Comparison of 18F-FDG PET and arterial spin labeling MRI in evaluating Alzheimer's disease and amnestic mild cognitive impairment using integrated PET/MR.

BACKGROUND: Developing biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR. RESULTS: Analyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR. CONCLUSION: ASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI.

Multiparametric hippocampal signatures for early diagnosis of Alzheimer's disease using 18F-FDG PET/MRI Radiomics.

PURPOSE: This study aimed to explore the utility of hippocampal radiomics using multiparametric simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) for early diagnosis of Alzheimer's disease (AD). METHODS: A total of 53 healthy control (HC) participants, 55 patients with amnestic mild cognitive impairment (aMCI), and 51 patients with AD were included in this study. All participants accepted simultaneous PET/MRI scans, including 18F-fluorodeoxyglucose (18F-FDG) PET, 3D arterial spin labeling (ASL), and high-resolution T1-weighted imaging (3D T1WI). Radiomics features were extracted from the hippocampus region on those three modal images. Logistic regression models were trained to classify AD and HC, AD and aMCI, aMCI and HC respectively. The diagnostic performance and radiomics score (Rad-Score) of logistic regression models were evaluated from 5-fold cross-validation. RESULTS: The hippocampal radiomics features demonstrated favorable diagnostic performance, with the multimodal classifier outperforming the single-modal classifier in the binary classification of HC, aMCI, and AD. Using the multimodal classifier, we achieved an area under the receiver operating characteristic curve (AUC) of 0.98 and accuracy of 96.7% for classifying AD from HC, and an AUC of 0.86 and accuracy of 80.6% for classifying aMCI from HC. The value of Rad-Score differed significantly between the AD and HC (p < 0.001), aMCI and HC (p < 0.001) groups. Decision curve analysis showed superior clinical benefits of multimodal classifiers compared to neuropsychological tests. CONCLUSION: Multiparametric hippocampal radiomics using PET/MRI aids in the identification of early AD, and may provide a potential biomarker for clinical applications.

Effect of APOE ε4 genotype on amyloid-ß, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The presence of apolipoprotein E ε4 (APOE ε4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE ε4 on amyloid-ß (Aß) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI). METHODS: We included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1-weighted magnetic resonance imaging, 18 F-florbetapir positron emission tomography (PET), and 18 F-fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24-month scans were included for follow-up study. RESULTS: Voxelwise analysis revealed that APOE ε4 carriers exhibited greater baseline Aß deposition than APOE ε4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE ε4 noncarriers and APOE ε4 carriers in terms of 18 F-FDG PET standardized uptake value ratio and GM volume. Region of interest-based analysis showed statistically significant greater Aß deposition in APOE ε4 carriers than APOE ε4 noncarriers only in aMCI patients. Furthermore, APOE ε4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in Aß deposition than APOE ε4 noncarriers in both diagnostic groups. CONCLUSIONS: Our findings suggest a differential effect of APOE ε4 on Aß pathology, glucose metabolism, and GM volume. Studying APOE ε4-related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage.

Multimodal Classification of Alzheimer's Disease and Amnestic Mild Cognitive Impairment: Integrated 18F-FDG PET and DTI Study.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and memory impairment. Amnestic mild cognitive impairment (aMCI) is the intermediate stage between normal cognitive aging and early dementia caused by AD. It can be challenging to differentiate aMCI patients from healthy controls (HC) and mild AD patients. OBJECTIVE: To validate whether the combination of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and diffusion tensor imaging (DTI) will improve classification performance compared with that based on a single modality. METHODS: A total of thirty patients with AD, sixty patients with aMCI, and fifty healthy controls were included. AD was diagnosed according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable. aMCI diagnosis was based on Petersen's criteria. The 18F-FDG PET and DTI measures were each used separately or in combination to evaluate sensitivity, specificity, and accuracy for differentiating HC, aMCI, and AD using receiver operating characteristic analysis together with binary logistic regression. The rate of accuracy was based on the area under the curve (AUC). RESULTS: For classifying AD from HC, we achieve an AUC of 0.96 when combining two modalities of biomarkers and 0.93 when using 18F-FDG PET individually. For classifying aMCI from HC, we achieve an AUC of 0.79 and 0.76 using the best individual modality of biomarkers. CONCLUSION: Our results show that the combination of two modalities improves classification performance, compared with that using any individual modality.

Longitudinal Changes of Sensorimotor Resting-State Functional Connectivity Differentiate between Patients with Thalamic Infarction and Pontine Infarction.

Purpose. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine infarction. Methods. Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. Results. At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. Conclusions. The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.

Signal intensity ratio of draining vein on silent MR angiography as an indicator of high-flow arteriovenous shunt in brain arteriovenous malformation.

