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Biomedical subjects

B Sadzot

Publications and source records attributed to B Sadzot.

At least 55 records · Page 3Linked to original sources
PubMed1995

Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls.

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.

Adult↗
PubMed1995

Is positron emission tomography a useful tool for studying migraine?

Despite the high prevalence of migraine in the population, the pathophysiology of this condition remains poorly understood. Vascular changes have been postulated. With positron emission tomography and various radiotracers, it is possible to have a non-invasive access to a number of parameters of interest in migraine research. These are presented and discussed in this article. PET has great potential for answering some basic questions concerning the physiological or biochemical changes that can occur during and between migraine attacks. Few studies have been published, however, probably because of (i) limitations inherent to the technique and (ii) problems in study design.

Cerebrovascular Circulation↗
PubMed1994

PET studies of patients with partial epilepsy: visual interpretation vs. semi-quantification/quantification.

One of the advantages of PET is to allow for precise regional measurements of radioactive tracers in slices of brain. Furthermore, complex compartment modelling methods have been designed to transform the regional radioactive concentrations into biological units. The question is often raised whether quantification of PET studies is necessary in clinical practice. In epileptology, the regional biochemical changes associated with temporal lobe epilepsy are easily detected by experienced eyes and quantification is not required for diagnosis purposes. By contrast, inter-patient or inter-population comparisons can only be performed if regional measures have been obtained; if the PET method has been previously validated, simple measurements (regional activity) are sufficient and (kinetic) compartmental modelling is not necessary in routine.

Brain↗
PubMed1994

Differential diagnosis of Alzheimer's disease with PET.

UNLABELLED: PET studies have demonstrated bilateral temporo-parietal hypoperfusion and hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other dementias. METHODS: To evaluate the diagnostic power of cerebral metabolic distribution patterns for "cortical" degenerative dementias, PET scans obtained from 129 patients referred for differential diagnosis of dementia were analyzed visually. RESULTS: Sixty-five patients had a final clinical diagnosis of probable AD. Ninety-seven percent (97%) of those had abnormal metabolic scans and 94% showed a suggestive pattern of bilateral or unilateral temporo-parietal hypometabolism (with or without frontal involvement). Hypometabolism was unilateral in 23% of patients. Five subjects with a neuropathologically proven diagnosis of Alzheimer's disease had a suggestive metabolic pattern. One of those was an early case with frontal hypometabolism exceeding temporo-parietal involvement. Two patients with Alzheimer's-type dementia had isolated bilateral frontal hypometabolism. CONCLUSIONS: This alternative metabolic pattern may correspond to a non-Alzheimer pathology occurring in 10%-20% of patients suffering from clinically probable Alzheimer's disease. Most of the patients with possible but atypical Alzheimer's-type dementia showed isolated bilateral frontal involvement. This metabolic pattern probably corresponds to different diseases, such as Pick's disease, frontal lobe dementia or progressive subcortical gliosis.

Alzheimer Disease↗
PubMed1993

Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil.

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration (Bmax) and equilibrium dissociation constant (Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/k2 estimate of 0.68 +/- 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma (f1) was determined for each study (high SA f1: 0.50 +/- 0.03; low SA f1: 0.48 +/- 0.05). The free fraction in brain (f2) was calculated using the inhibition K1/k2 ratio and each volunteer's mean f1 value (f2 across volunteers = 0.72 +/- 0.03 ml/ml). Three methods (Methods I-III) were examined. Method I determined five kinetic parameters simultaneously [K1, k2, k3 (= konf2Bmax), k4, and konf2/SA] with no priori constraints. An average kon value of 0.030 +/- 0.003 nM-1 min-1 was estimated for receptor-rich regions using Method I. In Methods II and III, the konf2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/mumol). Four parameters were determined simultaneously using Method II. In Method III, K1/k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 +/- 25 nM in the occipital cortex, 64 +/- 18 nM in the cerebellum, and 38 +/- 5.5 nM in the thalamus; the average Kd was 8.9 +/- 1.0 nM (five brain regions).

Adult↗
PubMed1992

Cerebral glucose utilization during stage 2 sleep in man.

