Primary or working memory in frontal lobe epilepsy: An 18FDG-PET study of dysfunctional zones.

INTRODUCTION: We previously demonstrated that patients with frontal lobe epilepsy show deficits on a visual working memory paradigm and that this paradigm produces increased 18FDG uptake in the dorsolateral prefrontal cortex (DPFC), premotor cortex, angular and supramarginal gyri, basal forebrain, and ventral frontal poles of normal subjects when compared with a control task. We hypothesized that subjects with frontal lobe epilepsy would have impaired frontal activation during this task. METHODS: One resting and two activated images were obtained with 18FDG-PET in 15 subjects and 14 controls. One was a delayed (DMS) and one an immediate (IMS) match to sample paradigm. Discriminant and factor analyses were used to analyze the data, supplemented by selected t tests. RESULTS: No differences in glucose uptake were found between the DMS and IMS in the epilepsy subjects, in distinct contrast to controls. A comparison between controls and epilepsy subjects showed differences both ipsilateral and contralateral to the epileptic focus in the frontal regions involved in the task, with small changes in nonfrontal, task-related regions as well. The task itself brought out or highly exaggerated differences seen at rest. There was weak evidence that other frontal and temporal regions were attempting to compensate for the DPFC deficit. CONCLUSION: A unilateral epileptic focus is capable of suppressing function along a large task-related circuit ipsilateral and contralateral to the focus. Peripheral cortical regions compensate poorly for the area of dysfunction.

Cerebral metabolic change in patients with AIDS: report of a six-month follow-up using positron-emission tomography.

The authors examined change in cerebral metabolic function over time by using PET in HIV-infected individuals diagnosed with AIDS. Ten subjects with AIDS received [18F]2-fluoro-2-deoxy-D-glucose PET scans and completed a comprehensive neuropsychological battery. The scan and test battery were repeated after 6 months. Over time, the subjects showed increased relative basal ganglia metabolism as well as increased parietal lobe metabolism. There were no statistically significant changes in neuropsychological performance. These results suggest that PET may be more sensitive than traditional neuropsychological evaluation to subtle central nervous system changes in AIDS.

Age-associated memory loss: initial neuropsychological and cerebral metabolic findings of a longitudinal study.

To determine the relationships between clinical and brain function in persons with a familial risk for Alzheimer's disease, the authors assessed subjective and objective cognitive abilities, mood state, and cerebral glucose metabolism (using positron emission tomography) in 43 persons with age-associated memory impairment, with and without first-degree relatives with a clinical diagnosis of Alzheimer's disease. Subjective complaints of memory loss, mood state ratings, and objective memory measures were similar in persons with a family history of Alzheimer's disease (n = 29) compared to those without such a history (n = 14). Metabolic ratios in the frontal regions correlated with a decrease in a specific type of subjective memory complaint (mnemonics usage; p < .001) and some mood state ratings. These results indicate that parietal and temporal hypometabolism is not evident in persons with mild age-related memory complaints, even when such subjects have a familial risk for Alzheimer's disease. Moreover, self-reports of mnemonics usage may be sensitive indicators of decreased frontal lobe function. Longitudinal study will determine whether such clinical and metabolic measures will predict eventual disease progression.

An automated high pressure reaction vessel for routine preparation of short-lived radiopharmaceuticals.

A remote, automated high-pressure/temperature system for preparation of radiopharmaceuticals is described. The system was routinely employed in our laboratories in the production of multimillicurie amounts of 11C labeled D,L-amino acids in more than 90 production runs, with typical final D,L-product activities of 240-400 mCi. The high pressure system, however, is not restricted only to the production of 11C labeled amino acids, but for application in any synthetic procedure requiring high pressure (approximately 300 psia) and temperature (greater than 300 degrees C).

Enzymatic synthesis of [1-11C]pyruvic acid, L-[1-11C]lactic acid and L-[1-11C]alanine via DL-[1-11C]alanine.

L-[1-11C]Lactic acid was prepared enzymatically from [1-11C]pyruvic acid by way of DL-[1-11C]alanine, using remote, semiautomated procedures. The DL isomers of alanine were prepared by a modification of the Bucherer-Strecker reaction from no-carrier-added (NCA) hydrogen [11C]cyanide. The enantiomer mixture was transformed to [1-11C]pyruvic acid by successive elution through columns of (a) immobilized D-amino acid oxidase (D-AAO)/catalase and (b) immobilized L-alanine dehydrogenase (L-AID) or L-amino acid oxidase (L-AAO/catalase). [1-11C]-Pyruvic acid was subsequently converted to L-[1-11C]lactic acid by passage through a L-lactic dehydrogenase (L-LDH) column. L-[1-11C]Alanine and [1-11C]-pyruvic acid were separated chromatographically by way of a cation-exchange column (AG50W-X2, H+ form). Typically the synthesis time was 35-40 min after cyclotron production of hydrogen [11C]cyanide (400 mCi), with radiochemical yields of 25 mCi (25%) for L-[1-11C]lactic acid, 35 mCi (29%) for [1-11C]pyruvic acid, and 20 mCi (20%) for L-[1-11C]alanine. The use of immobilized enzymes eliminates the possibility of protein contamination and assures the production of sterile, pyrogen-free products, allowing for rapid and effective regio- and stereo-specific transformations.

L-[1-11C]leucine: routine synthesis by enzymatic resolution.

L-[1-11C]leucine, suitable for the determination of cerebral protein synthesis rates in man using positron emission tomography, has been synthesized using a modified Bucherer-Strecker reaction sequence. The isolation of the pure L-amino acid isomer from the enantiomeric mixture, initially obtained using either an open or closed reaction vessel, was achieved using a D-amino acid oxidase/catalase enzyme complex immobilized on a Sepharose support. The O2 required by the D-amino acid oxidase as the hydrogen acceptor was supplied by catalase. The L-[1-11C]leucine was obtained with a radiochemical purity of greater than 99% and with a radiochemical yield of 25%. Using a remote, semiautomated synthesis system, typical production time was 30-40 min after preparation of H11CN. The use of immobilized enzymes for rapid and effective resolution of amino acid enantiomers eliminates the possibility of protein contamination and assures the production of a sterile, pyrogen-free product.