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Object: The aim of this study was to compare the contribution of the tracers 11C-methionine (Met) and 18F-fluorodeoxy-glucose (FDG) in positron emission tomography (PET)-guided stereotactic brain biopsy., Methods: Forty-five patients underwent combined Met-PET and FDG-PET studies associated with computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy. Each patient presented with a lesion that was in proximity to the cortical or subcortical gray matter. The Met-PET and FDG-PET scans were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histologically based diagnoses were rendered in all patients (39 tumors, six nontumorous lesions) and biopsies were performed in all tumors with the aid of PET guidance. When tumor FDG uptake was higher than that in the gray matter (18 tumors), FDG was used for target definition. When FDG uptake was absent or equivalent to that in the gray matter (21 tumors), Met was used for target definition. Parallel review of all histological and imaging data showed that all tumors had an area of abnormal Met uptake and 33 had abnormal FDG uptake. All six nontumorous lesions had no Met uptake and biopsies were performed using CT or MR guidance only. All tumor trajectories had an area of abnormal Met uptake; all nondiagnostic trajectories in tumors had no abnormal Met uptake., Conclusions: When FDG shows limitations in target selection, Met is a good alternative because of its high specificity in tumors. Moreover, in the context of a single-tracer procedure and regardless of FDG uptake, Met is a better choice for PET guidance in neurosurgical procedures.

Unlabelled: We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach., Methods: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume., Results: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%)., Conclusion: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.

Background and Objectives: To assess the value of FDG positron emission tomography (PET) for early detection of incomplete tumor destruction after radiofrequency ablation (RFA) for liver metastasis., Methods: Twenty-eight unresectable liver metastases in 17 patients were treated by RFA. Patients underwent computed tomography (CT) and FDG-PET preoperatively, at 1 week, 1 month, and 3 months postoperatively. Postoperative CT and FDG-PET at 1 week and 1 month were analyzed to identify hypervascular and hypermetabolic residual tumors at the RFA site. These results were correlated with follow-up CT and, in case of reintervention, with pathologic results., Results: In 24/28 of RFA-treated metastases, CT and FDG-PET at 1 week and 1 month showed no tumor residues. During follow-up, none of these 13 patients developed local recurrence at RFA site. In four patients, FDG-PET at 1 week and 1 month showed peripheral hypermetabolic residue after RFA, whereas CT did not revealed residual tumor. In three patients, local persistence of viable tumor cells was biopsy-proven at reintervention. In the fourth, follow-up CT showed subsequent development of a local recurrence., Conclusions: FDG-PET accurately monitors the local efficacy of RFA for treatment of liver metastases, as it early recognizes incomplete tumor ablation, not detectable on CT.

Because brain tumors can be histologically heterogeneous, stereotactic brain biopsies (SBB) may lead to inaccurate diagnosis or grading. Positron emission tomography (PET) has been used in pediatric neuro-oncology to help in the understanding and management of brain neoplasms. We combined PET and magnetic resonance (MR) imaging in the planning of SBB in 9 children (5 males and 4 females, aged 2-14 years) with infiltrative, ill-defined brain lesions. Tracers used for PET were (18)F-2-fluoro-2-deoxy-D-glucose in 4 cases, (11)C-methionine in 2 cases and both tracers in 3 cases. Biopsy targets were selected in hypermetabolic areas. PET-guided SBB provided accurate histological diagnosis in all patients and allowed a reduction of the number of trajectories in lesions located in functional areas. It also helped in better understanding and management of complex cases. This preliminary series suggests that combining PET and MR imaging in the planning of SBB in children (1) improves the diagnostic yield of SBB in infiltrative, ill-defined brain lesions, (2) makes it possible to reduce the sampling in high-risk/functional areas and (3) improves the quality of therapeutic management of pediatric brain tumors., (Copyright 2003 S. Karger AG, Basel)

Object: The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS)., Methods: Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography-guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas., Conclusions: Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

Serotonin-1A (5-HT(1A)) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[ N-(2"-pyridinyl)- p-[(18)F]fluorobenzamido] ethyl] piperazine ( p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT(1A) receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT(1A) receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT(1A) receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT(1A) receptor human studies.

