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Find video protocols related to scientific articles indexed in Pubmed.
Visual Versus Semi-Quantitative Analysis of 18F-FDG-PET in Amnestic MCI: An European Alzheimer's Disease Consortium (EADC) Project.
J. Alzheimers Dis.
PUBLISHED: 11-02-2014
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We aimed to investigate the accuracy of FDG-PET to detect the Alzheimer's disease (AD) brain glucose hypometabolic pattern in 142 patients with amnestic mild cognitive impairment (aMCI) and 109 healthy controls. aMCI patients were followed for at least two years or until conversion to dementia. Images were evaluated by means of visual read by either moderately-skilled or expert readers, and by means of a summary metric of AD-like hypometabolism (PALZ score). Seventy-seven patients converted to AD-dementia after 28.6 ± 19.3 months of follow-up. Expert reading was the most accurate tool to detect these MCI converters from healthy controls (sensitivity 89.6%, specificity 89.0%, accuracy 89.2%) while two moderately-skilled readers were less (p < 0.05) specific (sensitivity 85.7%, specificity 79.8%, accuracy 82.3%) and PALZ score was less (p < 0.001) sensitive (sensitivity 62.3%, specificity 91.7%, accuracy 79.6%). Among the remaining 67 aMCI patients, 50 were confirmed as aMCI after an average of 42.3 months, 12 developed other dementia, and 3 reverted to normalcy. In 30/50 persistent MCI patients, the expert recognized the AD hypometabolic pattern. In 13/50 aMCI, both the expert and PALZ score were negative while in 7/50, only the PALZ score was positive due to sparse hypometabolic clusters mainly in frontal lobes. Visual FDG-PET reads by an expert is the most accurate method but an automated, validated system may be particularly helpful to moderately-skilled readers because of high specificity, and should be mandatory when even a moderately-skilled reader is unavailable.
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Imaging frontotemporal lobar degeneration.
Curr Neurol Neurosci Rep
PUBLISHED: 08-31-2014
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The term frontotemporal lobar degeneration (FTLD) refers to a group of neurodegenerative disorders that target the frontal and temporal lobes. It accounts for approximately 10 % of pathologically confirmed dementias but has been demonstrated to be as prevalent as Alzheimer's disease in patients below the age of 65. The 3 major clinical syndromes associated with FTLD include behavioral variant frontotemporal dementia, semantic and nonfluent variants of primary progressive aphasia. The more recently introduced term logopenic variant appears to represent an atypical form of Alzheimer's disease in the majority of cases. The neuropathology underlying these clinical syndromes is very heterogeneous and does not correlate well with the clinical phenotype. This causes great difficulties in early and reliable diagnosis and treatment of FTLD. However, significant advances have been made in recent years via the application of magnetic resonance imaging and positron emission tomography imaging methods as biomarkers. The current review aims to provide a synopsis on the value of magnetic resonance imaging-based and molecular imaging procedures in FTLD.
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Clinical significance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) for metastatic sentinel lymph node involvement in breast cancer.
Anticancer Res.
PUBLISHED: 07-31-2014
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Urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) are key factors for tumor invasion and development of metastases in breast cancer. Prospective studies confirmed the prognostic significance of these factors for development of distant metastases. The predictive impact of uPA and PAI-1 for metastatic sentinel lymph node involvement is unclear.
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Disrupted Intrinsic Networks Link Amyloid-? Pathology and Impaired Cognition in Prodromal Alzheimer's Disease.
Cereb. Cortex
PUBLISHED: 07-06-2014
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Amyloid-? pathology (A?) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link A?-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: A?-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link A?-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo A?-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between A?-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links A?-pathology with cognitive impairment in early AD.
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In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.
Brain Connect
PUBLISHED: 05-30-2014
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In patients with Alzheimer's disease (AD), prominent hypometabolism has been observed in brain regions with minor amyloid load. These hypometabolism-only (HO) areas cannot be explained merely as a consequence of local amyloid toxicity. The aim of this multimodal imaging study was to explore whether such HO phenomenon may be related to pathologies in functionally connected, remote brain regions. Nineteen AD patients and 15 matched controls underwent examinations with [(11)C]PiB-PET and [(18)F]FDG-PET. Voxel-based statistical group comparisons were performed to obtain maps of significantly elevated amyloid burden and reduced cerebral glucose metabolism, respectively, in patients. An HO area was identified by subtraction of equally thresholded result maps (hypometabolism minus amyloid burden). To identify the network typically functionally connected to this HO area, it was used as a seed region for a functional connectivity analysis in resting-state functional magnetic resonance imaging data of 17 elderly healthy controls. The resulting intrinsic connectivity network (HO-ICN) was retransferred into the brains of AD patients to be able to analyze pathologies within this network in the positron emission tomography (PET) datasets. The most prominent HO area was detected in the left middle frontal gyrus of AD patients. The HO-ICN in healthy controls showed a major overlap with brain areas significantly affected by both amyloid deposition and hypometabolism in patients. This association was substantiated by the results of region-of-interest-based and voxel-wise correlation analyses, which revealed strong correlations between the degree of hypometabolism within the HO region and within the HO-ICN. These results support the notion that hypometabolism in brain regions not strongly affected by locoregional amyloid pathology may be related to ongoing pathologies in remote but functionally connected regions, that is, by reduced neuronal input from these regions.
