Brain network markers of abnormal cerebral glucose metabolism and blood flow in Parkinson's disease.
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ABSTRACT:
SUBMITTER: Peng S
PROVIDER: S-EPMC4556355 | biostudies-other | 2014 Oct
REPOSITORIES: biostudies-other
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Project description:RationaleIn Parkinson's disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP).MethodsThe PDRPNL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRPIT was identified in 20 controls and 20 "de-novo" PD patients from an Italian cohort. A further 24 controls and 18 "de-novo" Italian patients were used for validation. The PDRPSP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy.ResultsA PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in "de-novo" PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRPIT, PDRPNL, and PDRPSP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA.ConclusionThe PDRP is a reproducible disease characteristic across PD populations and scanning platforms globally. Further study is needed to identify the topography of specific PD subtypes, and to identify and correct for center-specific effects.
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Project description:UnlabelledBackgroundPositron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18 F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMRglu and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMRglu is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated.MethodsThirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [15O]H2O scan and a dynamic [18 F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler derived input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods.ResultsAfter quality control, 9 CMRglu and 11 CBF scans were available for analysis. Average GM CMRglu values were 0.33 ± 0.04 μmol/cm3 per minute, and average CBF values were 0.43 ± 0.09 mL/cm3 per minute. Good correlation between NLR and parametric CMRglu measurements was obtained as well as between NLR and parametric CBF values. For CMRglu Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates.ConclusionNonlinear regression analysis, allowing for the derivation of regional CBF and CMRglu values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMRglu measurements do not require invasive arterial sampling to define the input function.Trial registrationClinicalTrials.gov NCT00626080.
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Project description: Not available
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Project description:Human infancy is characterized by most rapid regional cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF changes spatiotemporally across the brain and how the rCBF increase supports emergence of functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of 48 infants cross-sectionally, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology-function coupling across infancy. We found that faster rCBF increases in the DMN than visual and sensorimotor networks. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extraneuronal metabolic demands in the DMN maturation. These results offer insights into the physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.
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Project description:Many studies have shown abnormal cerebral blood flow (CBF) in schizophrenia; however, it remains unclear how topological properties of CBF network are altered in this disorder. Here, arterial spin labeling (ASL) MRI was employed to measure resting-state CBF in 96 schizophrenia patients and 91 healthy controls. CBF covariance network of each group was constructed by calculating across-subject CBF covariance between 90 brain regions. Graph theory was used to compare intergroup differences in global and nodal topological measures of the network. Both schizophrenia patients and healthy controls had small-world topology in CBF covariance networks, implying an optimal balance between functional segregation and integration. Compared with healthy controls, schizophrenia patients showed reduced small-worldness, normalized clustering coefficient and local efficiency of the network, suggesting a shift toward randomized network topology in schizophrenia. Furthermore, schizophrenia patients exhibited altered nodal centrality in the perceptual-, affective-, language-, and spatial-related regions, indicating functional disturbance of these systems in schizophrenia. This study demonstrated for the first time that schizophrenia patients have disrupted topological properties in CBF covariance network, which provides a new perspective (efficiency of blood flow distribution between brain regions) for understanding neural mechanisms of schizophrenia.
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Project description:Subclinical systemic microvascular dysfunction exists in asymptomatic patients with type 1 diabetes. We hypothesized that microangiopathy, resulting from long-standing systemic hyperglycemia and hyperinsulinemia, may be generalized to the brain, resulting in changes in cerebral blood flow (CBF) and metabolism in these patients. We performed dynamic [(15)O]H2O and [(18)F]-fluoro-2-deoxy-d-glucose brain positron emission tomography scans to measure CBF and cerebral glucose metabolism (CMRglu), respectively, in 30 type 1 diabetic patients and 12 age-matched healthy controls after an overnight fast. Regions of interest were automatically delineated on coregistered magnetic resonance images and full kinetic analysis was performed. Plasma glucose and insulin levels were higher in patients versus controls. Total gray matter CBF was 9%, whereas CMRglu was 21% lower in type 1 diabetic subjects versus control subjects. We conclude that at real-life fasting glucose and insulin levels, type 1 diabetes is associated with decreased resting cerebral glucose metabolism, which is only partially explained by the decreased CBF. These findings suggest that mechanisms other than generalized microangiopathy account for the altered CMRglu observed in well-controlled type 1 diabetes.
