence explaining the reduced cerebral concentration of catecholamines.

Unlabelled: We investigated FDG-PET in patients undergoing hyperthermic isolated limb perfusion (HILP) with rTNF-alpha, rIFN-gamma and melphalan for locally advanced soft-tissue sarcoma of the extremities., Methods: Twenty patients (11 women, 9 men; aged 18-80 yr, mean age 49 yr) were studied. FDG-PET studies were performed before, 2 and 8 wk after HILP. After the final PET study, the tumor was resected and pathologically graded. Patients with pathologically complete response (pCR) showed no viable tumor after treatment. Those with pathologically partial response (pPR) showed various amounts of viable tumor in the resected specimens., Results: Seven patients showed a pCR (35%) and 12 patients showed a pPR (60%). In one patient, pathological examination was not performed (5%). The pre-perfusion glucose consumption in the pCR group was significantly higher than in the pPR group (p<0.05). Visual analysis of the PET images after perfusion showed a rim of increased FDG uptake around the core of absent FDG uptake in 12 patients. The rim signal contained a fibrous pseudocapsule with inflammatory tissue in the pCR group, viable tumor was seen in the pPR group. The glucose consumption in the pCR group at 2 and 8 wk after perfusion had decreased significantly (p<0.05) in comparison to the glucose consumption in the pPR., Conclusion: Based on the pretreatment glucose consumption in soft-tissue sarcomas, one could predict the probability of a patient achieving complete pathological response after HILP. FDG-PET indicated the pathological tumor response to HILP, although the lack of specificity of FDG, in terms of differentiation between an inflammatory response and viable tumor tissue, hampered the discrimination between pCR and pPR.

Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'-[18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.

Differences between two states of cerebral activation were studied in eight subjects by positron emission tomography (PET) of regional cerebral blood flow (rCBF) and subsequent statistical parameter mapping. Subjects had to respond to a row of numbers presented on tape. In one condition they had to repeat each number. In the other condition the last heard number had to be added to the number presented before. Cerebral activity specifically related to the serial addition task was distributed over supplementary motor area (SMA), left premotor cortex and superior dorsal parietal cortex bilaterally, without significant involvement of prefrontal cortex. This indicated circuitry related to mental performance characterised by a fixed strategy of executing serial manipulation of numbers within "internal space". The main aim of this communication is to discuss the similarity between circuitry underlying higher order motor control and pure cognitive performance.

Unlabelled: PET with 18F-fluoro-2-deoxy-D-glucose (FDG) was used to study soft-tissue lesions. The goals of the study were to establish FDG uptake in soft-tissue sarcoma, to determine the sensitivity of this technique, to investigate the correlation between histologic grade and glucose consumption and to determine whether FDG-PET can discriminate between benign and malignant lesions., Methods: PET imaging was performed in 18 patients with soft-tissue sarcoma and 4 patients with a benign soft-tissue lesion. Glucose consumption in the tumors was calculated using Patlak's graphical analysis with an assumption made for the lumped constant. Standardized uptake values also were calculated., Results: All soft-tissue sarcomas were clearly depicted. The median glucose consumption was 13.0 mumole/100 g/min (range 2.9-41.8 mumole/100 g/min). A correlation was found between glucose metabolism and the histopathologic malignancy grade. Such a correlation was not demonstrated for the standardized uptake values. One benign lesion was also visualized. Benign lesions were not visualized in two patients and in the remaining patient an equivocal scan was obtained. Benign lesions could be distinguished from high-grade malignant lesions but not consistently from lesions with low or intermediate malignancy grades., Conclusion: PET with FDG is an effective technique to visualize soft-tissue sarcomas. We found a sensitivity of 100%. There is a correlation between glucose metabolic rate and tumor malignancy grade. FDG appears to be unsuitable for discriminating benign lesions from soft-tissue sarcomas with low or intermediate malignancy grades.

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury.

Unlabelled: We studied the potential of L-[1-11C]tyrosine ([1-11C]Tyr) and L-[methyl-11C]methionine ([Me-11C]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models., Methods: In the liver and plasma of control and cycloheximide-treated mice injected with [1-14C]Tyr and [Me-3H]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with 11C-labeled analogs and PET., Results: In mice, liver uptake of [Me-3H]Met was over twice as large as that of [1-14C]Tyr. Similar uptake patterns of the 11C-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, approximately 69%-73% of the 14C was detected in the protein fraction, whereas approximately 65%-70% of the 3H was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were approximately 73%-76% for 14C and approximately 36%-46% for 3H. Gel-filtration analysis suggested that 80% of the 14C-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide, the liver uptake of the [1-14C]Tyr and the protein-incorporation of 14C in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-3H]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction., Conclusion: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-11C]Met mainly reflects phospholipid synthesis through the transmethylation process.

