Biomedical subjects

Otto Muzik

Publications and source records attributed to Otto Muzik.

32 records · Page 2Linked to original sources

PubMed2004

Evaluation with alpha-[11C]methyl-L-tryptophan positron emission tomography for reoperation after failed epilepsy surgery.

PURPOSE: Reoperation after failed cortical resection can alleviate seizures in patients with intractable neocortical epilepsy, provided that previously nonresected epileptic regions are accurately defined and removed. Most imaging modalities have limited value in identifying such regions after a previous surgery. Positron emission tomography (PET) using alpha-[11C]methyl-L-tryptophan (AMT) can detect epileptogenic cortical areas as regions with increased tracer uptake. This study analyzed whether increased cortical AMT uptake can detect nonresected epileptic foci in patients with previously failed neocortical resection. METHODS: Thirty-three young patients (age 3-26 years; mean age, 10.8 years) with intractable epilepsy of neocortical origin, and a previously failed cortical resection performed at various epilepsy centers, underwent further presurgical evaluation for reoperation. AMT-PET scans were performed 6 days to 7 years after the first surgery. Focal cortical areas with increased AMT uptake were objectively identified and correlated to ictal EEG data as well as clinical variables (age, postsurgical time, etiology). RESULTS: Cortical increases of AMT uptake were detected on the side of the previous resections in 12 cases. In two patients scanned shortly (within a week) after surgery, diffuse hemispheric increases were observed, without any further localization value. In contrast, in 10 (43%) of 23 patients scanned >2 months but within 2.3 years after surgery, focal cortical increases occurred, concordant with seizure onset on ictal EEG. Age, etiology (lesional vs. cryptogenic), epileptiform EEG activity during PET, or time of the last seizure were not significantly related to the presence of increased AMT uptake. All patients with localizing AMT-PET, who underwent reoperation, became seizure free (n = 5) or showed considerable improvement of seizure frequency (n = 2). CONCLUSIONS: AMT-PET can identify nonresected epileptic cortex in patients with a previously failed neocortical epilepsy surgery and, with proper timing for the scan, can assist in planning reoperation.

Adolescent↗

PubMed2004

Metabolic changes of subcortical structures in intractable focal epilepsy.

PURPOSE: Intractable focal epilepsy is commonly associated with cortical glucose hypometabolism on interictal 2-deoxy-2[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET). However, subcortical brain structures also may show hypometabolism on PET and volume changes on magnetic resonance imaging (MRI) studies, and these are less well understood in terms of their pathophysiology and clinical significance. In the present study, we analyzed alterations of glucose metabolism in subcortical nuclei and hippocampus by using FDG-PET in young patients with intractable epilepsy. METHODS: Thirty-seven patients (mean age, 7.5 years; age range, 1-27 years) with intractable frontal (n = 23) and temporal (n = 14) lobe epilepsy underwent FDG-PET scanning as part of their presurgical evaluation. Normalized glucose metabolism was measured in the thalamus and caudate and lentiform nuclei, as well as in hippocampus, both ipsi- and contralateral to the epileptic focus, and correlated with duration and age at onset of epilepsy, presence or absence of secondary generalization, location of the epileptic focus, and extent of cortical glucose hypometabolism. RESULTS: Long duration of epilepsy was associated with lower glucose metabolism in the ipsilateral thalamus and hippocampus. Duration of epilepsy was a significant predictor of ipsilateral thalamic glucose metabolism in both temporal and frontal lobe epilepsy. Presence of secondarily generalized seizures also was associated with lower normalized metabolism in the ipsilateral thalamus and hippocampus. Extent of cortical hypometabolism did not correlate with subcortical metabolism, and glucose metabolism in the caudate and lentiform nuclei did not show any correlation with the clinical variables. CONCLUSIONS: The findings suggest that metabolic dysfunction of the thalamus ipsilateral to the seizure focus may become more severe with long-standing temporal and frontal lobe epilepsy, and also with secondary generalization of seizures.

Adolescent↗

PubMed2004

Is intraoperative electrocorticography reliable in children with intractable neocortical epilepsy?

