Reproducibility or precision was measured for a current positron emission tomographic (PET) system and was simulated by both computer and experimental methods for potential future systems. The present and potential future precision of PET systems is on the order of 1 to 2% for equilibrium studies (such as fluorodeoxyglucose metabolism measurements) with a few million counts per image, and better than 10% for dynamic studies with a few hundred thousand counts per image. To take advantage of this high precision, the instrumental accuracy of PET systems should match or better the precision of the measurements. The major sources of inaccuracy in PET, outside of deficiencies in electronic or computer hardware and software, are poor resolution, nonuniform resolution, and scatter. The use of narrow bismuth germanate detectors, adequately large detector ring diameters, and properly designed interplane septa will provide substantial improvements in all of these deficiencies.

Brain↗

PubMed1984

Human sensory stimulation and deprivation: positron emission tomographic results and strategies.

Fluorine-18-labeled fluorodeoxyglucose was used to measure local cerebral glucose metabolism by means of positron emission tomography (PET) in patients and in normal subjects. Various states of audiovisual stimulation and deprivation were explored. Our experience in performing neurobehavioral PET studies in over 145 normal right-handed individuals is described. In normal subjects metabolic left-right symmetry was found in states of partial sensory deprivation (eyes patched or ears plugged). Metabolic asymmetries (right less than left) were observed in subjects with more complete sensory deprivation (eyes patched and ears plugged). Auditory stimulation studies in normal subjects demonstrated metabolic evidence of cerebral lateralization. No correlation between site of metabolic response and side of stimulation was observed. Both the site and the side (left versus right) of maximal metabolic response correlated with the type (verbal versus nonverbal) and content of the stimulus as well as with the strategy used by the subject to solve the listening task. Visual stimuli of increasing complexity produced symmetrical increases in metabolic rate for the primary and secondary visual cortices. Focal stimulation of the central portion of the retina produced focal responses limited to the occipital poles, while full-field visual stimulation produced increased metabolic activity throughout the entire extent of the primary visual cortex. Patients with lesions of the visual pathway that spared the visual cortex itself demonstrated abnormalities in visual cortical metabolic rate that correlated with clinical symptoms. The refinement of neurobehavioral PET studies is discussed in terms of the limitations presently induced by spatial resolution, temporal resolution, anatomical localization accuracy, experimental neuropsychological paradigm design, and data analysis techniques. These limitations, as well as future prospects for using PET to study human brain function in both normal and pathological states, are discussed.

Acoustic Stimulation↗

PubMed1984

Positron emission tomographic study of affective disorders: problems and strategies.

Because anatomical studies of psychiatric disorders in humans have been largely unsuccessful, and because pharmacological interventions in patients with mental illness can be analyzed by means of biochemical assay techniques, positron emission tomography (PET) provides an exciting new means to study mental illness. Using fluorine-18-labeled fluorodeoxyglucose and PET to measure local cerebral glucose utilization, the investigators examined patients with affective disorders and normal age-matched controls. Patients with unipolar depression were studied in a drug-free baseline state following short-term administration of methylphenidate and in a euthymic state in long-term follow-up. Patients with bipolar disorders were studied in either the manic or depressed phases of illness and again in a euthymic state in long-term follow-up. Age-matched controls were studied both with and without methylphenidate administration. The results demonstrate that metabolic subgrouping of patients may be possible. Mood changes produced by pharmacological agents resulted in changes in the patterns of metabolism when compared with the baseline state. Problems associated with the use of PET to study mental illness fall into the categories of patient classification (diagnosis, state, trait, ambient conditions, and mental processes) and data analysis (anatomical and statistical). These problems, the limitations of the present techniques, and strategies for their improvement are discussed. Despite these difficulties, PET should prove to be a fruitful means of exploring the human biochemical abnormalities associated with mental illness.

Bipolar Disorder↗

PubMed1984

Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography.

