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Biomedical subjects

M Mandelkern

Publications and source records attributed to M Mandelkern.

At least 127 records · Page 7Linked to original sources

Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer.

To determine the sensitivity, specificity, and accuracy of staging mediastinal nodal disease in potentially resectable lung cancer using fluorodeoxyglucose-positron emission tomography (FDG-PET), computed tomography (CT), or both and compare these results to surgical staging. We also assessed whether PET scanning results changed clinical management. From 1992 to 1997, 50 patients underwent CT, and PET scanning before or close to the time of surgical staging. Sensitivity, specificity, accuracy, and predictive values were then calculated based on pathology results. A retrospective review of the records was performed to determine how PET results affected clinical treatment decisions. Forty-seven of 50 patients had non-small-cell lung cancer. The prevalence of pathologically confirmed mediastinal and hilar involvement was 38%. The sensitivity, specificity, and accuracy of mediastinal disease staging were as follows: CT alone = 73%, 77%, 76%; PET alone = 73%, 94%, 87%; PET + CT = 82%, 96%, 91%, respectively. PET was more specific and accurate than CT (p = 0.025). The results of PET changed management decisions in 12 of 50 cases (24%). Using FDG-PET in conjunction with CT scanning provides the most accurate staging of mediastinal disease in lung cancer by contributing complementary information. Furthermore, PET can affect clinical decision-making and allow some patients considered unresectable a chance for resection.

Adult↗

Relationship between brain electrical activity and cortical perfusion in normal subjects.

Cerebral glucose uptake and perfusion are accepted as tightly coupled measures of energy utilization in both normal and diseased brain. The coupling of brain electrical activity to perfusion has been demonstrated, however, only in the presence of chronic brain disease. Very few studies have examined the relationship between cerebral electrical activity and energy utilization in normal brain tissue. To clarify this relationship, we performed 33 H2(15)O-positron emission tomography (PET) scans in six normal subjects both at rest and during a simple motor task, and acquired surface-recorded quantitative electroencephalogram (QEEG) data simultaneously with isotope injection. We examined the associations between cerebral perfusion directly underlying each recording electrode and three QEEG measures (absolute power, relative power, and cordance). All EEG measures had moderately strong coupling with perfusion at most frequency bands, although the directions of the associations differed from those previously reported in subjects with stroke or dementia. Of the three QEEG measures examined, cordance had the strongest relationship with perfusion (multiple R2 = 0.58). Cordance and PET were equally effective in detecting lateralized activation associated with the motor task, while EEG power did not detect this activation. Electrodes in the concordant state had a significantly higher mean perfusion than those in the discordant state. These results indicate that normal brain electrical activity has a moderately strong association with cerebral perfusion. Cordance may be the most useful QEEG measure for monitoring cerebral perfusion in subjects without chronic brain disease.

Adult↗

Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria.

To test the effect of selegiline, a specific monoamine oxidase B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence.

Adult↗

Assessing the accuracy of topographic EEG mapping for determining local brain function.

OBJECTIVE: There has been considerable discussion regarding the accuracy of topographic electroencephalographic (EEG) maps for assessing local cerebral function. We performed this study to test the accuracy of EEG mapping by examining the association between electrical activity and the perfusion under each electrode as another measure of local cerebral function. METHODS: EEG mapping was performed simultaneously with (H15)2O positron emission tomography (PET) scanning in 6 normal adult subjects, both at rest and during a simple motor task. EEG data were processed using 3 different montages; two EEG power measures (absolute and relative power) were examined. RESULTS: Relative power had much stronger associations with perfusion than did absolute power. In addition, calculating power for bipolar electrode pairs and averaging power over electrode pairs sharing a common electrode yielded stronger associations with perfusion than data from referential or single source montages. CONCLUSIONS: These findings indicate (1) that topographic EEG mapping can accurately reflect local brain function in a way that is comparable to other methods, and (2) that the choice of EEG measure and montage have a significant influence on the degree with which maps reflect this local activity and function.

Adult↗

EEG power correlates with subcortical metabolic activity in AIDS.

