Appearance modeling of 11C PiB PET images: characterizing amyloid deposition in Alzheimer's disease, mild cognitive impairment and healthy aging

Beta-amyloid (Abeta) deposition is one of the neuropathological hallmarks of Alzheimer's disease (AD), Abeta burden can be quantified using (11)C PiB PET. Neuropathological studies have shown that the initial plaques are located in the temporal and orbitofrontal cortices, extending later to the cingulate, frontal and parietal cortices (Braak and Braak, 1997). Previous studies have shown an overlap in (11)C PiB PET retention between AD, mild cognitive impairment (MCI) patients and normal elderly control (NC) participants. It has also been shown that there is a relationship between Abeta deposition and memory impairment in MCI patients. In this paper we explored the variability seen in 15 AD, 15 MCI and 18 NC by modeling the voxel data from spatially and uptake normalized PiB images using principal component analysis. The first two principal components accounted for 80% of the variability seen in the data, providing a clear separation between AD and NC, and allowing subsequent classification. The MCI cases were distributed along an apparent axis between the AD and NC group, closely aligned with the first principal component axis. The NC cases that were PiB(+) formed a distinct cluster that was between, but separated from the AD and PiB(-) NC clusters. The PiB(+) MCI were found to cluster with the AD cases, and exhibited a similar deposition pattern. The primary principal component score was found to correlate with episodic memory scores and mini mental status examination and it was observed that by varying the first principal component, a change in amyloid deposition could be derived that is similar to the expected progression of amyloid deposition observed from post mortem studies.     

Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant

Researchers employing Pittsburgh Compound B positron emission tomography (PIB-PET) imaging have consistently indentified old normal control (oNC) subjects with elevated tracer uptake, suggesting the presence of beta-amyloid deposition in these individuals. However, a consensus regarding the level at which PIB reveals a biologically meaningful signal does not exist (ie. an appropriate cutoff value for PIB positivity remains unclear). In this exploratory study, we sought to investigate the range of PIB distribution volume ratio (DVR) values present in our oNC cohort (N = 75, age range = 58-97). oNC subjects were classified based on global PIB index values (average DVR across prefrontal, parietal, lateral temporal and cingulate cortices) by employing two approaches: (1) an iterative outlier approach that revealed a cutoff value of 1.16 (IO-cutoff) and (2) an approach using data from a sample of young normal control subjects (N = 11, age range = 20-30) that yielded a cutoff value of 1.08 (yNC-cutoff). oNC subjects falling above the IO-cutoff had values similar to AD subjects (“PIB+”, 15%). Subjects falling between the 2 cutoffs were considered to have ambiguous PIB status (“Ambig”, 20%) and the remaining oNC were considered “PIB-“ (65%). Additional measures capturing focal DVR magnitude and extent of elevated DVR values were consistent with the classification scheme using PIB index values, and revealed evidence for elevated DVR values in a subset of PIB- oNC subjects. Furthermore, there were a greater proportion of ambiguously elevated values compared to low values, and these elevated values were present in regions known to show amyloid deposition. The analyses presented in this study, in conjunction with recently published pathological data, suggest a biological relevance of slight PIB elevations in aging.     

Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer's disease

Semantic dementia (SD) is a rare clinical syndrome, assigned to the group of frontotemporal lobar degenerations (FTLD). Histopathological analysis has not revealed the deposition of amyloid plaques in the majority of SD cases, in contrast to dementia of the Alzheimer type (AD). However, based on clinical examination alone a reliable differentiation of the underlying pathology cannot be guaranteed, i.e. AD and SD may be confused in some cases. Our aim was to determine, whether AD and SD can be differentiated in vivo by means of amyloid plaque PET imaging. In groups of AD and SD patients, matched for gender, age and overall degree of cognitive impairment, cerebral glucose metabolism was examined with [(18)F]Fluorodeoxyglucose (FDG)-PET and cerebral amyloid plaque density was assessed using [(11)C]6-OH-BTA-1 (PIB)-PET. A volume-of-interest analysis (VOI), using the cerebellum as a reference region, and voxel-based statistical group comparisons (SPM2) were carried out between the patient groups and matched groups of healthy controls. To control for a potential influence of atrophy on the PET findings, a correction of partial volume effects was performed. Characteristic patterns of hypometabolism could be demonstrated in both clinically defined AD and SD with some regional overlap and subtle differences (AD: bilateral posterior cingulate, temporoparietal and frontal cortex; SD: left>right polar temporal, frontal mesial cortex). Compared with healthy controls, significant [(11)C]PIB amyloid plaque tracer binding was observed only in patients with AD (in bilateral temporoparietal, frontal and posterior cingulate cortex and the precuneus) but not in SD. This difference in amyloid plaque deposition could be reproduced in direct statistical comparison of AD and SD and clearly extended the metabolic differences between the patient groups. These findings support the notion that SD can be diagnosed in vivo as a separate entity from AD using amyloid plaque imaging. In general, amyloid plaque PET may complement neuropsychological assessment regarding reliable differential diagnosis of AD and FTLD dementias based on characterization of underlying pathology and may improve the definition of individual prognosis and the selection of patients for scientific trials.     

