A relationship between metabolism in frontal lobes and cerebellum in normal subjects studied with PET.

Lesions of one cerebral hemisphere are associated with decreased glucose metabolism, oxygen metabolism, and blood flow in the contralateral cerebellar hemisphere. We used positron emission tomography to look for a functional relationship in cerebral metabolism between the cerebral cortex and the contralateral cerebellum in normal human subjects. Twenty-four normal subjects were scanned with [18F]fluoro-2-deoxy-D-glucose while in a resting state. Asymmetry in local CMRglu (LCMRglu) in the frontal cortex was strongly correlated with asymmetry in LCMRglu in the opposite direction in the cerebellar hemispheres (r = -0.60, p less than 0.001). Widespread subregions of the frontal cortex were found to contribute to this relationship. Considering these results together with previous studies demonstrating that frontal lesions are associated with decreased metabolism in the contralateral cerebellum, we conclude that the frontal cortex exerts a strong modulating influence on metabolism in the contralateral cerebellum in normal subjects, and that this influence may be asymmetrical.

Normal caudate glucose metabolism in persons at risk for Huntington's disease.

Glucose metabolism was examined by positron emission tomographic scanning with F-2-fluoro-2-deoxy-D-glucose in 29 persons at risk for Huntington's disease (HD), 28 age-matched controls, nine patients with stage I, and eight patients with stage II symptomatic HD. Absolute caudate metabolic rates and normalized indexes of caudate metabolism for at-risk persons were normal compared with controls. No at-risk person had caudate indexes outside two SDs of the controls' mean. Caudate metabolism in the earliest HD cases was significantly reduced compared with controls and at-risk persons, but within the 99% confidence levels of both groups. Stage II patients had caudate measures that were significantly depressed compared with those of stage I HD patients. Measurement of caudate glucose hypometabolism is unlikely to be sufficiently sensitive to serve as a presymptomatic marker of heterozygote status, although it will provide a sensitive marker for progressive caudate dysfunction in HD.

Neuronal mapping of the heart with 6-[18F]fluorometaraminol.

The false neurotransmitter metaraminol labeled with fluorine-18 has been used to noninvasively assess regional adrenergic nerve density in the canine heart. Intravenous administration of 6-[18F]fluorometaraminol (FMR) results in high, selective accumulation of radioactivity in the heart; drug blocking studies with desipramine and reserpine confirm the neuronal locus of FMR. Iodine-125 labeled metaraminol, however, shows no selective accumulation in the canine heart. Positron emission tomography (PET) analyses with FMR of closed-chest dogs bearing left ventricular neuronal defects clearly delineate the region of neuronal impairment; blood perfusion in the left ventricle wall was homogeneous as determined by [13N]NH3 tomograms. The accumulation of FMR in regionally denervated dog heart correlates closely (r = 0.88) with endogenous norepinephrine concentrations. PET-generated 18F time-activity curves demonstrate marked kinetic differences between normal and denervated myocardium. FMR/PET analysis could be used to assess the heterogeneity of sympathetic innervation in human heart disease contingent on the development of FMR with sufficiently high specific activity to clearly avoid pressor activity.

Examination of assumptions for local cerebral blood flow studies in PET.

Two common assumptions made in most positron emission tomography (PET) cerebral blood flow techniques have been examined in detail. These are (1) that the blood-borne radioactivity component in the measured PET data is negligible, and (2) that differences in arrival time of the arterial bolus across the brain cause insignificant biases in the estimated cerebral blood flow (CBF) values. Biases in CBF values due to partial failure of these assumptions have been predicted by computer simulation studies and also quantitated for both dynamic and single scan PET methods using H2 15O. Both computer simulations and measured PET data indicate that these assumptions can sometimes cause significant errors in the estimated flow values. The magnitude of these errors depends on the PET technique used (dynamic or static) and on the interval of data included in the flow calculations. The bias caused when these assumptions fail can be considerably reduced by omitting approximately 40 sec of data immediately following tracer administration from the CBF calculations.

An automated analysis program for the evaluation of cardiac PET studies: initial results in the detection and localization of coronary artery disease using nitrogen-13-ammonia.

Positron emission tomography (PET), in combination with myocardial blood flow tracers, allows highly accurate diagnosis of coronary artery disease using visual data interpretation. To increase the objectivity of data analysis and to reduce interobserver variability, we developed an automated analysis method for the three-dimensional definition of myocardial activity, which includes true volumetric data extraction and mathematical constraints of activity sampling to the expected shape of the left ventricle. Data are displayed in a standardized polar map or three-dimensional format for comparison with a normal database. The first clinical evaluation of this method in 52 patients using receiver operating characteristics (ROC) curve analysis demonstrated high diagnostic accuracy for detection as well as localization of coronary artery stenosis in predefined vascular territories. The interobserver and intraobserver agreement for localization of disease was excellent, with correlation coefficients varying from 0.85 to 0.99 for individual vascular territories. Thus, this automated quantitative analysis program provides highly accurate and reproducible evaluation of cardiac PET flow studies. Definite determination of its diagnostic accuracy requires a prospective multicenter trial in a larger patient population employing the criteria for abnormality established in this initial clinical evaluation.

Anxiety and cerebral cortical metabolism in normal persons.

The State-Trait Anxiety Inventory (STAI) was administered to 43 normal volunteers immediately before and after a positron emission tomography (PET) procedure with [18F]-2-fluoro-2-deoxy-D-glucose (18F-FDG). High trait-anxious individuals had significantly higher state (situational) anxiety associated with the PET scan procedure than did low trait-anxious persons. State anxiety decreased significantly for all respondents following the PET scan procedure. No significant relationships between global or regional cortical metabolic rates and state anxiety were observed. The direct cortical metabolic effects of heightened anxiety in the scan setting, should they exist, are likely obscured in the normal variance of the 18F-FDG method.