J O Rinne

Turku University Hospital, Turku, Province of Western Finland, Finland

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Publications (410)1699.36 Total impact

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    ABSTRACT: Purpose α 2C -Adrenoceptors share inhibitory presynaptic functions with the more abundant α 2A -adrenoceptor subtype, but they also have widespread postsynaptic modulatory func-tions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α 2 -adrenoceptor subtypes. Methods PET imaging with the specific α 2C -adrenoceptor antagonist tracer [ 11 C]ORM-13070 was performed twice in six healthy male subjects to investigate the test–retest reliabil-ity of tracer binding. Results The bound/free ratio of tracer uptake relative to non-specific uptake into the cerebellum during the time interval of 5 – 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test– retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [ 11 C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autora-diography. PET data analysis results obtained with a compart-mental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method. Conclusion The results of this study support the use of [ 11 C]ORM-13070 PET in the quantitative assessment of α 2C -adrenoceptors in the human brain in vivo. Reliable as-sessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios.
    European journal of nuclear medicine and molecular imaging 09/2014; · 5.11 Impact Factor
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    ABSTRACT: Although there is a relationship between the extent of striatal dopaminergic defect and the severity of motor symptoms in Parkinson's disease (PD), studies investigating associations between dopamine and mortality in PD have been scarce. If a relationship were established, dopamine restoring neuroprotective treatments could be used to decrease mortality. The objective of this study was to determine whether the initial degree of hypodopaminergic defect, as measured by 6-[(18)F]fluoro-L-DOPA positron emission tomography (FDOPA-PET), can predict patient survival.
    Parkinsonism & Related Disorders 06/2014; · 3.27 Impact Factor
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    ABSTRACT: Purpose 11C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl]-4-(3-methoxy-methylpyridin-2-yl)-piperazine (11C-ORM-13070) is a novel PET tracer for imaging of α2C-adrenoceptors in the human brain. Brain α2C-adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer’s disease. To validate the use of 11C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. Methods Radiometabolism was studied in a test–retest setting in six healthy men. After intravenous injection of 11C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time–activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of 11CORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling.Results Two radioactive metabolites of 11C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged 11C-ORM-13070 decreased from 81±4 % of total radioactivity at 4 min after tracer injection to 23±4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged 11C-ORM-13070 in arterial plasma were 0.0117±0.0056 min−1 and 73.6±35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 – 4.2 μSv/MBq Conclusion 11C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of 11C-ORM-13070 was in the same range as that of other 11C-labelled brain receptor tracers. An injection of 500 MBq of 11C-ORM-13070 would expose a subject to 2.0 mSv of radiation. This supports the use of 11C-ORM-13070 in repeated PET scans, for example, in receptor occupancy trials with novel drug candidates.
    European journal of nuclear medicine and molecular imaging 05/2014; 41:1947. · 5.11 Impact Factor
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    ABSTRACT: PET imaging of amyloid-beta (Abeta) in vivo holds promise for aiding in earlier diagnosis and intervention in Alzheimer's disease (AD) and mild cognitive impairment. AD-like Abeta pathology is a common comorbidity in patients with idiopathic normal pressure hydrocephalus (iNPH). Fifty patients with iNPH needing ventriculo-peritoneal shunting or intracranial pressure monitoring underwent [18F]flutemetamol PET before (N = 28) or after (N = 22) surgery. Cortical uptake of [18F]flutemetamol was assessed visually by blinded reviewers, and also quantitatively via standard uptake value ratio (SUVR) in specific neocortical regions in relation to either cerebellum or pons reference region: the cerebral cortex of (prospective studies) or surrounding (retrospective studies) the biopsy site, the contralateral homolog, and a calculated composite brain measure. Abeta pathology in the biopsy specimen (standard of truth [SoT]) was measured using Bielschowsky silver and thioflavin S plaque scores, percentage area of grey matter positive for monoclonal antibody to Abeta (4G8), and overall pathology impression. We set out to find (1) which pair(s) of PET SUVR and pathology SoT endpoints matched best, (2) whether quantitative measures of [18F]flutemetamol PET were better for predicting the pathology outcome than blinded image examination (BIE), and (3) whether there was a better match between PET image findings in retrospective vs. prospective studies. Of the 24 possible endpoint/SoT combinations, the one with composite-cerebellum SUVR and SoT based on overall pathology had the highest Youden index (1.000), receiver operating characteristic area under the curve (1.000), sensitivity (1.000), specificity (1.000), and sum of sensitivity and specificity for the pooled data as well as for the retrospective and prospective studies separately (2.00, for all 3). The BIE sum of sensitivity and specificity, comparable to that for quantitation, was highest using Bielschowsky silver as SoT for all SUVRs (ipsilateral, contralateral, and composite, for both reference regions). The composite SUVR had a 100% positive predictive value (both reference regions) for the overall pathology diagnosis. All SUVRs had a 100% negative predictive value for the Bielschowsky silver result. Bielschowsky silver stain and overall pathology judgment showed the strongest associations with imaging results.
