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- In situ Dissolved Methane Concentrations in Gas Hydrate-Rich Systems. Part 2: Investigating Mechanisms Controlling Hydrate Dissolution. presented at 2010 Fall Meeting, AGU
"... Purpose: To evaluate, in vivo, at the cellular level, glucose metabolism in the rat inner retina, and to determine how inner retinal glucose metabolism is affected by photoreceptor degeneration. Methods: Glucose metabolism was evaluated using the 2-deoxyglucose technique. This is an autoradiographic ..."
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Purpose: To evaluate, in vivo, at the cellular level, glucose metabolism in the rat inner retina, and to determine how inner retinal glucose metabolism is affected by photoreceptor degeneration. Methods: Glucose metabolism was evaluated using the 2-deoxyglucose technique. This is an autoradiographic technique that permits evaluation of glucose uptake at the cellular level. The three experimental groups consisted of normal rats (n=13), dystrophic Royal College of Surgeons rats (n=3), and rats previously treated with argon green photocoagulation (n=5). Results: Deoxyglucose uptake in the normal rat was not uniform across the inner retina. Uptake was greatest at the junc-tion of the outer plexiform and inner nuclear layers, and in the inner plexiform layer. Following focal or diffuse pho-toreceptor loss, there was a marked decrease in the amount of deoxyglucose uptake at the junction of the outer plexi-form and inner nuclear layers. Conclusion: The pattern of uptake of deoxyglucose in the inner retina is consistent with abundant uptake of deoxyglu-cose by Müller cells and at sites of synaptic transmission. The decline in deoxyglucose uptake following diffuse or focal photoreceptor loss indicates that there is diminished inner retinal glucose uptake following photoreceptor loss. This change in inner retinal glucose metabolism following photoreceptor loss may help to explain the inner retinal vascular changes observed following photocoagulation and in retinal dystrophies.
The layout of orientation and ocular dominance domains in area 17 of strabismic cats
- Eur. J. Neurosci
, 1998
"... In the primary visual cortex of strabismic cats, the elimination of correlated activity between the two eyes enhances the segregation of the geniculocortical afferents into alternating ocular dominance domains. In addition, both tangential intracortical fibres and neuronal synchronization are severe ..."
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In the primary visual cortex of strabismic cats, the elimination of correlated activity between the two eyes enhances the segregation of the geniculocortical afferents into alternating ocular dominance domains. In addition, both tangential intracortical fibres and neuronal synchronization are severely reduced between neurons activated by different eyes. Consequently, ocular dominance columns belonging to different eyes are functionally rather independent. We wondered whether this would also affect the organization of orientation preference maps. To this end, we visualized the functional architecture of area 17 of strabismic cats with both optical imaging based on intrinsic signals and double labelling of orientation and ocular dominance columns with [ 14 C]2-deoxyglucose and [ 3 H]proline. As expected, monocular iso-orientation domains had a patchy appearance and differed for the two eyes, leading to a clear segregation of the ocular dominance domains. Comparison of ‘angle maps ’ revealed that orientation domains exhibit a pinwheel organization as in normally reared cats. Interestingly, the map of orientation preferences did not show any breaks at the borders between ocular dominance columns: iso-orientation domains were continuous across these borders. In addition, iso-orientation contours tended to cross the borders of adjacent ocular dominance columns at right angles. These data suggest that the basic relations between the layout of orientation maps and ocular dominance columns are not disturbed by artificial decorrelation of binocular input. Therefore in cat area 17, the orientation map does not seem to be modified by experience-dependent changes of thalamic input connections. This suggests the possibility that usedependent rearrangement of geniculocortical afferents into ocular dominance columns is due to Hebbian modifications whereby postsynaptic responsivity is constrained by the scaffold of the orientation map.
S.: COMKAT: compartment model kinetic analysis tool
- J. Nucl. Med
, 2001
"... Compartment models are the basis for most physiologically based quantification of nuclear medicine data. Although some software packages are available for this purpose, many are expensive, run on relatively few types of computers or are of limited capability, and cannot be extended because of the un ..."
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Compartment models are the basis for most physiologically based quantification of nuclear medicine data. Although some software packages are available for this purpose, many are expensive, run on relatively few types of computers or are of limited capability, and cannot be extended because of the unavailability of source code. Consequently, institutions with modeling expertise often develop software for themselves, which has the disadvantages of lack of standardization and possible replication of effort. Therefore, general-purpose compartmentmodeling software distributed with source code would be a welcome resource for the nuclear medicine community. Methods: We formulated a mathematic framework within which compartment models containing unimolecular and bimolecular (receptor saturation) kinetics can be described. We implemented this framework within MATLAB and call the resultant software
Relations between PET-derived measures of thalamic glucose metabolism and EEG alpha power
- Psychophysiology
, 1998
"... Electroencephalogram ~EEG! alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have su ..."
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Electroencephalogram ~EEG! alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans. Descriptors: Electroencephalography, Positron emission tomography, Alpha, Thalamus Alpha electroencephalogram ~EEG! power is a commonly used measure of regional brain activity. It reflects an awake but resting state and is putatively inversely related to neural activity ~Shagass, 1972!. The thalamus has been hypothesized to be an important source of afferent projections that modulate cortical alpha rhythms
Six-month test-retest reliability of MRI-defined PET measures of regional cerebral glucose metabolic rate in selected subcortical structures
- Human Brain Mapping
, 2000
"... r r Abstract: Test–retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in sm ..."
