Sargo Aalto - Academia.edu (original) (raw)
Papers by Sargo Aalto
NeuroImage, 2008
[(11)C]Flumazenil is widely used in positron emission tomography (PET) studies to measure GABA(A)... more [(11)C]Flumazenil is widely used in positron emission tomography (PET) studies to measure GABA(A) receptors in vivo in humans. Although several different methods have been applied for the quantification of [(11)C]flumazenil binding, the reproducibility of these methods has not been previously examined. The reproducibility of a single bolus [(11)C]flumazenil measurements was studied by scanning eight healthy volunteers twice during the same day. Grey matter regions were analyzed using both regions-of-interest (ROI) and voxel-based analysis methods. Compartmental kinetic modelling using both arterial and reference region input function were applied to derive the total tissue distribution volume (V(T)) and the binding potential (BP) (BP(P) and BP(ND)) of [(11)C]flumazenil. To measure the reproducibility and reliability of each [(11)C]flumazenil binding parameter, absolute variability values (VAR) and intraclass correlation coefficients (ICC) were calculated. Tissue radioactivity concentration over time was best modelled with a 2-tissue compartmental model. V(T) showed with all methods good to excellent reproducibility and reliability with low VARs (mean of all brain regions) (5.57%-6.26%) and high ICCs (mean of all brain regions) (0.83-0.88) when using conventional ROI analysis. Also voxel-based analysis methods yielded excellent reproducibility (VAR 5.75% and ICC 0.81). In contrast, the BP estimates using pons as the reference tissue yielded higher VARs (8.08%-9.08%) and lower ICCs (0.35-0.80). In conclusion, the reproducibility of [(11)C]flumazenil measurements is considerably better with outcome measures based on arterial input function than those using pons as the reference tissue. The voxel-based analysis methods are proper alternative as the reliability is preserved and analysis automated.
Pain, 2003
Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We h... more Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We have previously demonstrated with positron emission tomography (PET) that striatal dopaminergic hypofunction may be involved in the burning mouth syndrome. The aim of the present study was to evaluate the nigrostriatal dopaminergic system in patients with atypical facial pain using PET. In seven patients with atypical facial pain, striatal presynaptic dopaminergic function was assessed with [18F]FDOPA and dopamine D1 and D2 receptor availabilities with [11C]NNC 756 and [11C]raclopride, respectively. The results were compared with those of healthy controls. A quantitative region-of-interest analysis showed that the uptakes of [18F]FDOPA and [11C]NNC 756 did not differ between patients and controls. There was a tendency of increased D2 receptor availability in the left putamen (P=0.056), and the D1/D2 ratio in the putamen was decreased bilaterally by 7.7% (P=0.002) in patients when compared to controls. In a voxel-based analysis, the uptake of [11C]raclopride was increased in the left putamen (P=0.025). In conclusion, the increase in D2 receptor availability in the left putamen and the decrease in D1/D2 ratio imply that alterations in the striatal dopaminergic system as evaluated by PET may be involved in chronic orofacial pain conditions.
Neurology, 2009
In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationshi... more In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationship with dementia severity are unclear. We investigated the brain uptake of the amyloid ligand (11)C-labeled Pittsburgh compound B ([(11)C]PIB) and volumetric brain changes over a 2-year follow-up in patients with AD and in aged healthy controls. Fourteen patients with AD (mean age 72 years, SD 6.6) and 13 healthy controls (mean age 68 years, SD 5.4) were examined at baseline and after 2 years (patients with AD: mean 2.0 years, SD 0.2; controls: mean 2.1 years, SD 0.6) with [(11)C]PIB PET, MRI, and neuropsychological assessments. [(11)C]PIB uptake was analyzed with a voxel-based statistical method (SPM), and quantitative data were obtained with automated region-of-interest analysis. MRI data were analyzed with voxel-wise tensor-based morphometry. The [(11)C]PIB uptake of the patients with AD did not increase significantly during follow-up when compared with that of the controls. MRI showed progressive brain volume change in the patients with AD, e.g., in the hippocampal region, temporal cortex, and precuneus (p < 0.05). The mean Mini-Mental State Examination score of the patients with AD declined from 24.3 (SD 3.1) at baseline to 21.6 (SD 3.9) at follow-up (p = 0.009). Cognitive decline was also evident in other neuropsychological test results. Baseline neocortical [(11)C]PIB uptake ratios predicted subsequent volumetric brain changes in the controls (r = 0.725, p = 0.005). The results suggest no (or only little) increase in (11)C-labeled Pittsburgh compound B ([(11)C]PIB) uptake during 2 years of Alzheimer disease progression, despite advancing brain atrophy and declining cognitive performance. Nevertheless, changes in [(11)C]PIB uptake during a longer follow-up cannot be excluded. High cortical [(11)C]PIB uptake may predict ongoing brain atrophy in cognitively normal individuals.
Journal of Cerebral Blood Flow & Metabolism, 2014
Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of... more Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.