PURPOSE: To study the relation between the spike frequency during intraoperative electrocorticography (ECoG) under general anesthesia with isoflurane and that during extraoperative ECoG monitoring in children with intractable neocortical epilepsy. METHODS: Twenty-one children (age, 1-16 years; 15 boys and six girls) who underwent intraoperative and extraoperative ECoG monitoring with subdural electrode arrays were studied. The spike frequency and the spatial pattern of spike frequency were compared between intraoperative and extraoperative ECoGs for each patient (by using Wilcoxon signed-ranks and Spearman's rank correlation, respectively). RESULTS: In 15 of 21 patients, the spike frequency was significantly lower during intraoperative than during extraoperative ECoG (mean z = -6.3; p < 0.001). In four of 21 patients, no significant difference was found in the spike frequency between intraoperative and extraoperative recordings. In two of 21 patients, spike frequency reached one spike/min neither during intraoperative nor extraoperative recording; therefore appropriate comparison of spike frequency was not possible. A significant positive correlation in the spike-frequency pattern was seen between intraoperative and extraoperative recordings in nine of nine cases who had > or = 10 spikes/min during intraoperative ECoG (mean rho = 0.62; p < 0.01), in five of six cases with one to nine spikes/min (mean rho = 0.50; p < 0.01), and in none of five cases with less than one spike/min (mean rho = 0.13). CONCLUSIONS: General anesthesia often decreases the spike frequency in children with neocortical epilepsy, yet intraoperative ECoG can reliably reflect the awake interictal spiking pattern when spike frequency exceeds one spike/min during intraoperative ECoG recording.

Adolescent↗

PubMed2003

Imaging [18F]FAU [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl) uracil] in dogs.

We have studied the biodistribution of [(18)F]FAU [(1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil], which previous work has shown is incorporated into DNA and functions as an inhibitor of DNA synthesis. It is being tested as a potential antineoplastic agent and imaging agent for PET. We have produced [(18)F]FAU and injected the tracer into 3 normal dogs and imaged them for up to 4 hours and removed tissues along with blood and urine samples for HPLC and activity analysis. The results showed that [(18)F]FAU evenly distributed to most of organs. In sharp contrast to our prior experience with thymidine and its analogs, marrow had less retention of [(18)F]FAU than the non-proliferating tissues.

Animals↗

PubMed2003

Quantitative interictal subdural EEG analyses in children with neocortical epilepsy.

PURPOSE: We studied the relation between quantitative interictal subdural EEG data and visually defined ictal subdural EEG findings in children with intractable neocortical epilepsy, and determined whether interictal EEG data are predictive of ictal EEG onset zones. METHODS: Thirteen children (aged 1.2-15.4 years) underwent prolonged intracranial EEG recording, using 48- to 120-channel subdural electrodes. Three distinct 10-min segments of the continuous interictal EEG recording were selected for each patient, and the spike frequency for each channel was determined by using an automatic spike-detection program. Subsequently the average spike frequency of each electrode was compared with ictal assessment (onset, spread, and no early ictal involvement). In addition, 50 distinct interictal spikes were averaged for each patient, and the amplitude and latency after the leading spike (averaged spike showing the earliest peak) were measured for each electrode and analyzed with respect to ictal EEG findings. RESULTS: Reproducibility of the spike-frequency pattern derived from three 10-min segments was high (Kendall's W, 0.85 +/- 0.08). Electrodes showing the highest spike frequency, the highest spike amplitude, and the leading spike were found to be a part of the seizure onset in 13 of 13, 12 of 13, and 10 of 13 cases, respectively. There was significant correlation between ictal assessment and spike frequency as well as spike amplitude. A receiver operating characteristics analysis showed that a cutoff threshold at 14% of the maximal spike frequency resulted in a specificity of 0.90 and a sensitivity of 0.77 for the detection of seizure-onset electrodes. CONCLUSIONS: Quantitative interictal subdural EEG may predict ictal-onset zones in children with intractable neocortical epilepsy.

Adolescent↗

PubMed2003

Quantitative analysis of gray- and white-matter volumes and glucose metabolism in Sturge-Weber syndrome.

The progressive nature of Sturge-Weber syndrome is well known, but the mechanisms of focal cortical and subcortical degeneration in this disorder are poorly understood. In the present study, we assessed the structural and functional integrity of gray and white matter in unihemispheric Sturge-Weber syndrome using quantitative magnetic resonance imaging (MRI) volumetry and MRI-based partial volume correction of [18F]fluorodeoxyglucose positron emission tomographic (PET) images. Gray- and white-matter volumes and glucose metabolism were measured in three brain regions (parieto-occipital underneath the angioma, temporal, and frontal) in six children with Sturge-Weber syndrome (two infants, ages 6 and 9 months; four older children, ages 4 to 14 years), all with unilateral parieto-occipital leptomeningeal angiomatosis. The gray-matter volumes ipsilateral to the angioma were smaller in all children, with the posterior regions underneath the angioma the most affected. In the infants, the white-matter volumes were increased in the region of the angioma, whereas in the regions remote from the angioma in the infants and in all regions of the older children, there were large decreases in white-matter volume. The decreases of frontal and temporal white-matter volume were more pronounced than the corresponding gray-matter volume decreases. The PET studies showed severe hypometabolism in the parieto-occipitalregion underneath the angioma in all of the children. However, the two infants showed glucose hypermetabolism in the frontal and temporal cortical gray matter, whereas these regions had relatively preserved metabolism in the older patients. These results demonstrate differential involvement of gray and white matter in Sturge-Weber syndrome. Both structural and functional abnormalities extend well beyond the angioma, indicating widespread abnormalities of growth and development of the affected hemisphere. Furthermore, whereas increased white-matter volume underlying the angioma may be seen in infants, ipsilateral white-matter regions outside the angioma show volume loss both in infants and in older patients. Extensive gray- and white-matter volume loss and hypometabolism ipsilateral to the angioma likely contribute to the frequently observed progressive cognitive dysfunction in these patients, regardless of the extent of the angioma.

