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Biomedical subjects

C C Meltzer

Publications and source records attributed to C C Meltzer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regional cerebral blood flow after recovery from bulimia nervosa.

When ill, women with bulimia nervosa (BN) show alterations of regional cerebral blood flow (rCBF). In this study we investigated rCBF in nine women in long-term recovery from BN (RBN, n=9), i.e. more than 1 year without bingeing/purging behavior, normal weight, stable food intake, and regular menses, and compared them with age-matched healthy control women (CW, n=13). Positron emission tomography (PET) was used for the assessment of rCBF. There were no significant differences in rCBF between groups. However, rCBF was significantly inversely related to length of recovery in RBN for the left and right prefrontal cortex (BA 10), right medial orbital frontal cortex (BA 11), left subgenual cingulate (BA 25), right anterior cingulate (BA 32), left sensory motor cortex (BA 1,2,3,4), left and right lateral temporal (BA 21), and left occipital cortex (BA 17), as well as left thalamus. This finding suggests that previously reported alterations in rCBF during the ill state of BN may be a state-related phenomenon that remits with recovery. It is also possible that reductions in rCBF occur in a later stage of recovery from BN.

Adult↗
PubMed2000

Towards a neurobiology of dysfunctional arousal in depression: the relationship between beta EEG power and regional cerebral glucose metabolism during NREM sleep.

This study sought to clarify the neurobiological basis of variations in one aspect of central nervous system 'arousal' in depression by characterizing the functional neuroanatomic correlates of beta electroencephalographic (EEG) power density during non-rapid eye movement (NREM) sleep. First, nine healthy (n=9) subjects underwent concurrent EEG sleep studies and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans during their first NREM period of sleep in order to generate hypotheses about specific brain structures that show a relationship between increased beta power and increased relative glucose metabolism. Second, brain structures identified in the healthy subjects were then used as a priori regions of interest in similar analyses from identical studies in 12 depressed subjects. Statistical parametric mapping was used to identify the relationship between beta power and relative regional cerebral glucose metabolism (rCMRglu) during NREM sleep. Regions that demonstrated significant correlations between beta power and relative cerebral glucose metabolism in both the healthy and depressed subjects included the ventromedial prefrontal cortex and the right lateral inferior occipital cortex. During a baseline night of sleep, depressed patients demonstrated a trend toward greater beta power in relation to a separate age- and gender-matched healthy control group. In both healthy and depressed subjects, beta power negatively correlated with subjective sleep quality. Finally, in the depressed group, there was a trend for beta power to correlate with an indirect measure of absolute whole brain metabolism during NREM sleep. This study demonstrates a similar relationship between electrophysiological arousal and glucose metabolism in the ventromedial prefrontal cortex in depressed and healthy subjects. Given the increased electrophysiological arousal in some depressed patients and the known anatomical relations between the ventromedial prefrontal cortex and brain activating structures, this study raises the possibility that the ventromedial prefrontal cortex plays a significant role in mediating one aspect of dysfunctional arousal found in more severely aroused depressed patients.

Adult↗
PubMed2000

A fenfluramine-activated FDG-PET study of borderline personality disorder.

BACKGROUND: Impulsive aggression in patients with personality disorders is associated with diminished levels of cerebrospinal fluid (CSF) 5-HIAA, blunted neuroendocrine responses to serotonergic agonists, and decreased glucose utilization in the prefrontal cortex. We tested the hypothesis that impulsive aggression in borderline personality disorder (BPD) may be associated with diminished serotonergic regulation in the prefrontal cortex, using positron-emission tomography (PET) neuroimaging during pharmacologic challenge with d,l fenfluramine (FEN). METHODS: A 2-day, single-blind, placebo-controlled FEN challenge study was conducted in five patients with BPD (and no Axis I MDD) and eight healthy control participants. On Day 1, 4 mCi [(18)F]-fluorodeoxyglucose (FDG) was injected 3 hours after ingestion of placebo; on Day 2, FDG was injected 3 hours after ingestion of.8 mg/kg to 60 mg of d,l fenfluramine. After 30 min, a 45-min emission scan was acquired on the Siemans/CTI 951r/31 scanner. PET data were aligned to MR images and analyzed by Statistical Parametric Mapping (SPM96). RESULTS: In response to placebo, uptake of FDG was greater in control participants than patients in large areas of the prefrontal cortex including medial and orbital regions bilaterally (BA 10-11), left superior temporal gyrus, and right insular cortex. There were no areas in which patients had greater relative regional uptake than control participants. In response to FEN, relative regional uptake of FDG (relative to placebo) was greater in control participants compared to patients in medial and orbital regions of right prefrontal cortex (BA 10), left middle and superior temporal gyri (BA 22-23), left parietal lobe (BA 40), and left caudate body. CONCLUSIONS: Patients with BPD have diminished response to serotonergic stimulation in areas of prefrontal cortex associated with regulation of impulsive behavior.

