Human brain mapping under increasing cognitive complexity using regional cerebral blood flow measurements and positron emission tomography
Measurement of the regional cerebral blood flow (rCBF) is an important parameter in the evaluatio... more Measurement of the regional cerebral blood flow (rCBF) is an important parameter in the evaluation of cerebral function. With positron emission tomography (PET) rCBF has predominantly been quantified using the short-lived radiotracer oxygen-15 labelled water (H 2 15 O) and an adaptation of the Kety one-tissue compartment autoradiographic model. The values attained in putative grey matter, however, are systematically underestimated because of the limited scanner resolution. For this reason we applied a dynamic kinetic two-tissue compartment model including a fast and a slow flow component each with a perfusable tissue fraction. In the fast component rCBF was 2-2.5 times greater than grey matter values using traditional autoradiography in both human and monkey. Visual stimulation in human gave a corrected rCBF increase of approximately 40%. Visual stimulation was also used to indirectly validate carbon-10 labelled carbondioxide ( 10 CO 2 ), a new very short-lived rCBF PET tracer with a half-life of only 19.3 seconds. This allowed an increase in the number of independent PET scans per subject from 12-14 using H 2 15 O to 64 using 10 CO 2 . The experiment demonstrated a maximal activation response in the visual cortex at a 10-15 Hz stimulation frequency. The use of the rCBF PET mapping technique is illustrated by studies of the organization of language and the oculomotor system. With respect to the former, we found confirmation of neuropsychological evidence of the involvement of the left supramarginal/angular gyrus in reading in Japanese of a phonologically based script system, Kana, and of the left posterior inferior temporal gyrus in reading of a morphogram based script system, Kanji. Concerning the organization of the oculomotor system we found overlapping areas in fronto-parietal cortex involved in maintaining visual fixation, and performing visually guided and imagined eye movements. These data show that overt eye movements are not a prerequisite of the activation of classical cortical oculomotor regions and underscore the involvement of these areas in other behaviours such as visual attention and saccade inhibition. During eye movements in the dark an increased activation response in the parieto-occipital cortex can be found. This can be interpreted as effects of the gaze-sensitive neurons that are used to objectively localize objects relative to the body, and efferent copies of motor commands, used to predict the visual consequences of eye movements to maintain visual continuity. Defect efferent copies are in some neurobiological models of schizophrenia thought to contribute to passivity phenomena. The clinical perspective of brain mapping techniques is to preoperatively locate eloquent areas, e.g. motor function, language, and memory, allowing the achievement of optimal neurosurgical resection with the preservation of neurological function.
Subthalamic High-Frequency Deep Brain Stimulation Reduces Addiction-Like Alcohol Use and Suppresses the Overconsumption Induced by the Peer’s Presence
RationalThe immediate social context significantly influences alcohol consumption in humans. Rece... more RationalThe immediate social context significantly influences alcohol consumption in humans. Recent studies have revealed that peer presence could modulate drugs use in rats. The most efficient condition to reduce cocaine intake is the presence of a stranger peer, naive to drugs. Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN), which was shown to have beneficial effects on addiction to cocaine or alcohol, also modulate the protective influence of peer’s presence on cocaine use.ObjectivesThis study aimed to: 1) explore how the presence of an alcohol-naive stranger peer affects recreational and escalated alcohol intake, and 2) assess the involvement of STN on alcohol use and in the modulation induced by the presence of an alcohol-naïve stranger peer.MethodsRats with STN DBS and control animals self-administered 10% (v/v) ethanol in presence, or absence, of an alcohol-naive stranger peer, before and after escalation of ethanol intake (observed after intermittent alcohol (...