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r r Abstract: Test–retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in small subcortical structures may be more variable than in larger cortical regions. We chose to study these subcortical regions because of their particular interest to our laboratory in its investigations of the neurocircuitry of emotion and depression. Twelve normal subjects (seven female, mean age 5 32.42 years, range 21–48 years) underwent two FDG-PET scans separated by approximately 6 months (mean 5 25 weeks, range 17–35 weeks). A region-of-interest approach with PET-MRI coregistration was used for analysis of rCMR reliability. Good test–retest reliability was found in the left amygdala, right and left hippocampus, right and left thalamus, and right and left anterior caudate nucleus. However, rCMR in the right amygdala did not show good test–retest reliability. The implications of these data and their import for studies that include a repeat-test design are considered. Hum.
on Negative Dip In BOLD fMRI Is Caused By Blood Flow— Oxygen Consumption Uncoupling In Humans
, 2001
"... The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption a ..."
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The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect. © 2002 Elsevier Science Key Words: functional magnetic resonance imaging; blood oxygen level-dependent (BOLD) effect; cerebral blood oxygen saturation; cerebral autoregulation; cerebrovascular reserve capacity.
Kinetic modeling of 3′-deoxy-3′-fluorothymidine in somatic tumors: mathematical studies. J Nucl Med 2005;46:371–80
"... We present a method to measure the regional rate of cellular proliferation using a positron-emitting analog of thymidine (TdR) for human imaging studies. The method is based on the use of 3-deoxy-3-18F-fluorothymidine (FLT) to estimate the flux of TdR through the exogenous pathway. The model reflect ..."
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We present a method to measure the regional rate of cellular proliferation using a positron-emitting analog of thymidine (TdR) for human imaging studies. The method is based on the use of 3-deoxy-3-18F-fluorothymidine (FLT) to estimate the flux of TdR through the exogenous pathway. The model reflects the retention of FLT-monophosphate (FLTMP), which is generated by the phosphorylation of FLT by thymidine kinase 1 (TK1), the initial step in the exogenous pathway. Methods: A model of FLT kinetics has been designed based on the assumptions of a steady-state synthesis and incorporation of nucleotides into DNA, an equilibration of the free nucleoside in tissue with the plasma level, and the relative rates of FLT and TdR phosphor-ylation from prior data using direct analysis with in vitro assays. A 2-compartment model with 4 rate constants adequately de-scribes the kinetics of FLT uptake and retention over 120 min and leads to an estimation of the rate of cellular proliferation using the measured FLT blood clearance and the dynamic FLT uptake curve. Results: Noise characteristics of kinetic param-eter estimates for 3 tissues were assessed under a range of conditions representative of human cancer patient imaging. The FLT flux in these tissues can be measured with a SE of 5%, and FLT transport can be estimated with a SE of 15%. Ab-breviating the data collection to 60 min or neglecting k4, giving a 3-parameter model, results in an unsatisfactory loss of accu-racy in the flux constant in tumor simulations. Conclusion: These analyses depict model behavior and provide expected values for the accuracy of parameter estimates from FLT imag-ing in human patients. Our companion paper describes the performance of the model for human data in patients with lung cancer. Further studies are necessary to determine the fidelity of KFLT (FLT flux) as a proxy for KTDR (thymidine flux), the gold standard for imaging cellular proliferation. Key Words: 3-deoxy-3-fluorothymidine; thymidine kinase 1; compartmental modeling; kinetic analysis
Visualizing Sweetness: Increasingly Diverse Applications for Fluorescent-Tagged Glucose Bioprobes and Their Recent Structural Modifications
, 2012
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Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats
- J Neurosci
, 1984
"... Aged rats (22 to 24 months) and young control rats (3 months) were tested in a battery of behavioral tests which included tests of learning, place navigation, sensorimotor integration, motor coordination, activity, and exploration. Following testing all animals were analyzed in an unanesthetized sta ..."
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Aged rats (22 to 24 months) and young control rats (3 months) were tested in a battery of behavioral tests which included tests of learning, place navigation, sensorimotor integration, motor coordination, activity, and exploration. Following testing all animals were analyzed in an unanesthetized state for their local glucose utilization. Significant differences in glucose utilization were found between the aged and young groups on some behaviors and in some brain regions. There was considerable variability in the aged group in both their behavioral performance and their glucose utilization scores; thus, attempts were made to determine whether the variability in the degree of impairment within any particular behavioral test was correlated to the regional glucose utilization scores in any of the 45 brain regions analyzed. In two of the behavioral tests employed (i.e., one for learning and one for place navigation), the decline in performance correlated significantly with the decrement in regional glucose utilization. Moreover, the performance in these two tests showed significant correlation with glucose use in only five regions (dentate gyrus, medial septum-diagonal band area, hippocampal CAI, hippocampal CA3, and prefrontal cortex). These results show that the learning impairments in the aged rats are related to the extent of decrease in glucose utilization in restricted areas of the limbic system. In addition, the results show that the individual rats within an aged rat population develop cognitive impairments
FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice
"... Hypothalamic “metabolic-sensing ” neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that;50 % of these neurons responded to oleic acid (O ..."
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Hypothalamic “metabolic-sensing ” neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that;50 % of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucida-tion of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, wean-ling rats were injected in the VMH with CD36 AAV shRNA. De-spite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on