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Systematic Comparison of the Performance of Integrated Whole-Body PET/MR Imaging to Conventional PET/CT for 18F-FDG Brain Imaging in Patients Examined for Suspected Dementia.
J. Nucl. Med.
PUBLISHED: 05-15-2014
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Technologic specifications of recently introduced integrated PET/MR instrumentation, such as MR-based attenuation correction, may particularly affect brain imaging procedures. To evaluate the qualitative performance of PET/MR in clinical neuroimaging, we systematically compared results obtained with integrated PET/MR with conventional PET/CT in the same patients examined for assessment of cognitive impairment.
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Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Diseases.
J. Nucl. Med.
PUBLISHED: 05-12-2014
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Neurodegenerative disorders such as Alzheimer disease are among today's most alarming health problems in our aging society. The clinical assessment of neurodegenerative disorders benefits from recent innovations in the field of imaging technology. These innovations include emerging tracers for molecular imaging of neurodegenerative pathology and the introduction of novel integrated PET/MR imaging instruments. Because both PET and MR imaging procedures have shown critical value in the diagnostic work-up of neurodegenerative disorders, the combination of both imaging modalities in the form of an integrated PET/MR imaging system may be of value. This combination includes practical methodologic advantages and an improved workflow facilitated by the combined acquisition of dual-modality data. It offers clinical advantages because of the systematic combination of complementary information, potentially allowing the creation of novel integrated imaging biomarkers. The effectiveness of new disease-modifying treatments may depend on the timely initiation of therapy before irreversible neuronal damage in slowly progressive neurodegenerative disorders. Integrated PET/MR imaging may be able to improve such early diagnosis through both structural and functional information.
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Assessment of tumor size reduction improves outcome prediction of positron emission tomography/computed tomography after chemotherapy in advanced-stage Hodgkin lymphoma.
J. Clin. Oncol.
PUBLISHED: 05-05-2014
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Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT).
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Local activity determines functional connectivity in the resting human brain: a simultaneous FDG-PET/fMRI study.
J. Neurosci.
PUBLISHED: 05-03-2014
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Over the last decade, synchronized resting-state fluctuations of blood oxygenation level-dependent (BOLD) signals between remote brain areas [so-called BOLD resting-state functional connectivity (rs-FC)] have gained enormous relevance in systems and clinical neuroscience. However, the neural underpinnings of rs-FC are still incompletely understood. Using simultaneous positron emission tomography/magnetic resonance imaging we here directly investigated the relationship between rs-FC and local neuronal activity in humans. Computational models suggest a mechanistic link between the dynamics of local neuronal activity and the functional coupling among distributed brain regions. Therefore, we hypothesized that the local activity (LA) of a region at rest determines its rs-FC. To test this hypothesis, we simultaneously measured both LA (glucose metabolism) and rs-FC (via synchronized BOLD fluctuations) during conditions of eyes closed or eyes open. During eyes open, LA increased in the visual system, and the salience network (i.e., cingulate and insular cortices) and the pattern of elevated LA coincided almost exactly with the spatial pattern of increased rs-FC. Specifically, the voxelwise regional profile of LA in these areas strongly correlated with the regional pattern of rs-FC among the same regions (e.g., LA in primary visual cortex accounts for ? 50%, and LA in anterior cingulate accounts for ? 20% of rs-FC with the visual system). These data provide the first direct evidence in humans that local neuronal activity determines BOLD FC at rest. Beyond its relevance for the neuronal basis of coherent BOLD signal fluctuations, our procedure may translate into clinical research particularly to investigate potentially aberrant links between local dynamics and remote functional coupling in patients with neuropsychiatric disorders.
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Within-patient correspondence of amyloid-? and intrinsic network connectivity in Alzheimer's disease.
Brain
PUBLISHED: 04-26-2014
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There is striking overlap between the spatial distribution of amyloid-? pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-? and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-? plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-? exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-? on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-? and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-? on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-? distributions. Here we compared spatial patterns of amyloid-?-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-? and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-? aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-?-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-? pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-?-plaque concentration. The local negative association between amyloid-? and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-? on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-? and intrinsic connectivity, with the distribution of amyloid-? pathology following functional connectivity gradients within and across intrinsic networks.
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Combined PET/MR: Where are we now? Summary report of the second international workshop on PET/MR imaging April 8-12, 2013, Tubingen, Germany.
Mol Imaging Biol
PUBLISHED: 03-27-2014
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This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tübingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.
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Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease.
Alzheimers Dement
PUBLISHED: 02-13-2014
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New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen ?, 0.24-0.34), in accord with a high rate of conflicting findings (26%-41%). Neither diagnosis nor APOE ?4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement tended to be higher in individuals with abnormal versus normal CSF ?-amyloid (A?1-42) levels. Prospective diagnostic criteria for AD should address the relative importance of markers of neuronal injury and elaborate a way of dealing with conflicting biomarker findings.
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Small Vessel Disease, but Neither Amyloid Load nor Metabolic Deficit, Is Dependent on Age at Onset in Alzheimer's Disease.
Biol. Psychiatry
PUBLISHED: 01-17-2014
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There is controversy concerning whether Alzheimer's disease (AD) with early onset is distinct from AD with late onset with regard to amyloid pathology and neuronal metabolic deficit. We hypothesized that compared with patients with early-onset AD, patients with late-onset AD have more comorbid small vessel disease (SVD) contributing to clinical severity, whereas there are no differences in amyloid pathology and neuronal metabolic deficit.
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LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo.