Adolescent↗
PubMed2000

Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography.

PURPOSE: The aim of the authors in this study was to critically evaluate the role of whole-body positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) in staging esophageal cancer, and further to compare this method with conventional imaging with computed tomography (CT). MATERIALS AND METHODS: The authors performed independent, blinded retrospective evaluations of FDG PET images obtained in 47 patients referred for the initial staging of esophageal cancer before minimally invasive surgical staging. Twenty PET studies from patients with nonesophageal thoracic cancers were randomly selected for inclusion in the PET readings. In a subset of 37 of 47 cases, the PET findings were compared with independent readings of CT studies acquired within the same 6-week interval. The utility of the imaging findings was evaluated using a high-sensitivity interpretation (i.e., assigning equivocal findings as positive) and a low-sensitivity interpretation (i.e., assigning equivocal findings as negative). RESULTS: PET was less sensitive (41% in high-sensitivity mode, 35% in low-sensitivity mode) than CT (63% to 87%) for diagnosing tumor involvement in locoregional lymph nodes, which was identified by surgical assessment in 72% of patients. Notable, however, was the greater specificity of PET-determined nodal sites (to approximately 90%) compared with CT (14% to 43%). In detecting histologically proved distant metastases (n = 10), PET performed considerably better when applied in the high-sensitivity mode, with a sensitivity rate of approximately 70% and a specificity rate of more than 90% in the total group and in the subset of patients with correlative CT data. In the low-sensitivity mode, CT identified only two of seven metastatic sites, whereas the high-sensitivity mode resulted in an unacceptably high rate of false-positive readings (positive predictive value, 29%). PET correctly identified one additional site of metastasis that was not detected by CT. CONCLUSIONS: The relatively low sensitivity of PET for identifying locoregional lesions precludes its replacement of conventional CT staging. However, the primary advantage of PET imaging is its superior specificity for tumor detection and improved diagnostic value for distant metastatic sites, features that may substantially affect patient management decisions. In conclusion, PET imaging is useful in the initial staging of esophageal cancer and provides additional and complementary information to that obtained by CT imaging.

Adenocarcinoma↗
PubMed2000

Image analysis in patients with cancer studied with a combined PET and CT scanner.

PURPOSE: To compare combined whole-body PET and CT images of different cancers with PET images alone. MATERIALS AND METHODS: Thirty-two patients with known or possible cancers were examined using a combined positron emission tomographic (PET) and computed tomographic (CT) scanner. All data were acquired using this same combined scanner. After an injection of F-18 fluorodeoxyglucose (FDG), noncontrast helical CT imaging of the neck, chest, abdomen, or pelvis was performed. The spiral CT was followed by a PET scan covering the same axial extent as the CT. RESULTS: Coregistered PET-CT images identified and localized 55 lesions. In 10 patients (31%), areas with variable amounts of normal physiologic FDG uptake were distinguished from potential uptake of FDG in a nearby neoplastic lesion. Improved localization was achieved in 9 patients (for a total of 13 lesions, or 24%). CONCLUSION: Combined PET-CT images appear more effective than PET images alone to localize precisely neoplastic lesions and to distinguish normal variants from juxtaposed neoplastic lesions.

Aged↗
PubMed2000

Planned ictal FDG PET imaging for localization of extratemporal epileptic foci.