The principles and initial results of the use of PET to measure the local cerebral metabolic rate for protein synthesis ( lCRPS ) in humans are described. The labeling of leucine, phenylalanine, and methionine in the carboxyl position provides a strategy (selective position labeling) for discriminating between the incorporation of these amino acids into proteins and metabolic oxidation. In metabolic oxidation the label is removed from tissue through decarboxylation. The resulting labeled carbon dioxide is diluted by the tissue carbon dioxide pool, cleared from cerebral tissue by blood flow, and subsequently ventilated by the lungs. This approach also provides a plasma input function that is free of other labeled amino acids produced through systemic reactions, such as those that occur for methionine labeled in the methyl group. The measured lCRPS is in good agreement with values determined by Smith and Sokoloff by autoradiographic and biochemical assay techniques, as are the measured kinetic rate constants of bidirectional transport, incorporation into proteins, and metabolism, as determined in monkeys and humans using L-leucine labeled with carbon-11 in position 1 (L-[1-11C]leucine) with PET. The tissue leucine precursor pool exhibits a rapid turnover rate (1.5 to 2 minutes), while the metabolic pathway has a half-time (about 18 minutes) that is close to the radioactive half-life of carbon-11. The dietary state was found to affect the branching ratio of lCRPS /metabolism, with a fasted value of 0.4 and carbohydrate feed values ranging up to 1.7. The principle of the method appears sound, and a first-order model provides good fits to data, but much more work is required to determine and validate the model structure and to optimize the study conditions and estimation criteria.

Amino Acids↗

PubMed1984

Correlations of glucose metabolism and structural damage to language function in aphasia.

Studies of aphasic patients using [18F]fluorodeoxyglucose positron computed tomographs have shown areas of metabolic depression in the left hemisphere larger than the area of infarction noted on CT. To evaluate these metabolic differences in relationship to language abnormalities, 11 patients had metabolic scans, CT, and were administered the Boston Diagnostic Aphasia Battery and the Porch Index of Communicative Ability. Correlation analyses were computed between metabolic, CT, and language data. CT demonstrated reliable correlations of speaking, oral reading, and repetition to Wernicke' area, consistent with current anatomic language models, while metabolic data from areas posterior, inferior, and superior to the traditional Wernicke's area and the head of the caudate nucleus also had reliable correlations with aphasic language function. The utilization of both structural and metabolic brain measures may improve our understanding of the anatomy of language as related to aphasia.

Adult↗

PubMed1984

Positron computed tomography for the in vivo assessment of regional myocardial function.

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Animals↗

PubMed1984

Cerebral metabolic relationships for selected brain regions in healthy adults.

The local cerebral metabolic rate for glucose was determined in 26 regions of the brain in 31 healthy subjects who underwent resting fluorodeoxyglucose positron emission tomography. Intercorrelations among the 26 regional measures were accepted as reliable at p less than 0.01 (r greater than 0.45), uncorrected for the number of measures. From the matrix two apparently separate functional metabolic systems were identified: (1) a superior system involving the superior and middle frontal gyri, the inferior parietal lobule, and the occipital cortex; and (2) an inferior system involving the inferior frontal, Broca's, and posterior temporal regions. Evidence is presented to suggest that the superior system is involved in visual processing, memory recognition, and decision making, while the inferior system seems to at least participate in language-related functions.

Adult↗

PubMed1984

Cerebral metabolic relationships for selected brain regions in Alzheimer's, Huntington's, and Parkinson's diseases.

Local CMRGlc values were determined for 13 regions in each hemisphere from tomographs of patients with Alzheimer's, Huntington's, and Parkinson's diseases who were studied using [18F]fluorodeoxyglucose with positron emission computed tomography. Intercorrelations among the 26 regional measures were calculated for each disease state and for normal controls, and were accepted as reliable at p less than 0.01, uncorrected for the number of comparisons. The number of reliable correlations was found to be decreased in Parkinson's and Huntington's diseases, two primarily subcortical disorders, and increased in Alzheimer's disease, a primarily cortical disorder. The changes suggest that one role of the basal ganglia involves coordinating or pacing the ability of cortical brain regions to function as a unit.

Aged↗

PubMed1984

A kinetic evaluation of blood-brain barrier permeability in human brain tumors with [68Ga]EDTA and positron computed tomography.

Twelve patients with primary and metastatic brain tumors were evaluated with [68Ga]ethylenediaminetetraacetate (EDTA) and positron computed tomography. Using a two-compartment tracer kinetic model, forward (K1) and reverse (k2) rate constants for molecular diffusion across the blood-brain barrier (BBB) were obtained and averaged 0.0029 +/- 0.0016 (mean +/- SD) ml/min/g for K1 and 0.0310 +/- 0.0156 min-1 for k2. Most tracer kinetic models are based on the assumption that tissue radioactivity contains no vascular component or require independent measures of cerebral blood volume (CBV) which are then subtracted from the measure tissue activity. The model in this work differs from that approach by assuming a vascular compartment in the tissue kinetic data. This vascular parameter is estimated from sequential measurements of activity concentrations in regions with an intact BBB or from measurements of 68Ga concentrations in the plasma (the input function). Thus, this approach does not require the assumption of a zero vascular contribution, does not require a separate measurement of CBV, and uses the criteria of constrained estimation to provide estimates of the local CBV and molecular diffusion through the BBB. Estimates of the relative CBV of the lesions in four studies (three subjects) with [68Ga]EDTA correlated well with those obtained with the C15O hemoglobin technique (correlation coefficient of 0.97).