    Acta neuropathologica communications. 04/2014; 2(1):46.
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    ABSTRACT: The northern terrestrial net ecosystem carbon balance (NECB) is contingent on inputs from vegetation gross primary productivity (GPP) to offset the ecosystem respiration (Reco) of carbon dioxide (CO2) and methane (CH4) emissions, but an effective framework to monitor the regional Arctic NECB is lacking. We modified a terrestrial carbon flux (TCF) model developed for satellite remote sensing applications to evaluate wetland CO2 and CH4 fluxes over pan-Arctic eddy covariance (EC) flux tower sites. The TCF model estimates GPP, CO2 and CH4 emissions using in situ or remote sensing and reanalysis-based climate data as inputs. The TCF model simulations using in situ data explained >70% of the r2 variability in the 8 day cumulative EC measured fluxes. Model simulations using coarser satellite (MODIS) and reanalysis (MERRA) records accounted for approximately 69% and 75% of the respective r2 variability in the tower CO2 and CH4 records, with corresponding RMSE uncertainties of �1.3 gCm−2 d−1 (CO2) and 18.2 mg Cm−2 d−1 (CH4). Although the estimated annual CH4 emissions were small (<18 gCm−2 yr−1) relative to Reco (>180 gCm−2 yr−1), they reduced the across-site NECB by 23%and contributed to a global warming potential of approximately 165±128 gCO2eqm−2 yr−1 when considered over a 100 year time span. This model evaluation indicates a strong potential for using the TCF model approach to document landscape-scale variability in CO2 and CH4 fluxes, and to estimate the NECB for northern peatland and tundra ecosystems.
    Biogeosciences 04/2014; 11:1961-1980. · 3.75 Impact Factor
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    ABSTRACT: Patients with secondary progressive multiple sclerosis (SPMS) are lacking efficient medication to slow down the progression of their disease. PET imaging holds promise as a method to study, at the molecular level and in vivo, the central nervous system pathology of SPMS. PET might thus help to elucidate potential therapeutic targets and be useful as an imaging biomarker in future treatment trials of progressive multiple sclerosis. The objective of this study was to evaluate whether translocator protein (TSPO) imaging could be used to visualize the diffuse inflammation located in the periplaque area and in the normal-appearing white matter (NAWM) in the brains of patients with SPMS. This was an imaging study using MR imaging and PET with (11)C-PK11195 binding to TSPO, which is expressed in activated, but not in resting, microglia. Ten SPMS patients with a mean expanded disability status scale score of 6.3 (SD, 1.5) and eight age-matched healthy controls were studied. The imaging was performed using High-Resolution Research Tomograph PET and 1.5-T MR imaging scanners. Microglial activation was evaluated as the distribution volume ratio (DVR) of (11)C-PK11195 from dynamic PET images. DVR estimations were performed with special interest in NAWM and gray matter using region-of-interest and parametric image-based approaches. The DVR of (11)C-PK11195 was significantly increased in the periventricular and total NAWM (P = 0.016 and P < 0.001, respectively) and in the thalamic ROIs (P = 0.027) of SPMS patients, compared with the control group. Similarly, parametric image analysis showed widespread increases of (11)C-PK11195 in the white matter of SPMS patients, compared with healthy controls. Increased perilesional TSPO uptake was present in 57% of the chronic T1 lesions in MR imaging. The finding of increased (11)C-PK11195 binding in the NAWM of SPMS patients is in line with the neuropathologic demonstration that activated microglial cells are the source of diffuse NAWM inflammation. Evaluating microglial activation with TSPO-binding PET ligands provides a unique tool to assess diffuse brain inflammation and perilesional activity in progressive multiple sclerosis in vivo.