Increased FDG uptake in the ipsilesional sensorimotor cortex in congenital hemiplegia

The resting brain metabolism was estimated in six children suffering from a right congenital hemiplegia (CH) of subcortical origin. This estimate was based on the 18F-labeled 2-deoxy-2-fluoro-d-glucose (FDG) uptake measured by means of positron emission tomography and compared, using statistical parametric mapping (SPM99), with that of six control subjects. The contrast [CH children - Controls] showed that CH children had two loci of relatively higher FDG uptake. The larger voxel cluster was found in the ipsilesional hemisphere and comprised the primary motor and somatosensory cortices and left inferior parietal lobule. The other cluster was located in the contralesional hemisphere and encompassed the primary motor cortex, callosomarginal sulcus, and cingulate gyrus. The reverse contrast [Controls - CH children] showed that control subjects had a relatively higher FDG uptake bilaterally in the temporal and hippocampal gyri, the rostral part of the brain stem, the thalami, the putamen, and the superior frontal gyri. A crossed cerebellar diaschisis was not observed in CH children. This relatively higher FDG uptake in the ipsi- and contralesional motor areas of CH children stands out in contrast to the hypometabolism (diaschisis) frequently observed in adult stroke patients with a subcortical lesion. This increased FDG uptake in the disconnected ipsilesional motor areas may reflect a long-term adaptation leading, for example, to an increased synaptic density and/or activity or to a change in the density of glucose transporters.     

Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer's disease

Recently developed positron emission tomography (PET) tracers, such as PIB and FDDNP, help to visualize amyloid plaques and neurofibrillary tangles in living subjects. FDDNP binds to both amyloid plaques and tangles, whereas PIB selectively labels amyloid plaques. Therefore, it will be interesting to see a direct comparison of the regional binding of the two radiotracers for plaques (PIB) and plaques and tangles (FDDNP) using multitracer PET imaging for both PIB and FDDNP in the same subjects with and without Alzheimer's disease. Here we report that multitracer PET images of PIB and FDDNP in the same Alzheimer subjects show negligible PIB but strong FDDNP binding in the medial temporal cortex (hippocampus, amygdala, and parahippocampal gyrus), whereas there are significant quantities of both PIB and FDDNP binding in neocortical areas. These results suggest that tangles rather than amyloid plaques are the dominant pathology in the medial temporal cortex of living Alzheimer patients. In nondemented elderly normal subjects, PIB binding shows a significant increase in the posterior cingulate cortex compared with other brain regions, whereas in the same normal subjects we found significant FDDNP binding in the medial temporal cortex. Interestingly, the medial temporal FDDNP uptake values in normal elderly subjects were inversely correlated with long delay recall scores in the California Verbal Learning Test, a measure of episodic memory performance. We conclude that multitracer PET imaging of amyloid plaques and tangles using FDDNP and PIB in both nondemented and demented subjects provides important insight into these complicated pathological processes in living subjects.     