The authors studied the relationship between brain metabolic activity and quantitative electroencephalographic power in AIDS. Basal ganglia and thalamic metabolic activity, measured with positron emission tomography, correlated positively with EEG power in the 6-10-Hz band across most head regions. Metabolic activity of anatomically defined cortical regions did not correlate with EEG power recorded over each region. These results support previously reported associations between abnormalities in subcortical metabolic activity and EEG activity. The lack of correlation between cortical metabolic activity and EEG activity suggests that previously observed abnormalities in EEG activity are primarily subcortical in origin.

Acquired Immunodeficiency Syndrome↗

Studies of working memory using 18FDG-positron emission tomography in normal controls and subjects with epilepsy.

We have studied three groups of subjects with a working memory paradigm, using 18FDG-PET. Controls show the greatest increase on uptake in dorsolateral prefrontal cortex, basal forebrain and angular gyrus. A group of subjects with focal frontal epilepsy did not show increases compared to a control task of attention. Primary generalized epilepsy subjects show the greatest changes in angular gyrus, dorsal temporal, medial frontal and parietal regions. Factor and regression analyses extend these observations and show reliance of both patient groups on the medial and inferior temporal lobe. We propose that the normal network of working memory is disrupted by these two forms of epilepsy and different networks are accessed. Declarative memory may be used as a compensatory system, which results in decreased performance.

Adult↗

Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer.

Glycolysis is increased in tumor tissues. [18F]fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue radiopharmaceutical used in positron emission tomography (PET) to trace glucose metabolism. We investigated the sensitivity and specificity of FDG-PET imaging in the diagnosis and staging of lung cancer. One hundred and seven patients who had abnormal chest roentgenograms underwent whole-body PET imaging using FDG. PET scan results were classified as positive or negative based on the presence or absence of increased FDG uptake in the lung and/or in the mediastinum. All 82 patients with lung cancer had increased FDG uptake in the lungs, whereas only 12 of 25 patients with nonmalignant diseases had increased FDG uptake. Sixteen lung cancer patients with mediastinal metastases had increased FDG uptake in the mediastinum, of whom three had no lymphadenopathy on computed tomography of the chest. Sixteen lung cancer patients without mediastinal nodal involvement had no FDG uptake in the mediastinum. Seven of these patients had lymphadenopathy on computed tomography. FDG-PET imaging is 100% accurate in predicting mediastinal involvement in patients with lung cancer. It is 100% sensitive and 52% specific in predicting the malignant nature of a chest radiographic abnormality.

Adenocarcinoma↗

Primary or working memory in frontal lobe epilepsy: An 18FDG-PET study of dysfunctional zones.

INTRODUCTION: We previously demonstrated that patients with frontal lobe epilepsy show deficits on a visual working memory paradigm and that this paradigm produces increased 18FDG uptake in the dorsolateral prefrontal cortex (DPFC), premotor cortex, angular and supramarginal gyri, basal forebrain, and ventral frontal poles of normal subjects when compared with a control task. We hypothesized that subjects with frontal lobe epilepsy would have impaired frontal activation during this task. METHODS: One resting and two activated images were obtained with 18FDG-PET in 15 subjects and 14 controls. One was a delayed (DMS) and one an immediate (IMS) match to sample paradigm. Discriminant and factor analyses were used to analyze the data, supplemented by selected t tests. RESULTS: No differences in glucose uptake were found between the DMS and IMS in the epilepsy subjects, in distinct contrast to controls. A comparison between controls and epilepsy subjects showed differences both ipsilateral and contralateral to the epileptic focus in the frontal regions involved in the task, with small changes in nonfrontal, task-related regions as well. The task itself brought out or highly exaggerated differences seen at rest. There was weak evidence that other frontal and temporal regions were attempting to compensate for the DPFC deficit. CONCLUSION: A unilateral epileptic focus is capable of suppressing function along a large task-related circuit ipsilateral and contralateral to the focus. Peripheral cortical regions compensate poorly for the area of dysfunction.

Adult↗

Visual working memory in primary generalized epilepsy: an 18FDG-PET study.

