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Biomedical subjects

J C Mazziotta

Publications and source records attributed to J C Mazziotta.

At least 19 recordsLinked to original sources
PubMed1992

Cerebral glucose utilization in motor neuron disease.

Positron emission tomography with fluorodeoxyglucose F 18 (18F-fluorodeoxyglucose) was used to examine regional cerebral glucose metabolism in individuals with motor neuron disease. Motor neuron disease involves selective loss of motor neurons, large pyramidal cells in the motor cortex, and corticospinal tract degeneration. We postulated that the local cerebral metabolic rate of glucose should correlate with this regional neuronal cell loss. Glucose metabolism values in patients with motor neuron disease were reduced compared with those of controls in several regions; however, when corrected for multiple comparisons, no significant difference was observed between patients with motor neuron disease and age-matched controls. No correlation was noted between the local cerebral metabolic rate of glucose and duration or severity of illness. Correlation between metabolic changes with objective findings on neurologic examination, including motor weakness and tendon reflexes, provided interesting results, including a decline in glucose metabolism with progressive weakness and upper motor neuron dysfunction. Moreover, in supplementary motor areas, there appears to be an increase in regional glucose metabolism as the neurologic condition deteriorates, possibly representing increased metabolic activity of the motor association cortex in response to primary loss of pyramidal cells.

Adult↗
PubMed1992

Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.

OBJECTIVE: To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN: Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING: Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS: Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS: None. OUTCOME MEASURES: Onset of chorea and imaging results. RESULTS: The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS: The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.

Adult↗
PubMed1992

Psychiatric, genetic, and positron emission tomographic evaluation of persons at risk for Huntington's disease.

We examined chorea-free subjects at risk for Huntington's disease (n = 52) for lifetime psychiatric diagnoses, present mood, genetic marker status, and caudate glucose metabolic rates with positron emission tomography. Based on previous work, a caudate-ipsilateral hemisphere ratio less than 1.15 was defined as abnormal and predictive of Huntington's disease. None of three methods used to segregate subjects into groups more and less likely to develop Huntington's disease gave significant group rate differences for any formal psychiatric diagnoses. On present mood testing, however, subjective "anger/hostility" was significantly higher in those likely, compared with those less likely, to develop Huntington's disease, as determined by all three methods.

Adult↗
PubMed1992

Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder.

We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessive-compulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessive-compulsive disorder symptoms.

Adult↗
PubMed1992

The use of positron emission tomography in the clinical assessment of dementia.

A number of reasons can be cited for performing a test that identifies patients early in their course who have fatal and currently untreatable neurological disorders. At this stage of illness there is clinical ambiguity. The patient, family, and physician are typically faced with a battery of negative test results and an ambiguous clinical impression that can lead to periodic repetition of tests that involve cost, inconvenience, potential morbidity to the patient, and lack of definitive diagnosis. An accurate test would lead to the avoidance of these low-yield, repetitive, and costly evaluations. In addition, such studies can identify homogeneous groups of individuals with degenerative disorders leading to dementia who could be enrolled in experimental therapeutic programs. In these programs therapies could be monitored in an objective and noninvasive fashion using positron emission tomography (PET). The magnitude of the health problems resulting from the dementing illnesses is great in terms of medical practice, economics, and family hardship. The number of individuals with these disorders is predicted to increase dramatically in the future. The ability to provide an accurate diagnosis and more clear prognosis early in the disease course should diminish ambiguity for patients, families, and physicians. Ample evidence is cited in this article to show that PET has the ability to provide such information objectively and noninvasively.

Alzheimer Disease↗
PubMed1992

Human functional anatomy of visually guided finger movements.

The functional anatomy of visually guided movement was investigated in 18 normal subjects performing visuomotor tracking tasks during positron emission tomography imaging. Tracking a moving target with the index finger defined a network of focal responses of relative cerebral blood flow (relCBF) located in the primary motor cortex, dorsal parietal cortex, precuneate cortex, supplementary motor area (SMA) and ipsilateral anterior cerebellum relative to visual tracking alone. When the temporal complexity of the tracking task was altered by introducing a 'no go' contingency that allowed for greater time for movement preparation, there was a significant increase of relCBF in the SMA (P less than 0.0001). When the spatial complexity was augmented by adding a secondary target that provided directional cues for the primary target, there were additional significant increases of relCBF in bilateral dorsal parietal cortex (P less than 0.05) and precuneate cortex (P less than 0.05). Although the cued 'no go' task was subjectively easier, relCBF responses were similar to the uncued 'no go' task in motor areas. Performing the tracking task with different body parts produced somatotopically distributed responses in only the motor cortex. The findings are concordant with clinical reports of patients with brain lesions and physiological evidence that identifies this distributed network for performing visually guided movement. The results provide direct human evidence in the normal brain that the supplementary motor area contributes in part to the sequencing of movements and the medial and dorsal parietal cortex participates in the integration of spatial attributes during selection of movements.