In this contribution we show how neuroimaging methods can augment behavioural methods to discover processing stages. Event Related Brain Potentials (ERPs), Brain Electrical Source Analysis (BESA) and regional changes in cerebral blood flow (rCBF) do not necessarily require behavioural responses. With the aid of rCBF we are able to discover several cortical and subcortical brain systems (processors) active in selective attention and memory search tasks. BESA describes cortical activity with high temporal resolution in terms of a limited number of neural generators within these brain systems. The combination of behavioural methods and neuroimaging provides a picture of the functional architecture of the brain. The review is organized around three processors: the Visual, Cognitive and Manual Motor Processors.

For the synthesis of [18F]Fluoro-Org 6141 via a nucleophilic substitution reaction with 18F-, the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. The biodistribution of the high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand [18F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85 MBq of [18F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18F activity uptake were monitored for 3 h using a stationary double-headed positron emission tomography (PET) camera, and the biodistribution was assessed by ex vivo determination of radioactivity in several tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX animals contained more concentration on a wet weight basis than blood. Three hours post injection, radioactivity was retained in bladder, trachea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of 18F activity in spleen, testes, and brain areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET scans suggested that 18F activity uptake in the brain had not yet reached a maximum at this interval. Although [18F]Fluoro-Org 6141 is not useful for PET studies of glucocorticoid receptors (GRs), the results obtained with this compound indicate a synthetic strategy suitable for the synthesis of high-affinity radioligands for GRs.

Purpose: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors., Materials and Methods: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate (PSR) and tumor-to-background ratio. Findings were compared with histologic findings., Results: Primary brain tumor was proved in 22 patients histologically, as well as metastatic cancer of unknown origin, primary non-Hodgkin lymphoma, meningioma, atypical infarction, and vasculitis in one patient each. At PET, 20 of 22 primary tumors, the metastasis, and non-Hodgkin lymphoma were correctly depicted. A false-positive finding was obtained with the infarction, and the meningioma and vasculitis were not depicted. The calculated sensitivity was 92%; specificity, 67%; and accuracy, 89%. There were no statistically significant relationships between histologic findings, PSR, and tumor-to-background ratio., Conclusion: L-[1-C-11]-tyrosine is a valid tracer for diagnosis of brain tumors and allowed quantification of PSR.

Multiple sclerosis (MS) is an immune-mediated disease of the white matter in the brain that can have a progressive course. However, the progression of relapsing-remitting (RR) MS into relapsing-progressive (RP) MS might represent a more fundamental change in disease activity, i.e. decay of vulnerable neurons and oligodendrocytes. In RP-MS, this may imply that the major loss of brain tissue structure is caused by a combination of demyelination and cellular loss, both of which are likely to cause disability in MS. We used the PET isotope cobalt-55 (Co) as a calcium (Ca) tracer to visualize brain tissue damage, based on the fact that Ca influx is essential in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine whether Co-PET detects any RP-MS lesions and, if so, to assess any correlation with the progression rate (PR) of the disease and with MS lesions as detected by MRI. Seven RP-MS patients (Poser) with EDSS > 4.0 (Kurtzke) and 7 healthy controls underwent MRI (Miller, Barkhof) and Co-PET. Comparison of both image modalities was made by merging. Co-PET lesion frequency was assessed and correlated with the PR of the disease. Co-PET demonstrated significantly more lesions in the MS brain than in the healthy brain, both periventricular and cortical. Every single MRI lesion could be retrieved as a Co-PET lesion. The Co-PET lesion frequency correlated significantly with PR. Our pilot study possibly suggests Co-PET as a tool in estimating disease activity in RP-MS.(ABSTRACT TRUNCATED AT 250 WORDS)

In 32 patients with gliomas, one- and two-dimensional proton magnetic resonance spectroscopy (1H-MRS) has been conducted, the latter allowing reconstruction of spectroscopic data into a spectroscopic image (MRSI), showing the distribution of the various metabolite concentrations over the cross-sectional plane. For lack of absolute concentrations, the measured concentrations of phosphocholine (CHOL), N-acetyl-L-aspartate (NAA), and lactate (LAC) were conventionally expressed in ratios relative to that of creatine (CREAT). Compared to normal brain tissue, an increased CHOL/CREAT ratio was found in all groups of tumours, in glioblastomas, high-, middle- and low-grade astrocytomas both at the margin and the core of the tumours, but in oligodendrogliomas only at the margin. This is consistent with an increased phosphocholine turnover in relation to membrane biosynthesis by the proliferating cells. The NAA/CREAT ratio was decreased in all groups of tumours, both in the centre and at the margin, reflecting replacement of functioning neurons by neoplastic cells. The LAC/CREAT ratio was elevated in the core of malignant gliomas, which may be the result of a prevailing glycolysis, characteristic of tumours, possibly in conjunction with hypoxia/ischaemia. In the perifocal oedema, there was neither elevation of the CHOL/CREAT ratio nor decrease of the NAA/CREAT ratio; an increased LAC/CREAT ratio therefore rather reflected ischaemia/hypoxia probably due to locally elevated pressure and compromised regional perfusion. In the normal brain, the metabolite ratios of grey matter did not differ from those of white matter. The frontal lobe and basal ganglia showed lower NAA/CREAT ratios than the other cerebral areas.(ABSTRACT TRUNCATED AT 250 WORDS)