Neuroimage Clin
PUBLISHED: 01-01-2014
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Impaired amyloid clearance has been proposed to contribute to ?-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of ?-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [(11)C]PiB.
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Perspective on future role of biological markers in clinical therapy trials of Alzheimers disease: A long-range point of view beyond 2020.
Biochem. Pharmacol.
PUBLISHED: 10-03-2013
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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimers disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD.
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18F-fluorodeoxyglucose uptake pattern in patients with suspected spondylodiscitis.
Nucl Med Commun
PUBLISHED: 09-13-2013
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Infections of the spine are rare and often discovered late, but they can have a severe outcome with hospital case fatality rates of up to 17%. Efficient and early diagnosis is important, because early diagnosis and therapy improve outcome. The aim of the current study was to evaluate the clinical value of F-fluorodeoxyglucose (18F-FDG) uptake pattern in PET as a diagnostic modality for the detection of spondylodiscitis.
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The usefulness of amyloid imaging in predicting the clinical outcome after two years in subjects with mild cognitive impairment.
Curr Alzheimer Res
PUBLISHED: 08-22-2013
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Mild cognitive impairment (MCI) is a syndrome heterogeneous with regards to etiology and prognosis. Amyloid imaging enables to visualize a hallmark pathology of Alzheimers disease (AD). Therefore we aimed to assess the usefulness of [(11)C]PiB PET for predicting clinical outcome of MCI patients after an interval of 2 years.
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18-Fluorodeoxyglucose positron emission tomography/computed tomography for assessment of response to brentuximab vedotin treatment in relapsed and refractory Hodgkin lymphoma.
Leuk. Lymphoma
PUBLISHED: 07-29-2013
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Brentuximab vedotin has emerged as a possible treatment option in patients suffering from relapsed and refractory Hodgkin lymphoma (HL). We investigated the role of 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for monitoring treatment response to brentuximab vedotin in patients with relapsed and refractory HL. Twelve consecutive, heavily pretreated patients with relapsed and refractory HL treated with brentuximab vedotin were available for analysis. FDG-PET/CT studies were performed early during treatment after a median of 3 cycles (range, 2-5 cycles), and were analyzed visually using a 5-point scale (5PS) and quantitatively using the maximum standardized uptake value (SUVmax) and the three-dimensional (3D) isocontour at 50% of the maximum pixel value (SUV50) in the hottest single lesion. The median follow-up in our study cohort was 16 months (range, 5-30 months). The median progression-free survival (PFS) was 12.5 months and PFS at 12 months was 58%. Patients treated with brentuximab vedotin and negative interim FDG-PET/CT assessed by visual or quantitative analysis demonstrated a significantly prolonged PFS compared to patients with positive interim FDG-PET/CT. The 1-year PFS was 100% in patients with negative interim FDG-PET/CT assessed by visual analysis, whereas patients with positive interim FDG-PET/CT had a worse outcome with a 1-year PFS of 38% (p = 0.033). The 1-year PFS was 75% in patients with negative interim FDG-PET/CT assessed by quantitative analysis using the SUV50, whereas patients with positive interim FDG-PET/CT had a worse outcome with a 1-year PFS of 25% (p = 0.017) Interim FDG-PET/CT might be a suitable diagnostic approach to predict response to brentuximab vedotin in relapsed and refractory HL.
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Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 05-14-2013
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To evaluate the performance of conventional [(11)C]choline PET/CT in comparison to that of simultaneous whole-body PET/MR.
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Metabolic networks underlying cognitive reserve in prodromal Alzheimer disease: a European Alzheimer disease consortium project.
J. Nucl. Med.
PUBLISHED: 04-16-2013
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This project aimed to investigate the metabolic basis for resilience to neurodegeneration (cognitive reserve) in highly educated patients with prodromal Alzheimer disease (AD).
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Voxel-based analysis of amyloid-burden measured with [(11)C]PiB PET in a double transgenic mouse model of Alzheimers disease.
Mol Imaging Biol
PUBLISHED: 04-11-2013
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The purpose of this study is to validate the feasibility of a voxel-based analysis of in vivo amyloid-? positron emission tomography (PET) imaging studies in transgenic mouse models of Alzheimers disease.
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Metabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults.
Neuroimage
PUBLISHED: 03-24-2013
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Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1 ± 5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n=18) and high (n=17) performance on digit span backward test as an index of verbal WM. In addition, fiber tractography based on PCC and MPFC nodes as way points was performed in a subset of subjects. FDG uptake in the DMN nodes did not differ between high and low performers. However, significantly (p=0.01) lower metabolic connectivity was found in the group of low performers. Furthermore, as compared to high performers, low performers showed lower density of the left superior cingulate bundle. Verbal WM performance is related to metabolic and structural connectivity within the DMN in young healthy adults. Metabolic connectivity as quantified with FDG-PET might be a sensitive marker of the normal variability in some cognitive functions.
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Atypical parkinsonism due to a D202N Gerstmann-Sträussler-Scheinker prion protein mutation: first in vivo diagnosed case.
Mov. Disord.
PUBLISHED: 02-26-2013
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Parkinsonism with dopa-sensitivity and a correlating DaTSCAN turned out to be due to a D202N mutation which is associated with the Gerstmann-Sträussler-Scheinker (GSS) disease.
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Reference cluster normalization improves detection of frontotemporal lobar degeneration by means of FDG-PET.