Adult↗
PubMed1992

Positron emission tomography and familial Alzheimer's disease: a pilot study.

OBJECTIVE: Local cerebral metabolic rates for glucose were compared between patients with familial Alzheimer's disease (FAD), sporadic Alzheimer's Disease (SAD), and normal controls (NC) to determine if FAD is associated with a unique pattern of brain metabolism. DESIGN: Case-control study matched to convenience sample of FAD. METHODS: Subjects in the three diagnostic groups were scanned using fluorodeoxyglucose and the Positron Emission Tomographic (PET) technique. The criterion standard of a detailed clinical history and examination were compared to scan results. SETTING: Patients in a university hospital. SUBJECTS: Ambulatory controls and Alzheimer's patients, both sporadic (n = 8) and familial (n = 7). The two groups were similar in severity of cognitive dysfunction. RESULTS: FAD and SAD patients did not significantly differ in terms of local cerebral metabolic rates for glucose.

Aged↗
PubMed1992

Bilateral fetal grafts for Parkinson's disease: 22 months' results.

Five patients with severe Parkinson's disease underwent bilateral multiple graft implants of nondissociated fetal mesodiencephalic tissues. Graft implantation was performed in China following CT-guided stereotactic placement of a novel delivery system. Follow-up has demonstrated substantially reduced levodopa requirements and clinical improvements of motor, postural functions and reduction of freezing and on-off phenomenon. PET utilizing [18F]-dopa, at 14 months in the first case, suggested graft-induced restoration of dopaminergic transmission in the striatum.

Brain Tissue Transplantation↗
PubMed1992

Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET.

The functional anatomy of motor skill acquisition was investigated in six normal human subjects who learned to perform a pursuit rotor task with their dominant right hand during serial positron emission tomography (PET) imaging of relative cerebral blood flow (relCBF). The effect of motor execution, rather than learning, was identified by a comparison of four motor performance scans with two control scans (eye movements only). Motor execution was associated with activation of a distributed network involving cortical, striatonigral, and cerebellar sites. Second, the effect of early motor learning was examined. Performance improved from 17% to 66% mean time on target across the four PET scans obtained during pursuit rotor performance. Across the same scans, significant longitudinal increases of relCBF were located in the left primary motor cortex, the left supplementary motor area, and the left pulvinar thalamus. The results demonstrate that changes of regional cerebral activity associated with early learning of skilled movements occur in sites that are a subset of a more widely distributed network that is active during motor execution.

Adult↗
PubMed1992

The effects of carbidopa administration on 6-[18F]fluoro-L-dopa kinetics in positron emission tomography.

Carbidopa (L-alpha-hydrazino-alpha-methyl-b-(3,4-dihydroxyphenyl) propionic acid is a known inhibitor of aromatic amino acid decarboxylase. In both humans and monkeys, we studied the effects of carbidopa on plasma and brain kinetics of 6-[18F]fluoro-L-DOPA (FDOPA), an analog of L-DOPA used for PET studies of the central dopaminergic system. Pretreatment with carbidopa resulted in increases in the plasma levels of FDOPA and 3-O-methyl-6-[18F]fluoro-L-DOPA (3-OMFD). Total striatal and cerebellar activities measured with PET were also increased. Furthermore, increases observed in the specific striatal activity (striatum minus cerebellum total activity) were correlated with increases in the plasma FDOPA curve. Carbidopa pretreatment did not affect the influx rate constant (K) for FDOPA from plasma to striatum in humans as determined by Patlak graphical analysis. Thus, an increase in measured striatal tomographic activity was secondary to the increase in plasma FDOPA levels rather than as a result of changes in the FDOPA influx rate constant.

Adult↗
PubMed1991

Relating structure to function in vivo with tomographic imaging.

For the normal physiological responses of the brain or the pathophysiological changes that accompany disease states to be evaluated, it is necessary to compare data sets between different imaging modalities for individual subjects. Similarly, it is important to compare data between individuals both within and across imaging modalities for individual subjects. In a collaborative project with a number of university groups we have developed a system that allows for the within-subject alignment and registration of three-dimensional data sets obtained from different modalities for the same individual. This analysis takes into account the error induced by image acquisition, registration and alignment with regard to scaling, translation and rotation. A more difficult problem is the between-subject warping of individual brain anatomy to match that of another individual or of an idealized model. If the principles of morphometrics and homologous landmarks are applied, three-dimensional brain warping can provide this type of between-subject comparison. The results of accomplishing these two tasks is a system that allows data obtained in a given individual to be compared across structure and function, as obtained from magnetic resonance imaging (MRI) and from positron emission tomography (PET), respectively. It also allows comparison of the resultant information with averaged between-subject data from populations of normal individuals or patients with specific neurological disorders. This system provides the means by which to compare quantitative data between individuals in an objective and automated fashion.