Effect of partial volume correction on estimates of the influx and cerebral metabolism of 6‐[18F]fluoro‐L‐dopa studied with PET in normal control and Parkinson's disease subjects
Synapse, Aug 1, 2000
The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the acc... more The poor spatial resolution of positron emission tomography (PET) is a limiting factor in the accurate assay of physiological processes investigated by compartmental modeling of tracer uptake and metabolism in living human brain. The radioactivity concentration in a region-of-interest is consequently altered by loss of signal from that structure and contamination from adjacent brain regions, phenomena known as partial volume effects. We now apply an MRI-based algorithm to compensate for partial volume effects in the special case of compartmental modeling of the cerebral uptake of 6-[(18)F]fluoro-L-dopa (FDOPA), an exogenous substrate of dopa decarboxylase. High-resolution MRI scans were obtained from normal volunteers (n = 4) and patients with Parkinson's disease (n = 4) in order to segment specific brain regions and calculate the partial volume correction factors. Dynamic 2D PET scans were acquired during 90 min following intravenous infusion of FDOPA. After partial volume correction, the apparent net blood-brain clearance of FDOPA (K(i)) was greatly increased in caudate and putamen of normal subjects and in caudate of Parkinson's disease patients. The equilibrium distribution volume of FDOPA (V(D)(e)) in cerebral cortex increased by 35% in all subjects. Using a two-compartment model, the relative activity of dopa decarboxylase with respect to FDOPA (k(D)(3)) in the basal ganglia was increased 2-3 times in normal subjects, to the range obtained previously in brain of living rat. The partial volume correction also increased the magnitude of k(D)(3) in caudate of Parkinson's disease patients, but did not alter k(D)(3) in putamen. A three-compartment model correcting for elimination of decarboxylated metabolites also yielded higher estimates of k(D)(3), but with a penalty in precision of the estimates. Together, these observations suggest that the limited spatial resolution of PET results in substantial underestimation of the true rate of FDOPA uptake and metabolism in vivo, and may also tend to obscure regional heterogeneity in the neurochemical pathology of Parkinson's disease.
1543-P: The Effect of Insulin Resistance on Brain Glucose Uptake—A Systematic Review and Meta-analysis
Diabetes, Jun 20, 2023
Objective: We investigated the association between peripheral insulin resistance (IR) and brain g... more Objective: We investigated the association between peripheral insulin resistance (IR) and brain glucose uptake (BGU) and further determined if testing condition (fasting vs. hyperinsulinemic-euglycemic clamp) was a moderator of the association. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science, studies assessing an association between measures of or clinical proxies for IR (e.g. diabetes and obesity) and BGU were included. Effect sizes were standardized and transformed into correlation coefficients and a random effect meta-analysis performed. Further, a subgroup analysis on testing condition was conducted. Results: Twenty-one studies (n = 3,620) were included in the meta-analysis. The pooled correlation (-0.13 [95% CI: -0.37; 0.12], p=0.3) showed a substantial heterogeneity (I2 = 98%). Subgroup analysis revealed that IR negatively correlated with BGU when subjects were examined at fasting conditions (-0.42 [95% CI: -0.59; -0.21], I2 = 99%) and positively correlated when subjects were examined during a hyperinsulinemic-euglycemic clamp (0.53 [ 0.38; 0.66], I2 = 47%)(figure 1). Test condition significantly moderated the association (p <0.01) and explained 55% of the heterogeneity. Conclusion: Across the studies IR results in abnormal BGU in both fasting and hyperinsulinemic states, clamp conditions reverse the low BGU in IR. Disclosure N.J.Jensen: None. A.J.Porse: None. H.Speyer: None. J.Krogh: None. M.Gejl: None. A.H.Gjedde: None. J.Rungby: Advisory Panel; Abbott, Consultant; Novo Nordisk, Speaker's Bureau; Boehringer-Ingelheim, AstraZeneca.
Generation of Maps of Dispersion Time Constant and Tracer Arrival Delay Using [15O]Carbon Monoxide
This chapter proposes a method for generating the averaged maps of dispersion time constant (τ) a... more This chapter proposes a method for generating the averaged maps of dispersion time constant (τ) and tracer arrival delay (δ) using [ 15 O]carbon monoxide and dynamic positron emission tomography data. Because the time course of radioactivity measured in the periphery is usually modulated in terms of dispersion and tracer arrival delay, radioactivity measured in the periphery does not represent the time course of radioactivity at the site of tracer exchange between the circulation and the organ of interest. A method was previously developed for determining the dispersion time constant and tracer arrival delay simultaneously, using [ 15 O]carbon monoxide (CO), which is retained in red blood cells and does not enter the brain. In this chapter, this method is extended to the estimation of dispersion time constant and tracer arrival delay pixel by pixel to generate averaged maps for the investigation of regional differences in these parameters.