Anesthesia & Analgesia, 2004
Based on in vitro studies and animal data, most anesthetics are supposed to act via ␥-aminobutyri... more Based on in vitro studies and animal data, most anesthetics are supposed to act via ␥-aminobutyric acid type A (GABA A ) receptors. However, this fundamental characteristic has not been extensively investigated in humans. We studied 11 C-flumazenil binding to GABA A receptors during sevoflurane and propofol anesthesia in the living human brain using positron emission tomography (PET). Fourteen healthy male subjects underwent 2 60-min dynamic PET studies with 11 Clabeled flumazenil, awake and during anesthesia. Anesthesia was maintained with 2% end-tidal sevoflurane (n ϭ 7) or propofol at a target plasma concentration of 9.0 Ϯ 3.0 (mean Ϯ sd) g/mL (n ϭ 7). The depth of anesthesia was measured with bispectral index (BIS). Values of regional distribution volumes (DV) of 11 Cflumazenil were calculated in several brain areas using metabolite-corrected arterial plasma curves and a two-compartment model. Separate voxel-based statistical analysis using parametric DV images was performed for detailed visualization. The average BIS index was 35 Ϯ 6 in the sevoflurane group and 28 Ϯ 8 in the propofol group (P ϭ 0.02). Sevoflurane increased the DV of 11 C-flumazenil significantly (P Ͻ 0.05) in all brain areas studied except the pons and the white matter. In the propofol group the increases were significant (P Ͻ 0.05) in the caudatus, putamen, cerebellum, thalamus and the frontal, temporal, and parietal cortices. Furthermore, the DV increases in the frontal, occipital, parietal, and temporal cortical areas and in the putamen were statistically significantly larger in the sevoflurane than in the propofol group. Our findings support the involvement of GABA A receptors in the mechanism of action of both anesthetics in humans.
Anaesthesia, 2005
ENTROPY TM index monitoring, based on spectral entropy of the electroencephalogram, is a promisin... more ENTROPY TM index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.5 and 19.0 lg.ml )1 plasma drug concentrations of propofol. Spectral entropy from the frequency band 0.8-32 Hz was calculated and cerebral blood flow assessed using positron emission tomography and [ 15 O]-labelled water at baseline and at each anaesthesia level. Both drugs induced significant reductions in spectral entropy and cortical and global cerebral blood flow. Midfrontal-central spectral entropy was associated with individual frontal and whole brain blood flow values across all conditions, suggesting that this novel measure of anaesthetic depth can depict global changes in neuronal activity induced by the drugs. The cortical areas of the most significant associations were remarkably similar for both drugs.
Anesthesia & Analgesia, 2008
Anesthesiology, 2004
The authors have recently shown with positron emission tomography that subanesthetic doses of rac... more The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ketamine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism. 18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level. In addition, voxel-based analysis was performed for the relative changes in rGMR using statistical parametric mapping. The mean +/- SD measured ketamine serum concentration was 326.4+/-86.3 ng/ml. The mean arterial pressure was slightly increased (maximally by 16.4%) during ketamine infusion (P < 0.001). Ketamine increased absolute rGMR significantly in most regions of interest studied. The greatest increases were detected in the thalamus (14.6+/-15.9%; P = 0.029) and in the frontal (13.6+/-13.1%; P = 0.011) and parietal cortices (13.1+/-11.2%; P = 0.007). Absolute rGMR was not decreased anywhere in the brain. The voxel-based analysis revealed relative rGMR increases in the frontal, temporal, and parietal cortices. Global increases in rGMR seem to parallel ketamine-induced increases in cerebral blood flow detected in the authors' earlier study. Therefore, ketamine-induced disturbance of coupling between cerebral blood flow and metabolism is highly unlikely. The previously observed decrease in oxygen extraction fraction may be due to nonoxidative glucose metabolism during ketamine-induced increase in glutamate release.
Anesthesiology, 2003
Background: Animal experiments have demonstrated neuroprotection by ketamine. However, because of... more Background: Animal experiments have demonstrated neuroprotection by ketamine. However, because of its propensity to increase cerebral blood flow, metabolism, and intracranial pressure, its use in neurosurgery or trauma patients has been questioned.
Anesthesiology, 2003
Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to pert... more Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography. 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2O (S+N), (3) propofol alone, and (4) propofol plus 70% N2O (P+N). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level. The mean +/- SD end-tidal concentration of sevoflurane was 1.5 +/- 0.3% during sevoflurane alone and 1.2 +/- 0.3% during S+N (P < 0.001). The measured propofol concentration was 3.7 +/- 0.7 microg/ml during propofol alone and 3.5 +/- 0.7 microg/ml during P+N (not significant). Sevoflurane alone decreased rCBF in some (to 73-80% of baseline, P < 0.01), and propofol in all brain structures (to 53-70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83-86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56-70% and 50-68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during S+N, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone. Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. S+N especially reduced the oxygen extraction fraction, suggesting disturbed flow-activity coupling in humans at a moderate depth of anesthesia.