11C]PIB binding in Parkinson's disease dementia

[(11)C]PIB ((11)C-6-OH benzothiazole) reflects the regional distribution of amyloid (beta-sheeted proteins) in patients with Alzheimer's disease (AD). Proteinaceous inclusions in Parkinson's disease with dementia (PDD), so-called Lewy bodies, also consist of fibrillar, misfolded proteins, chiefly alpha-synuclein. To test whether PDD subjects show specific amyloid binding in vivo and whether this could reflect fibrillar alpha-synuclein accumulation, we investigated 10 PDD subjects with [(11)C]PIB-PET. Radioligand binding was compared to that in 11 control and 6 AD subjects. Furthermore, postmortem sections of 4 patients with Parkinson's disease (PD), therefrom 2 with dementia (PDD), and of 6 controls were stained with PIB to evaluate the histological distribution of the fluorescent ligand in the brainstem. In PET, only 2 PDD patients displayed increased PIB binding to cortical amyloid comparable to AD patients. The other 8 patients showed control-like cortical findings but elevated PIB binding in the pons and mesencephalon. Fluorescence microscopy showed PIB binding to Lewy bodies and neuromelanin in the substantia nigra of PD and PDD brainstem sections, but not in controls. These data suggest that PIB-PET can be used to further differentiate PDD with respect to cortical amyloid. Furthermore, we provide evidence that--in addition to nonspecific binding--PIB uptake in the brainstem may also reflect PDD related amyloid.     

Strategies for the generation of parametric images of [C]PIB with plasma input functions considering discriminations and reproducibility

Pittsburgh compound B or [¹¹C]PIB is an amyloid imaging agent which shows a clear differentiation between subjects with Alzheimer's disease (AD) and controls. However the observed signal difference in other forms of dementia such as dementia with Lewy bodies (DLB) is smaller, and mild cognitively impaired (MCI) subjects and some healthy elderly normals may show intermediate levels of [¹¹C]PIB binding. The cerebellum, a commonly used reference region for non-specific tracer uptake in [¹¹C]PIB studies in AD may not be valid in Prion disorders or monogenic forms of AD. The aim of this work was to: 1—compare methods for generating parametric maps of [¹¹C]PIB retention in tissue using a plasma input function in respect of their ability to discriminate between AD subjects and controls and 2—estimate the test–retest reproducibility in AD subjects. 12  AD subjects (5 of which underwent a repeat scan within 6 weeks) and 10 control subjects had 90 minute [¹¹C]PIB dynamic PET scans, and arterial plasma input functions were measured. Parametric maps were generated with graphical analysis of reversible binding (Logan plot), irreversible binding (Patlak plot), and spectral analysis. Between group differentiation was calculated using Student's t-test and comparisons between different methods were made using p values. Reproducibility was assessed by intraclass correlation coefficients (ICC). We found that the 75 min value of the impulse response function showed the best group differentiation and had a higher ICC than volume of distribution maps generated from Logan and spectral analysis. Patlak analysis of [¹¹C]PIB binding was the least reproducible.     

Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease

PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxel-based morphometry (VBM); VBM was optimized for template mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52 ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.     

Inter-rater reliability of manual and automated region-of-interest delineation for PiB PET

A major challenge in positron emission tomography (PET) amyloid imaging studies of Alzheimer's disease (AD) is the reliable detection of early amyloid deposition in human brain. Manual region-of-interest (ROI) delineation on structural magnetic resonance (MR) images is generally the reference standard for the extraction of count-rate data from PET images, as compared to automated MR-template(s) methods that utilize spatial normalization and a single set of ROIs. The goal of this work was to assess the inter-rater reliability of manual ROI delineation for PiB PET amyloid retention measures and the impact of CSF dilution correction (CSF) on this reliability for data acquired in elderly control (n=5) and AD (n=5) subjects. The intraclass correlation coefficient (ICC) was used to measure reliability. As a secondary goal, ICC scores were also computed for PiB outcome measures obtained by an automated MR-template ROI method and one manual rater; to assess the level of reliability that could be achieved using different processing methods. Fourteen ROIs were evaluated that included anterior cingulate (ACG), precuneus (PRC) and cerebellum (CER). The PiB outcome measures were the volume of distribution (V(T)), summed tissue uptake (SUV), and corresponding ratios that were computed using CER as reference (DVR and SUVR). Substantial reliability (ICC≥0.932) was obtained across 3 manual raters for V(T) and SUV measures when CSF correction was applied across all outcomes and regions and was similar in the absence of CSF correction. The secondary analysis revealed substantial reliability in primary cortical areas between the automated and manual SUV [ICC≥0.979 (ACG/PRC)] and SUVR [ICC≥0.977/0.952 (ACG/PRC)] outcomes. The current study indicates the following rank order among the various reliability results in primary cortical areas and cerebellum (high to low): 1) V(T) or SUV manual delineation, with or without CSF correction; 2) DVR or SUVR manual delineation, with or without CSF correction; 3) SUV automated delineation, with CSF correction; and 4) SUVR automated delineation, with or without CSF correction. The high inter-rater reliability of PiB outcome measures in primary cortical areas (ACG/PRC) is important as reliable methodology is needed for the detection of low levels of amyloid deposition on a cross-sectional basis and small changes in amyloid deposition on a longitudinal basis.     