Adolescent↗

PubMed2002

Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study.

The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region-specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin.

Adolescent↗

PubMed2002

Hypotheses from functional neuroimaging studies.

Functional neuroimaging, especially positron emission tomography (PET) using various tracers, provided new insights into the pathophysiology of West syndrome in the past decade. Glucose PET studies revealed a unique corticosubcortical circuitry assumed to be involved in the age-dependent generalization of seizure activity leading to symmetric spasms. The findings strongly suggested that cortical abnormalities, mostly consistent with dysplastic lesions or diffuse cortical dysfunction due to an underlying systemic disorder, trigger brain stem nuclei and activate basal ganglia bilaterally. PET is also able to investigate developmental abnormalities of serotonergic and GABAergic neurotransmitter systems in vivo. Involvement of these systems in the pathophysiology of infantile spasms is strongly supported by animal data and can be further elucidated by future PET studies. In addition, the development of new PET tracers (such as neurotracers for imaging NMDA receptors) could help further clarify the role of altered neurotransmission in generation of spasms. This review of the most important functional neuroimaging findings illustrates how human PET and single photon emission computed tomography data help answer basic questions regarding the pathomechanisms involved in this often devastating condition and how these findings might facilitate development of a useful animal model of West syndrome.

Brain Diseases↗

PubMed2002

Kinetics of 3'-deoxy-3'-[F-18]fluorothymidine uptake and retention in dogs.

We have developed 3'-deoxy-3'-[F-18] fluorothymidine ([F-18]FLT) as an agent to image cellular proliferation with PET. Recent work has demonstrated that [F-18]FLT is stable to degradation and produces high contrast images of proliferating tissues and tumors. To increase our understanding for the use of this agent we have explored the kinetics of [F-18]FLT clearance from the blood and uptake into tissues in normal and tumor bearing dogs. The results indicate that [F-18]FLT is readily modeled in canines with a three-compartment model, with parameter k(3) representing phosphorylation by thymidine kinase. During the first 60 minutes, little loss was measured from the phosphorylated compartment, therefore parameter k(4) could not be differentiated from zero. The extraction of marrow from normal dogs was consistent with this model and demonstrated retention of phosphorylated [F-18]FLT. It is concluded that [F-18]FLT produces images of the DNA synthetic pathway by phosphorylation via thymidine kinase. This pathway can be readily modeled using a three-compartment model.

Journal Article↗

PubMed2002

Alpha[11C] methyl-L-typtophan positron emission tomography in patients with alternating hemiplegia of childhood.

Based on previous reports suggesting a role of the neurotransmitter serotonin in the pathomechanism of alternating hemiplegia of childhood and speculation that it may be a migraine variant, we measured brain serotonin synthesis in children with alternating hemiplegia of childhood. Clinical and neurodevelopmental data, as well as standard uptake values in 25 brain regions and whole-brain serotonin synthesis capacity (unidirectional uptake rate constant or K-complex), were assessed in six patients with alternating hemiplegia of childhood (three girls and three boys; mean age = 7 6/12 years) using alpha[11C]methyl-L-tryptophan positron emission tomography (PET). The PET studies were performed interictally in three patients, during the ictal state in two patients, and postictally in one patient. The PET data were compared to those obtained interictally from six age-matched patients with focal epilepsy (two girls and four boys; mean age = 7 8/12 years) and six non-age-matched apparently normal siblings of autistic children (two girls and four boys; mean age = 9 11/12 years). Patients with alternating hemiplegia of childhood studied in the ictal or postictal state showed increased serotonin synthesis capacity in the frontoparietal cortex, lateral and medial temporal structures, striatum, and thalamus when compared to controls, and subjects with alternating hemiplegia of childhood studied interictally. The involvement of these brain regions was consistent with the semiology of the hemiplegic attacks. In patients with interictal studies and in the controls, the PET scans revealed similar and bilaterally symmetric regional patterns of serotonin synthesis capacity. Increased whole-brain serotonin synthesis capacity (reported in migraine subjects without aura) was not found in the alternating hemiplegia of childhood group. There was no correlation between the neurodevelopmental scores and regional standard uptake values; however, patients with a larger estimated lifetime attack number showed greater delay in communication (P = .005) and daily living skills (P = .042). These studies suggest increased regional serotonergic activity associated with attacks in alternating hemiplegia of childhood. Furthermore, the attack number may have an effect on neurodevelopmental delay, thus supporting the notion that alternating hemiplegia of childhood may be a progressive disorder.