Anesthesiology, 2002
The authors report a positron emission tomography (PET) study on humans with parallel exploration... more The authors report a positron emission tomography (PET) study on humans with parallel exploration of the dose-dependent effects of an intravenous (propofol) and a volatile (sevoflurane) anesthetic agent on regional cerebral blood flow (rCBF) using quantitative and relative (Statistical Parametric Mapping [SPM]) analysis. Using H(2)(15)O, rCBF was assessed in 16 healthy (American Society of Anesthesiologists [ASA] physical status I) volunteers awake and at three escalating drug concentrations: 1, 1.5, and 2 MAC/EC(50), or specifically, at either 2, 3, and 4% end-tidal sevoflurane (n = 8), or 6, 9, and 12 microg/ml plasma concentration of propofol (n = 8). Rocuronium was used for muscle relaxation. Both drugs decreased the bispectral index and blood pressure dose-dependently. Comparison between adjacent levels showed that sevoflurane initially (0 vs. 1 MAC) reduced absolute rCBF by 36-53% in all areas, then (1 vs. 1.5 MAC) increased rCBF in the frontal cortex, thalamus, and cerebellum (7-16%), and finally (1.5 vs. 2 MAC) caused a dual effect with a 23% frontal reduction and a 38% cerebellar increase. In the propofol group, flow was also initially reduced by 62-70%, with minor further effects. In the SPM analysis of the "awake to 1 MAC/EC(50)" step, both anesthetic agents reduced relative rCBF in the cuneus, precuneus, posterior limbic system, and the thalamus or midbrain; additionally, propofol reduced relative rCBF in the parietal and frontal cortices. Both anesthetic agents caused a global reduction of rCBF (propofol > sevoflurane) at the 1 MAC/EC(50) level. The effect was maintained at higher propofol concentrations, whereas 2 MAC sevoflurane caused noticeable flow redistribution. Despite the marked global changes, SPM analysis enabled detailed localization of regions with the greatest relative decreases.
Anesthesiology, 2005
Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its ef... more Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO 2 ), and glucose metabolic rate (GMR) have not been comprehensively studied in humans.
Anesthesiology, 2007
Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in pa... more Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in patients with cerebral pathology could be compromised by deleterious effects on regional cerebral blood flow (rCBF). 15O-labeled water was used to determine rCBF in nine healthy male subjects at baseline and during 1 minimum alveolar concentration (MAC) of xenon (63%). Anesthesia was based solely on xenon. Absolute changes in rCBF were quantified using region-of-interest analysis and voxel-based analysis. Mean arterial blood pressure and arterial partial pressure for carbon dioxide remained unchanged. The mean (+/-SD) xenon concentration during anesthesia was 65.2+/-2.3%. Xenon anesthesia decreased absolute rCBF by 34.7+/-9.8% in the cerebellum (P<0.001), by 22.8+/-10.4% in the thalamus (P=0.001), and by 16.2+/-6.2% in the parietal cortex (P<0.001). On average, xenon anesthesia decreased absolute rCBF by 11.2+/-8.6% in the gray matter (P=0.008). A 22.1+/-13.6% increase in rCBF was detected in the white matter (P=0.001). Whole-brain voxel-based analysis revealed widespread cortical reductions and increases in rCBF in the precentral and postcentral gyri. One MAC of xenon decreased rCBF in several areas studied. The greatest decreases were detected in the cerebellum, the thalamus and the cortical areas. Increases in rCBF were observed in the white matter and in the pre- and postcentral gyri. These results are in clear contradiction with ketamine, another N-methyl-D-aspartate antagonist and neuroprotectant, which induces a general increase in cerebral blood flow at anesthetic concentrations.
The Journal of …, 2005
Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulat... more Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulation of working memory (WM) functions in the prefrontal cortex. In humans, blood flow studies show prefrontal involvement in WM functions, but direct evidence for the involvement of the dopaminergic system in WM is lacking. Using positron emission tomography with a recently developed high-affinity dopamine D 2 receptor tracer, [ 11 C]FLB 457, we explored frontal, temporal, and parietal D 2 receptor availability in 12 healthy volunteers while they were performing verbal WM and sustained attention tasks. During the performance of both tasks, reduced D 2 receptor availability was observed in the left ventral anterior cingulate, suggesting an attention or arousal-related increase in dopamine release during these tasks. Compared with the sustained attention task, the verbal WM task reduced D 2 receptor availability in the ventrolateral frontal cortex bilaterally and in the left medial temporal structures (amygdala, hippocampus), suggesting that dopamine release in these regions might have a specific role in WM. In addition, correlation analyses indicated that increased dopamine release in the right ventrolateral frontal cortex and the left ventral anterior cingulate during the WM task was associated with faster and more stable WM performance, respectively. Our results indicate that regionally specific components of the frontotemporal dopaminergic network are functionally involved in WM performance in humans.
Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of... more Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.
