Biomedical subjects

J L Eberling

Publications and source records attributed to J L Eberling.

33 records · Page 2Linked to original sources

PubMed1997

A methodology for specifying PET VOI's using multimodality techniques.

Volume-of-interest (VOI) extraction for radionuclide and anatomical measurements requires correct identification and delineation of the anatomical feature being studied. We have developed a toolset for specifying three-dimensional (3-D) VOI's on a multislice positron emission tomography (PET) dataset. The software is particularly suited for specifying cerebral cortex VOI's which represent a particular gyrus or deep brain structure. A registered 3-D magnetic resonance image (MRI) dataset is used to provide high-resolution anatomical information, both as oblique two-dimensional (2-D) sections and as volume renderings of a segmented cortical surface. VOI's are specified indirectly in two dimensions by drawing a stack of 2-D regions on the MRI data. The regions are tiled together to form closed triangular mesh surface models, which are subsequently transformed into the observation space of the PET scanner. Quantification by this method allows calculation of radionuclide activity in the VOI's, as well as their statistical uncertainties and correlations. The methodology for this type of analysis and validation results are presented.

Brain↗

PubMed1996

Functional imaging predicts cognitive decline in Alzheimer's disease.

Eighteen patients with Alzheimer's disease were studied with positron emission tomographic measurements of regional cerebral metabolism of glucose. All patients were initially diagnosed and evaluated, underwent positron emission tomography, and then were followed with annual reevaluations, at which time the Mini-Mental State Examination (MMSE) was performed. Patients were followed for an average of 2.5 years, and the rate of cognitive decline was calculated by determining the rate of change in the MMSE score defined as the MMSE score at the initial evaluation minus the MMSE score at the last examination, divided by the number of months between testing. The regional cerebral metabolic rates for glucose determined at the time of the first MMSE were then regressed on these changes in scores. Results showed that glucose metabolic rates in posterior temporal and primary visual cortex regions were significantly correlated with the subsequent rate of cognitive deterioration. These associations were not confounded by age, length of follow-up, baseline MMSE score, or education. Stratification on gender suggested that these associations were much stronger in women than in men. These results replicate previous findings showing that functional brain imaging is predictive of the rate of cognitive decline in Alzheimer's disease.

Age Factors↗

PubMed1996

Iodine-123-5-iodo-6-nitroquipazine: SPECT radiotracer to image the serotonin transporter.

UNLABELLED: Because serotonergic function has been implicated in the pathophysiology of a number of diseases of the nervous system, efforts to image this system in vivo have received considerable recent attention. Promising preliminary results with the tracer 5-iodo-6-nitroquipazine (INQUIP) have prompted us to perform further studies designed to validate the use of the tracer as an in vivo ligand for the serotonin transporter. METHODS: We studied six adult macaca mulatta in eight experiments which involved SPECT imaging at 17 to 24 hr post-tracer injection, including three experiments with coinjection of the 123I-and 125I-radiolabeled tracer for direct comparison of autoradiography and SPECT, and three experiments in which animals were lesioned with the serotonergic neurotoxin (+/-)3,4-methyl-enedioxymethamphetamine (MDMA). In addition, we evaluated the metabolism of the tracer in the brain and periphery. RESULTS: SPECT images obtained at 17 and 24 hr reflected the known pattern of distribution of serotonin transporters and also showed close correspondence to the autoradiograms. Ratios of binding in the brain-stem to binding in the cerebellum were close to 3 at 17 hr. autoradiograms from an MDMA-treated animal showed up to 95% reductions of binding, while the SPECT data showed smaller reductions. Virtually all of the tracer in the brain stem was in the form of unmetabolized parent compound, but plasma showed rapid peripheral metabolism of the tracer. CONCLUSION: These results demonstrate that INQUIP SPECT images are sensitive measures of in vivo binding to the serotonin transporter, and support the further development of the tracer as a method for the in vivo study of serotonergic neurons in humans.

Animals↗

PubMed1995

Temporal lobe perfusion on single photon emission computed tomography predicts the rate of cognitive decline in Alzheimer's disease.

