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Objective: Integrating positron emission tomographic (PET) images into the image-guided resection of high-grade gliomas (HGG) has shown that metabolic information on tumor heterogeneity and distribution are useful for planning surgery, improve tumor delineation, and provide a final target contour different from that obtained with magnetic resonance imaging (MRI) alone in about 80% of the procedures. Moreover, PET guidance helps to increase the amount of tumor removed and to target image-guided resection to anaplastic tissue areas. The present study aims to evaluate whether PET-guided volumetric resection (VR) in supratentorial HGG might add benefit to the patient's outcome., Methods: PET images using [18F]fluorodeoxyglucose (n=23) and [11C]methionine (n=43) were combined with MRI scans in the planning of VR procedures performed at the initial stage in 66 consecutive patients (43 M/23 F) with supratentorial HGG according to the technique previously described. In all cases (35 anaplastic gliomas [20 astrocytomas, 10 oligoastrocytomas, 5 oligodendrogliomas] and 31 glioblastomas [GBM]), level and distribution of PET tracer uptake were analyzed to define a PET contour projected on MRI scans to define a final target contour for VR. Maximal tumor resection was accomplished in each case, with the intention to remove the entire abnormal metabolic area comprised in the surgical planning. Early postoperative MRI and PET assessed tumor resection. Survival analysis was performed separately in anaplastic gliomas and glioblastoma multiforme according to the presence or absence of residual tracer uptake on postoperative PET and according to the presence or absence of residual contrast enhancement on postoperative MRI., Results: Preoperatively, metabolic information helped the surgical planning. In all procedures, PET contributed to define a final target contour different from that obtained with MRI alone. Postoperatively, 46 of 66 patients had no residual PET tracer uptake (total PET resection), 23 of 66 had no residual MRI contrast enhancement. No additional neurological morbidity due to the technique was reported. A total PET tracer uptake resection was associated with a significantly longer survival in anaplastic gliomas (P = 0.0071) and in glioblastoma multiforme (P = 0.0001), respectively. A total MRI contrast enhancement resection was not correlated with a significantly better survival, neither in anaplastic gliomas (P = 0.6089) nor in glioblastoma multiforme (P = 0.6806)., Conclusions: Complete resection of the increased PET tracer uptake prolongs the survival of HGG patients. Because PET information represents a more specific marker than MRI enhancement for detecting anaplastic tumor tissue, PET-guidance increases the amount of anaplastic tissue removed in HGG.

Background and Purpose: MR imaging-based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging-based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies., Materials and Methods: Eighteen patients (9 men, 9 women; age range, 19-78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test., Results: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=-0.36, P < .05), whereas no significant correlation was found between ADC and cell density., Conclusion: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.

Background and Purpose: Vascularity, metabolism, and histologic grade are related in gliomas but the exact determinants of these relationships are not fully defined. We used image coregistration and stereotactic biopsies to regionally compare cerebral blood volume (CBV) and (11)C-methionine (MET) uptake measurements in brain gliomas and to assess their relationship by histopathologic examination., Materials and Methods: Fourteen patients with brain gliomas underwent MR imaging, including dynamic susceptibility contrast-enhanced MR and positron-emission tomography (PET) using MET acquired in identical stereotactic conditions before biopsy. MR-based CBV maps were calculated and both CBV maps and PET images were coregistered to anatomic images. Sixty-five biopsy samples were obtained on trajectories targeted toward high MET uptake area. The following histopathologic features were semiquantified in each sample: mitotic activity, endothelial proliferation, cellular pleomorphism, and tumor necrosis. CBV and MET uptake values were measured in the biopsy area and normalized to contralateral white matter. CBV ratios were compared with MET uptake ratios, and both measurements were compared with histologic features of each sample., Results: CBV ratios ranged from 0.08 to 10.24 (median = 1.73), and MET uptake ratios ranged from 0.30 to 4.91 (median = 1.67). There was a positive correlation between CBV ratios and MET uptake ratios (r = 0.65, P < .001). Both CBV and MET uptake ratios were found to be significantly related to endothelial proliferation and mitotic activity (P < .01)., Conclusion: Within glial tumors, there is a local relationship between CBV and MET uptake measurements. Both provide indices of focal malignant activity.

