Donald Margouleff

The metabolic topography of parkinsonism.

We used [18F]fluorodeoxyglucose/positron emission tomography (18F-FDG/PET) and a statistical model of regional covariation to study brain topographic organization in parkinsonism. We studied 22 patients with Parkinsons disease (PD), 20 age-matched normal volunteers, and 10 age- and severity-matched patients with presumed striatonigral degeneration (SND). We used FDG/PET to calculate global, regional, and normalized metabolic rates for glucose (GMR, rCMRglc, rCMRglc/GMR). Metabolic parameters in the three groups were compared using an analysis of variance, with a correction for multiple comparisons, and discriminant analysis. The scaled subprofile model (SSM) was applied to the combined rCMRglc dataset to identify topographic covariance profiles that distinguish PD patients from SND patients and normals. GMR, rCMRglc, and rCMRglc/GMR were normal in PD; caudate and lentiform rCMRglc/GMR was reduced in the SND group (p < 0.01). SSM analysis of the combined group of patients and normals revealed a significant topographic profile characterized by increased metabolic activity in the lentiform nucleus and thalamus associated with decreased activity in the lateral frontal, paracentral, inferior parietal, and parietooccipital areas. Individual subject scores for this profile were significantly elevated in PD patients compared with normals and SND patients (p < 0.001) and discriminated the three groups. In the PD group, subject scores for this factor correlated with individual subject Hoehn and Yahr (H&Y) scores (p < 0.02), and with quantitative rigidity (p < 0.01) and bradykinesia (p < 0.03) ratings, but not with tremor ratings. SSM analysis of right-left metabolic asymmetries yielded a topographic contrast profile that accurately discriminated mildly affected PD patients (H&Y Stage I) from normals. Our findings demonstrate that abnormal topographic covariance profiles exist in parkinsonism. These profiles have potential clinical application as neuroimaging markers in parkinsonism.

Striatal 18F-DOPA Uptake: Absence of an Aging Effect

l-[18F]6-Fluoro-DOPA (l-[18F]6-fluoro-3,4-dihydroxyphenylalanine; FDOPA) has been used with quantitative positron emission tomography (PET) to assess presynaptic nigrostriatal dopaminergic function in life. The relationship of estimated kinetic rate constants for striatal FDOPA uptake [Ki(FDOPA)] to the normal aging process has been the subject of conflicting reports. Resolution of this issue has been hampered by methodological differences in previous FDOPA/PET investigations. We studied 19 healthy normal subjects (aged 27–77 years) and measured striatal Ki-(FDOPA) according to each of the earlier methods. While significant correlations (p < 0.005) existed between Ki(FDOPA) values estimated by the various techniques, none correlated with normal aging. We conclude that normal striatal Ki(FDOPA) values estimated using quantitative FDOPA/PET are uncorrelated with the aging process.

Radiosynthesis of [18F] N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane and the first human study with positron emission tomography☆

A procedure for the routine preparation of [18F]FP-CIT has been developed. Purification of the final product was achieved by preparative HPLC using phenethyl column without decomposition or epimerization. [18F] labeled-N-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane was prepared and PET imaging was performed on human subjects. A high uptake into striatal regions was observed. HPLC plasma analysis using [18F]FP-CIT indicated the presence of only one metabolite. By directly comparing the behavior of these three radiotracers ([18F]DOPA, [123I]FP-CIT, and [18F]FP-CIT) in the same subjects, we can enhance our understanding of the dopaminergic system as well as the relative potential of these techniques in a clinical research setting.

Feasibility of total thyroidectomy in the treatment of thyroid carcinoma: Postoperative radioactive iodine evaluation of 140 cases☆

The objective of this study was to evaluate our experience with so-called total thyroidectomy. Fifty cases (the retrospective group) had been operated on before the start of the study and had been on thyroid replacement therapy; this was discontinued, thyroid-stimulating hormone was administered, and iodine-131 studies were performed. Ninety cases (the prospective group) were evaluated 3 or more weeks postoperatively with no thyroid hormone having been administered. All patients were given 50 microcuries of iodine-131 and uptake studies were performed 24 hours later. All the patients were evaluated at a time when it was believed that practically all circulating hormone secreted by the thyroid gland before its removal had been metabolized or excreted from the body. If the patients with iodine-131 uptakes only in the region of the pyramidal lobe are considered to have had total thyroidectomy, we find that 85.7% of the patients studied had an uptake of less than 1.5%, and 96.4% had an uptake of less than 2.5%. There is increasing evidence to indicate that total thyroidectomy is the procedure of choice in the treatment of differentiated thyroid carcinoma. The present study indicates that with proper technique, total resection of the thyroid gland is feasible in nearly all cases of thyroid carcinoma.

Idiopathic hypertrophic subaortic stenosis: Evaluation of anginal symptoms with thallium-201 myocardial imaging

The evaluation of angina pectoris in patients with idiopathic hypertrophic subaortic stenosis is difficult in those in the age group prone to coronary artery disease. Ten patients with angina pectoris, normal coronary angiograms and idiopathic hypertrophic subaortic stenosis were studied with thallium-201 myocardial imaging performed in conjunction with submaximal treadmill exercise testing. The resting electrocardiogram demonstrated left ventricular hypertrophy with S-T segment abnormalities in seven patients, thereby vitiating the further increase in S-T segment abnormalities that developed in these patients during exercise or in the postexercise period. Of the three patients with a normal resting electrocardiogram, one had significant exercise-induced S-T segment depression. Thallium-201 myocardial imaging revealed no significant perfusion defects in 9 of the 10 patients (90 percent). In one patient with severe left ventricular hypertrophy significant perfusion defects developed after exercise that were not present at rest. Stress thallium-201 myocardial perfusion imaging is a useful noninvasive technique that assists in ruling out the presence of significant coronary artery disease in patients with idiopathic hypertrophic subaortic stenosis.