PLoS ONE
PUBLISHED: 02-25-2013
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Positron emission tomography with [18F] fluorodeoxyglucose (FDG-PET) plays a well-established role in assisting early detection of frontotemporal lobar degeneration (FTLD). Here, we examined the impact of intensity normalization to different reference areas on accuracy of FDG-PET to discriminate between patients with mild FTLD and healthy elderly subjects. FDG-PET was conducted at two centers using different acquisition protocols: 41 FTLD patients and 42 controls were studied at center 1, 11 FTLD patients and 13 controls were studied at center 2. All PET images were intensity normalized to the cerebellum, primary sensorimotor cortex (SMC), cerebral global mean (CGM), and a reference cluster with most preserved FDG uptake in the aforementioned patients group of center 1. Metabolic deficits in the patient group at center 1 appeared 1.5, 3.6, and 4.6 times greater in spatial extent, when tracer uptake was normalized to the reference cluster rather than to the cerebellum, SMC, and CGM, respectively. Logistic regression analyses based on normalized values from FTLD-typical regions showed that at center 1, cerebellar, SMC, CGM, and cluster normalizations differentiated patients from controls with accuracies of 86%, 76%, 75% and 90%, respectively. A similar order of effects was found at center 2. Cluster normalization leads to a significant increase of statistical power in detecting early FTLD-associated metabolic deficits. The established FTLD-specific cluster can be used to improve detection of FTLD on a single case basis at independent centers - a decisive step towards early diagnosis and prediction of FTLD syndromes enabling specific therapies in the future.
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Extended postinterventional tumor necrosis-implication for outcome in liver transplant patients with advanced HCC.
PLoS ONE
PUBLISHED: 01-22-2013
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Locoregional interventional bridging therapy (IBT) is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC). However, the prognostic value of IBT in patients with advanced HCC is still undefined.
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Aberrant intrinsic connectivity of hippocampus and amygdala overlap in the fronto-insular and dorsomedial-prefrontal cortex in major depressive disorder.
Front Hum Neurosci
PUBLISHED: 01-01-2013
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Neuroimaging studies of major depressive disorder (MDD) have consistently observed functional and structural changes of the hippocampus (HP) and amygdale (AY). Thus, these brain regions appear to be critical elements of the pathophysiology of MDD. The HP and AY directly interact and show broad and overlapping intrinsic functional connectivity (iFC) to other brain regions. Therefore, we hypothesized the HP and AY would show a corresponding pattern of aberrant intrinsic connectivity in MDD. Resting-state functional MRI was acquired from 21 patients with MDD and 20 healthy controls. ß-Maps of region-of-interest-based FC for bilateral body of the HP and basolateral AY were used as surrogates for iFC of the HP and AY. Analysis of variance was used to compare ß-maps between MDD and healthy control groups, and included covariates for age and gender as well as gray matter volume of the HP and AY. The HP and AY of MDD patients showed an overlapping pattern of reduced FC to the dorsomedial-prefrontal cortex and fronto-insular operculum. Both of these regions are known to regulate the interactions among intrinsic networks (i.e., default mode, central executive, and salience networks) that are disrupted in MDD. These results provide the first evidence of overlapping aberrant HP and AY intrinsic connectivity in MDD. Our findings suggest that aberrant HP and AY connectivity may interact with dysfunctional intrinsic network activity in MDD.
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Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles.
Circ. Res.
PUBLISHED: 12-29-2011
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Stroke is the third most common cause of death in industrialized countries. The main therapeutic target is the ischemic penumbra, potentially salvageable brain tissue that dies within the first few hours after blood flow cessation. Hence, strategies to keep the penumbra alive until reperfusion occurs are needed.
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Asymmetric loss of parietal activity causes spatial bias in prodromal and mild Alzheimers disease.
Biol. Psychiatry
PUBLISHED: 05-09-2011
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In Alzheimers disease (AD), loss of effective neuronal activity is reflected by cortical glucose hypometabolism. Hypometabolism in the posterior parietal cortex (PPC) is among the first in vivo signs of AD; however, its functional impact on large-scale brain mechanisms and behavior is poorly understood. The lateral PPC contributes to spatial attention constituting a basic function of the human brain. We hypothesized 1) that lateral PPC hypometabolism is associated with impaired spatial attention in very early AD and 2) that impaired competition of effective neuronal activity across hemispheres might underlie this deficit in terms of brain mechanisms.
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Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden.
Brain
PUBLISHED: 04-13-2011
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Disruption of functional connectivity between brain regions may represent an early functional consequence of ?-amyloid pathology prior to clinical Alzheimers disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity. Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism. Subtle connectivity disruptions and hypometabolism were already present in amyloid-positive asymptomatic subjects. Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy. Whole-brain connectivity values and metabolism showed a positive correlation with each other and a negative correlation with amyloid burden. These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimers disease pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimers-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection.
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Regional expansion of hypometabolism in Alzheimers disease follows amyloid deposition with temporal delay.
Biol. Psychiatry
PUBLISHED: 03-26-2011
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Cross-sectional imaging studies suggest that patterns of hypometabolism (measured by [(18)F] fluorodeoxyglucose positron emission tomography [FDG-PET]) and amyloid deposition (measured by [(11)C] Pittsburgh Compound B [PiB]- PET) in Alzheimers disease (AD) show some overlap with each other. This indicates that neuronal dysfunction might spread within the anatomical pattern of amyloid deposition. The aim of this study was to examine longitudinal regional patterns of amyloid deposition and hypometabolism in the same population of mild AD subjects and to establish their regional relationship to each other.