Mapping of Change in Cerebral Glucose Utilization Using [18F]FDG Double Injection and New Graphical Analysis
The authors developed a method for mapping the change in cerebral glucose utilization at two diff... more The authors developed a method for mapping the change in cerebral glucose utilization at two different physiological states using [(18 )F]fluorodeoxyglucose (FDC) double infection and the constrained weighted-integration method. The authors studied young normal subjects without (baseline-baseline group, n=5) and with (baseline-stimulation group, n=5) vibrotactile stimulation of the fingertips of the right hand. Dynamic scans were performed using positron emission tomography (PET) following an initial dose (the first session, 0-30 min) and an additional dose (the second session, 30-60 min). The parametric images of the net clearance of FDG from blood to brain (K*), unidirectional blood-to-brain clearance (K(1)*), and cerebral metabolic rate of glucose (CMR(glc)) of the two sessions were generated. The averaged subtraction (second minus first session) and t-statistic images were generated, which were rendered into Talairach's stereotaxic coordinates and merged with the averaged magnetic resonance imaging (MRI) image. In the baseline-baseline group, regional K*, K(1)* and CMR(glc) in the first and second sessions were strongly correlated (r(2)=0.953, 0.935, and 0.951, respectively, n=330). In the baseline-stimulation group, significant increases in these estimates were obtained in the contralateral primary somatosensory cortex (SI) (from 3.43+/-0.78 to 4.02+/-1.01 ml/100 g/min for K*, 7.85+/-1.88 to 9.09+/-1.71 ml/100 g/min for K(1)*, and 280+/-5.9 to 32.3+/-5.5 mumol/100 g/min for CMR(glc)), while there were no significant changes in the ipsilateral SI (from 3.45+/-0.83 to 359+/-0.72 ml/100 g/min for K*, 8.17+/-2.33 to 837+/-1.75 ml/100 g/min for K(1 )* and 29.5+/-8.1 to 29.1+/-8.2 mumol/100 g/mln for CMR (glc)), Significant increases in K* and CMR(glc) in the contralateral SI were clearly demonstrated in the t-statistic image. In conclusion, the proposed method allows mapping of changes in cerebral glucose utilization during physiological stimulation of the brain, and will be useful for studying the relationship between neural activity and regional cerebral glucose metabolism.
Impact of Partial Volume Correction on Kinetic Parameters: Preliminary Experience in Patient Studies
Elsevier eBooks, 1998
Two radioligands specific for the dopamine system were used to study the influence of correction ... more Two radioligands specific for the dopamine system were used to study the influence of correction for partial volume effects on quantitative binding data obtained from positron emission tomography from various brain regions. [11C]Raclopride binds to the dopamine D2 and D3 receptors, and [11C]WIN 35,428 binds to the dopamine transporter. Both are highly concentrated in the basal ganglia but not in the cerebellum. Normal subjects and patients with Lesch-Nyhan syndrome, a disease in which brain atrophy occurs, were studied before and after correction for the partial volume effect. A dramatic elevation in rate constants, especially the k3/k4 ratio, was observed after correction in both normal subjects and patients. The patients, who initially had a decrease in [11C]WIN 35,428 binding at the dopamine transporter site compared to normal subjects, retained this separation after the correction algorithm was applied.
Abstraet-Cerebral blood flow (CBF) and the cerebral-metabolic rates for oxygen, glucose, acetoace... more Abstraet-Cerebral blood flow (CBF) and the cerebral-metabolic rates for oxygen, glucose, acetoacetate, 8-hydroxybutyrate and lactate were measured in 1-to 5day old Beagle dogs under nitrous oxide anesthesia. CBF was determined by 13Xe washout with mechanically integrated blood samples withdrawn simultaneously from a femoral artery and from the posterior one-third of the superior sagittal sinus. CBF and CMROz in normocapnia (PaC02 40 f 1 m m Hg) were 48 f 5 m1/100 g/min and 2.15 m1/100 g/min, respectively. There was a positive, linear relationship between CBF and PaCOz. calculated for P a C 0 2 values ranging from 26 to 70 mm Hg. Induced hypocapnia (PaC02 31 f I mm Hg) or hypercapnia (paC02 58 f 2mm Hg) did not alter the CMR02. Glucose and acetoacetate were taken up by the brain at all PaCO, levels examined; however, the cerebral uptake of glucose always exceeded the combined uptake of ketone bodies by more than a factor of ten. The cerebral metabolic rate for glucose (94.6 f 3.6 prno1/100 g/min) more than accounted for overall cerebral oxygen consumption, and yielded an oxygen:glucose ratio (mol:mol) of 5.1. Thus, as in adult animals, PaCOZ is an important regulator of cerebral blood flow in puppies, and glucose is the major substrate for oxidative energy production in the immature brain. The oxidation of ketone bodies by the newborn dog brain accounts for not more than 6% of the in uiuo cerebral oxygen consumption.
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