    Journal of Nuclear Medicine 04/2014; · 5.77 Impact Factor
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    ABSTRACT: Curcumin is a neuroprotective compound that inhibits the formation of amyloid oligomers and fibrils and binds to β-amyloid plaques in Alzheimer's disease (AD). We aimed to synthesize an (18)F-labeled curcumin derivate ([(18)F]4) and to characterize its positron emission tomography (PET) tracer-binding properties to β-amyloid plaques in a transgenic APP23 mouse model of AD. We utilized facile one-pot synthesis of [(18)F]4 using nucleophilic (18)F-fluorination and click chemistry. Binding of [(18)F]4 to β-amyloid plaques in the transgenic APP23 mouse brain cryosections was studied in vitro using heterologous competitive binding against PIB. [(18)F]4 uptake was studied ex vivo in rodents and in vivo using PET/computed tomography of transgenic APP23 and wild-type control mice. The radiochemical yield of [(18)F]4 was 21±11%, the specific activity exceeded 1TBq/μmol, and the radiochemical purity exceeded 99.3% at the end of synthesis. In vitro studies of [(18)F]4 with the transgenic APP23 mouse revealed high β-amyloid plaque binding. In vivo and ex vivo studies demonstrated that [(18)F]4 has fast clearance from the blood, moderate metabolism but low blood-brain barrier (BBB) penetration. [(18)F]4 was synthesized in high yield and excellent quality. In vitro studies, metabolite profile, and fast clearance from the blood indicated a promising tracer for Aβ imaging. However, [(18)F]4 has low in vivo BBB penetration and thus further studies are needed to reveal the reason for this and to possibly overcome this issue.
    Bioorganic & medicinal chemistry 03/2014; · 2.82 Impact Factor
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    ABSTRACT: Background/Objective: Our aim was to elucidate factors that contribute to amyloid-β (Aβ) accumulation in the brains of the seemingly healthy elderly population, and whether there is interplay between those factors. Methods: We conducted a cross-sectional positron emission tomography (PET) study with the amyloid tracer 11C-PIB, in 64 cognitively healthy subjects (54-89 years). In addition to PET, magnetic resonance imaging, neuropsychological testing, and APOE genotyping was performed. The results were assessed with a statistical general linear model as well as with Statistical Parametric Mapping (SPM). Results: The effects of age (p < 0.001), APOE ε4 carrier status (p = 0.003), and gender (p = 0.001) on composite cortical 11C-PIB uptake were all significant. The effect of educational level was non-significant (p = 0.37). No significant interactions were found between any of the factors. Cortical 11C-PIB uptake increased, on the average, by 0.015 cortex/cerebellar cortical ratio unit, with every year of age. APOE ε4 positive subjects exhibited higher cortical 11C-PIB uptake than APOE ε4 negative subjects (unadjusted means 1.49 ± 0.34 versus 1.29 ± 0.26) and males had higher uptake than females (1.49 ± 0.39 versus 1.29 ± 0.22), irrespective of age. The results of the voxel-based (SPM) analysis were similar. In addition, SPM analysis showed that lower CERAD score was associated with higher 11C-PIB uptake in the frontal cortex. Conclusions: Age and APOE ε4 genotype were associated with higher 11C-PIB uptake. In this sample of cognitively healthy elderly individuals, men exhibited higher 11C-PIB uptake than women. Possible gender differences in Aβ accumulation have not been addressed in detail in previous studies, and deeper evaluation in the future is warranted.