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Relationship between occupation attributes and brain metabolism in frontotemporal dementia.
Neuropsychologia
PUBLISHED: 02-15-2011
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Occupation has been associated with cognitive reserve in healthy aging and Alzheimers disease. Here we assess the relationship between cerebral metabolic deficits in behavioral variant frontotemporal dementia (bvFTD) and occupation characteristics. Using factor analysis, we derived verbal, physical and visuospatial occupation scores from the US Department of Labor, Occupational Information Network and related these scores to regional cerebral metabolic rate of glucose utilization in 31 patients diagnosed with behavioral variant bvFTD, controlling for cognitive status (CERAD neuropsychological assessment battery), gender and education. Regression analyses showed a marked inverse association between glucose metabolism and (a) verbal occupation scores in left prefrontal cortex and, (b) physical occupation characteristics in right supplementary motor area. We concluded that, consistent with the cognitive reserve hypothesis, lifelong occupation characteristics are related to focal cerebral metabolic deficits in bvFTD. Specific occupation demands spanning decades may strengthen cognitive resistance to pathology.
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Synthesis and evaluation of 11C-labeled imidazo[2,1-b]benzothiazoles (IBTs) as PET tracers for imaging ?-amyloid plaques in Alzheimers disease.
J. Med. Chem.
PUBLISHED: 01-28-2011
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We report a novel series of (11)C-labeled imidazo[2,1-b]benzothiazoles (IBTs) as tracers for imaging of cerebral ?-amyloid (A?) deposits in patients with Alzheimers disease (AD) by means of positron emission tomography (PET). From a series of 11 compounds, candidates were identified to have a high binding affinity for A?. Selected compounds were prepared as O- or N-[(11)C]methyl derivatives and shown to have a high initial brain uptake in wild-type mice (range 1.9-9.2% I.D./g at 5 min). 2-(p-[(11)C]Methylaminophenyl)-7-methoxyimidazo[2,1-b] benzothiazole ([(11)C]5) was identified as a lead based on the combined favorable properties of high initial brain uptake, rapid clearance from normal brain, and high in vitro affinity for A?(1-40) (K(i) = 3.5 nM) and A?(1-42) (5.8 nM), which were superior to the Pittsburgh compound B (1a). In an APP/PS1 mouse model of AD (Tg), we demonstrate a specific uptake of [(11)C]5 in A?-containing telencephalic brain regions by means of small-animal PET that was confirmed by regional brain biodistribution, ex vivo autoradiography, and immunohistochemistry. Analysis of brain sections of Tg mice receiving a single bolus injection of [(11)C]5 and [(3)H]1a together revealed that the tracers bind to A? plaques in the brain of Tg mice in a comparable pattern. Taken together, these data suggest that IBTs represent useful PET imaging agents for high-sensitivity detection of A? plaques.
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Spinal long-term potentiation is associated with reduced opioid neurotransmission in the rat brain.
Clin Physiol Funct Imaging
PUBLISHED: 07-29-2010
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Neuronal events leading to development of long-term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying hyperalgesia. In the present study, we examine if induction of spinal LTP may be associated with functional changes in the supraspinal opioidergic system. The opioid receptors (ORs) play a key role in nociceptive processing and controlling the descending modulatory system to the spinal cord.
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Progression of cerebral amyloid load is associated with the apolipoprotein E ?4 genotype in Alzheimers disease.
Biol. Psychiatry
PUBLISHED: 01-28-2010
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Pittsburgh Compound B ([¹¹C] PiB) is a specific positron emission tomography (PET) marker of cerebral amyloid deposits. Only few data have been published on in vivo longitudinal changes of amyloid load in Alzheimers disease (AD) patients, with conflicting results. Therefore, little is known about the factors that influence these changes.
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Amyloid-plaque imaging in early and differential diagnosis of dementia.
Ann Nucl Med
PUBLISHED: 01-16-2010
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The increasing life expectancy in our society results in a continuously growing number of patients suffering from neurodegenerative disorders, particularly Alzheimers disease (AD). Apart from the deleterious consequences for patients and their relatives, this issue has also alarming effects on our social systems. These facts have justified increased scientific efforts regarding the identification of basic pathomechanisms of dementia and the development of new treatment options. Increased production of specific proteins and their pathologic aggregation in the brain appears to be a pathomechanism which occurs early in the course of many different neurodegenerative diseases. Among the most well-known of these protein aggregations are amyloid plaques, which arise from the aggregation of the ?-amyloid protein. Currently, this amyloid-aggregation pathology is regarded as a key pathology, playing a causal role in the development of AD. Consequently, modern therapy approaches are directed towards this target. Limited access to brain tissue has so far restricted the definite diagnosis of AD to postmortem histopathological assessment of brain tissue. For the same reason, a clear association between extent of amyloid deposition pathology and clinical course of AD has not been established so far. However, particularly with regard to new therapeutic options, a reliable in vivo diagnosis is required. Modern molecular imaging tracers such as [11C]PIB do now open the possibility to visualize amyloid depositions in vivo, using positron emission tomography. This type of "in vivo histopathology" approach allows the characterization of neurodegenerative disorders on the basis of the underlying pathology rather than on their symptomatic appearance. In this manuscript, we will discuss the options of amyloid-plaque imaging regarding early and differential diagnosis of different forms of dementia as well as for patient selection for therapy trials and for objective therapy monitoring.