Object: Positron emission tomography with L-[methyl-11C]methionine (MET-PET) provides information on the metabolism of gliomas. The aim of this study was to determine the predictive value of MET-PET in the treatment of patients with gliomas., Methods: Since 1992, 85 patients with a World Health Organization (WHO) classification-verified glioma underwent PET studies in which MET was injected before (74 cases) or after treatment (11 cases). Analysis of PET data was conducted by the same investigator using two scales: a qualitative visual grading scale and a quantitative scale (ratio between tumor uptake and normal brain uptake, classified on a seven-level scale). Uptake of MET was present in 98% of gliomas. The investigator judged this uptake to be moderate to very high based on visual inspection (qualitative scale). For all grades of gliomas, a visual grade of 3 was statistically associated with a shorter patient survival period (p < 0.005). The tumor/normal brain uptake ratio was significantly influenced by the histological grade of the tumor. A statistically poor outcome was demonstrated when this ratio was higher than a threshold of 2.2 for a WHO Grade II tumor and 2.8 for WHO Grade III tumor. For Grade II and III tumors, oligodendrogliomas had a higher uptake of MET than astrocytomas., Conclusions: Uptake of MET was present in 98% of the gliomas studied. A high uptake is statistically associated with a poor survival time. The intensity of MET uptake represents a prognostic factor for WHO Grade II and III tumors considered separately.

Object: In the management of brainstem lesions, the place of stereotactic biopsy sampling remains debatable. The authors compared the results of magnetic resonance (MR) imaging, positron emission tomography (PET) scanning, and histological studies obtained in 30 patients who underwent MR imaging- and PET-guided stereotactic biopsy procedures for a brainstem mass lesion., Methods: Between July 1991 and December 1998, 30 patients harboring brainstem mass lesions underwent a stereotactic procedure in which combined MR imaging and PET scanning guidance were used. Positron emission tomography scanning was performed using [18F]fluorodeoxyglucose in 16 patients, methionine in two patients, and both tracers in 12 patients. Definite diagnosis was established on histological examination of the biopsy samples. Interpretation of MR imaging findings only or PET findings only was in agreement with the histological diagnosis in 63% and 73% of cases, respectively. Magnetic resonance imaging and PET findings were concordant in 19 of the 30 cases; in those cases, imaging data correlated with histological findings in 79%. Treatment based on information derived from MR imaging was concordant with therapy based on histological findings in only 17 patients (57%). Combining MR imaging and PET scanning data, the concordance between the neuroimaging-based treatment and treatments based on histological findings increased to 19 patients (63%). In seven patients who underwent biopsy procedures with one PET-defined and one MR imaging-defined trajectory, at histological examination the PET-guided samples were more representative of the tumor's nature and grade than the MR imaging-guided samples in four cases (57%). In 18 patients PET scanning was used to define a biopsy target and provided a diagnostic yield in 100% of the cases., Conclusions: Although the use of combined PET and MR imaging improves radiological interpretation of a mass lesion in the brainstem, it does not accurately replace histological diagnosis that is provided by a stereotactically obtained biopsy sample. Combining information provided by MR imaging and PET scanning in stereotactic conditions improves the accuracy of targeting and the diagnostic yield of the biopsy sample; an MR imaging- and PET-guided stereotactic biopsy procedure is a safe and efficient modality for the management of mass lesions of the brainstem.

Positron emission tomography (PET) is a method making use of short half-life radioactive compounds which allow imaging and quantification of functional and metabolic data at the level of multiple organs. This method has been initially oriented towards neurological and cardiological applications but gets now a more widespread use in oncology. This recent development has been made possible thanks to methodological progresses allowing "whole body" imaging and thanks to the use of a practical tracer, the 2-[18 F]fluoro-2-deoxy-D-glucose (FDG). The uptake of this tracer is enhanced in diverse cancer tissues. Recent studies has clarified the biological processes which lead to this enhanced uptake of FDG in cancers. This new insight allows a rational and helpful usage of PET in diverse aspects of clinical oncology: diagnosis of lesion, staging, follow-up of patients and treatment evaluation.

Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) studies of 42 subjects ages 6 to 38 years were analyzed using statistical parametric mapping to identify age-related changes in regional distribution of glucose metabolism adjusted for global activity. Whereas adults were normal volunteers, children had idiopathic epilepsy. We studied polynomial expansions of age to identify nonlinear effects and found that adjusted glucose metabolism varied very significantly in the thalamus and the anterior cingulate cortex and to a lesser degree in the basal ganglia, the mesencephalon, and the insular, posterior cingulate, frontal, and postcentral cortices. Regression plots slowed that the best fit was not linear: adjusted glucose metabolism increased mainly before the age of 25 years and then remained relatively stable. Effects persisted when anti-epileptic drug intake and sleep during the FDG uptake were considered as confounding covariates. To determine if the metabolic changes observed were not due to the epileptic condition of the children, PET data obtained in adults with temporal lobe epilepsy were compared with those in our group of normal adult subjects, resulting in the absence of mapping in the age-related regions. This study suggests that brain maturation from the age of 6 years gives rise to a relative increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic connections. Increased metabolic activity in the anterior cingulate cortex is probably related to these thalamic changes and suggests that the limbic system is involved in the processes of brain maturation.

This reports positron emission tomography and [18F]fluorodeoxyglucose (PET-FDG) in a 69-year-old woman who underwent resection of the left cerebellar hemisphere for an acoustic neurinoma 17 years earlier. Functional impairment in cerebral cortical and subcortical structures was evaluated by studying the level of glucose metabolic activity at rest. Relative glucose metabolism was reduced in the prefrontal cortex contralateral to the cerebellar lesion. Contralateral thalamic metabolism was reduced significantly. The results suggest that this phenomenon of "crossed cerebello-thalamo-cerebral diaschisis" is related to a functional depression of the cerebello-thalamo-cortical pathway.

We investigated, by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) (FDG-PET), brain glucose metabolism in 19 patients with parkinsonian features. We compared local pattern of FDG uptake and asymmetry indexes in patients with therapeutic response to levodopa (L-dopa) (group 1, presumed Parkinson's disease, n = 9) and patients without L-dopa therapeutic response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia was present in 11% of patients in group 1 and in 40% of patients in group 2. Asymmetry in basal ganglia metabolism was distributed differently in the two groups (analysis of variance, p < 0.04). In superior and inferior putamen, superior and middle caudate, ventral striatum, and inferior thalamus, relative reduction in metabolism on the side contralateral to predominant parkinsonian signs was associated with L-dopa unresponsiveness. On the contrary, in middle caudate, ventral striatum, and inferior thalamus, a relative increase in metabolism on the side contralateral to the predominant side, parkinsonian signs were found in L-dopa-responsive patients. Our FDG-PET study using simple statistical procedures demonstrates inverse asymmetry of basal ganglia glucose metabolism in parkinsonian patients grouped on the sole basis of L-dopa responsiveness.

Background: Serotonin receptors may play an important role in the pathophysiology of affective disorders. We studied type-2 serotonin (5-HT2) receptors in the brain of patients with major depression., Method: Using positron emission tomography (PET) and the selective radioligand [18F]altanserin, we investigated 5-HT2 receptor distribution in eight drug-free unipolar depressed patients and 22 healthy subjects. Data were analysed using Statistical Parametric Mapping 95., Results: In depressed patients, [18F]altanserin uptake was significantly reduced in a region of the right hemisphere including the posterolateral orbitofrontal cortex and the anterior insular cortex. A trend to similar changes was found in the left hemisphere. No correlation was found between the uptake and the Hamilton rating scale score., Conclusions: Pathophysiology of depression may involve changes in 5-HT2 receptor in brain regions selectively implicated in mood regulation.

Unlabelled: Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies., Methods: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples., Results: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C-MET., Conclusion: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures.