脑淀粉样血管病与阿尔茨海默病18F-FDG PET/CT代谢改变图型对比研究

目的 比较脑淀粉样血管病(cerebral amyloid angiopathy,CAA)与阿尔茨海默病(Alzheimer's disease,AD)患者的脑代谢差异,评价18 F-脱氧葡萄糖(fluorodeoxy glucose,FDG)正电子发射断层显像/计算机体层成像(pos-itron emission t...     

The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT

Mild cognitive impairment (MCI) comprises a heterogeneous group with a variety of clinical outcomes and they are at risk for developing Alzheimer's disease (AD). The prediction of conversion from MCI to AD using the initial neuroimaging studies is an important research topic. We investigated the initial regional cerebral blood flow (rCBF) measurements using single photon emission computed tomography (SPECT) in individuals with 76 amnesic MCI (52 subjects converted to AD and 24 subjects did not convert to AD at 3-year follow-up) and 57 age- and gender-matched controls. We sought functional profiles associated with conversion to AD, then evaluated the predictive value of the initial rCBF SPECT. As compared with controls, AD converters demonstrated reduced blood flow in the bilateral parahippocampal gyri, precunei, posterior cingulate cortices, bilateral parietal association areas, and the right middle temporal gyrus. Non-converters also demonstrated significant reduction of rCBF in the posterior cingulated cortices and the right caudate nucleus when compared to controls. As compared with non-converters, converters showed reductions of rCBF in the bilateral temporo-parietal areas and the precunei. The logistic regression model revealed that reduced rCBF in the inferior parietal lobule, angular gyrus, and precunei has high predictive value and discriminative ability. Although a cross-validation study is needed to conclude the usefulness of rCBF SPECT for the prediction of AD conversion in individuals with MCI, our data suggest that the initial rCBF SPECT studies of individuals with MCI may be useful in predicting who will convert to AD in the near future.     

多探针PET成像观察轻度认知障碍

目的 观察轻度认知障碍患者(MCI)β淀粉样蛋白(Aβ)斑块、tau蛋白沉积和FDG PET特征.方法 自ADNI数据库下载半年内接受Aβ-PET、tau-PET和FDG-PET成像的40例MCI患者及30名健康人(NC组),基于视觉判断其有/无皮层Aβ滞留,并据此将MCI患者分为Aβ+ MCI组和Aβ-MCI组.分别...     

Activation in the premotor cortex during mental calculation in patients with Alzheimer's disease: relevance of reduction in posterior cingulate metabolism

In vivo brain imaging of people with Alzheimer's disease (AD) has suggested the presence of functional disintegration in the posterior-anterior brain network from the posterior cingulate cortex (PCC) to the prefrontal cortex. To investigate the relationship between the baseline posteromedial metabolism and prefrontal neural activity during cognitomnemonic tasks in AD patients, we measured both glucose metabolism at baseline and cerebral blood flow (CBF) during the execution of mental calculation tasks (serial number subtraction) in 10 early-stage AD patients and six healthy subjects. The present study employed positron emission tomography with (18)F-fluorodeoxyglucose and H(2)(15)O. Group comparison using the region-of-interest (ROI) method and voxel-based statistical parametric mapping (SPM99) showed significant reduction in glucose metabolism in the PCC of the AD group. The PCC metabolism in the AD group was negatively correlated with scores on the Mini-Mental State Examination and with correct responses to the arithmetic task. During the arithmetic task, regional CBF increased significantly in the left parietal and bilateral prefrontal cortices in the normal group, whereas the bilateral premotor cortices were significantly activated in the AD group. Regression analysis showed a significant inverse correlation between the premotor activation and the baseline PCC metabolism in the AD group. These results suggest that the premotor cortex plays a compensatory role in executing mental calculations in AD patients with reduced posteromedial functions, which might reflect the dynamic aspect of the pathophysiology of early AD.     