![Research paper thumbnail of The effects of d-amphetamine on extrastriatal dopamine D2/D3 receptors: a randomized, double-blind, placebo-controlled PET study with [11C]FLB 457 in healthy subjects](https://attachments.academia-assets.com/46346511/thumbnails/1.jpg)
](European Journal of Nuclear Medicine and Molecular Imaging, 2009
Purpose The dopamine D 2 /D 3 receptor ligand [ 11 C]FLB 457 and PET enable quantification of low... more Purpose The dopamine D 2 /D 3 receptor ligand [ 11 C]FLB 457 and PET enable quantification of low-density extrastriatal D 2 /D 3 receptors, but it is uncertain whether [ 11 C]FLB 457 can be used for measuring extrastriatal dopamine release. Methods We studied the effects of d-amphetamine (0.3 mg/ kg i.v.) on extrastriatal [ 11 C]FLB 457 binding potential (BP ND ) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. Results The effects of d-amphetamine on [ 11 C]FLB 457 BP ND and distribution volume (V T ) in the frontal cortex were not different from those of placebo. Small decreases in [ 11 C]FLB 457 BP ND were observed only in the posterior cingulate and hippocampus. The regional changes in [ 11 C] FLB 457 BP ND did not correlate with d-amphetamineinduced changes in subjective ratings of euphoria.
![Research paper thumbnail of Reproducibility of automated simplified voxel-based analysis of PET amyloid ligand [11 C] PIB uptake using 30-min scanning data](https://attachments.academia-assets.com/46346523/thumbnails/1.jpg)
](European journal of …, 2009
Purpose Positron emission tomography (PET) with 11C-labelled Pittsburgh compound B ([11C]PIB) ena... more Purpose Positron emission tomography (PET) with 11C-labelled Pittsburgh compound B ([11C]PIB) enables the quantitation of β-amyloid accumulation in the brain of patients with Alzheimer's disease (AD). Voxel-based image analysis techniques conducted in a ...
Psychopharmacology, 2002
Rationale: A glutamate-dopamine interaction has been implicated in the psychosis-like effects of ... more Rationale: A glutamate-dopamine interaction has been implicated in the psychosis-like effects of glutamate N-methyl-d-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine. However, recent imaging studies addressing striatal glutamatedopamine interaction directly in vivo in man have been controversial. Objectives: To examine whether the NMDA receptor antagonist ketamine in high subanesthetic concentrations decreases striatal [ 11 C]raclopride binding potential in man. To further evaluate whether changes in striatal [ 11 C]raclopride binding are associated with ketamine-induced behavioral effects. Methods: The effect of computer-driven subanesthetic ketamine infusion on striatal dopamine release was studied in healthy male subjects using a controlled study design. Dopamine release was studied using positron emission tomography and the [ 11 C]raclopride displacement paradigm. A conventional region of interest-based analysis and voxelbased analysis were applied to the positron emission tomography data. Results: The average plasma ketamine concentration was 293€29 ng/ml. Ketamine did not alter striatal [ 11 C]raclopride binding. Ketamine induced typical behavioral effects, such as hallucinations but there was no correlation between these effects and displacement of [ 11 C]raclopride binding. Conclusions: This controlled study indicates that ketamine does not decrease striatal [ 11 C]raclopride binding. Striatal dopamine release is of minor importance in the psychosis-like effects of ketamine.
Psychopharmacology, 2005
Rationale The noncompetitive glutamate N-methyl-d-aspartate receptor antagonist ketamine induces... more Rationale The noncompetitive glutamate N-methyl-d-aspartate receptor antagonist ketamine induces transient psychotic symptoms in man. Involvement of dopaminergic mechanisms in these effects has been suggested. Objectives The purpose of this article is to study the effects of ketamine on extrastriatal dopamine receptor availability in healthy subjects and extracellular dopamine levels in rat cortex. Materials and methods The effect of computer-driven subanesthetic ketamine infusion on cortical dopamine release was studied in healthy male subjects using a controlled study design. Dopamine D2/D3 receptor availability was quantified using positron emission tomography (PET) and [11C]FLB 457. A conventional region of interest-based analysis and voxel-based analysis was applied to the PET data. The ketamine-induced cortical dopamine release in rats was studied using in vivo microdialysis. Results Ketamine infusion reduced significantly the [11C]FLB 457 binding potential (BP) in the pos...
Dementia and Geriatric Cognitive Disorders
The relationship between baseline (11)C-Pittsburgh compound B ((11)C-PIB) uptake and cognitive de... more The relationship between baseline (11)C-Pittsburgh compound B ((11)C-PIB) uptake and cognitive decline during a 2-year follow-up was studied in 9 patients with mild cognitive impairment (MCI) who converted to Alzheimer's disease (AD) and 7 who remained with MCI. (11)C-PIB PET scan was conducted at baseline and cognitive assessment both at baseline and at follow-up. To obtain quantitative regional values of (11)C-PIB uptake, automated region of interest analysis was done using spatially normalized parametric ratio (region-to-cerebellar cortex) images. At baseline, there were statistically significant differences in (11)C-PIB uptake, but not in cognitive test performances between the converters and nonconverters. Memory and executive function declined only in the converters during follow-up. In the converters, lower baseline frontal (11)C-PIB uptake was associated with faster decline in verbal learning. Higher baseline uptake in the caudate nucleus was related to faster decline in memory consolidation, and higher temporal uptake was associated with decline in executive function. Higher (11)C-PIB uptake in the caudate nucleus and temporal lobe was related to decline in memory and executive functions, whereas lower frontal uptake was related to decline in verbal learning. The results indicate that in prodromal AD, frontal amyloid accumulation reaches its maximum in the MCI stage, characterized by memory problems without full-blown dementia.