It is generally believed that patients with primary generalized epilepsy have normal cognition and neuroimaging studies. We have previously shown that patients with juvenile myoclonic epilepsy (JME) have impaired visual working memory. In this study we examined relative regional changes in 18FDG uptake during a visual working memory paradigm in patients with JME. At rest, there were regional decreases in relative glucose uptake compared to controls. Unlike control subjects, increased activity in the dorsolateral prefrontal cortex was not found during the working memory task. Other regions with increased uptake in controls, such as premotor cortex and basal frontal cortex, also showed no increases, whereas medical temporal structures appeared to play a role in JME but not in control subjects' task performance. The data suggest that JME, a type of primary generalized epilepsy, may suffer from cortical disorganization that affects both the epileptogenic potential and frontal lobe cognitive functioning.

Adult↗

Improved sensitivity of 18FDG-positron emission tomography scans in frontal and "frontal plus" epilepsy.

We evaluated three techniques of analyzing 18FDG-positron emission tomography-(PET) scans in 23 cases of presumed frontal lobe epilepsy (FLE): routine visual or "qualitative linear," "qualitative normalized," and quantitative normalized approaches. Patients were then classified as having pure frontal, probable frontal, frontoparietal and frontotemporal epilepsy based on prolonged surface EEG monitoring with video, magnetic resonance imaging (MRI), chronic intracranial recording (CIR), and results of surgical excision. Overall sensitivity and accuracy of the scans was 52 and 48%for qualitative linear analysis, which was equivalent to that of MRI, and 69 and 43% for qualitative normalized analysis. Quantitative normalized analysis had 96% sensitivity and 74 - 78% accuracy and also detected 9 of 11 (81%) abnormalities in nonlesional cases, improving routine sensitivity from 1 of 11 (9%). We conclude that qualitative linear (routine) analysis is inadequate for diagnosis of FLE lobe or "frontal-plus" epilepsies and does not add to the MRI scan. Because qualitative normalized images improve on routine analysis only slightly, quantitative techniques should be applied for preoperaive evaluations.

Adult↗

An 18FDG-PET study of cortical activation during a short-term visual memory task in humans.

Studies of subhuman primates and man have shown that the prefrontal cortex is important for spatial working memory. We have used 18fluorodeoxyglucose positron emission tomography (18FDG-PET) to study a non-spatial, abstract visual memory task of in man. Using a regions-of-interest approach with discriminant analysis of the relative regional cerebral metabolic rate of glucose consumption (rCMRGlc), we found that changes in dorsal prefrontal, premotor/motor frontal and posterior cingulate areas differentiated the primary memory task from the control task. Less robust increases in glucose uptake were observed in lateral parietal cortex, while some subcortical and limbic regions showed decreases. This is the first activation study with a non-spatial, visual task. These results complement previous studies in that they substantiate the role of the prefrontal cortex in the mediation of cross-temporal contingencies of behavior, and point to a role of the premotor region in this mediation as well.

Adult↗

Somatosensory evoked response source localization using actual cortical surface as the spatial constraint.

We localized right median nerve somatosensory evoked responses in a normal human subject using an equivalent dipole method applied to magnetic field recordings. High resolution, 3-dimensional MRI data were used to confine source locations to the cortical surface. Results localized in Brodmann area 3b corresponding to location of hand somatosensory cortex derived from direct brain stimulation studies. The solution was unique and total computational time for an exhaustive, brute-force search was small and the results realistic due to applied anatomical constraints. This study demonstrates feasibility of accurate, non-invasive, realistic localization of dynamic human cortical function using spatial constraints provided by MRI images.

Adult↗

Regional metabolic dependency in obstructive sleep apnea.

Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (microM/min/100 g) was determined by positron-emission tomography using [18F]-2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency.

Adult↗

EEG coherence in men with AIDS: association with subcortical metabolic activity.

The authors studied the relationship between cerebral metabolism and brain electrical activity in patients with acquired immunodeficiency syndrome (AIDS), using positron-emission tomography and quantitative electroencephalography. Electroencephalographic coherence in the 6-to 10-Hz band correlated positively with thalamic metabolic activity. Coherence adjusted for background activity correlated strongly and positively with basal ganglia metabolic activity. Posterior interhemispheric coherence showed the highest correlations with measures of metabolic activity. These results suggest that changes in coherence may reflect AIDS-related subcortical disease. The high correlations between the two different measures of cerebral activity support the validity of electroencephalographic coherence measures in studies of AIDS-related neuropsychiatric dysfunction.

AIDS Dementia Complex↗