    Journal of Alzheimer's disease: JAD 03/2014; · 4.17 Impact Factor
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    ABSTRACT: It remains unclear how different translocator protein (TSPO) ligands reflect the spatial extent of astrocyte or microglial activation in various neuroinflammatory conditions. Here, we use a reproducible lipopolysaccharide (LPS)-induced model of acute central nervous system inflammation to compare the binding performance of a new TSPO ligand (18)F-GE-180 with (11)C-(R)-PK11195. Using immunohistochemistry, we also explore the ability of the TSPO ligands to detect activated microglial cells and astrocytes. Lewis rats (n = 30) were microinjected with LPS (1 or 10 μg) or saline (1 μL) into the left striatum. The animals were imaged in vivo at 16 h after the injection using PET radiotracers (18)F-GE-180 or (11)C-(R)-PK11195 (n = 3 in each group) and were killed afterward for autoradiography of the brain. Immunohistochemical assessment of OX-42 and glial fibrillary acidic protein (GFAP) was performed to identify activated microglial cells and reactive astrocytes. In vivo PET imaging revealed an increase in the ipsilateral TSPO binding, compared with binding in the contralateral hemisphere, after the microinjection of 10 μg of LPS. No increase was observed with vehicle. By autoradiography, the TSPO radiotracer binding potential in the injected hemisphere was increased after striatal injection of 1 or 10 μg of LPS. However, the significant increase was observed only when using (18)F-GE-180. The area of CD11b-expressing microglial cells extended beyond that of enhanced GFAP staining and mapped more closely to the extent of (18)F-GE-180 binding than to (11)C-(R)-PK11195 binding. The signal from either PET ligand was significantly increased in regions of increased GFAP immunoreactivity and OX-42 colocalization, meaning that the presence of both activated microglia and astrocytes in a given area leads to increased binding of the TSPO radiotracers. (18)F-GE-180 is able to reveal sites of activated microglia in both gray and white matter. However, the signal is increased by the presence of activated astrocytes. Therefore, (18)F-GE-180 is a promising new fluorinated longer-half-life tracer that reveals the presence of activated microglia in a manner that is superior to (11)C-(R)-PK11195 due to the higher binding potential observed for this ligand.
    Journal of Nuclear Medicine 02/2014; · 5.77 Impact Factor
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    ABSTRACT: Backgound/Objective: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site. Methods: Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain. Results: Four of the 17 patients (23.5%) had amyloid-β pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-β levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-β level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%. Conclusions: [(18)F]Flutemetamol detects brain amyloid-β in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population. © 2013 S. Karger AG, Basel.
    Neurodegenerative Diseases 11/2013; · 3.41 Impact Factor
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    ABSTRACT: Background: Free recall memory deficits are common in Parkinson's disease (PD), even at early stages before mild cognitive impairment or dementia. Their association with brain structural changes has not been established. Objective: We studied local gray matter volumes in relation to different memory tasks in early stage PD. Methods: Magnetic resonance images (MRI) and neuropsychological data were obtained from 28 non-demented, medicated PD patients, and 28 healthy controls. The gray matter segments of T1-weighted MRI images were analyzed using voxel-based morphometry in relation to visual and verbal memory tasks. Measures of immediate free recall, verbal learning, delayed recall and memory consolidation were obtained. A novel measure of incidental memory was included. Results: Patients and controls showed no significant group differences in local gray matter volumes. Voxel-based morphometry analyses revealed that worse performance on an incidental visual memory task was associated with smaller right parietal gray matter volume (Family-wise error corrected P = 0.002). This association was present in the PD group (corrected P = 0.005), but not in controls (corrected P > 0.99). No associations between gray matter volumes and the other memory tasks were found in either group. Conclusions: The results suggest that right parietal cortical gray matter volume is related to free recall memory deficits in early stage PD in conditions not involving an intention to memorize visual items. This preliminary finding needs to be established in further studies utilizing incidental memory tasks in PD.