NeuroImage, 2008
[(11)C]Flumazenil is widely used in positron emission tomography (PET) studies to measure GABA(A)... more [(11)C]Flumazenil is widely used in positron emission tomography (PET) studies to measure GABA(A) receptors in vivo in humans. Although several different methods have been applied for the quantification of [(11)C]flumazenil binding, the reproducibility of these methods has not been previously examined. The reproducibility of a single bolus [(11)C]flumazenil measurements was studied by scanning eight healthy volunteers twice during the same day. Grey matter regions were analyzed using both regions-of-interest (ROI) and voxel-based analysis methods. Compartmental kinetic modelling using both arterial and reference region input function were applied to derive the total tissue distribution volume (V(T)) and the binding potential (BP) (BP(P) and BP(ND)) of [(11)C]flumazenil. To measure the reproducibility and reliability of each [(11)C]flumazenil binding parameter, absolute variability values (VAR) and intraclass correlation coefficients (ICC) were calculated. Tissue radioactivity concentration over time was best modelled with a 2-tissue compartmental model. V(T) showed with all methods good to excellent reproducibility and reliability with low VARs (mean of all brain regions) (5.57%-6.26%) and high ICCs (mean of all brain regions) (0.83-0.88) when using conventional ROI analysis. Also voxel-based analysis methods yielded excellent reproducibility (VAR 5.75% and ICC 0.81). In contrast, the BP estimates using pons as the reference tissue yielded higher VARs (8.08%-9.08%) and lower ICCs (0.35-0.80). In conclusion, the reproducibility of [(11)C]flumazenil measurements is considerably better with outcome measures based on arterial input function than those using pons as the reference tissue. The voxel-based analysis methods are proper alternative as the reliability is preserved and analysis automated.
Pain, 2003
Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We h... more Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We have previously demonstrated with positron emission tomography (PET) that striatal dopaminergic hypofunction may be involved in the burning mouth syndrome. The aim of the present study was to evaluate the nigrostriatal dopaminergic system in patients with atypical facial pain using PET. In seven patients with atypical facial pain, striatal presynaptic dopaminergic function was assessed with [18F]FDOPA and dopamine D1 and D2 receptor availabilities with [11C]NNC 756 and [11C]raclopride, respectively. The results were compared with those of healthy controls. A quantitative region-of-interest analysis showed that the uptakes of [18F]FDOPA and [11C]NNC 756 did not differ between patients and controls. There was a tendency of increased D2 receptor availability in the left putamen (P=0.056), and the D1/D2 ratio in the putamen was decreased bilaterally by 7.7% (P=0.002) in patients when compared to controls. In a voxel-based analysis, the uptake of [11C]raclopride was increased in the left putamen (P=0.025). In conclusion, the increase in D2 receptor availability in the left putamen and the decrease in D1/D2 ratio imply that alterations in the striatal dopaminergic system as evaluated by PET may be involved in chronic orofacial pain conditions.
Neurology, 2009
In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationshi... more In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationship with dementia severity are unclear. We investigated the brain uptake of the amyloid ligand (11)C-labeled Pittsburgh compound B ([(11)C]PIB) and volumetric brain changes over a 2-year follow-up in patients with AD and in aged healthy controls. Fourteen patients with AD (mean age 72 years, SD 6.6) and 13 healthy controls (mean age 68 years, SD 5.4) were examined at baseline and after 2 years (patients with AD: mean 2.0 years, SD 0.2; controls: mean 2.1 years, SD 0.6) with [(11)C]PIB PET, MRI, and neuropsychological assessments. [(11)C]PIB uptake was analyzed with a voxel-based statistical method (SPM), and quantitative data were obtained with automated region-of-interest analysis. MRI data were analyzed with voxel-wise tensor-based morphometry. The [(11)C]PIB uptake of the patients with AD did not increase significantly during follow-up when compared with that of the controls. MRI showed progressive brain volume change in the patients with AD, e.g., in the hippocampal region, temporal cortex, and precuneus (p < 0.05). The mean Mini-Mental State Examination score of the patients with AD declined from 24.3 (SD 3.1) at baseline to 21.6 (SD 3.9) at follow-up (p = 0.009). Cognitive decline was also evident in other neuropsychological test results. Baseline neocortical [(11)C]PIB uptake ratios predicted subsequent volumetric brain changes in the controls (r = 0.725, p = 0.005). The results suggest no (or only little) increase in (11)C-labeled Pittsburgh compound B ([(11)C]PIB) uptake during 2 years of Alzheimer disease progression, despite advancing brain atrophy and declining cognitive performance. Nevertheless, changes in [(11)C]PIB uptake during a longer follow-up cannot be excluded. High cortical [(11)C]PIB uptake may predict ongoing brain atrophy in cognitively normal individuals.