Coupled Imaging with [<Superscript>18</Superscript>F]FBB and [<Superscript>18</Superscript>F]FDG in AD Subjects Show a Selective Association Between Amyloid Burden and Cortical Dysfunction in the Brain

Purpose

The present study was aimed to investigate the relationships between dysfunction of cortical glucose metabolism as detectable by means of 2-deoxy-2-[¹⁸F]fluoro -D-glucose ([¹⁸F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) and amyloid burden as detectable by means of 4-{(E)-2-[4-(2-{2-[2-[¹⁸F]fluoroethoxy]ethoxy}ethoxy)phenyl]vinyl}-N-methylaniline (florbetaben; [¹⁸F]FBB) in a group of patients affected by Alzheimer’s disease (AD).

Procedures

We examined 38 patients newly diagnosed with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a PET/CT scan using both [¹⁸F]FDG and [¹⁸F]FBB with an average interval of 1 month. We used statistical parametric mapping (SPM8) implemented in Matlab R2012b and WFU pickatlas for the definition of a region of interest (ROI) mask including the whole cortex. These data were then normalized on the counts of the cerebellum and then used for a regression analysis on [¹⁸F]FDG scans in SPM. Furthermore, 58 control subjects were used as control group for [¹⁸F]FDG PET/CT scans.

Results

SPM analysis in AD patients showed a significant negative correlation between [¹⁸F] FBB and [¹⁸F] FDG uptake in temporal and parietal lobes bilaterally. Of note, these areas in AD patients displayed a marked glucose hypometabolism compared to control group.

Conclusions

Combined imaging with [¹⁸F]FBB and [¹⁸FFDG shows that amyloid burden in the brain is related to cortical dysfunction of temporal and parietal lobes in AD.

     

功能连接密度图观察内侧颞叶癫痫

目的 采用静息态fMRI功能连接密度（FCD）方法观察内侧颞叶癫痫（mTLE）脑功能活动改变的分布模式。方法 分别采集47例mTLE患者与32名正常志愿者（正常对照组）的静息态fMRI数据,通过两样本t检验,观察mTLE患者相对正常对照组的FCD活动改变,并采用基于体素的相关分析观察mTLE患者FCD改变脑区与癫痫病程的关系。结果 与正常对照组相比,mTLE患者发作间期FCD降低区域以双侧内侧颞叶、后扣带回、外侧颞叶和顶叶区为主;FCD增高区域主要分布于双侧感觉运动区（P<0.05,FWR多重校正）。基于体素的相关性分析显示,mTLE病程与双侧内侧颞叶、后扣带回及顶叶区的FCD值呈负相关（P<0.05,FDR多重校正）。结论 mTLE表现为默认网络及感觉运动区的功能连接异常;这些区域功能异常可能与mTLE的病理生理机制有关。     

Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.     

早期相11C-PIB PET显像探讨阿尔茨海默病患者脑功能网络改变

目的 探讨阿尔茨海默病（AD）和轻度认知功能障碍（MCI）患者¹¹C-匹兹堡化合物（¹¹C-pPIB）脑灌注网络改变。方法 对14例AD（AD组）、12例MCI（MCI组）和14名认知功能正常志愿者（对照组）行¹⁸F-FDG及¹¹C-PIB双示踪剂PET显像,采用平行独立成分分析法（pICA）计算¹¹C-pPIB和¹⁸F-FDG数据中高度相关的脑网络,以双样本t检验比较AD组与对照组间和MCI组与对照组间¹⁸F-FDG低代谢与¹¹C-pPIB低灌注的差异,获得组间有差异的脑区。结果 ¹¹C-pPIB获得的脑灌注网络与¹⁸F-FDG代谢网络高度相关（r=0.92）,并与默认网络（DMN）存在空间重叠。与对照组比较,AD组¹⁸F-FDG低代谢区与¹¹C-pPIB低灌注区存在空间重叠,包括颞上回、边缘叶/海马旁回、顶上小叶、后扣带回和前扣带回;MCI组¹⁸F-FDG的低代谢脑区位于右侧直回/眶额回、左侧后扣带回、右侧颞下回和右侧顶下小叶/颞上回,¹¹C-pPIB低灌注脑区为右侧顶下小叶。结论 AD患者¹¹C-pPIB低灌注脑区与¹⁸F-FDG低代谢高度相关,并与DMN存在空间重叠。¹¹C-pPIB显像可为诊断AD提供与¹⁸F-FDG显像互补的信息。     

Comparison of impaired subcortico-frontal metabolic networks in normal aging, subcortico-frontal dementia, and cortical frontal dementia.