Algorithms↗
PubMed1991

Changes in glucose metabolism in dementia of the Alzheimer type compared with depression: a preliminary report.

We evaluated positron emission tomography (PET) in the differential diagnosis of depression and Alzheimer's disease. The local cerebral metabolic rate for glucose (LCMRGlc) in the parahippocampal gyrus-hippocampus and the dorsolateral prefrontal cortex were determined. The ratio of the LCMRGlc in those two regions was examined in patients with unipolar depression, bipolar depression, and Alzheimer's dementia. An analysis of variance revealed significant overall intergroup differences in values for both hemispheres. Student's t test showed significant differences in LCMRGlc for both unipolar and bipolar depression as compared with Alzheimer's dementia. These data indicate that PET may be useful in the differential diagnosis of dementia vs. depression.

Aged↗
PubMed1991

Kinetics and modeling of L-6-[18F]fluoro-dopa in human positron emission tomographic studies.

Kinetics of L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) in striatum and cerebellum were measured in 10 normal human subjects with positron emission tomography (PET) from 0 to 120 min after an intravenous bolus injection of the tracer. The time course of the arterial plasma concentrations of the tracer and its metabolites was also assayed biochemically. FDOPA compartmental models that are based on biochemical information were investigated for their consistency with the measured striatal and cerebellar tissue kinetics. A modeling approach was also developed for separating plasma FDOPA and metabolite time-activity curves from the measured total 18F time-activity curve in plasma. Results showed that a model consisting of three separate compartments for tissue FDOPA, tissue 6-[18F]fluorodopamine (FDA) and its metabolites, and tissue L-3,4-dihydroxy-6-[18F]fluoro-3-O-methylphenylalanine (3-OMFD) could describe adequately the striatal kinetics in humans. Based on this model, the FDOPA transport constant across the blood-brain barrier (BBB) (K1), the FDOPA decarboxylation rate constant (k3), and the turn-over rate constant of FDA and its metabolites (k4) could be estimated by model fitting to the tissue kinetics and were found for the normal subjects to be 0.031 +/- 0.006 ml/min/g (mean +/- SD), 0.041 +/- 0.015/min, and 0.004 +/- 0.002/min, respectively. About 50% of the FDOPA that crossed the BBB from plasma to striatum was decarboxylated. The decarboxylation constant with respect to plasma FDOPA (K3) was 0.015 +/- 0.003 ml/min/g. The BBB transport corresponded to a permeability-surface area product of 0.032 ml/min/g for FDOPA. For 3-OMFD, the BBB transport was 1.7 times faster. The effects of tissue heterogeneity on the FDOPA kinetics and on the estimated model parameters were also investigated. The usefulness and implications of these findings for interpretation of PET FDOPA studies are discussed.

Adult↗
PubMed1991

Assessment of accuracy of PET utilizing a 3-D phantom to simulate the activity distribution of [18F]fluorodeoxyglucose uptake in the human brain.

A three-dimensional brain phantom has been developed to simulate the activity distributions found in human brain studies currently employed in positron emission tomography (PET). The phantom has a single contiguous chamber and utilizes thin layers of lucite to provide apparent relative concentrations of 5, 1, and 0 for gray matter, white matter, and CSF structures, respectively. The phantom and an ideal image set were created from the same set of data. Thus, the user has a basis for comparing measured images with an ideal set that allows a quantitative evaluation of errors in PET studies with an activity distribution similar to that found in patients. The phantom was employed in a study of the effect of deadtime and scatter on accuracy in quantitation on a current PET system. Deadtime correction factors were found to be significant (1.1-2.5) at count rates found in clinical studies. Deadtime correction techniques were found to be accurate to within 5%. Scatter in emission and attenuation correction data consistently caused 5-15% errors in quantitation, whereas correction for scatter in both types of data reduced errors in accuracy to less than 5%.

Brain↗
PubMed1991

Region of interest issues: the relationship between structure and function in the brain.

The comparison of data sets from individual subjects between imaging modalities is necessary in order to evaluate the normal physiologic responses of the brain or the pathophysiological changes that accompany disease states. Similarly, it is critical to compare data between individuals both within and across imaging modalities. In a collaborative project with a number of university groups, we have developed a system that allows for the within-subject alignment and registration of three-dimensional data sets obtained from different modalities for the same individuals. These data make use of proposed criteria for the optimal solution to positron emission tomography image acquisition and analysis originally established through a series of international workshops. The analysis takes into account errors induced by image acquisition, registration, and alignment with regard to scaling, translation, and rotation. Using the principles of morphometrics and homologous landmarks, the between-subject warping of individual brain anatomy to match that of other individuals, groups or an idealized model can be obtained. Resultant information can provide averaged between-subject data for populations of normal individuals or patients with specific neurologic disorders. Such a system, provides the means by which to compare objectively quantitative data between individuals in a highly automated fashion.

Brain↗