Purpose: To evaluate in brain gliomas the relationship between tumor vascularity measured by MR-based maximum regional cerebral blood volume (rCBV) and tumor amino-acid metabolism based on maximum carbon-11 methionine (MET) uptake on positron emission tomography (PET)., Materials and Methods: Eighteen patients with histologically proven primary brain gliomas were included in the study. In addition to conventional MR sequences, dynamic MR images, including a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence and a PET study using MET, were acquired. Eleven patients had low-grade gliomas, and seven had high-grade gliomas. rCBV ratios and MET uptake ratios normalized to the contralateral white matter (WM) corresponding values were measured in each tumor. Both maximum rCBV ratios and maximum MET uptake ratios were correlated to histopathology. The maximum rCBV ratios were correlated to the maximum MET uptake ratios., Results: Both the maximum rCBV ratios and maximum MET uptake ratios of high-grade gliomas were significantly higher than those of low-grade gliomas (P<0.05). There was a significant positive correlation between maximum rCBV ratios and maximum MET uptake ratios (Spearman: r=0.89, P<0.00001)., Conclusion: The maximum rCBV ratio and maximum MET uptake ratio are significantly correlated in gliomas, reflecting a close link between amino acid uptake and vascularity in these tumors., (Copyright (c) 2006 Wiley-Liss, Inc.)

Unlabelled: We compared the contributions of the labeled tracers (11)C-methionine (Met) and (18)F-FDG for PET-guided stereotactic biopsy of brain gliomas., Methods: In 32 patients with glioma, stereotactic Met PET and (18)F-FDG PET were integrated in the planning of stereotactic brain biopsy. PET images were analyzed to determine which tracer offered the best information for target definition. The stereotactic coregistration of PET images allowed accurate comparison of the level, distribution, and extent of uptake for both tracers according to tumor location and grade., Results: A histologic diagnosis was obtained for all patients. All gliomas had an area of abnormal Met uptake, and 27 showed abnormal (18)F-FDG uptake. (18)F-FDG was used for target selection when its uptake was higher in tumor than in gray matter (14 gliomas). Seven were in the basal ganglia or brain stem. Met was used for target selection when there was no (18)F-FDG uptake or when (18)F-FDG uptake was equivalent to that in the gray matter (18 gliomas). Thirteen were in the cortex. Sixty-one of the 70 stereotactic trajectories obtained from the 32 patients were based on PET-defined targets and had an area of abnormal Met uptake. These 61 Met-positive trajectories always yielded a diagnosis of tumor. All nondiagnostic trajectories (n = 9) were obtained in areas with no increased uptake of Met. In all patients with increased uptake of both tracers, the focus of highest Met uptake corresponded to the focus of highest (18)F-FDG uptake. However, the extent of uptake of both tracers was variable., Conclusion: Distributions of highest Met and (18)F-FDG uptake are similar in brain gliomas. Because Met provides a more sensitive signal, it is the molecule of choice for single-tracer PET-guided neurosurgical procedures in gliomas.

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.

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.

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.

Background: Positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) is widely applied to the study of gliomas. The histology of most gliomas is regionally heterogeneous. The relationship between histologic features and glucose metabolism evaluated by PET with FDG may therefore vary within the limits of the tumor. PET with FDG integrated in the planning of stereotactic brain biopsy allows precise comparison between local FDG uptake and histology. Using this approach, the authors investigated whether glucose metabolism of gliomas is related to anaplasia, and whether PET with FDG detects metabolic heterogeneity that parallels histologic heterogeneity of gliomas., Methods: A total of 161 biopsy samples collected from 20 PET-guided procedures performed in patients with gliomas (8 low grade astrocytomas, 8 anaplastic astrocytomas, 1 anaplastic oligoastrocytoma, and 3 glioblastomas) were analyzed for the presence or absence of 8 histologic features. Stereotactic coordinates were used to calculate the metabolic rate of glucose (MRGlu) in the region of each biopsy sample. Gray and white matter MRGlu were used to define four metabolic grades that were compared with local histology., Results: The difference in MRGlu expressed as micromoles per 100 g per minute was highly significant between anaplastic and nonanaplastic samples; the median +/- quartile deviation was 23 +/- 16 in anaplastic samples and 18 +/- 5 in nonanaplastic samples (P < 0.005). Even more significant differences were found when MRGlu was normalized to the cortex or to the white matter. Metabolic grades were different in anaplastic and nonanaplastic samples (P < 0.0001). Approximately 75% of samples metabolically graded 3 or 4 demonstrated signs of anaplasia, compared with 10% of samples graded 0 or 1., Conclusions: FDG uptake in gliomas is anatomically heterogeneous and is regionally related to the presence of anaplasia.