OBJECTIVE: To examine the ability of relative regional cerebral blood flow as measured by single photon emission computed tomography to predict longitudinal course of cognitive decline in Alzheimer's disease. DESIGN: Single photon emission computed tomography using the blood flow tracer 123I-N-isopropyl-p-iodoamphetamine was performed at initial evaluation and was used to predict the rate of cognitive decline over a follow-up period from 1 to 4 years. SETTING: Outpatient university dementia clinic and center for functional imaging. PARTICIPANTS: Twenty-nine patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probably or possible AD. RESULTS: Temporal lobe regional cerebral blood flow ratio at initial evaluation correlated with rate of decline in Mini-Mental State Examination over the longitudinal follow-up. Temporal regional cerebral blood flow ratio also predicted rate of decline of specific memory measures on the California Verbal Learning Test. Neither parietal nor frontal ratios predicted rate of cognitive decline. Dorsolateral frontal hypoperfusion was associated with the emergence of perseverative behaviors over time. Age, prior dementia duration, estimated prior rate of decline, and initial severity did not predict rate of cognitive decline. CONCLUSION: Results suggest that regional perfusion on single photon emission computed tomography may predict cognitive decline in Alzheimer's disease better than these demographic and course variables.

Aged↗

PubMed1995

Reduced temporal lobe glucose metabolism in aging.

The results of a positron emission tomography study of regional cerebral metabolic rates of glucose are reported for 8 healthy old subjects (mean age, 66 yr; standard deviation [SD], 5) and 9 young subjects (mean age, 27 yr; SD, 4.6) using a high-resolution positron emission tomograph and the glucose metabolic tracer 18F-fluorodeoxyglucose. Older subjects showed significantly lower cerebral metabolic rates than did the young subjects, in anterior, middle, and posterior temporal neocortex and in mesial temporal cortex, with the largest differences occurring in anterior temporal cortex (temporal pole). The current findings may reflect either decreases in regional cerebral metabolic rates for glucose that occur with normal aging, or early indications of cognitive dysfunction that is associated with age-related disorders.

Adult↗

PubMed1993

The cortical topography of temporal lobe hypometabolism in early Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a pathological process with specific predilection for association neocortex and the mesial temporal lobes. Recently developed high-resolution positron emission tomographs (PET) are able to quantitate regional cerebral metabolic rates for glucose (rCMRglc) in these brain regions and map the distribution of the metabolic consequences of Alzheimer pathology. In order to evaluate the relative involvement of mesial and neocortical temporal lobe brain regions in AD, we studied 22 AD patients, 11 of whom were mildly demented and 11 of whom were moderately demented in comparison to 8 age-matched control subjects. We used a PET instrument with 2.6 mm in-plane resolution and quantitated rCMRglc in anterior, middle, and posterior temporal neocortex, visual association cortex, primary visual cortex, and mesial temporal cortex. Although the moderately demented AD patients showed significantly lower metabolic rates than controls in visual association cortex and all temporal lobe regions except right anterior temporal neocortex, the mildly demented patients were different from the controls in only middle temporal neocortex. Considerable variability was found in the relative involvement of mesial temporal lobes and temporal neocortex in the AD patients, however, as shown by greater variance of a ratio of mesial temporal lobe rCMRglc to temporal neocortical rCMRglc (MES/NEO ratio) in the AD patients than the controls. A series of stepwise multiple regressions showed that this ratio was related to patient cognitive symptomatology, with more severely memory-impaired patients showing lower MES/NEO ratios, while patients with visuospatial disturbances showed higher MES/NEO ratios. In addition, the only biological variable that was related to this ratio was patient age, with older patients showing lower MES/NEO ratios. These results indicate that mesial temporal lobe structures are not invariably the earliest nor the most severely metabolically involved brain regions in AD and that the relative involvement of the mesial and neocortical temporal lobe is related to the patient's cognitive symptoms and age.

Aged↗

PubMed1993

In vivo imaging of the 5-hydroxytryptamine reuptake site in primate brain using single photon emission computed tomography and [123I]5-iodo-6-nitroquipazine.

Previous experiments have demonstrated that 5-iodo-6-nitro-2-piperazinylquinoline (5-I-6-NQP) is a potent and selective ligand for studying brain 5-hydroxytryptamine (5-HT) reuptake sites. We performed in vivo imaging in non-human primates using single photon emission computed tomography (SPECT) and the 123I-labeled compound [123I]5-I-6-NQP. These studies showed rapid brain uptake, with slow egress of the tracer from the brainstem, a region rich in 5-HT reuptake sites. Loss of the tracer from regions with a lower density of these sites, such as cerebellum, was relatively more rapid. Pretreatment of animals with paroxetine increased the washout of tracer from the brainstem to rates similar to that seen in cerebellum. Brainstem to cerebellar ratios of tracer accumulation were > 2 by 8 h after injection, and in paroxetine pretreated animals remained close to 1. These results indicate that the radiotracer has characteristics suitable for use as a SPECT imaging agent of serotonin reuptake sites.