    Journal of Parkinson's disease. 11/2013;
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    ABSTRACT: The northern terrestrial net ecosystem carbon balance (NECB) is contingent on inputs from vegetation gross primary productivity (GPP) to offset ecosystem respiration (Reco) of carbon dioxide (CO2) and methane (CH4) emissions, but an effective framework 5 to monitor the regional Arctic NECB is lacking. We modified a terrestrial carbon flux (TCF) model developed for satellite remote sensing applications to estimate peatland and tundra CO2 and CH4 fluxes over a pan-Arctic network of eddy covariance (EC) flux tower sites. The TCF model estimates GPP, CO2 and CH4 emissions using either in-situ or remote sensing based climate data as input. TCF simulations 10 driven using in-situ data explained > 70% of the r 2 variability in 8 day cumulative EC measured fluxes. Model simulations using coarser satellite (MODIS) and reanalysis (MERRA) data as inputs also reproduced the variability in the EC measured fluxes relatively well for GPP (r 2 =0.75), Reco (r 2 =0.71), net ecosystem CO2 exchange (NEE, r 2 =0.62) and CH4 emissions (r 2 =0.75). Although the estimated annual CH4 emissions were small (< 18 gCm−2 yr−1) relative to Reco (> 180 gCm−2 yr−1), they reduced the across-site NECB by 23% and contributed to a global warming potential of approximately 165±128 gCO2eqm−2 yr−1 when considered over a 100 yr time span. This model evaluation indicates a strong potential for using the TCF model approach to document landscape scale variability in CO2 and CH4 fluxes, and to estimate the NECB 20 for northern peatland and tundra ecosystems.
    Biogeosciences Discussions 10/2013; 10(10):16491-16549.
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    ABSTRACT: We describe the implementation of a biochemical model of isoprene emission that depends on the electron requirement for isoprene synthesis into the Farquhar-Ball-Berry leaf model of photosynthesis and stomatal conductance that is embedded within a global chemistry-climate simulation framework. The isoprene production is calculated as a function of electron transport-limited photosynthesis, intercellular and atmospheric carbon dioxide concentration, and canopy temperature. The vegetation biophysics module computes the photosynthetic uptake of carbon dioxide coupled with the transpiration of water vapor and the isoprene emission rate at the 30 min physical integration time step of the global chemistry-climate model. In the model, the rate of carbon assimilation provides the dominant control on isoprene emission variability over canopy temperature. A control simulation representative of the present-day climatic state that uses 8 plant functional types (PFTs), prescribed phenology and generic PFT-specific isoprene emission potentials (fraction of electrons available for isoprene synthesis) reproduces 50% of the variability across different ecosystems and seasons in a global database of 28 measured campaign-average fluxes. Compared to time-varying isoprene flux measurements at 9 select sites, the model authentically captures the observed variability in the 30 min average diurnal cycle (R2 = 64-96%) and simulates the flux magnitude to within a factor of 2. The control run yields a global isoprene source strength of 451 TgC yr-1 that increases by 30% in the artificial absence of plant water stress and by 55% for potential natural vegetation.
    ATMOSPHERIC CHEMISTRY AND PHYSICS 10/2013; 13(20):10243-10269. · 5.51 Impact Factor
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    ABSTRACT: The northern terrestrial net ecosystem carbon balance (NECB) is contingent on inputs from vegetation gross primary productivity (GPP) to offset ecosystem respiration (Reco) of carbon dioxide (CO2) and methane (CH4) emissions, but an effective framework 5 to monitor the regional Arctic NECB is lacking. We modified a terrestrial carbon flux (TCF) model developed for satellite remote sensing applications to estimate peatland and tundra CO2 and CH4 fluxes over a pan-Arctic network of eddy covariance (EC) flux tower sites. The TCF model estimates GPP, CO2 and CH4 emissions using either in-situ or remote sensing based climate data as input. TCF simulations 10 driven using in-situ data explained > 70% of the r 2 variability in 8 day cumulative EC measured fluxes. Model simulations using coarser satellite (MODIS) and reanalysis (MERRA) data as inputs also reproduced the variability in the EC measured fluxes relatively well for GPP (r 2 =0.75), Reco (r 2 =0.71), net ecosystem CO2 exchange (NEE, r 2 =0.62) and CH4 emissions (r 2 =0.75). Although the estimated annual CH4 emissions were small (< 18 gCm−2 yr−1) relative to Reco (> 180 gCm−2 yr−1), they reduced the across-site NECB by 23% and contributed to a global warming potential of approximately 165±128 gCO2eqm−2 yr−1 when considered over a 100 yr time span. This model evaluation indicates a strong potential for using the TCF model approach to document landscape scale variability in CO2 and
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    ABSTRACT: The aim of this study was to evaluate the longitudinal changes in [(11)C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer's disease (AD) over a long-term follow-up. Six AD patients, ten MCI patients and eight healthy subjects underwent a [(11)C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months. The MCI group showed a significant increase in [(11)C]PIB uptake over time (p < 0.001), with a similar increase from baseline to 2 years (4.7 % per year) and from 2 to 5 years (5.0 % per year). Eight MCI patients (80 %) converted to AD, and two of these patients showed a normal [(11)C]PIB scan at baseline but increased uptake later. There was an increase in [(11)C]PIB uptake with time in the AD group (p = 0.02), but this did not significantly differ from the change in the control group. Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [(11)C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD.