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Metabolic alterations associated with impaired clock drawing in Lewy body dementia.
Psychiatry Res
PUBLISHED: 01-13-2010
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The clock drawing test (CDT) is a widely used dementia screening instrument that assesses executive and visuospatial abilities; studies in patients with Alzheimers disease (AD) suggest frontoposterior networks to be involved in clock drawing. Clock drawing errors are also often observed in dementia with Lewy bodies (DLB), but the functional neuroanatomical substrate of impaired clock drawing has not been firmly established in this disorder. The present study was designed to provide initial evidence for brain metabolic alterations associated with CDT performance in DLB. Twenty-one patients with DLB were enrolled. CDT ratings were correlated with the regional cerebral metabolic rate of glucose (rCMRglc) measured by (18)F-fluoro-2-deoxy-glucose positron emission tomography ((18)F-FDG PET) in the statistical parametric mapping software package SPM5, controlling for overall cognitive impairment as measured by the Mini-Mental-State Examination (MMSE) score. There was a significant negative association between test scores and rCMRglc in a left-hemispheric posterofrontal network including the temporoparietal and dorsal pre-motor cortices and the precuneus. The present study provides evidence for a direct association between frontoparietal dysfunction and impaired CDT performance in DLB. These findings also suggest that the CDT is an appropriate screening instrument for this disorder and that metabolic dysfunction, and therefore disease severity, is mirrored by performance on the test.
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Evaluation of the kappa-opioid receptor-selective tracer [(11)C]GR103545 in awake rhesus macaques.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 01-05-2010
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The recent development in radiosynthesis of the (11)C-carbamate function increases the potential of [(11)C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (kappa-OR) with PET. In the present study, [(11)C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound.
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Diagnosis of Alzheimers disease with [18F]PET in mild and asymptomatic stages.
Behav Neurol
PUBLISHED: 10-23-2009
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With longer life expectancy, dementia based on the age-related Alzheimers disease (AD) has turned into one of the most prevalent disorders of older age, representing a serious medical and socio-economic issue. There has been growing interest in early diagnosis of this disease, particularly regarding the initiation of new treatment strategies ahead of the onset of irreversible neuronal damage. It is accepted that the pathologic changes underlying AD appear in the brain years to decades before the symptomatic stages. Consequently, clinical measures of cognitive impairment, as used for definition of dementia, will not allow early diagnosis of AD-pathology in the mild or asymptomatic stages. Thus, a need for complementary sensitive biomarkers is apparent. Brain imaging markers are among the most promising candidates for this diagnostic challenge. Particularly, [18F]FDG PET as a marker of regional neuronal function has been demonstrated to represent a most sensitive and specific method for early identification of AD-pathology and thus for prediction of dementia of the Alzheimer type (DAT), even in the mild and asymptomatic stages. Currently, systematic data of comparable quality are hardly available for any other imaging procedure. The purpose of this article is to describe the typical findings of [18F]FDG PET in different stages of AD and to demonstrate its value for early and reliable diagnosis of Alzheimers disease, particularly ahead of the stage of dementia of the Alzheimers type.
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Right prefrontal hypometabolism predicts delusions in dementia with Lewy bodies.
Neurobiol. Aging
PUBLISHED: 10-10-2009
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Delusions (DEL) are frequent in dementia with Lewy bodies (DLB); however, the neural equivalent is poorly understood. The present study therefore aimed to identify the cerebral metabolic pattern of glucose of a DLB group suffering from DEL (DLB+DEL) as compared to a non-delusional group (DLB-DEL) and a control group (NL); and to determine the predictive value of the regional metabolic deficit for DEL symptomatology in comparison to other clinical variables significantly associated with DEL. Voxel-wise comparisons were conducted between the patient and control groups in SPM2. The most significant regional metabolic deficit of the DLB+DEL group was used a predictor for DEL symptomatology in a logistic regression analysis along with other variables significantly associated with DEL, such as visual hallucinations (VH), and overall cognitive impairment. A significant relative hypometabolism of the right prefrontal cortex was found in the DLB+DEL group, which predicted DEL symptomatology in the regression analysis. VH and overall cognitive dysfunction were no significant predictors. These results underline the significance of right prefrontal damage for DEL in DLB.
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Synthesis and evaluation of a full-agonist orvinol for PET-imaging of opioid receptors: [11C]PEO.
J. Med. Chem.
PUBLISHED: 08-22-2009
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Antagonist radiotracers have shown only a low sensitivity for detecting competition from high-efficacy agonists at opioid receptors (ORs) in vivo. We report that [(11)C]PEO binds with high affinity to mu and kappa-opioid receptors, is a full agonist, and concentrates in brain regions of rats with a high density of the mu-OR after intravenous injection. Blocking studies with mu and kappa-OR selective compounds demonstrated that the binding of [(11)C]PEO is saturable and selective to the mu-OR in rat brain.
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Kinetic modelling of [11C]flumazenil using data-driven methods.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 08-14-2009
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[(11)C]Flumazenil (FMZ) is a benzodiazepine receptor antagonist that binds reversibly to central-type gamma-aminobutyric acid (GABA-A) sites. A validated approach for analysis of [(11)C]FMZ is the invasive one-tissue (1T) compartmental model. However, it would be advantageous to analyse FMZ binding with whole-brain pixel-based methods that do not require a-priori hypotheses regarding preselected regions. Therefore, in this study we compared invasive and noninvasive data-driven methods (Logan graphical analysis, LGA; multilinear reference tissue model, MRTM2; spectral analysis, SA; basis pursuit denoising, BPD) with the 1T model.