Animals↗

PubMed1993

Cognitive correlates of regional cerebral blood flow in Alzheimer's disease.

OBJECTIVE: To study the relationship between relative regional cerebral blood flow (rCBF) and performance on a variety of neuropsychological tests in a group of subjects with Alzheimer's disease. DESIGN: Analysis of the relationship between relative rCBF and neuropsychological performance using stepwise multiple regressions and Pearson Product-Moment Correlation coefficients. SETTING: University dementia clinic and research laboratory. PARTICIPANTS: Twelve mildly demented patients with Alzheimer's disease (Mini-Mental State examination [MMSE] scores, 24 to 29; age, 56 to 78 years); 38 moderately demented patients with Alzheimer's disease (MMSE scores, 0 to 23; age, 59 to 86 years); and eight normal control subjects (MMSE scores, 27 to 30; age, 61 to 79 years). MAIN OUTCOME MEASURES: Single photon emission computed tomography and the blood flow tracer N-isopropyl-p-iodoamphetamine iodine 123 were used to measure relative rCBF. Cognitive performance was assessed by grouping neuropsychological tests into clusters reflecting frontal lobe abilities, perseveration, memory, and visuoconstructive abilities. RESULTS: While MMSE score was a significant (P < .05) predictor of visuoconstruction, frontal lobe, and memory cluster scores, relative rCBF was a weaker predictor of neuropsychological performance, with only right orbitofrontal relative rCBF emerging as a significant (P < .05) predictor of the frontal cluster score and right parietal relative rCBF as a significant (P < .05) predictor of the visuoconstruction cluster score. CONCLUSIONS: These results support our a priori grouping of neuropsychological tests into frontal and visuoconstruction clusters and suggest that these two clusters are good measures of frontal and parietal lobe function, respectively.

Aged↗

PubMed1992

Cognitive function and regional cerebral blood flow in Parkinson's disease.

In order to investigate relationships between cognition and regional brain function, we studied 20 non-demented patients with idiopathic Parkinson's disease (PD), 21 mildly demented patients with Alzheimer's disease (AD) and 24 control subjects using cognitive testing and single photon emission computerized tomographic (SPECT) measurements of relative regional cerebral blood flow (rCBF). Neuropsychological tests were grouped into clusters reflecting frontal lobe executive abilities, perseveration, memory and visuospatial ability, with a summary score summarizing performance in all four of these spheres. SPECT imaging utilized the tracer [123I]N-isopropyl-p-iodoamphetamine with a relative measure of regional tracer uptake normalized to occipital radiotracer uptake (rCBF ratios). Patients with PD performed more poorly than controls in all cognitive domains, and were intermediate to AD patients and controls in tests of memory and overall cognitive functioning. Those PD patients who performed most poorly on neuropsychological testing showed lowest rCBF ratios in left and right temporal lobes. Using a stepwise multiple regression procedure, we examined patterns of correlations between cognitive clusters and predictor variables, including rCBF ratios, in the PD patients. We found that while patient age was a strong determinant of performance on the memory cluster and the summary score, dorsolateral frontal lobe perfusion and scores on a depression inventory accounted for a greater proportion of the variance of the frontal lobe and perseveration clusters than did age. These results imply that different neural mechanisms are responsible for the different aspects of cognitive decline seen in PD patients, with overall cognitive function closely related to age and temporal perfusion, while frontal lobe abilities are more linked to frontal perfusion and the presence of depression.

Aged↗

PubMed1991

MRI, CT, SPECT, PET: their use in diagnosing dementia.

The differential diagnosis of the dementia syndrome may pose a difficult clinical problem, since the most common dementia, Alzheimer's disease (AD), is marked by normal laboratory tests. Neuroimaging has played an important role in evaluating the demented patient, and its uses are growing. Computed tomography (CT) is useful for excluding reversible and treatable causes of dementia, such as subdural hematoma and tumor. More recently, magnetic resonance imaging (MRI) has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on CT. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), techniques that visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence supportive of the diagnosis of AD.

Alzheimer Disease↗

PubMedDate not supplied

Reduced temporal lobe blood flow in Alzheimer's disease.

