A novel, integrated PET-guided MRS technique resulting in more accurate initial diagnosis of high-grade glioma.

Glioblastoma multiforme (GBM) is the most common and lethal malignant glioma in adults. Currently, the modality of choice for diagnosing brain tumor is high-resolution magnetic resonance imaging (MRI) with contrast, which provides anatomic detail and localization. Studies have demonstrated, however, that MRI may have limited utility in delineating the full tumor extent precisely. Studies suggest that MR spectroscopy (MRS) can also be used to distinguish high-grade from low-grade gliomas. However, due to operator dependent variables and the heterogeneous nature of gliomas, the potential for error in diagnostic accuracy with MRS is a concern. Positron emission tomography (PET) imaging with (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) has been shown to add additional information with respect to tumor grade, extent, and prognosis based on the premise of biochemical changes preceding anatomic changes. Combined PET/MRS is a technique that integrates information from PET in guiding the location for the most accurate metabolic characterization of a lesion via MRS. We describe a case of glioblastoma multiforme in which MRS was initially non-diagnostic for malignancy, but when MRS was repeated with PET guidance, demonstrated elevated choline/N-acetylaspartate (Cho/NAA) ratio in the right parietal mass consistent with a high-grade malignancy. Stereotactic biopsy, followed by PET image-guided resection, confirmed the diagnosis of grade IV GBM. To our knowledge, this is the first reported case of an integrated PET/MRS technique for the voxel placement of MRS. Our findings suggest that integrated PET/MRS may potentially improve diagnostic accuracy in high-grade gliomas.

Radiation dose to the fetus from [(18)F]-FDG administration during the second trimester of pregnancy.

The authors estimated the fetal radiation dose from [(18)F]-FDG in a rare case of a woman who underwent a PET/CT scan during the second trimester of pregnancy. The patient, a 27-y-old female with a paraganglioma, received 181.3 MBq [(18)F]-FDG. From the concentrations of radioactivity measured on the images, the time-integrated activity coefficients of the fetus and the placenta were derived. The time-integrated activity coefficients of the mother's organs were taken from the standard values of ICRP publication 106. The final fetal dose was calculated using the 6-mo pregnant model of the OLINDA/EXM software. The fetus showed an overall low and homogeneous [(18)F]-FDG uptake, with an average concentration of 2.41 kBq cm(-3). The uptake in the placenta was generally higher (average concentration = 3.69 kBq cm(-3)). The estimated time-integrated activity coefficients were 0.0130 and 0.0058 Bq h Bq(-1) for the fetus and the placenta, respectively. The final average dose to the fetus was 1.97 × 10(-2) mGy MBq(-1) (3.6 mGy in this patient who received 181.3 MBq). Therefore, the dose to the fetus from [(18)F]-FDG administration during the second trimester of pregnancy is low. When medically indicated, pregnancy should not be a categorical basis for withholding [(18)F]-FDG PET scans.

Advanced adenoma diagnosis with FDG PET in a visibly normal mucosa: a case report.

BACKGROUND: An accurate, early diagnosis and treatment of adenomatous polyp can curtail progression to colorectal cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) reveals the biochemical changes associated with the development of many cancers which precede the appearance of gross anatomical changes that may be visualized during surgical resection or via imaging with MR or CT. INTERVENTION: We detail the history of a 64 year old female who had a whole-body FDG PET scan as a part of an employee wellness program. A dose of 12.2 mCi of F-18 labeled FDG was administered. RESULTS: A focal cecal uptake with a standardized uptake value (SUV) of 8.9 was found on the PET scan. Conversely, only normal mucosa was observed during a colonoscopy done 2 months after the PET scan. Motivated by the PET scan finding, the colonoscopist performed a biopsy which revealed a villous adenoma without high grade dysplasia. Pathology from tissue extracted during an exploratory laparatomy completed one month later found the lesion to be a villous adenoma with high grade dysplasia. CONCLUSION: Whole-body FDG PET scan revealed the biochemical metabolic changes in malignancy that preceded the appearance of any gross anatomical abnormality. A positive FDG PET scan indicative of colorectal cancer should be followed up with a colonoscopy and biopsy even in a visibly normal mucosa.

Image guidance during abdominal exploration for recurrent colorectal cancer.

BACKGROUND: Real-time intraoperative image guidance has been successfully applied to malignancies of the head, neck and central nervous system. Few attempts have been made to apply this technology to gastrointestinal cancers. Our purpose was to determine if a computer-assisted navigation system could be accurately used at the time of abdominal exploration. METHODS: Fourteen patients with resectable recurrent colorectal cancer underwent computer tomography (CT) imaging of the abdomen and pelvis. The CT images were uploaded to a StealthStation (Medtronic, Inc., Minneapolis, MN), a device that tracks the motion of a handheld probe in the operating field and displays its position, in real time, on the uploaded images. Various anatomic points were utilized to match, or register, the patient to the images in the navigation system. After four or more anatomic points were registered, the accuracy of the registration process was computed by the navigation system and reported as the global error. RESULTS: A total of 23 different anatomic structures were used for registration. The median number of points used for registration per patient was 6.5 (range 5-9). The anatomic sites most commonly used were the anterior superior iliac spines, aortic bifurcation, sacral promontory, symphysis pubis, and iliac artery bifurcation. The median global error was 10.0 mm (range 6.7 mm-27.0 mm). CONCLUSION: Computer-assisted navigation systems can be used to accurately deliver image guidance at the time of abdominal exploration. Future work will be directed at determining the value of this technology in the localization and resection of tumors.

