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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 11C-methionine (MET) and 18F-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.

Brain tumors are a heterogeneous group, with the most common being meningiomas (35.5%) and gliomas (30%), with 54% of gliomas being highly malignant glioblastomas. The projected survival for a patient is based upon histologic grading, which may not accurately represent the actual pathology, given the frequent heterogeneity of gliomas and nonspecific guidance that comes from traditional anatomic imaging such as magnetic resonance (MR) and computed tomography. Molecular imaging, including glucose and amino acid transporters, is increasingly implemented in neuro-oncology since it provides additional metabolic and functional information about the tumor. Fully integrated within a comprehensive multidisciplinary clinical program, positron-emission tomography (PET) imaging with amino acid tracers, such as methionine, combined with traditional anatomic imaging information can be utilized to optimize the full course of patient care, including accurate initial diagnosis, fused PET/MR image-guided surgery, and evaluation of response to therapy as part of a patient-specific personalized treatment plan.

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. 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. 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). 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.

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.

Objectives: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-d-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy.

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.

Summary Purpose. To determine the metabolic characterization of a large solitary demyelinating lesion. Methods. Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) studies with 2-deoxy-2-[F-18]fluoro- d -glucose (FDG), carbon-11-methionine (methionine) and carbon-11-choline (choline) were done on the demyelinating lesion. Results. The demyelinating lesion exhibited a low glucose uptake, prominent methionine uptake and a minimal choline uptake on the PET studies. MRS data revealed an increased choline to creatine (cho/cr) ratio and a decreased N-acetyl-aspartate to creatine (NAA/cr) ratio, which demonstrated a return to near normal ratios on follow-up study. Conclusion. The report summarizes the metabolic characteristics of a demyelinating plaque.

Brain tumors are histologically heterogeneous. A technique for three-dimensional fusing of computed tomography (CT) or magnetic resonance images (MRI) with positron emission tomography (PET) images is described. This allows the anatomic detail provided by CT or MRI scans to be combined with the information about metabolic activity provided by PET scans. The fused images allowed selection of the most metabolically active portions of tumors. Fusion of CT and MRI images with PET scans has allowed first-pass diagnostic yield by providing the surgeon with a map of anatomical as well as functional (metabolic) detail. We describe a technique to allow routine fusion of MRI, CT, and PET information to help guide the neurosurgeon.

Brain tumors are histologically heterogeneous. A technique for three-dimensional fusing of computed tomography (CT) or magnetic resonance images (MRI) with positron emission tomography (PET) images is described. This allows the anatomic detail provided by CT or MRI scans to be combined with the information about metabolic activity provided by PET scans. The fused images allowed selection of the most metabolically active portions of tumors. Fusion of CT and MRI images with PET scans has allowed first-pass diagnostic yield by providing the surgeon with a map of anatomical as well as functional (metabolic) detail. We describe a technique to allow routine fusion of MRI, CT, and PET information to help guide the neurosurgeon.

Fourteen compounds (fluoroalkanes and fluoroethers), including the two most utilized inhalation anesthetics Isoflurane (CF 3 CHClOCF 2 H) and Halothane (CF 3 CHBrCl), have been labeled with fluorine-18 via a facile 18 F-for- 19 F exchange reaction. The compounds include ten inhalation anesthetics which span a ten-fold range in potency and four structurally related non-anesthetics. All the compounds possess a trifluoromethyl group ( CF 3 ) adjoining a carbon atom with an acidic α-hydrogen and at least one halogen or a strong electron withdrawing group ( X ), { CF 3 CHXR }. We postulate the isotopic fluoride exchange reaction proceeds through a carbanion transition state resulting from α-proton transfer to base. The carbanion stability is attributed to the inductive effect of the CF 3 group and the electron withdrawing capability of X. Compounds labeled in dimethyl sulfoxide (DMSO) at 125°C in 15 min include Isoflurane-CF 3 CHClOCF 2 H ( 1 ) (97% [ 18 F]fluorine incorporation, 99% radiochemical purity, respectively), Sevoflurane-CF 3 CHCF 3 OCFH 2 ( 2 ) [98%, 99%], CF 3 CHBrOCF 2 H ( 3 ) [85%, 80%], Desflurane-CF 3 CHFOCF 2 H ( 4 ) [50%, 99%], Fluroxene-CF 3 CH 2 OCHCH 2 ( 5 ) [25%, 99%], Fluothyl-CF 3 CH 2 OCH 2 CF 3 ( 6 ) [60%, 10% at a temperature of 175°C], Halothane-CF 3 CHBrCl ( 7 ) [98%, 95%], CF 3 CH 2 I ( 8 ) [99%, 98%], CF 3 CH 2 Br ( 9 ) [18%, 98%], CF 3 CH 2 Cl ( 10 ) [95%, 98%], CF 3 CHCl 2 ( 11 ) [90%, 20%], CF 3 CHClCF 3 ( 12 ) [95%, 99%], (CF 3 ) 3 CH ( 13 ) [99%, 99%] and HF-134a-CF 3 CFH 2 ( 14 ) (15%, 93% at a temperature of 175°C).