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Project description:Spinocerebellar ataxia type 19 (SCA19), allelic with spinocerebellar ataxia type 22 (SCA22), is a rare syndrome caused by mutations in the KCND3 gene which encodes the potassium channel Kv4.3. Only 18 SCA19/22 families and sporadic cases of different ethnic backgrounds have been previously reported. As in other SCAs, the SCA19/22 phenotype is variable and usually consists of adult-onset slowly progressive ataxia and cognitive impairment; myoclonus and seizures; mild Parkinsonism occurs in some cases. Here we describe a Swedish SCA19/22 family spanning five generations and harboring the T377M mutation in KCND3. For the first time for this disease, 18F-fluorodeoxyglucose PET was assessed revealing widespread brain hypometabolism. In addition, we identified white matter abnormalities and found unusual features for SCA19/22 including early age of onset and fast rate of progression in the late course of disease in the oldest patient of this family.
| S-EPMC6028832 | biostudies-literature
Project description:IntroductionWe examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]).MethodsWe included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi-center Heart-Brain Study. We used pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains.ResultsCBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning.DiscussionWe found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart-brain axis.
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Project description:White matter hyperintensities (WMHs) are common neuroimaging findings in the aging population and are associated with various clinical symptoms, especially cognitive impairment. Abnormal global cerebral blood flow (CBF) and specific functional connections have been reported in subjects with higher WMH loads. Nevertheless, the comprehensive functional mechanisms underlying WMH are yet to be established. In this study, by combining resting-state functional magnetic resonance imaging and arterial spin labeling, we investigated the neurovascular dysfunction in subjects with WMH in CBF, functional connectivity strength (FCS), and CBF-FCS coupling. The whole-brain alterations of all these measures were explored among non-dementia subjects with different WMH loads using a fine-grained Human Brainnetome Atlas. In addition, exploratory mediation analyses were conducted to further determine the relationships between these neuroimaging indicators, WMH load, and cognition. The results showed that subjects with higher WMH loads displayed decreased CBF and FCS mainly in regions involving the cognitive- and emotional-related brain networks, including the default mode network, salience network, and central executive network. Notably, subjects with higher WMH loads also showed an abnormal regional CBF-FCS coupling in several regions of the thalamus, posterior cingulate cortex, and parahippocampal gyrus involving the default mode network. Furthermore, regional CBF in the right inferior temporal gyrus and right dorsal caudate may mediate the relationship between WMH load and cognition in WMH subjects. These findings indicated characteristic changes in cerebral blood supply, brain activity, and neurovascular coupling in regions involving specific brain networks with the development of WMH, providing further information on pathophysiology underpinnings of the WMH and related cognitive impairment.
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Project description:PURPOSE:Cerebral blood flow (CBF) and glucose metabolism are important and significant factors in ischaemic cerebrovascular disease. The objective of this study was to use quantitative hybrid PET/MR to evaluate the effects of surgery treatment on the symptomatic unilateral internal carotid artery/middle cerebral artery steno-occlusive disease. METHODS:Fifteen patients diagnosed with ischaemic cerebrovascular disease were evaluated using a hybrid TOF PET/MR system (Signa, GE Healthcare). The CBF value measured by arterial spin labelling (ASL) and the standardized uptake value ratio (SUVR) measured by 18F-FDG PET were obtained, except for the infarct area and its contralateral side, before and after bypass surgery. The asymmetry index (AI) was calculated from the CBF and SUVR of the ipsilateral and contralateral cerebral hemispheres, respectively. The ?CBF and ?SUVR were calculated as the percent changes of CBF and SUVR between before and after surgery, and paired t tests were used to determine whether a significant change occurred. Spearman's rank correlation was also used to compare CBF with glucose metabolism in the same region. RESULTS:The analysis primarily revealed that after bypass surgery, a statistically significant increase occurred in the CBF on the affected side (P < 0.01). The postprocedural SUVR was not significantly higher than the preprocedural SUVR (P > 0.05). However, the postprocedural AI values for CBF and SUVR were significantly lower after surgery than before surgery (P < 0.01). A significant correlation was found between the AI values for preoperative CBF and SUVR on the ipsilateral hemisphere (P < 0.01). CONCLUSIONS:The present study demonstrates that a combination of ASL and 18F-FDG PET could be used to simultaneously analyse changes in patients' cerebral haemodynamic patterns and metabolism between before and after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery. This therefore represents an essential tool for the evaluation of critical haemodynamic and metabolic status in patients with symptomatic unilateral ischaemic cerebrovascular disease.
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