Functional imaging in Lhermitte-Duclose disease.

PURPOSE: A comprehensive metabolic characterization of a patient with dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos Disease (LDD) is presented. PROCEDURES: Assessment using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), carbon-11-labeled methionine (11C-MET), carbon-11-labeled choline (11C-Choline) positron emission tomography (PET), and 1H-proton magnetic resonance spectroscopy (MRS) was carried out in a 30-year-old Caucasian woman. RESULTS: FDG-PET revealed hypermetabolism of the tumor. 11C-MET-PET revealed moderate uptake and 11C-Choline showed no uptake. 1H-MRS demonstrated an elevated level of lactate and decreased levels of choline (Cho) and myoinositol. CONCLUSION: Functional imaging in LDD reflects the dual pathological features of neoplasm and hamartoma.

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy.

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Brain imaging of 18F-fallypride in normal volunteers: blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors.

Human studies of dopamine D2/D3 receptors using 18F-fallypride-PET in normal volunteers were performed to evaluate brain distribution in striatal and extrastriatal regions, evaluate metabolites in blood plasma, establish PET imaging protocol for this new radiotracer, evaluate graphical methods of analysis to quantitate D2/D3 receptors, and assess the ability of 18F-fallypride to measure changes in D2/D3 receptors with aging as a model. Subjects (6; 21-63 years) had a PET scan on a Siemens HR+ scanner with 18F-fallypride and a T1-weighted MRI scan on a 1.5T GE scanner for purposes of anatomical coregistration with PET. A 3-h PET scan with 18F-fallypride (0.07 mCi/Kg) was carried out on each subject and repeated in 4-6 weeks. Arterial or arterialized venous blood was obtained in all subjects in order to evaluate blood activity levels and analyze metabolites in the plasma. Brain regions-of-interest were identified and drawn using PET and PET-MR coregistered images. PET data was analyzed using graphical methods in which cerebellum was used as the reference region providing distribution volume ratios (DVR) from which binding potential (BP) was derived and used as a measure of concentration of receptors. Distribution of 18F-fallypride was consistent in all subjects studied and the rank order of receptor concentration was putamen > caudate > thalamus = pituitary > amygdala > colliculi > substantia nigra > hippocampus = temporal cortex > parietal cortex = occipital cortex = orbitofrontal cortex. For younger subjects, BP ranged from 37 for the putamen to 0.4 for orbitofrontal cortex, with a test-retest error of about 10%. Both hydrophilic and lipophilic metabolites were observed in arterial blood plasma and analyses showed approx. 30-40% of plasma radioactivity at 3 h was 18F-fallypride. With aging, all brain regions exhibited a significant decrease (>10% per decade) in binding of 18F-fallypride. PET studies with 18F-fallypride are thus suitable to study changes in D2/D3 receptors in striatal and extrastriatal brain regions.

A comparative study on the uptake and incorporation of radiolabeled methionine, choline and fluorodeoxyglucose in human astrocytoma.

PURPOSE: The goal of this investigation was to evaluate uptake and incorporation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG), 11C-methionine, and 11C-choline in 17 patients suspected of grade-II and grade-III tumors using positron emission tomography (PET) and use in vitro astrocytoma cell lines in order to support in vivo findings. METHODS: Seventeen patients with suspected astrocytomas (9 grade-II and 8 grade-III) were studied by PET with FDG and 11C-methionine; and one patient (grade-III) with FDG, 11C-methionine and 11C-choline. Uptake of PET molecular imaging probe was quantitative based on tumor to corresponding contralateral-region uptake ratio, tumor to mean-cortical-uptake ratio, and tumor to white matter uptake ratio. This was correlated with World Health Organization histology grading system and clinical follow-up. Uptake and incorporation of 3H-methionine, 3H-choline and FDG into lipid, RNA, DNA, and protein were investigated in a grade-III human tumor brain-14 astrocytoma cell line. RESULTS: A time-dependent increase in the total uptake of 3H-methionine, 3H-choline and FDG was observed in human tumor brain-14 astrocytoma-III cell line. 3H-methionine was incorporated predominantly into proteins (in excess of 40% at 1 h) while 3H-choline incorporated primarily into lipids (in excess of 60% at 1 hr). Total uptake of FDG was accounted for in the free-pool supernatant fraction. In all patients, PET images of 11C-methionine and FDG provided higher tumor to white matter ratios than tumor to corresponding contra-lateral region ratios and tumor to mean cortical uptake ratios. In grade II patients, FDG did not exhibit significant increase in tumor uptake, while 11C-methionine was a good predictor with ratios of approximately 1.50 +/- 0.48. In grade III patients, both FDG and 11C-methionine exhibited higher ratios than for grade II, with 11C-methionine being the greatest (ratios of 2.50 +/- 0.85), possibly suggesting enhanced protein synthesis. With respect to tumor delineating potential, 11C-choline may be equal to or slightly better than 11C-methionine in the subject evaluated with all three probes. CONCLUSIONS: Results suggest that a combination of FDG and 11C-methionine is useful in the prediction of histological grade of astrocytomas. In addition, 11C-methionine is better than FDG in delineating tumor boundary for low-grade gliomas. In vitro results suggest that 3H-methionine is significantly incorporated into proteins and provides the major driving force in the uptake of 11C-methionine observed in PET images.