Journal of Cerebral Blood Flow & Metabolism, 2014
Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of... more Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.
Anesthesia & Analgesia, 2004
Based on in vitro studies and animal data, most anesthetics are supposed to act via ␥-aminobutyri... more Based on in vitro studies and animal data, most anesthetics are supposed to act via ␥-aminobutyric acid type A (GABA A ) receptors. However, this fundamental characteristic has not been extensively investigated in humans. We studied 11 C-flumazenil binding to GABA A receptors during sevoflurane and propofol anesthesia in the living human brain using positron emission tomography (PET). Fourteen healthy male subjects underwent 2 60-min dynamic PET studies with 11 Clabeled flumazenil, awake and during anesthesia. Anesthesia was maintained with 2% end-tidal sevoflurane (n ϭ 7) or propofol at a target plasma concentration of 9.0 Ϯ 3.0 (mean Ϯ sd) g/mL (n ϭ 7). The depth of anesthesia was measured with bispectral index (BIS). Values of regional distribution volumes (DV) of 11 Cflumazenil were calculated in several brain areas using metabolite-corrected arterial plasma curves and a two-compartment model. Separate voxel-based statistical analysis using parametric DV images was performed for detailed visualization. The average BIS index was 35 Ϯ 6 in the sevoflurane group and 28 Ϯ 8 in the propofol group (P ϭ 0.02). Sevoflurane increased the DV of 11 C-flumazenil significantly (P Ͻ 0.05) in all brain areas studied except the pons and the white matter. In the propofol group the increases were significant (P Ͻ 0.05) in the caudatus, putamen, cerebellum, thalamus and the frontal, temporal, and parietal cortices. Furthermore, the DV increases in the frontal, occipital, parietal, and temporal cortical areas and in the putamen were statistically significantly larger in the sevoflurane than in the propofol group. Our findings support the involvement of GABA A receptors in the mechanism of action of both anesthetics in humans.
Anaesthesia, 2005
ENTROPY TM index monitoring, based on spectral entropy of the electroencephalogram, is a promisin... more ENTROPY TM index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.5 and 19.0 lg.ml )1 plasma drug concentrations of propofol. Spectral entropy from the frequency band 0.8-32 Hz was calculated and cerebral blood flow assessed using positron emission tomography and [ 15 O]-labelled water at baseline and at each anaesthesia level. Both drugs induced significant reductions in spectral entropy and cortical and global cerebral blood flow. Midfrontal-central spectral entropy was associated with individual frontal and whole brain blood flow values across all conditions, suggesting that this novel measure of anaesthetic depth can depict global changes in neuronal activity induced by the drugs. The cortical areas of the most significant associations were remarkably similar for both drugs.
Anesthesia & Analgesia, 2008
Anesthesiology, 2004
The authors have recently shown with positron emission tomography that subanesthetic doses of rac... more The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ketamine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism. 18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level. In addition, voxel-based analysis was performed for the relative changes in rGMR using statistical parametric mapping. The mean +/- SD measured ketamine serum concentration was 326.4+/-86.3 ng/ml. The mean arterial pressure was slightly increased (maximally by 16.4%) during ketamine infusion (P < 0.001). Ketamine increased absolute rGMR significantly in most regions of interest studied. The greatest increases were detected in the thalamus (14.6+/-15.9%; P = 0.029) and in the frontal (13.6+/-13.1%; P = 0.011) and parietal cortices (13.1+/-11.2%; P = 0.007). Absolute rGMR was not decreased anywhere in the brain. The voxel-based analysis revealed relative rGMR increases in the frontal, temporal, and parietal cortices. Global increases in rGMR seem to parallel ketamine-induced increases in cerebral blood flow detected in the authors' earlier study. Therefore, ketamine-induced disturbance of coupling between cerebral blood flow and metabolism is highly unlikely. The previously observed decrease in oxygen extraction fraction may be due to nonoxidative glucose metabolism during ketamine-induced increase in glutamate release.
Anesthesiology, 2003
Background: Animal experiments have demonstrated neuroprotection by ketamine. However, because of... more Background: Animal experiments have demonstrated neuroprotection by ketamine. However, because of its propensity to increase cerebral blood flow, metabolism, and intracranial pressure, its use in neurosurgery or trauma patients has been questioned.
Anesthesiology, 2003
Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to pert... more Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography. 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2O (S+N), (3) propofol alone, and (4) propofol plus 70% N2O (P+N). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level. The mean +/- SD end-tidal concentration of sevoflurane was 1.5 +/- 0.3% during sevoflurane alone and 1.2 +/- 0.3% during S+N (P < 0.001). The measured propofol concentration was 3.7 +/- 0.7 microg/ml during propofol alone and 3.5 +/- 0.7 microg/ml during P+N (not significant). Sevoflurane alone decreased rCBF in some (to 73-80% of baseline, P < 0.01), and propofol in all brain structures (to 53-70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83-86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56-70% and 50-68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during S+N, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone. Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. S+N especially reduced the oxygen extraction fraction, suggesting disturbed flow-activity coupling in humans at a moderate depth of anesthesia.