PURPOSE: This work demonstrates the feasibility of planned ictal positron emission tomography (PET) with [18F]fluoro-2-deoxy-glucose (FDG) for localization of epileptic activity in patients with frequent partial seizures of extratemporal origin. METHODS: Ictal PET imaging was performed in four patients (two men and two women, ages 28-61) with continuous or very frequent (every 3-15 min) partial seizures. All patients had abnormalities apparent on magnetic resonance (MR) or computed tomographic (CT) imaging, two with extensive brain lesions that precluded precise localization of the seizure focus with interictal PET or single-photon emission tomography (SPECT) imaging. RESULTS: Ictal PET imaging demonstrated a restricted area of focal hypermetabolism concordant with surface electroencephalographic (EEG) recording in all cases. The PET images were registered to MR imaging data for further anatomic localization of hypermetabolic regions in three cases. The ictal PET data were used to guide neurosurgical intervention in one case. CONCLUSIONS: We conclude that planned ictal PET imaging may be a useful and potentially superior approach to ictal SPECT for identifying the epileptic focus in a selected group of patients with continuous or frequent simple partial seizures.

Adolescent↗
PubMed2000

Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction.

UNLABELLED: It remains a matter of controversy as to whether cerebral perfusion declines with healthy aging. In vivo imaging with PET permits quantitative evaluation of brain physiology; however, previous PET studies have inconsistently reported aging reductions in cerebral blood flow (CBF), oxygen metabolism, and glucose metabolism. In part, this may be because of a lack of correction for the dilution effect of age-related cerebral volume loss on PET measurements. METHODS: CBF PET scans were obtained using [15O]H2O in 27 healthy individuals (age range, 19-76 y) and corrected for partial-volume effects from cerebral atrophy using an MR-based algorithm. RESULTS: There was a significant difference (P = 0.01) in mean cortical CBF between young/midlife (age range, 19-46 y; mean +/- SD, 56+/-10 mL/100 mL/min) and elderly (age range, 60-76 y; mean +/- SD, 49+/-2.6 mL/100 mL/min) subgroups before correcting for partial-volume effects. However, this group difference resolved after partial-volume correction (young/midlife: mean +/- SD, 62+/-10 mL/100 mL/min; elderly: mean +/- SD, 61+/-4.8 mL/100 mL/min; P = 0.66). When all subjects were considered, a mild but significant inverse correlation between age and cortical CBF measurements was present in the uncorrected but not the corrected data. CONCLUSION: This study suggests that CBF may not decline with age in healthy individuals and that failure to correct for the dilution effect of age-related cerebral atrophy may confound interpretation of previous PET studies that have shown aging reductions in physiologic measurements.

Adult↗
PubMed1999

Survival of patients with high grade glioma treated with intrathecal thiotriethylenephosphoramide for ependymal or leptomeningeal gliomatosis.

BACKGROUND: The diagnosis of leptomeningeal dissemination of malignant glioma (meningeal gliomatosis) is associated with poor survival. Intrathecal (IT) chemotherapeutic agents used to achieve tumor control and improve survival include methotrexate, cytosine arabinoside (ara-C), thiotriethylenephosphoramide (thio-TEPA), neocarzinostatin, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros ourea hydrochloride (ACNU). Little information exists about survival following administration of IT chemotherapy. The authors report survival data from a series of patients with supratentorial anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) treated for ependymal or leptomeningeal gliomatosis with IT thio-TEPA. METHODS: The authors reviewed the records of 14 patients treated between 1991 and 1997 (GBM: n = 9; AA: n = 5). All patients were diagnosed with ependymal (n = 8) or leptomeningeal (n = 6) dissemination of tumor on the basis of clinical signs and symptoms, ependymal or leptomeningeal contrast enhancement on magnetic resonance imaging (MRI), and/or cerebrospinal fluid analysis. All 14 patients underwent placement of a ventricular reservoir system and subsequent instillation of IT thio-TEPA on a weekly basis for 6-12 weeks. Response to treatment was evaluated clinically and by MRI at intervals of 1-3 months and 3-6 months from the initiation of IT thio-TEPA. Data on survival from the time of diagnosis of dissemination was assessed. RESULTS: The median survival, from the time of diagnosis of ependymal or leptomeningeal dissemination, of patients who received IT thio-TEPA was 10 months (AA = 19 months; GBM = 10 months). Five of 14 patients had a radiographic response to treatment within 6 months. The median survival of patients with a radiographic response was 15.5 months, compared with 10 months for nonresponders. No significant neurotoxicity or myelopathy was observed. CONCLUSIONS: Early treatment with IT thio-TEPA may result in improved survival with minimal morbidity. Radiographic response may predict prolonged survival.

Adult↗
PubMed1999

Changes in forebrain function from waking to REM sleep in depression: preliminary analyses of [18F]FDG PET studies.