Using [18F]fluorodeoxyglucose method and positron emission tomography, we performed paired determinations of the cerebral glucose utilization at one week intervals during sleep and wakefulness, in 12 young normal subjects. During 6 of 28 sleep runs, a stable stage 2 SWS was observed that fulfilled the steady-state conditions of the model. The cerebral glucose utilization during stage 2 SWS was lower than during wakefulness, but the variation did not significantly differ from zero (mean variation: -11.5 +/- 25.57%, P = 0.28). The analysis of 89 regions of interest showed that glucose metabolism differed significantly from that observed at wake in 6 brain regions, among them both thalamic nuclei. We conclude that the brain energy metabolism is not homogeneous throughout all the stages of non-REMS but decreases from stage 2 SWS to deep SWS; we suggest that a low thalamic glucose metabolism is a metabolic feature common to both stage 2 and deep SWS, reflecting the inhibitory processes observed in the thalamus during these stages of sleep. Stage 2 SWS might protect the stability of sleep by insulating the subject from the environment and might be a prerequisite to the full development of other phases of sleep, especially deep SWS.

Adult↗
PubMed1992

Factor analysis of regional cerebral glucose metabolic rates in healthy men.

Cerebral glucose utilization measured with fluorine-18-fluoro-2-deoxy-D-glucose is characterized by considerable variability both among different persons and for the same person examined on different occasions. The goal of this study was to explore whether some regions of the brain were more variable than others with respect to glucose utilization and whether there was a pattern in their covariance. The global and regional cerebral utilization of glucose was measured in 12 healthy young volunteers on 3 or 4 occasions. In all, 24 regions were examined. The interrelation of the glucose utilization rates of the brain regions was investigated by factor analysis of the metabolic rates. Some 70% of the total variance was attributable to only 1 factor, while 80% of the total variance could be attributed to 2 factors. Regions making up the first factor were the frontal and temporal cortex, cingulate gyrus, caudate nucleus, thalamus and putamen. These regions are functionally related to the limbic system. Regions of the second factor were the parietal cortex, occipital cortex and cerebellum, regions more clearly related to sensory and motor functions. The 2-factor pattern was highly reproducible, being found with different algorithms for factor extraction and rotation. Under resting conditions, the variance of cerebral metabolism seems to be primarily related to regions which are closely involved with the limbic system. Cortical regions involved primarily in motor and sensory functions have less influence on the variance.

Adult↗
PubMed1992

Regional brain glucose metabolism in patients with complex partial seizures investigated by intracranial EEG.

We performed interictal 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) studies in 57 patients with complex partial epilepsy (CPE), not controlled by medical treatment and considered for surgical resection of their epileptic focus. A precise localization of the epileptic focus was obtained in 37 of these patients with a combination of subdural and depth electrodes. We visually inspected the metabolic images; we also measured glucose consumption in a number of brain regions and compared the values with those obtained in 17 normal controls. Eighty-two percent of the 57 patients had an area of glucose hypometabolism on the 18FDG-PET images. Six patients had a frontal epileptic focus, 3 of them had a frontal lobe hypometabolism. Twenty-six patients had a unilateral temporal lobe focus and all of them displayed a temporal lobe hypometabolism. The asymmetry was more pronounced in the lateral temporal cortex (-20%) than in the mesial part of the temporal lobe (-9.6%). In each cortical brain region on the side of the epileptic focus (except the sensorimotor cortex), glucose consumption rate was lower than in the contralateral region or than in controls. No differences could be found between patients with a seizure onset restricted to the hippocampus and patients with a seizure onset involving the hippocampus and the adjacent neocortex. Divergent metabolic patterns were obtained in 5 patients with bilateral temporal seizure foci. Combined with other non invasive techniques (EEG, neuroradiology), PET contributes increasingly to the selection of patients with CPE who could benefit from surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

Amygdala↗
PubMed1991

Quantification of human opiate receptor concentration and affinity using high and low specific activity [11C]diprenorphine and positron emission tomography.

[11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of [11C]diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of [11C]diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

Adult↗
PubMed1991

Global and regional cerebral metabolic rate of 2-[18F]fluoro-2-deoxy-D-glucose in the presence of ofloxacin, a gamma-aminobutyric acid a receptor antagonist.

We investigated the effects of ofloxacin, a new antibacterial quinolone gamma-aminobutyric acid A receptor antagonist, on the global and regional cerebral metabolic rates of glucose (cMRgl). Twelve healthy normal male volunteers (mean age, 26.7 years) were studied in a double-blind, placebo-controlled protocol of 11 days' duration. Results of a total of 42 positron emission tomography studies were obtained for these subjects: 12 base line, 18 during placebo, and 12 during ofloxacin administration. The conditions under which repeat positron emission tomography studies of the same subject were performed were reproduced as closely as possible. cMRgl was measured in 24 brain regions. The global cMRgl for base line, placebo, and ofloxacin were 8.82 +/- 1.17, 8.24 +/- 1.17, and 8.79 +/- 1.18 mg/min/100 g, respectively (mean +/- 1 standard deviation). The mean global differences between base line and placebo and between ofloxacin and placebo were 5.1 and 6.6%, respectively. Analysis of variance of both the global and the regional cMRgl showed no statistical difference between base-line, placebo, and ofloxacin studies. Variations in cMRgl found in this study were not related to the presence of ofloxacin. Results of our study demonstrate that ofloxacin does not increase or decrease cMRgl beyond the limits of variability of the study.