Anesthesiology, 2002
The authors report a positron emission tomography (PET) study on humans with parallel exploration... more The authors report a positron emission tomography (PET) study on humans with parallel exploration of the dose-dependent effects of an intravenous (propofol) and a volatile (sevoflurane) anesthetic agent on regional cerebral blood flow (rCBF) using quantitative and relative (Statistical Parametric Mapping [SPM]) analysis. Using H(2)(15)O, rCBF was assessed in 16 healthy (American Society of Anesthesiologists [ASA] physical status I) volunteers awake and at three escalating drug concentrations: 1, 1.5, and 2 MAC/EC(50), or specifically, at either 2, 3, and 4% end-tidal sevoflurane (n = 8), or 6, 9, and 12 microg/ml plasma concentration of propofol (n = 8). Rocuronium was used for muscle relaxation. Both drugs decreased the bispectral index and blood pressure dose-dependently. Comparison between adjacent levels showed that sevoflurane initially (0 vs. 1 MAC) reduced absolute rCBF by 36-53% in all areas, then (1 vs. 1.5 MAC) increased rCBF in the frontal cortex, thalamus, and cerebellum (7-16%), and finally (1.5 vs. 2 MAC) caused a dual effect with a 23% frontal reduction and a 38% cerebellar increase. In the propofol group, flow was also initially reduced by 62-70%, with minor further effects. In the SPM analysis of the "awake to 1 MAC/EC(50)" step, both anesthetic agents reduced relative rCBF in the cuneus, precuneus, posterior limbic system, and the thalamus or midbrain; additionally, propofol reduced relative rCBF in the parietal and frontal cortices. Both anesthetic agents caused a global reduction of rCBF (propofol > sevoflurane) at the 1 MAC/EC(50) level. The effect was maintained at higher propofol concentrations, whereas 2 MAC sevoflurane caused noticeable flow redistribution. Despite the marked global changes, SPM analysis enabled detailed localization of regions with the greatest relative decreases.
Anesthesiology, 2005
Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its ef... more Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO 2 ), and glucose metabolic rate (GMR) have not been comprehensively studied in humans.
Anesthesiology, 2007
Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in pa... more Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in patients with cerebral pathology could be compromised by deleterious effects on regional cerebral blood flow (rCBF). 15O-labeled water was used to determine rCBF in nine healthy male subjects at baseline and during 1 minimum alveolar concentration (MAC) of xenon (63%). Anesthesia was based solely on xenon. Absolute changes in rCBF were quantified using region-of-interest analysis and voxel-based analysis. Mean arterial blood pressure and arterial partial pressure for carbon dioxide remained unchanged. The mean (+/-SD) xenon concentration during anesthesia was 65.2+/-2.3%. Xenon anesthesia decreased absolute rCBF by 34.7+/-9.8% in the cerebellum (P<0.001), by 22.8+/-10.4% in the thalamus (P=0.001), and by 16.2+/-6.2% in the parietal cortex (P<0.001). On average, xenon anesthesia decreased absolute rCBF by 11.2+/-8.6% in the gray matter (P=0.008). A 22.1+/-13.6% increase in rCBF was detected in the white matter (P=0.001). Whole-brain voxel-based analysis revealed widespread cortical reductions and increases in rCBF in the precentral and postcentral gyri. One MAC of xenon decreased rCBF in several areas studied. The greatest decreases were detected in the cerebellum, the thalamus and the cortical areas. Increases in rCBF were observed in the white matter and in the pre- and postcentral gyri. These results are in clear contradiction with ketamine, another N-methyl-D-aspartate antagonist and neuroprotectant, which induces a general increase in cerebral blood flow at anesthetic concentrations.
The Journal of …, 2005
Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulat... more Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulation of working memory (WM) functions in the prefrontal cortex. In humans, blood flow studies show prefrontal involvement in WM functions, but direct evidence for the involvement of the dopaminergic system in WM is lacking. Using positron emission tomography with a recently developed high-affinity dopamine D 2 receptor tracer, [ 11 C]FLB 457, we explored frontal, temporal, and parietal D 2 receptor availability in 12 healthy volunteers while they were performing verbal WM and sustained attention tasks. During the performance of both tasks, reduced D 2 receptor availability was observed in the left ventral anterior cingulate, suggesting an attention or arousal-related increase in dopamine release during these tasks. Compared with the sustained attention task, the verbal WM task reduced D 2 receptor availability in the ventrolateral frontal cortex bilaterally and in the left medial temporal structures (amygdala, hippocampus), suggesting that dopamine release in these regions might have a specific role in WM. In addition, correlation analyses indicated that increased dopamine release in the right ventrolateral frontal cortex and the left ventral anterior cingulate during the WM task was associated with faster and more stable WM performance, respectively. Our results indicate that regionally specific components of the frontotemporal dopaminergic network are functionally involved in WM performance in humans.
Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of... more Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.