Based on recent functional brain imaging studies of healthy human REM sleep, we hypothesized that alterations in REM sleep in mood disorder patients reflect a functional dysregulation within limbic and paralimbic forebrain structures during that sleep state. Six unipolar depressed subjects and eight healthy subjects underwent separate [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans during waking and during their first REM period of sleep. Statistical parametric mapping contrasts were performed to detect changes in relative regional cerebral glucose metabolism (rCMRglu) from waking to REM sleep in each group as well as interactions in patterns of change between groups. Clinical and EEG sleep comparisons from an undisturbed night of sleep were also performed. In contrast to healthy control subjects, depressed patients did not show increases in rCMRglu in anterior paralimbic structures in REM sleep compared to waking. Depressed subjects showed greater increases from waking to REM sleep in rCMRglu in the tectal area and a series of left hemispheric areas including sensorimotor cortex, inferior temporal cortex, uncal gyrus-amygdala, and subicular complex than did the control subjects. These observations indicate that changes in limbic and paralimbic function from waking to REM sleep differ significantly from normal in depressed patients.

Adult↗
PubMed1999

Functional neuroanatomy of semantic memory: recognition of semantic associations.

In an effort to examine the functional neuroanatomy of semantic memory, we studied the relative cerebral blood flow of eight healthy young subjects using 15O-water positron emission tomography (PET). Relative to a visual baseline control condition, each of four visual matching-to-sample tasks activated components of the ventral visual processing stream, including the inferior occipital and temporal cortices. Contrasting the task with the highest semantic component, a variation on the Pyramids and Palm Trees paradigm, with a size discrimination task resulted in focal activation in the anterior inferior temporal lobe, focused in the parahippocampal gyrus. There was additional activation in BA47 of the inferior frontal cortex. These data replicate and extend previously reported results using similar paradigms, and are consistent with cognitive neuropsychological models that stress the executive role of BA47 in semantic processing tasks.

Adolescent↗
PubMed1999

A study of injected dose for brain mapping on the ECAT HR+: activation maps for a parametric verbal working memory task.

The success of the 15O-water PET technique to localize statistically significant changes in regional cerebral blood flow is dependent on factors such as the activity level injected and the magnitude of the flow change. Undetectable changes may occur if insufficient activity is injected leading to high levels of statistical noise or the task performed results in only small changes in blood flow. To explore the relationship between injected activity and statistical significance, we performed a series of studies with the ECAT EXACT HR+, a high resolution PET tomograph. A parametric verbal working memory task (the N-back task) was selected to examine the relationship between regional cerebral blood flow and working memory load across a range of injected doses of 15O-water. At each activity level the volunteers were required to perform four different levels of the N-back task, a task in which a letter displayed on a monitor is matched with the letter displayed N letters previously. With increasing N, this task places increased load on working memory. For this study, 5, 10, and 15 mCi of 15O-water were injected into nine normal volunteers. The complete sequence of four tasks (N = 0, 1, 2, and 3) at three activity levels was repeated twice, for a total of 24 injections of 15O-water. We show that the peak count rate performance for the HR+ is approached at injected activity levels of 15O-water around 15 mCi. For this particular choice of N-back task, robust activation maps can nevertheless be obtained with as little as 5 mCi injected dose.

Adult↗
PubMed1999

Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans.

BACKGROUND: Pilot studies suggest positron emission tomography (PET) scanning may be superior to conventional imaging in staging esophageal cancer, especially in the detection of radiographically occult distant metastases. This report summarizes our experience with PET in staging esophageal cancer. METHODS: One hundred consecutive PET scans in 91 patients with esophageal cancer referred for surgery were prospectively collected (1995 to 1998) and compared with computerized tomography (CT) and bone scan. PET images were acquired after injection of 18F-fluorodeoxyglucose and evaluated for abnormal uptake. Minimally invasive surgical staging (MIS) and/or clinical correlation were used to confirm or refute imaging results. RESULTS: MIS or clinical correlation confirmed 70 distant metastases in 39 cases. PET detected 51 metastases in 27 of 39 cases (69% sensitivity, 93.4% specificity, 84% accuracy) compared with CT, which detected 26 metastases in 18 of 39 cases (46.1% sensitivity, 73.8% specificity, 63% accuracy) (p < 0.01). CONCLUSIONS: PET was more accurate than CT in detecting distant metastases, but was only 69% sensitive compared with minimally invasive staging.

Adenocarcinoma↗
PubMed1999

MR imaging response of brain metastases after gamma knife stereotactic radiosurgery.

