Regional cerebral blood flow measurement with intravenous [15O]water bolus and [18F]fluoromethane inhalation.

In 20 patients with ischemic cerebrovascular disease, classic migraine, or angiomas, we compared paired dynamic positron emission tomographic measurements of regional cerebral blood flow using both [15O]water and [18F]fluoromethane as tracers. Cerebral blood flow was also determined according to the autoradiographic technique with a bolus injection of [15O]water. There were reasonable overall correlations between dynamic [15O]water and [18F]fluoromethane values for cerebral blood flow (r = 0.82) and between dynamic and autoradiographic [15O]water values for cerebral blood flow (r = 0.83). We found a close correspondence between abnormal pathologic findings and visually evaluated cerebral blood flow tomograms obtained with the two tracers. On average, dynamic [15O]water cerebral blood flow was 6% lower than that measured with [18F]fluoromethane. There also was a general trend toward a greater underestimation with [15O]water in high-flow areas, particularly in hyperemic areas, probably due to incomplete first-pass extraction of [15O]water. Underestimation was not detected in low-flow areas or in the cerebellum. Absolute cerebral blood flow values were less closely correlated between tracers and techniques than cerebral blood flow patterns. The variability of the relation between absolute flow values was probably caused by confounding effects of the variation in the circulatory delay time. The autoradiographic technique was most sensitive to this type error.

Positron emission tomography findings in dementia disorders: contributions to differential diagnosis and objectivizing of therapeutic effects.

At present, positron emission tomography (PET) is the only technology affording the quantitative three-dimensional imaging of various aspects of brain function. Since glucose is the dominant substrate of the brain's energy metabolism, studies of glucose metabolism by PET of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) are widely applied for investigating the participation of various brain systems in simple or complex stimulations and tasks. In focal or diffuse disorders of the brain, functional impairment of affected or inactivated brain regions is a reproducible finding. While glucose metabolism is decreased slightly with age in a regionally different degree, in most types of dementia severe changes of glucose metabolism are observed. Degenerative dementia of the Alzheimer type is characterized by a metabolic disturbance most prominent in the parietooccipito-temporal association cortex and later in the frontal lobe, while primary cortical areas, basal ganglia, thalamus, and cerebellum are not affected. By this typical pattern Alzheimer disease can be differentiated from other dementia syndromes, as e.g. Pick's disease (with the metabolic depression most prominent in the frontal and temporal lobe), multi infarct dementia (with multiple focal metabolic defects), and Huntington's chorea (with metabolic disturbance in the neostriatum). In demented patients PET studies can also be applied to the quantification of treatment effects on disturbed metabolism. Such studies demonstrated an equalization of metabolic heterogeneities in patients responding to muscarinergic cholinagonists and diffuse increase of metabolism during treatment with piracetam. The therapeutic relevance of such metabolic effects, however, must be proved in controlled clinical trials.

Effect of piracetam on cerebral glucose metabolism in Alzheimer's disease as measured by positron emission tomography.

The effect of piracetam (a putative enhancer of cerebral metabolism) on regional CMRGlu was studied by positron emission tomography of 2[18F]-fluoro-2-deoxy-D-glucose in nine patients with Alzheimer's disease, and in seven cases with multiinfarct dementia or unclassified dementia. In Alzheimer's disease, i.v. administration of piracetam, 6 g b.i.d. for 2 weeks, significantly improved rCMRGlu in most cortical areas, whereas no effect on CMRGlu of the drug was observed in the multiinfarct dementia/unclassified dementia groups. These results lend further support to the notion that adjuvant piracetam treatment is of benefit in Alzheimer's disease. They may also indicate that the typical metabolic depression in Alzheimer's disease is caused by complex interaction of disturbed transmitter and cellular function rather than by a specific deficit in the cholinergic system alone.