    European Journal of Nuclear Medicine 09/2013; · 4.53 Impact Factor
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    ABSTRACT: Verbal fluency impairments are frequent in Parkinson's disease (PD) and they may be present already at early stages. Semantic fluency impairment is associated with Parkinson's disease dementia and temporal, frontal and cerebellar cortical changes. Few studies have addres-sed cerebral structural correlates of different verbal fluency tasks in early stage PD. We therefore studied gray matter volumes of T1-weighted MRI images using voxel-based morphometry in relation to semantic, phonemic, and alternating verbal fluency in younger (mean age \65 years), early stage (mean disease duration \3 years), non-demented PD patients (n = 28) and healthy controls (n = 27). We found a significant association between worse phonemic fluency and smaller striatal, namely right caudate gray matter volume in the PD group only (family-wise error corrected p = 0.007). Reduced semantic fluency was associated with smaller gray matter volumes in left parietal cortex (p = 0.037) and at trend level with smaller bilateral cerebellum gray matter volume across groups (p = 0.062), but not in the separate PD or control groups. There were no significant relationships between alternating fluency and gray matter volumes in the whole sample or in the groups separately. The fact that phonemic fluency, but not semantic or alternating fluency, was associated with caudate gray matter volume at early stage PD suggests that different fluency tasks rely on different neural substrates, and that language networks supporting semantic search and verbal-semantic switching are unrelated to brain gray matter volume at early disease stages in PD.
    Journal of Neural Transmission - Parkinson s Disease and Dementia Section 08/2013;
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    ABSTRACT: Previous studies have suggested that impaired striatal dopamine function might be independently related to depression in patients with Parkinson's disease (PD), but the results are not uniform. In this study, we investigated de novo unmedicated and medicated PD patients with more advanced disease using fluorodopa-PET. In unmedicated de novo patients, but not in medicated patients, higher depression scores were associated with lower striatal 18F-fluorodopa uptake. These results indicate that impaired striatal dopaminergic function in PD is related to depressive symptoms and that these effects can be observed in de novo patients without the confounding effects of advanced neurodegeneration and medications.
    Journal of Parkinson's disease. 07/2013;
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    ABSTRACT: Follow-up of β-amyloid (Aβ) deposition in transgenic mouse models of Alzheimer disease (AD) would be a valuable translational tool in the preclinical evaluation of potential antiamyloid therapies. This study aimed to evaluate the ability of the clinically used PET tracer (11)C-Pittsburgh compound B ((11)C-PIB) to detect changes over time in Aβ deposition in the brains of living mice representing the APP23, Tg2576, and APPswe-PS1dE9 transgenic mouse models of AD. Mice from each transgenic strain were imaged with 60-min dynamic PET scans at 7-9, 12, 15, and 18-22 mo of age. Regional (11)C-PIB retention was quantitated as distribution volume ratios using Logan graphical analysis with cerebellar reference input, as radioactivity uptake ratios between the frontal cortex (FC) and the cerebellum (CB) during the 60-min scan, and as bound-to-free ratios in the late washout phase (40-60 min). Ex vivo autoradiography experiments were performed after the final imaging session to validate (11)C-PIB binding to Aβ deposits. Additionally, the presence of Aβ deposits was evaluated in vitro using staining with thioflavin-S and Aβ1-40, Aβ1-16, and AβN3(pE) immunohistochemistry. Neocortical (11)C-PIB retention was markedly increased in old APP23 mice with large thioflavin-S-positive Aβ deposits. At 12 mo, the Logan distribution volume ratio for the FC was 1.03 and 0.93 (n = 2), increasing to 1.38 ± 0.03 (n = 3) and 1.34 (n = 1) at 18 and 21 mo of age, respectively. An increase was also observed in bound-to-free ratios for the FC between young (7- to 12-mo-old) and old (15- to 22-mo-old) APP23 mice. Binding of (11)C-PIB to Aβ-rich cortical regions was also evident in ex vivo autoradiograms of APP23 brain sections. In contrast, no increases in (11)C-PIB retention were observed in aging Tg2576 or APPswe-PS1dE9 mice in vivo, although in the latter, extensive Aβ deposition was already observed at 9 mo of age with immunohistochemistry. The results suggest that (11)C-PIB binding to Aβ deposits in transgenic mouse brain is highly dependent on the AD model and the structure of its Aβ plaques. Longitudinal in vivo (11)C-PIB uptake studies are possible in APP23 mice.