We used single photon emission computed tomography with the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine (IMP) to study regional cerebral blood flow (rCBF) in 50 mildly and moderately demented Alzheimer's disease (AD) patients to evaluate rCBF as a function of disease severity. Relative rCBF (normalized to occipital cortex) was significantly lower than controls in temporal cortex for both mildly and moderately demented patients. Similar numbers of patients in both groups demonstrated perfusion abnormalities in temporal neocortex. Parietal cortex was more variably involved with greater numbers of moderately than mildly demented patients showing perfusion abnormalities. Relative rCBF in dirsolateral frontal cortex was reduced only in the moderately demented patients. Disease severity, as measured by the Mini Mental Status Examination, was associated with relative rCBF only in dorsolateral frontal and parietal cortex. These results suggest that the temporal lobes are the first neocortical regions affected by AD and that other cortical areas become involved as the disease progresses.

Aged↗

PubMedDate not supplied

Cortical glucose metabolism in Parkinson's disease without dementia.

There have been several reports of decreased regional cerebral metabolic rates for glucose (rCMRglc) in Parkinson's disease (PD), although others find no differences between PD patients and controls. Differences in the cognitive status of the PD patients may account for some of these inconsistencies. We report the results of a PET study using 18F-fluorodeoxyglucose (FDG) to measure rCMRglc in eight nondemented PD patients, six of whom were receiving dopaminergic medications, and eight age-matched control subjects. We scanned one tomographic level through the temporal lobes that included both temporal neocortex and mesial temporal cortex, and one tomographic level through the basal ganglia that included frontal and parietal cortex. Previously determined rate constants and an operational equation were used to determine rCMRglc. On average, rCMRglc values were 23% below control values for all regions studied, with the greatest differences in posterior brain regions (visual association cortex, primary visual cortex, and parietal cortex) and thalamus. These results indicate that PD patients may show neocortical hypometabolism, especially in posterior brain regions, in the absence of any demonstrable cognitive deficits.

Aged↗

PubMedDate not supplied

Human corpus callosum in aging and Alzheimer's disease: a magnetic resonance imaging study.

The involvement of the corpus callosum in aging and Alzheimer's disease (AD) is not clear. We measured cross sectional areas of the entire corpus callosum (CC), as well as the front 20% (genu), middle 60% (body), and posterior 20% (splenium) of the structure from a midsagittal MRI slice in AD patients (N = 20), and young (N = 16) and old (N = 13) control subjects. We found that mean CC area in young controls was 570 +/- 107 mm2. Aging did not significantly affect the mean area of the CC (562 +/- 98 mm2). A small, significant reduction was seen in AD in comparison to the young control group (480 +/- 133 mm2). However, AD is accompanied by a large and statistically significant reduction in the genu area in comparison to both young and old control subjects. A trend toward an age-dependent reduction in the body area is also accentuated in AD patients who showed significantly smaller callosal bodies than young controls. We conclude that selective changes within corpus callosum accompany aging and AD pathology.

Adult↗

PubMedDate not supplied

PET studies of cerebral glucose metabolism in conscious rhesus macaques.

A growing body of evidence suggests that rhesus macaques may be a good model of human brain aging. We used positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) to measure regional cerebral metabolic rates for glucose (rCMRglc) in young and aged rhesus macaques to determine if age-related decreases, such as those reported in humans, also occur in macaques. Whereas the aged animals had lower metabolic rates in every brain region studied, the largest differences were in left temporal cortex. The largest differences were also observed in left temporal cortex when relative rCMRglc values were used. Both rCMRglc and relative rCMRglc were marked by substantial individual variation within the aged group. This variation may parallel the variation observed in behavioral studies. Future studies that include both PET and behavioral measures should help determine if there is a relationship between age-related changes in rCMRglc and behavior.

Aging↗

PubMedDate not supplied

Cerebral glucose metabolism and memory in aged rhesus macaques.

Positron emission tomography and the glucose metabolic tracer [18F]fluorodeoxyglucose were used to evaluate the relationship between regional cerebral metabolic rates for glucose (rCMRglc), age, and performance on a delayed response (DR) test of memory in the aged monkey. Eleven aged animals, 21-26-years old, were included in the analysis. Regional CMRglc, normalized to values for the entire brain, were determined for the dorsal prefrontal cortex, orbitofrontal cortex, hippocampus, and temporal cortex. The aged animals exhibited significant DR deficits relative to a cohort of normal young monkeys. Variability in DR performance among the aged subjects was significantly correlated with relative hippocampal rCMRglc, and chronological age was a reliable predictor of orbitofrontal rCMRglc ratios. This pattern of results suggests that DR impairments in the aged monkey may partly reflect age-related dysfunction distributed among multiple limbic system structures that participate in normal learning and memory. Overall, the findings support the use of positron emission tomography in efforts to define the relationship between cognitive performance, age, and brain physiology in nonhuman primates.

Aging↗