This work describes a new rapid method for the production of no carrier added (nca) [18F]fluoromethane ([18F]CH3F) (1) which avoids the use of the volatile precursor iodomethane and low boiling solvents, such as CH3CN. The presented method relies on the microwave induced [18F]fluoro-demethylation of the substrate 2-acetyl-N,N,N-trimethylanilinium trifluoromethanesulfonate 2a. Yields approaching 70% in synthesis times of 99%. The specific activity of the [18F]CH3F exceeded the upper limit of detection (>400 Ci/mmol). The technique described permits routine large scale or batch production of the PET flow tracer [18F]CH3F.

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.

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).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.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%).Prospective.Student's "t" test.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).FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Purpose: The goal of this investigation was to evaluate uptake and incorporation of 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG), 11 C-methionine, and 11 C-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 11 C-methionine; and one patient (grade-III) with FDG, 11 C-methionine and 11 C-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 3 H-methionine, 3 H-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 3 H-methionine, 3 H-choline and FDG was observed in human tumor brain-14 astrocytoma-III cell line. 3 H-methionine was incorporated predominantly into proteins (in excess of 40% at 1 h) while 3 H-choline incorporated primarily into lipids (in excess of 60% at 1hr). Total uptake of FDG was accounted for in the free-pool supernatant fraction. In all patients, PET images of 11 C-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 11 C-methionine was a good predictor with ratios of approximately 1.50 ± 0.48. In grade III patients, both FDG and 11 C-methionine exhibited higher ratios than for grade II, with 11 C-methionine being the greatest (ratios of 2.50 ± 0.85), possibly suggesting enhanced protein synthesis. With respect to tumor delineating potential, 11 C-choline may be equal to or slightly better than 11 C-methionine in the subject evaluated with all three probes. Conclusions: Results suggest that a combination of FDG and 11 C-methionine is useful in the prediction of histological grade of astrocytomas. In addition, 11 C-methionine is better than FDG in delineating tumor boundary for low-grade gliomas. In vitro results suggest that 3 H-methionine is significantly incorporated into proteins and provides the major driving force in the uptake of 11 C-methionine observed in PET images. (Mol Imag Biol 2002;4:147–156)

WKNI completed a Cooperative Agreement with AFRL to attempt to develop an infrastructure and demonstration project to exhibit and utilize technological developments with applications potentially valuable to both a military and civilian mission. Integrating mission critical information from a variety of formats and sources, and making them available to a highly trained operator, were seen as parallels between Air Force pilot and flight crew needs and the needs of a neurosurgeon and surgery team. Using the specialized knowledge and experience of the Human Effectiveness Directorate, we attempted to apply this knowledge to a civilian environment in the application and development of this technology.

Because automated methods that segment tomographic (medical) images often involve errors, editing tools that can rapidly correct the errors are needed. The editing tools presented in this paper may be considered a part of a postprocessing operation that evaluates the accuracy of an automated segmentation and refines the errors.

A rapid synthesis of the chlorofluorocarbon replacement compound 1,1,1,2-tetrafluoroethane (HFA-134a) was identified and utilized to prepare 99 + % radiochemically pure [18F]HFA-134a in 20–35% radiochemical yield. Four rats were then exposed to no-carrier-added (NCA) [18F]HFA-134a and monitored via coincidence detection. Following withdrawal of the test atmosphere of [18F]HFA-134a, the me an half-life of [18F]HFA-134a in four rats was determined to be 7.8 ± 1.5 min following a 10 s exposure and 8.1 ± 1.7 minutes following a 10 min exposure.