    Journal of Nuclear Medicine 07/2013; · 5.77 Impact Factor
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    ABSTRACT: Background and purposeThis study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [18F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. Methods Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. Results[18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [18F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003). Conclusions[18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.
    European Journal of Neurology 07/2013; 20(7). · 4.16 Impact Factor

Publication Stats

10k Citations
1,699.36 Total Impact Points

Institutions

  • 1996–2014
    • Turku University Hospital
      • Turku PET Centre
      Turku, Province of Western Finland, Finland
  • 1985–2014
    • University of Turku
      • • Turku PET Centre
      • • Department of Neurology
      • • Division of Psychology
      Turku, Province of Western Finland, Finland
  • 1999–2013
    • University of Helsinki
      • • Department of Physics
      • • Department of Physical Sciences
      • • The Hospital for Children and Adolescents
      • • Institute of Biomedicine
      Helsinki, Southern Finland Province, Finland
    • Turku PET Centre
      Turku, Province of Western Finland, Finland
    • Research Institute of the Finnish Economy, Finland, Helsinki
      Helsinki, Southern Finland Province, Finland
    • Finnish Meteorological Institute
      • Air Quality Research
      Helsinki, Southern Finland Province, Finland
  • 2012
    • King Chulalongkorn Memorial Hospital
      Krung Thep, Bangkok, Thailand
  • 2008–2012
    • New York University
      • Department of Psychiatry
      New York City, NY, United States
    • University of Oxford
      Oxford, England, United Kingdom
    • Kuopio University Hospital
      • Department of Neurosurgery
      Kuopio, Province of Eastern Finland, Finland
    • University of Oulu
      Uleoborg, Oulu, Finland
  • 2011
    • Karolinska Institutet
      • Aging Research Center - ARC
      Solna, Stockholm, Sweden
  • 2010
    • Max Planck Institute for Chemistry
      Mayence, Rheinland-Pfalz, Germany
    • Odense University Hospital
      • Department of Nuclear Medicine
      Odense, South Denmark, Denmark
  • 2000–2010
    • Åbo Akademi University
      • • Department of Psychology and Logopedics
      • • Department of Biology
      Turku, Province of Western Finland, Finland
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
    • National Center for Atmospheric Research
      Boulder, Colorado, United States
  • 2009
    • IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia
      Brescia, Lombardy, Italy
  • 2008–2009
    • Imperial College London
      • Faculty of Medicine
      London, ENG, United Kingdom
  • 2002–2008
    • Centre National de Recherches Météorologiques
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2007
    • Finnish Forest Research Institute
      Vanda, Southern Finland Province, Finland
  • 1991–2000
    • Turku centre for biotechnology, finland
      Turku, Province of Western Finland, Finland
  • 1998
    • University of Tampere
      • Medical School
      Tampere, Western Finland, Finland
  • 1997
    • Stockholm University
      • Department of Psychology
      Stockholm, Stockholm, Sweden
  • 1995
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 1994
    • University of London
      • The School of Pharmacy
      Londinium, England, United Kingdom