PURPOSE: To characterize the magnetic resonance (MR) imaging response of brain metastases after gamma knife stereotactic radiosurgery and determine whether imaging features and tumor response rates correlate with local tumor control and survival. MATERIALS AND METHODS: Serial MR examinations were performed in 48 patients (25 men, 23 women; mean age, 58 years) with 78 lesions. Pretreatment and follow-up enhancing lesion volumes and imaging features were assessed. Rates of response to stereotactic radiosurgery were calculated. Prognostic imaging features affecting local control and survival were analyzed. RESULTS: Local tumor control was achieved in 66 (90%) of 73 metastases at 20 weeks after stereotactic radiosurgery; 61% maintained local control at 2 years. A homogeneous baseline enhancement pattern and initial good response rate (> 50% lesion volume reduction) predicted local control. Five metastases demonstrated a transient volume increase after treatment. The median survival time after stereotactic radiosurgery was 53 weeks and correlated with systemic disease burden and primary tumor type. CONCLUSION: Baseline homogeneous tumor enhancement and initial good response correlate with local control. Initial lesion growth does not preclude local control and may represent radiation-related change. Recognition of these serial MR imaging findings may guide image interpretation and influence treatment in patients with stereotactic radiosurgery-treated metastases.

Adult↗
PubMed1999

Brain tumor volume measurement: comparison of manual and semiautomated methods.

PURPOSE: To compare the reliability of two approaches to measuring enhancing brain tumor volumes--the conventional manual trace method and a threshold-based, semiautomated computer software method. MATERIALS AND METHODS: Two operators rated contrast material-enhanced, T1-weighted axial magnetic resonance (MR) image data sets from 16 patients aged 21-71 years with high-grade gliomas. Each MR data set was rated twice by using manual tracing and twice by using the semiautomated method. The semiautomated measurement method involved a thresholding algorithm based on mixture modeling. The data collection time for each method was recorded. Reliability was measured by using inter- and intraoperator agreement indexes. RESULTS: Mean intraoperator agreement indexes (+/- SD) were 0.90 +/- 0.09 (operator 1) and 0.83 +/- 0.15 (operator 2) for the manual trace method and 0.83 +/- 0.17 (operator 1) and 0.84 +/- 0.16 (operator 2) for the semiautomated measurement method. The mean interoperator agreement was 0.85 +/- 0.14 for the manual method and 0.82 +/- 0.18 for the semiautomated method. The semiautomated method was faster than the manual trace method by an average of 4.6 minutes per patient. CONCLUSION: The semiautomated computer method of measuring tumor volume was faster than the manual trace method. Semiautomated computer approaches offer an alternative to manual tracing for measuring serial tumor volumes in patients with high-grade brain neoplasms.

Adult↗
PubMed1999

PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders.

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.

Age Factors↗
PubMed1999

Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression.

OBJECTIVE: The treatment of geriatric depression is complicated by a variable and delayed response to antidepressant treatment. The present study was undertaken to test the hypothesis that combined total sleep deprivation and paroxetine treatment would produce a persistent reduction in glucose metabolism in the anterior cingulate cortex similar to that reported after long-term antidepressant treatment. METHOD: Six elderly depressed patients who met the DSM-IV criteria for major depressive disorder and six age-matched comparison subjects underwent serial positron emission tomography (PET) studies at baseline, after total sleep deprivation, after recovery sleep (after the initial paroxetine dose), and after 2 weeks of paroxetine treatment (patients only). The PET data were analyzed by using statistical parametric mapping methods. RESULTS: The patients' scores on a 13-item version of the Hamilton Depression Rating Scale were decreased after total sleep deprivation, after recovery sleep, and after 2 weeks of treatment. The Hamilton depression scores of the comparison subjects were not significantly altered. In the patients, the greatest reductions in normalized, relative glucose metabolism after sleep deprivation were observed in the anterior cingulate cortex (Brodmann area 24), and they persisted after recovery sleep and antidepressant treatment. The comparison subjects demonstrated increased metabolism in these areas. CONCLUSIONS: Improvement in the patients' depressive symptoms was accompanied by reduced glucose metabolism in the right anterior cingulate cortex and right medial frontal cortex. These preliminary data indicate that in elderly depressed patients, total sleep deprivation may accelerate the clinical and glucose metabolic response to antidepressant treatment.

Age Factors↗