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Clinical severity of Alzheimers disease is associated with PIB uptake in PET.
Neurobiol. Aging
PUBLISHED: 06-24-2009
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The positron emission tomography (PET) tracer [11C]-Pittsburgh Compound-B ([11C]PIB) allows the in vivo assessment of amyloid plaque burden in the brain. In a cross-sectional study we examined the association between the severity of dementia assessed using the Clinical Dementia Rating scale sum of boxes (CDR-SOB) and [11C]PIB-PET in patients with Alzheimers disease (AD).
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Fluoro-deoxy-glucose positron emission tomography correlates of impaired activities of daily living in dementia with Lewy bodies: implications for cognitive reserve.
Am J Geriatr Psychiatry
PUBLISHED: 05-21-2009
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1) To investigate the neural substrate of impaired activities of daily living (ADL) in dementia with Lewy bodies (DLB) and 2) to explore, in the context of cognitive reserve, if hypometabolism was more pronounced in well-educated patients at the same level of everyday impairment.
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Early-onset and robust amyloid pathology in a new homozygous mouse model of Alzheimers disease.
PLoS ONE
PUBLISHED: 04-22-2009
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Transgenic mice expressing mutated amyloid precursor protein (APP) and presenilin (PS)-1 or -2 have been successfully used to model cerebral beta-amyloidosis, one of the characteristic hallmarks of Alzheimers disease (AD) pathology. However, the use of many transgenic lines is limited by premature death, low breeding efficiencies and late onset and high inter-animal variability of the pathology, creating a need for improved animal models. Here we describe the detailed characterization of a new homozygous double-transgenic mouse line that addresses most of these issues.
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Brain metabolic correlates of cerebrospinal fluid beta-amyloid 42 and tau in Alzheimers disease.
Dement Geriatr Cogn Disord
PUBLISHED: 02-04-2009
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The cerebrospinal fluid (CSF) proteins beta-amyloid 42 (Abeta42) and Tau are believed to indirectly reflect some core pathological features of Alzheimers disease (AD). Their topographic origin and their association with synaptic dysfunction are still not well understood.
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Beta amyloid in Alzheimers disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid.
Biol. Psychiatry
PUBLISHED: 01-08-2009
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A decreased concentration of beta amyloid (1-42) (Abeta42) has consistently been found in the cerebrospinal fluid (CSF) of patients with Alzheimers disease (AD) and is considered a diagnostic biomarker. However, it is not clear to which extent CSF Abeta42 levels are reflective of cerebral pathology in AD. The aim of the study was to determine the association between cerebral amyloid plaque load, as measured by means of the positron emission tomography (PET) tracer carbon-11-labeled Pittsburgh Compound B ([11C]PiB) and CSF Abeta42 in AD.
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PET/MRI for neurologic applications.
J. Nucl. Med.
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PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation of the measured signals, creating opportunities impossible to realize using stand-alone instruments. This paper reviews the methodologic improvements and potential neurologic and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MRI data to improve the PET data quantification. On the MRI side, we present how improved PET quantification can be used to validate several MRI techniques. Finally, we describe promising research, translational, and clinical applications that can benefit from these advanced tools.
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A European multicentre PET study of fibrillar amyloid in Alzheimers disease.
Eur. J. Nucl. Med. Mol. Imaging
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Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimers disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies.
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Quantitative longitudinal interrelationships between brain metabolism and amyloid deposition during a 2-year follow-up in patients with early Alzheimers disease.
Eur. J. Nucl. Med. Mol. Imaging
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Similar regional anatomical distributions were reported for fibrillary amyloid deposition [measured by (11)C-Pittsburgh compound B (PIB) positron emission tomography (PET)] and brain hypometabolism [measured by (18)F-fluorodeoxyglucose (FDG) PET] in numerous Alzheimers disease (AD) studies. However, there is a lack of longitudinal studies evaluating the interrelationships of these two different pathological markers in the same AD population. Our most recent AD study suggested that the longitudinal pattern of hypometabolism anatomically follows the pattern of amyloid deposition with temporal delay, which indicates that neuronal dysfunction may spread within the anatomical pattern of amyloid pathology. Based on this finding we now hypothesize that in early AD patients quantitative longitudinal decline in hypometabolism may be related to the amount of baseline amyloid deposition during a follow-up period of 2 years.
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A case of multimodality multiparametric 11C-choline PET/MR for biopsy targeting in prior biopsy-negative primary prostate cancer.
Clin Nucl Med
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We introduce the case of a 70-years-old man with an elevated level of prostate-specific antigen and prior negative biopsy. For targeting rebiopsy, the patient underwent C-choline PET/CT and subsequent PET/MR. Both the high uptake in PET and the abnormal findings in MR gave strong evidence for prostate cancer at the ventral periphery of the right apex. This location is sometimes not covered by routine sextant biopsy. The following targeted rebiopsy was positive for prostate cancer. This case indicates the potential role of PET/MR for identifying primary prostate cancer because of its high soft tissue contrast and the possibility of a multimodality approach.
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Workflow and scan protocol considerations for integrated whole-body PET/MRI in oncology.