Blood Volume↗

PubMed1984

Complex carbohydrate diets are not capable of maintaining normal plasma calcium and phosphorus levels in vitamin D-deficient rats.

Substitution of Cerelose (glucose monohydrate) for complex carbohydrate (whole wheat flour) does not alter plasma calcium levels in vitamin D-deficient rats, contrary to a previous report. It is suspected that whole wheat flour may contain traces of vitamin D that result in a slower rate of depletion than found with Cerelose diets. Vitamin D-deficient rats showing low plasma 1,25-dihydroxyvitamin D3 levels and no detectable 25-hydroxyvitamin D3 levels in their blood show a hypocalcemia (5.6 mg/dl) and normal phosphatemia whether fed whole wheat or Cerelose diets.

Animals↗

PubMed1984

Kinetic characterization of 13NH3 and [13N]glutamine metabolism in rabbit heart.

The isolated arterially perfused rabbit interventricular septum was used to study the effects of methionine sulfoximine (MSO) on 13N-labeled ammonia (13NH3) and 13N-labeled glutamine [( 13N]gln) metabolism. Tissue time-activity curves were generated from bolus injections of 13NH3 or [13N]gln delivered interarterially during control conditions and in the presence of MSO. The fraction of 13N label retained in the tissue [EF(3)] was significantly (P less than 0.01) less after a bolus of [13N]gln than 13NH3. MSO significantly (P less than 0.05) decreased the EF(3) after a bolus of 13NH3 or [13N]gln. Chemical analyses using high-pressure liquid chromatography on tissue and effluent samples obtained after bolus injections of 13NH3 and [13N]gln with or without MSO present showed the following: 1) after a bolus of 13NH3 or [13N]gln the tissue 13N label is predominantly in [13N]gln at 6 min after injection, and 2) MSO significantly decreases the synthesis of [13N]gln after an 13NH3 bolus. Thus it would appear that the glutamine synthetase reaction is primarily responsible for the retention of the 13N label from 13NH3 as [13N]gln in rabbit myocardium.

Ammonia↗

PubMed1984

Local cerebral metabolic rates of glucose in movement and language disorders from positron tomography.

Positron-computed tomography with [18F]fluorodeoxyglucose to measure glucose metabolism has shown changes in the brain distant to a focal area of infarction, demonstrating that what appears as a focal abnormality represents a more widespread functional process. Several approaches are presented to better understand quantitative metabolic data and focus on caudate and basal ganglia function. Area-to-area correlations in Parkinson's and Huntington's diseases showed decreases in the number of cortical relationships compared with control subjects, suggesting that the basal ganglia are involved with the ability of cortical regions to function together. In aphasia, caudate metabolism correlated with several language measures that suggested a role in some undefined basic process, seemingly related to Broca's area function. The studies presented suggest that the caudate may involve integrating the processing of language and cognition with the execution of the resulting response. Motor and cognitive function seem related to similar and overlapping brain systems. The disruption of such systems may result in loss of both cognitive and motor aspects of a function.

Aphasia↗

PubMed1984

Tomographic mapping of human cerebral metabolism: subcortical responses to auditory and visual stimulation.

We measured cerebral glucose metabolism with positron computed tomography during audio-visual stimulation in 42 studies of 21 subjects. Metabolic activations and stimulus-induced asymmetries were examined in subcortical structures (thalamus, caudate, lenticular nuclei). Bilateral activations of the thalamus occurred with verbal stimuli. The head of the left caudate was activated when subjects used visual imagery as a strategy to identify sequences of tones. These two types of stimuli produced dominant (left) hemisphere cortical activations in this same group of subjects. Clinical evidence has implicated the participation of subcortical (thalamus and basal ganglia) structures in the processing of language and auditory information. The present results demonstrate this functional role directly in normal subjects.

Acoustic Stimulation↗

PubMed1983

[Positron-computer tomography: a new method for the quantitative determination of metabolism, blood supply and function of the heart].

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Cardiomegaly↗