Normal aging, progressive supranuclear palsy (PSP), and frontotemporal dementia (FTD) are characterized by different degrees of decline in frontal lobe functions. We used (18)FDG-PET and statistical parametric mapping (SPM96) to compare relative subcorticofrontal metabolic impairment at rest in 21 healthy elderly subjects (HES), 20 PSP patients, and 6 FTD patients. When HES were compared to 22 healthy young subjects, widespread decrease in metabolism was observed in bilateral medial prefrontal areas including anterior cingulate cortices, in dorsolateral prefrontal areas, in left lateral premotor area, in Broca's area, and in left insula. In PSP compared to the 43 healthy subjects (HS), we observed subcorticofrontal metabolic impairment including both motor and cognitive neural networks. Impairment of functional connections between midbrain tegmentum and cerebellar, temporal and pallidal regions was demonstrated in PSP as compared to HS. When comparing FTD to HS, glucose uptake was primarily reduced in dorsolateral and ventrolateral prefrontal cortices and in frontopolar and anterior cingulate regions. There was also bilateral anterior temporal, right inferior parietal, and bilateral striatal hypometabolism. Finally, FTD showed more severe striatofrontal metabolic impairment than PSP, while mesencephalothalamic involvement was only observed in PSP. Our data suggest that subcorticofrontal metabolic impairment is distributed in distinct subcorticocortical networks in normal aging, PSP, and FTD. Subcorticofrontal dementia in PSP is related to hypometabolism in discrete frontal areas, which are probably disconnected from certain subcortical structures. The concept of subcortical dementia is reinforced by our data, which show disrupted functional connections between mesencephalon and cerebellar cortex, inferior and medial temporal regions, and pallidum.     

轻度阿尔茨海默病脑血流灌注和脑灰质体积的改变

目的:探究轻度阿尔茨海默病(Alzheimer’s disease,AD)患者的脑血流(Cerebral blood flow,CBF)灌注和脑灰质体积的变化特点。方法:临床招募轻度AD患者和健康对照老年人进行包含3D-T1WI和3D伪连续动脉自旋标记(Three-dimensional pseudo-continuous arterial spin labeling,3D-pcASL)序列的磁共振扫描,运用统计参数图(Statistical parametric mapping,SPM)8软件对两组受试者全脑CBF图进行基于体素的全脑灌注差异的分析;采用基于体素的形态学测量方法(Voxel-based morphometry,VBM)比较两组受试者全脑灰质体积的差异;对灌注有差异的脑区的CBF与简易智力状态检查量表(Mini-mental state examination,MMSE)评分进行相关性分析。结果:共纳入轻度AD患者26例(年龄(73.0±6.8)岁,男16例),年龄、性别相匹配的健康对照者53例(年龄(73.7±8.2)岁,男23例)。与对照组相比,轻度AD组患者CBF灌注减低区主要位于双侧顶叶(以楔前叶、角回为主)、枕叶以及左侧颞叶和额叶;CBF灌注增高区主要位于右海马和海马旁回、右扣带回、基底节核团以及双侧额叶(以眶面和内侧面为主)(P<0.01,FDR校正,团块阈值>100像素)。轻度AD患者的脑灰质萎缩主要位于双侧颞叶内侧结构(海马、海马旁回、杏仁核),也累及双侧岛叶和基底节核团(P<0.01,FDR校正,团块阈值>100像素)。轻度AD组患者左颞顶叶脑回、双侧额上回的CBF值与MMSE评分呈现正相关;双侧内侧和旁扣带回、右前扣带回的CBF值与MMSE评分呈现负相关(P<0.05)。结论:轻度AD患者存在以顶叶为主的低灌注和以海马、基底节区、额叶为主的高灌注改变,而其灰质萎缩主要集中在双侧颞叶内侧结构。     

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve--an fMRI study in healthy women

AIMS: Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS: After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS: A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION: Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.