J. Nucl. Med.
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Integrated PET/MRI systems open exciting possibilities for clinical and research applications. However, compared with PET/CT, PET/MRI is a complex technique resulting in new problems and challenges, especially regarding workflow, scan protocols, and data analysis. This complexity applies in particular to examinations in oncology with partial- or whole-body coverage extending over several bed positions. Unlike diagnostic PET/CT, for which the clinical CT protocols can largely be copied from stand-alone CT, the design of a diagnostic MRI protocol for partial- or whole-body coverage is more complex and has to be adapted to the special requirements of PET/MRI to be both time-efficient and comprehensive. Here, we describe basic considerations concerning workflow, imaging protocols, and image analysis for whole-body PET/MRI in oncology, based on our experience with the first integrated PET/MRI scanner. The aim is to fully and optimally make use of the combined PET/MRI measurements in oncology, including identifying and reducing image artifacts as well as optimizing workflow beyond the mere fusion of 2 image datasets.
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18F-FDG PET detects inflammatory infiltrates in spinal cord experimental autoimmune encephalomyelitis lesions.
J. Nucl. Med.
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Multiple sclerosis (MS) is a heterogeneous disease with respect to lesion pathology, course of disease, and treatment response. Imaging modalities are needed that allow better definition of MS lesions in vivo. The aim of this study was to establish an MRI- and PET/CT-based imaging modality and to evaluate approved and promising PET tracers in experimental autoimmune encephalomyelitis (EAE), the animal model of MS.
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First clinical experience with integrated whole-body PET/MR: comparison to PET/CT in patients with oncologic diagnoses.
J. Nucl. Med.
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The recently introduced first integrated whole-body PET/MR scanner allows simultaneous acquisition of PET and MRI data in humans and, thus, may offer new opportunities, particularly regarding diagnostics in oncology. This scanner features major technologic differences from conventional PET/CT devices, including the replacement of photomultipliers with avalanche photodiodes and the need for MRI-based attenuation correction. The aim of this study was to evaluate the comparability of clinical performance between conventional PET/CT and PET/MR in patients with oncologic diseases.
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Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimers disease.
PLoS ONE
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In vivo imaging and quantification of amyloid-? plaque (A?) burden in small-animal models of Alzheimers disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of A? in mouse brain with [(11)C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure A? at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [(11)C]PiB uptake in individual brain regions with A? deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of A? pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [(11)C]PiB imaging of A? in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal A? imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice.
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White matter hyperintensities predict amyloid increase in Alzheimers disease.
Neurobiol. Aging
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Impaired amyloid clearance probably contributes to increased amyloid deposition in sporadic Alzheimers disease (AD). Diminished perivascular drainage due to cerebral small-vessel disease (CSVD) has been proposed as a cause of reduced amyloid clearance. White matter hyperintensities (WMHs) are considered to reflect CSVD and can be measured using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Amyloid deposition can be determined in vivo using Pittsburgh compound B ([11C]PiB) positron emission tomography (PET). We aimed to elucidate the association between WMH and the progression of amyloid deposition in patients with AD. Twenty-two patients with probable AD underwent FLAIR-MRI and [11C]PiB-PET examinations at baseline (BL) and after a mean follow-up (FU) interval of 28 months. The relationship between BL-WMH and the progression of cerebral amyloid between BL and FU was examined using a regions-of-interest (ROI) approach. The region-specific variability of this relationship was analyzed using a voxel-based method. The longitudinal analysis revealed a statistically significant association between the amount of BL-WMH and the progression of amyloid load between BL and FU (p = 0.006, adjusted R2 = 0.375, standardized coefficient ? = 0.384). The association was particularly observed in parieto-occipital regions and tended to be closer in regions adjacent to the brain surface. According to our knowledge, this is the first in vivo study in human being supporting the hypothesis that impaired amyloid clearance along perivascular drainage pathways may contribute to ?-amyloid deposition in sporadic AD. The extent of WMH might be a relevant factor to be assessed in antiamyloid drug trials.
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Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimers disease.
ScientificWorldJournal
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The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimers disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([¹¹C]PIB PET). [¹¹C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [¹¹C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.
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Increased intrinsic brain activity in the striatum reflects symptom dimensions in schizophrenia.
Schizophr Bull
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Striatal dysfunction is thought to be a fundamental element in schizophrenia. Striatal dopamine dysfunction impacts on reward processing and learning and is present even at rest. Here, we addressed the question whether and how spontaneous neuronal activity in the striatum is altered in schizophrenia. We therefore assessed intrinsic striatal activity and its relation with disorder states and symptom dimensions in patients with schizophrenia. We performed resting-state functional (rs-fMRI) and structural magnetic resonance imaging as well as psychometric assessment in 21 schizophrenic patients during psychosis. On average 9 months later, we acquired follow-up data during psychotic remission and with comparable levels of antipsychotic medication. Twenty-one age- and sex-matched healthy controls were included in the study. Independent component analysis of fMRI data yielded spatial maps and time-courses of coherent ongoing blood-oxygen-level-dependent signal fluctuations, which were used for group comparisons and correlation analyses with scores of the positive and negative syndrome scale. During psychosis, coherent intrinsic activity of the striatum was increased in the dorsal part and correlated with positive symptoms such as delusion and hallucination. In psychotic remission of the same patients, activity of the ventral striatum was increased and correlated with negative symptoms such as emotional withdrawal and blunted affect. Results were controlled for volumetric and medication effects. These data provide first evidence that in schizophrenia intrinsic activity is changed in the striatum and corresponds to disorder states and symptom dimensions.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.