Quantitative Brain PET. Comparison of 2D and 3D Acquisitions on the GE Advance Scanner.

PURPOSE: Recent developments in the design of positron emission tomography (PET) scanners have made three-dimensional (3D) data acquisition attractive because of significantly higher sensitivity compared to the conventional 2D mode (with lead/tungsten septa extended). However, the increased count rate in 3D mode comes at the cost of increased scatter, randoms, and dead time. Several schemes to correct for these effects have been proposed and validated in phantom studies. In this study, we evaluated the overall improvement afforded by 3D imaging in quantitative human brain PET studies carried out at our institution.METHODS: Subjects were studied using sequential/interleaved 2D and 3D data acquisition with a GE Advance scanner. We calculated regional and global cerebral glucose metabolism with [(18)F]flourodeoxyglucose (FDG) and estimated rate constants for striatal [(18)F]fluorodopa (FDOPA) uptake.RESULTS: FDG: Global mean glucose metabolic rates were in almost complete agreement (within 1%) between the two modes whereas the regional differences ranged from -7.7% to +9% for all cortical structures. However, for small regions (<2 cm(2)) like caudate nuclei, the maximum difference was 14.7%. FDOPA: A significant improvement in image quality was evident in 3D mode and there was complete agreement between the estimated parameters in the two scanning modes for the same noise equivalent counts: Striatal-to-occipital ratio (SOR) and striatal FDOPA uptake (K(i)(FD)) had mean differences of less than 2% and 5%, respectively.CONCLUSIONS: 3D FDG studies can be done with either half the injected dose or half the scan duration to a comparable 2D study. 3D PET imaging has distinct advantages over 2D in the quantitative fluorodopa studies.

Imaging cerebral function

The Scan Analysis and Visualization Processor (Scan/VP), a flexible, portable, Unix-based software package for visualizing and analyzing positron emission tomography (PET) images in a clinical-research setting, is described. PET systems are compared to computerized tomography (CT) and magnetic resonance imaging (MRI) systems. The imaging and software aspects of Scan/VP, and procedures devoted specifically to functional PET imaging, including mathematical modeling, image registration, regional thresholding, and derivation of regional covariation patterns, are discussed. Basic surface display, animation, and stereo techniques for visualizing variations in metabolic topology and underlying disease patterns are also discussed.<<ETX>>

A large scale manual production of [18F]FDG using a synthetic unit made of sterile disposable components and operated by a Master Slave Manipulator

A self contained, Master Slave Manipulator operated and largely disposable apparatus for the large scale production of [18F]FDG using nucleophilic fluorination methodology has been developed. The synthetic unit consists of readily available sterile disposable components and is easy to assemble. Operation of the synthetic unit is carried out in a hot cell under a closed system to minimize radiation exposure to personnel. Recovery of [18O]water by direct distillation from the reaction vial makes the system even more attractive. Normal production runs yield 25–150 mCi of [18F]FDG. Since no manual handling of radioactivity is involved, a scaled up production is feasible by this procedure. Synthesis is based on the nucleophilic fluorination of 1.3.4.6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-d-mannopyranose (tetraacetyl precursor). We have avoided the use of any permanent electrical liquid transfer devices in our system, thereby eliminating the possibility of pyrogen build up. An in-house radiopharmaceutical program to check the sterility and apyrogenicity of the short-lived radiopharmaceuticals is an added convenience at our institution.

Synthesis of 6-[18F]fluorodopamine with a synthetic unit made up of primarily sterile disposable components and operated by a master slave manipulator

Abstract A synthetic procedure for the routine preparation of 6-[18F]fluorodopamine has been developed. The synthesis is based on electrophilic fluorination of a 6-mercurated dopamine precursor. Fluorodemercuration of the dopamine precursor using [18F]acetylhypofluorite and hydrolysis by a mixture of acetic anhydride and HI gave the desired radiopharmaceutical with a radiochemical yield of 13.7 ± 0.7% calculated at the end of synthesis based on five synthetic preparations (without decay correction) and also based on the amount of total [18F]F2 recovered from the target. Radiochemical purity as well as chemical purity were > 98%. In order to maintain good sterility and pyrogenicity, the synthetic unit is made up of mostly sterile disposable components that are readily available. The routine operations of the synthetic unit are carried out in a closed hot cell, using a Master Slave Manipulator arm. Since no manual handling of radioactivity is involved, the operation of the synthetic unit is radiation safe and the radiation exposure to the operator is minimized.

Hepatobiliary scintigraphy after biliary tract surgery

Hepatobiliary scintigraphy provides a rapid, noninvasive, accurate means of assessing patients after biliary tract surgery. This is especially important, given the high incidence of biliary and enteric diseases. In this review article, the role of radionuclide imaging in postcholecystectomy and postgastroenteric surgery patients will be examined, as well as following invasive procedures and trauma.