Adolescent↗

PubMedDate not supplied

Mouse extrahepatic hepatoma detected on MicroPET using copper (II)-64 chloride uptake mediated by endogenous mouse copper transporter 1.

PURPOSE: This study was conducted to assess the positron-emitting copper (II)-64 chloride ((64)CuCl(2)) as a probe for imaging mouse extrahepatic hepatoma expressing mouse copper transporter 1 (mCtr1) with positron emission tomography (PET). PROCEDURES: Following the intravenous administration of (64)CuCl(2), athymic mice bearing extrahepatic hepatoma grafts were subjected to whole-body static PET imaging with a Concorde microPET R4 tomograph. Upon completion of the imaging study, immunohistochemistry (IHC) study of mCtr1 was performed with postmortem tissues. RESULTS: The mouse extrahepatic hepatoma grafts were well visualized on static microPET images. Quantitative analysis demonstrated that the tracer concentration in the hepatoma was significantly higher than those in the soft tissue of the right shoulder opposite to the tumor site and the brain (p < 0.001). mCtr1 immunoreactivity in the hepatoma graft was approximately 70% of that in liver, whereas (64)CuCl(2) concentration in the graft was approximately 11% of the liver concentration. CONCLUSIONS: The extrahepatic mouse hepatoma grafts may be visualized by Cu-64 PET, taking advantage of the (64)CuCl(2) uptake mediated by the functional endogenous mCtr1.

Animals↗

PubMedDate not supplied

Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.

The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

Adolescent↗

PubMedDate not supplied

Assessment of myocardial perfusion by dynamic N-13 ammonia PET imaging: comparison of 2 tracer kinetic models.

BACKGROUND: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH(3)) positron emission tomography (PET) uses tracer kinetic modeling to analyze time-activity curves. We compared 2 commonly used models with 2 compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary flow reserve (CFR). METHODS AND RESULTS: Seventy-seven patients underwent NH(3) PET at rest and during hyperemia. Time-activity curves for blood pool and myocardial segments were obtained from short-axis images of dynamic sequences. Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF values calculated by 2C and 3C models were 0.98 +/- 0.31 mL.min(-1).g(-1) and 1.11 +/- 0.37 mL.min(-1).g(-1), respectively, at rest (P < .0001) and 2.79 +/- 1.18 mL.min(-1).g(-1) and 2.46 +/- 1.02 mL.min(-1).g(-1), respectively, during hyperemia (P < .01), resulting in a CFR of 3.02 +/- 1.31 and 2.39 +/- 1.15 (P < .0001), respectively. Significant correlation was observed between the 2 models for calculation of resting MBF (r = 0.78), hyperemic MBF (r = 0.68), and CFR (r = 0.68). CONCLUSION: Measurements of MBF and CFR by 2C and 3C models are significantly related. However, quantification of MBF and CFR significantly differs between the methods. This difference needs to be considered when normal values are established or when measurements obtained with different methods need to be compared.

Adolescent↗

PubMedDate not supplied

Self-reported physical activity and myocardial flow reserve in postmenopausal women at risk for cardiovascular disease.

BACKGROUND: Regular exercise protects against coronary heart disease (CHD) events and improves vascular reactivity. Exercise effects on myocardial flow reserve (MFR) are not well studied. METHODS: We performed dynamic N-13 ammonia positron emission tomography (PET) in 16 postmenopausal women (60 +/- 6 years) to measure myocardial blood flow (MBF) and MFR. We also obtained information from each woman on her self-reported physical activity. RESULTS: Of the 16 patients, 6 reported moderate regular physical activity, and 10 did not. Women who reported regular, at least moderate physical activity had a higher percentage increase in adenosine MBF from rest compared with women who did not exercise (268% vs. 129%, p = 0.04) and had a significantly higher mean maximal MFR (3.68 vs. 2.29, p = 0.04). CONCLUSIONS: These findings provide further mechanistic support for the beneficial cardiovascular effects of exercise.

Aged↗