European Journal of Nuclear Medicine and Molecular Imaging, 2009
Purpose The dopamine D 2 /D 3 receptor ligand [ 11 C]FLB 457 and PET enable quantification of low... more Purpose The dopamine D 2 /D 3 receptor ligand [ 11 C]FLB 457 and PET enable quantification of low-density extrastriatal D 2 /D 3 receptors, but it is uncertain whether [ 11 C]FLB 457 can be used for measuring extrastriatal dopamine release. Methods We studied the effects of d-amphetamine (0.3 mg/ kg i.v.) on extrastriatal [ 11 C]FLB 457 binding potential (BP ND ) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. Results The effects of d-amphetamine on [ 11 C]FLB 457 BP ND and distribution volume (V T ) in the frontal cortex were not different from those of placebo. Small decreases in [ 11 C]FLB 457 BP ND were observed only in the posterior cingulate and hippocampus. The regional changes in [ 11 C] FLB 457 BP ND did not correlate with d-amphetamineinduced changes in subjective ratings of euphoria.
European journal of …, 2009
Purpose Positron emission tomography (PET) with 11C-labelled Pittsburgh compound B ([11C]PIB) ena... more Purpose Positron emission tomography (PET) with 11C-labelled Pittsburgh compound B ([11C]PIB) enables the quantitation of β-amyloid accumulation in the brain of patients with Alzheimer's disease (AD). Voxel-based image analysis techniques conducted in a ...
Psychopharmacology, 2002
Rationale: A glutamate-dopamine interaction has been implicated in the psychosis-like effects of ... more Rationale: A glutamate-dopamine interaction has been implicated in the psychosis-like effects of glutamate N-methyl-d-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine. However, recent imaging studies addressing striatal glutamatedopamine interaction directly in vivo in man have been controversial. Objectives: To examine whether the NMDA receptor antagonist ketamine in high subanesthetic concentrations decreases striatal [ 11 C]raclopride binding potential in man. To further evaluate whether changes in striatal [ 11 C]raclopride binding are associated with ketamine-induced behavioral effects. Methods: The effect of computer-driven subanesthetic ketamine infusion on striatal dopamine release was studied in healthy male subjects using a controlled study design. Dopamine release was studied using positron emission tomography and the [ 11 C]raclopride displacement paradigm. A conventional region of interest-based analysis and voxelbased analysis were applied to the positron emission tomography data. Results: The average plasma ketamine concentration was 293€29 ng/ml. Ketamine did not alter striatal [ 11 C]raclopride binding. Ketamine induced typical behavioral effects, such as hallucinations but there was no correlation between these effects and displacement of [ 11 C]raclopride binding. Conclusions: This controlled study indicates that ketamine does not decrease striatal [ 11 C]raclopride binding. Striatal dopamine release is of minor importance in the psychosis-like effects of ketamine.
Psychopharmacology, 2005
Rationale The noncompetitive glutamate N-methyl-d-aspartate receptor antagonist ketamine induces... more Rationale The noncompetitive glutamate N-methyl-d-aspartate receptor antagonist ketamine induces transient psychotic symptoms in man. Involvement of dopaminergic mechanisms in these effects has been suggested. Objectives The purpose of this article is to study the effects of ketamine on extrastriatal dopamine receptor availability in healthy subjects and extracellular dopamine levels in rat cortex. Materials and methods The effect of computer-driven subanesthetic ketamine infusion on cortical dopamine release was studied in healthy male subjects using a controlled study design. Dopamine D2/D3 receptor availability was quantified using positron emission tomography (PET) and [11C]FLB 457. A conventional region of interest-based analysis and voxel-based analysis was applied to the PET data. The ketamine-induced cortical dopamine release in rats was studied using in vivo microdialysis. Results Ketamine infusion reduced significantly the [11C]FLB 457 binding potential (BP) in the pos...
Dementia and Geriatric Cognitive Disorders
The relationship between baseline (11)C-Pittsburgh compound B ((11)C-PIB) uptake and cognitive de... more The relationship between baseline (11)C-Pittsburgh compound B ((11)C-PIB) uptake and cognitive decline during a 2-year follow-up was studied in 9 patients with mild cognitive impairment (MCI) who converted to Alzheimer's disease (AD) and 7 who remained with MCI. (11)C-PIB PET scan was conducted at baseline and cognitive assessment both at baseline and at follow-up. To obtain quantitative regional values of (11)C-PIB uptake, automated region of interest analysis was done using spatially normalized parametric ratio (region-to-cerebellar cortex) images. At baseline, there were statistically significant differences in (11)C-PIB uptake, but not in cognitive test performances between the converters and nonconverters. Memory and executive function declined only in the converters during follow-up. In the converters, lower baseline frontal (11)C-PIB uptake was associated with faster decline in verbal learning. Higher baseline uptake in the caudate nucleus was related to faster decline in memory consolidation, and higher temporal uptake was associated with decline in executive function. Higher (11)C-PIB uptake in the caudate nucleus and temporal lobe was related to decline in memory and executive functions, whereas lower frontal uptake was related to decline in verbal learning. The results indicate that in prodromal AD, frontal amyloid accumulation reaches its maximum in the MCI stage, characterized by memory problems without full-blown dementia.