Adult↗
PubMed1991

Decrease of frontal metabolism demonstrated by positron emission tomography in a population of healthy elderly volunteers.

Frontal metabolism measured with positron emission tomography is shown to be decreased relatively to that in other cortical or sub-cortical areas, in a population of healthy elderly compared to young volunteers. Cortical atrophy or neuronal depopulation are unlikely to entirely explain this physiological phenomenon, and sub-cortico-cortical deactivation should play a role, analogous to that proposed in subcortical diseases.

Aged↗
PubMed1990

Localization of peripheral cholecystokinin receptors in vivo using the cholecystokinin antagonist [3H](+/-)-MK-329.

Cholecystokinin (CCK) regulates various gastrointestinal functions through specific receptors. The mechanisms responsible for disorders of these functions could be elucidated by non-invasively localizing CCK receptors and quantifying their number in vivo. MK-329 is a highly selective and very high affinity antagonist at the peripheral CCK receptor. We investigated the in vivo binding of [3H](+/-)-MK-329 in mice to determine if binding to CCK receptors could be detected after systemic administration of the tracer. The uptake of [3H](+/-)-MK-329 increased in the pancreas from 5 min to 4 h after administration. The binding was saturable, stereospecific, and more than 80% specific. A total/non-specific binding ratio of 43 was reached at 8 h post-injection. The pancreas was the only organ where specific binding could be detected. Our results suggest that MK-329 labeled with a positron emitter such as C-11 could be used with positron emission tomography to image and quantify peripheral CCK receptors in man.

Animals↗
PubMed1990

Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose method.

Using the [18F]fluorodeoxyglucose method and positron emission tomography, we studied cerebral glucose utilization during sleep and wakefulness in 11 young normal subjects. Each of them was studied at least thrice: during wakefulness, slow wave sleep (SWS) and rapid eye movement sleep (REMS), at 1 week intervals. Four stage 3-4 SWS and 4 REMS fulfilled the steady state conditions of the model. The control population consisted of 9 normal age-matched subjects studied twice during wakefulness at, at least, 1 week intervals. Under these conditions, the average difference between the first and the second cerebral glucose metabolic rates (CMRGlu was: -7.91 +/- 15.46%, which does not differ significantly from zero (P = 0.13). During SWS, a significant decrease in CMRGlu was observed as compared to wakefulness (mean difference: -43.80 +/- 14.10%, P less than 0.01). All brain regions were equally affected but thalamic nuclei had significantly lower glucose utilization than the average cortex. During REMS, the CMRGlu were as high as during wakefulness (mean difference: 4.30 +/- 7.40%, P = 0.35). The metabolic pattern during REMS appeared more heterogeneous than at wake. An activation of left temporal and occipital areas is suggested. It is hypothetized that energy requirements for maintaining membrane polarity are reduced during SWS because of a decreased rate of synaptic events. During REMS, cerebral glucose utilization is similar to that of wakefulness, presumably because of reactivated neurotransmission and increased need for ion gradients maintenance.

Adult↗
PubMed1990

Selective hypometabolism in the inferior frontal lobe in depressed patients with Parkinson's disease.

Depression is a frequent finding in patients with Parkinson's disease (PD). Regional cerebral glucose metabolism was measured in depressed and nondepressed patients with PD and in age-comparable normal control subjects using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). Relative metabolic activity in the caudate and orbital-inferior region of the frontal lobe was significantly lower in the depressed patients with PD as compared to both nondepressed patients and control subjects. There was a significant inverse correlation between relative glucose metabolism in the orbital-inferior area of the frontal lobe and depression scores. This study suggests that depression in PD is associated with dysfunction in the caudate and orbital-inferior area of the frontal lobe. This metabolic pattern is unlike that seen in patients with PD who have other behavioral deficits such as dementia, and suggests that disruption of basal ganglia circuits involving the inferior region of the frontal lobe may affect the regulation of mood.

Aged↗