The first applications of positron emission tomography (PET) for the study of brain tumours appeared early in the development of this technology. New trends in these particular PET applications tend to take into account the histological heterogeneity of these tumours and the necessity to integrate PET data in their surgical management. Better knowledge on PET tracers behavior in brain tumours should lead to new clinical uses, in particular in the promising field of cancer treatment evaluation.

Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters.

The aim of the present study was to compare the contribution of the labelled tracers [C-11]methionine (Met) and [F-18]-fluorodeoxyglucose (FDG) in positron emission tomography (PET)-guided stereotactic biopsy of non resectable brain lesions. Twenty-five patients underwent combined Met-PET-, FDG-PET- and computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy according to a previously described technique for stereotactic FDG-PET. Met-PET and FDG-PET images were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histological diagnosis was obtained in all patients (23 tumours and 2 non-tumorous lesions). All tumours had an area of abnormal Met uptake and were biopsied under PET-guidance. FDG uptake in the tumour was higher than in the grey matter and was used for target selection in 12 of 23 tumours. Eleven of them were located in the basal ganglia or the brainstem. Met was used for target selection in 11 of 23 tumours where there was no FDG uptake or where FDG uptake was equivalent to that of the grey matter. Ten of them were located in the cortex. Two nontumoral lesions had no Met uptake and were biopsied under CT- or MR-guidance only. Forty-three out of 53 stereotactic trajectories obtained in these 25 patients were based on PET-defined targets and had an area of abnormal Met uptake. These trajectories always yielded a diagnosis of tumour. Moreover, all tumorous trajectories had an area of abnormal Met uptake. Finally, all non-diagnostic trajectories (n = 4) were CT/MR-defined because there was no area of abnormal Met uptake. These results suggest that patients who can benefit the most from Met-PET guidance could be selected pre-operatively. In conclusion, this work shows that Met is a good alternative to FDG for target selection in PET-guided stereotactic brain biopsy.

Objective: The natural history of the supratentorial low-grade glioma (LGG) of the adult is variable, and its malignant transformation is hardly predictable. Because positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG) has prognostic value in high-grade gliomas, this study was designed to search for a possible relationship between glucose metabolism and risk of malignant evolution in LGGs., Methods: Positron emission tomography with FDG was performed in 28 patients with LGGs (22 at the time of diagnosis and 6 after the diagnosis). A metabolic grading system based on the visual inspection of the positron emission tomographic images was used., Results: In 19 patients, no area of FDG uptake higher than in the white matter was detected (metabolic Grade 1). All of those patients were alive at the end of the follow-up period. Only one of the patients presented a histological modification 7 months after the diagnosis. Nine patients presented areas of increased FDG uptake (metabolic Grade 2 or 3). Those areas were found in the tumor area in eight patients and in an area of radionecrosis in one. Of the nine patients with FDG "hot spots," six died, two had recurrence but were alive at the end of the follow-up period, and the patient with radionecrosis had no signs of recurrence., Conclusions: The presence of areas of increased FDG uptake in a histologically proven LGG predicts, in most cases, a deleterious evolution. This metabolic feature, detectable with a noninvasive procedure, may provide a clue to cellular changes, announcing malignant transformation in a tumor that retains the histological features of an LGG. Protocols with aggressive therapeutic strategies in this situation should be considered for evaluation.

Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) is frequently used to study the metabolic correlates of movement and mental disorders. These studies generally focus on changes in the frontal cortex and the basal ganglia. The reproducibility of glucose metabolism estimates in these structures was tested in 13 normal subjects studied at rest using a standard and simple protocol. A reproducible dorsoventral metabolic gradient was demonstrated in the frontal cortex. Such a gradient was not present in the basal ganglia when the upper region of interest in the caudate nucleus, where the lower metabolic rate of glucose was probably attributable to partial volume effects, was not considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% in the frontal cortex and by 6.8 to 14.7% in the basal ganglia. Variations in normalized values in the basal ganglia ranged from 4.0 to 8.6%. The number of subjects required to detect statistical differences in group comparison or in test-retest studies was calculated for different anticipated levels of change. With the variability detected in this experiment, less than 10 subjects were expected to be sufficient to detect a 15% change in most regions and in both types of studies.