OBJECTIVES: To evaluate whether the signal intensity ratio (rSI) of the draining vein on silent MR angiography is correlated with arteriovenous (A-V) transit time on digital subtraction angiography (DSA), thereby identifying high-flow A-V shunt in brain arteriovenous malformation (BAVM), and to analyze whether the rSI and the characteristic of draining veins on silent MRA are associated with hemorrhage presentation. METHODS: Eighty-one draining veins of 46 participants with BAVM (mean age 33.2 ± 16.9 years) who underwent silent MRA and DSA were evaluated retrospectively. The correlation between the rSI of the draining vein on silent MRA and A-V transit time on DSA was examined. The AUC-ROC was obtained to evaluate the performance of the rSI in determining the presence of high-flow A-V shunt. The characteristics of draining veins with the maximum rSI (rSImax) were further compared between the hemorrhagic and non-hemorrhagic untreated BAVM. RESULTS: The rSI of each draining vein on silent MRA was significantly correlated with A-V transit time from DSA (r = -0.81, p < .001). The AUC-ROC was 0.89 for using the rSI to determine the presence of high-flow A-V shunt. A cut-off rSI value of 1.09 yielded a sensitivity of 82.4% and a specificity of 82.8%. The draining vein with rSImax and no ectasia was significantly more observed in the hemorrhagic group (p = 0.045). CONCLUSIONS: The rSI of the draining vein on silent MRA is significantly correlated with A-V transit time on DSA, and it can be used as an indicator of high-flow A-V shunt in BAVM. KEY POINTS: • The signal intensity ratio (rSI) of the draining vein on silent MRA significantly correlated with arteriovenous (A-V) transit time of brain arteriovenous malformation (BAVM) on digital subtraction angiography (DSA). • The area under the receiver operating characteristic curve (AUC) was 0.89 for using the rSI of draining veins to determine high-flow A-V shunt. • Draining veins with maximum rSI and no ectasia were significantly more observed in the hemorrhagic group of BAVM (p = 0.045).

Concomitant KIAA1549-BRAF fusion and IDH mutation in Pediatric spinal cord astrocytoma: a case report and literature review.

Primary tumors of the spinal cord are rare, accounting for 3-6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed to difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicating a tentative diagnosis of astrocytoma. The patient underwent resection of the lesion in the spinal canal from the cervical 6 level to the thoracic 2 level. Histopathology confirmed diagnosis of astrocytoma, WHO grade 2. Genetic analysis showed both IDH1 R132H mutation and KIAA1549-BRAF fusion. Therefore, our integrated diagnosis was astrocytoma, IDH mutation, WHO grade 2. Its molecular analyses include IDH1 R132H mutation and KIAA1549-BRAF fusion. After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.

Pilot Study of Voxel-Based Morphometric MRI Post-processing in Patients With Non-lesional Operculoinsular Epilepsy.

Objective: The aim of this study was to use voxel-based MRI post-processing in detection of subtle FCD in drug-resistant operculoinsular epilepsy patients with negative presurgical MRI, and by combining magnetoencephalography (MEG) to improve the localization of epileptogenic zone. Methods: Operculoinsular epilepsy patients with a negative presurgical MRI were included in this study. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. Clinical information including semiology, MEG, scalp electroencephalogram (EEG), intracranial EEG and surgical strategy was retrospectively reviewed. The pertinence of MAP-positive areas was confirmed by surgical outcome and pathology. Results: A total of 20 patients were diagnosed with operculoinsular epilepsy had non-lesional MRI during 2010-2018, of which 11 patients with resective surgeries were included. MEG showed clusters of single equivalent current dipole (SECD) in inferior frontal regions in five patients and temporal-insular/ frontal-temporal-insular/parietal-insular regions in five patients. Four out of 11 patients had positive MAP results. The MAP positive rate was 36.4%. The positive regions were in insular in one patient and operculoinsular regions in three patients. Three of the four patients who were MAP-positive got seizure-free after successfully resect the MAP-positive and MEG-positive regions (the pathology results were FCD IIb in two patients and FCD IIa in one patient). Conclusions: MAP is a useful tool in detection the epileptogenic lesions in patients with MRI-negative operculoinsular epilepsy. Notably, in order to make a right surgical regime decision, MAP results should always be interpreted in the context of the patient's anatomo-electroclinical presentation.

Multiparametric imaging hippocampal neurodegeneration and functional connectivity with simultaneous PET/MRI in Alzheimer's disease.

PURPOSE: The objective of this study is to investigate the hippocampal neurodegeneration and its associated aberrant functions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients using simultaneous PET/MRI. METHODS: Forty-two cognitively normal controls (NC), 38 MCI, and 22 AD patients were enrolled in this study. All subjects underwent 18F-FDG PET/functional MRI (fMRI) and high-resolution T1-weighted MRI scans on a hybrid GE Signa PET/MRI scanner. Neurodegeneration in hippocampus and its subregions was quantified by regional gray matter volume and 18F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on 18F-FDG PET images. Regional gray matter volume was estimated from voxel-based morphometric analysis with MRI. fMRI data were analyzed after slice time correction and head motion correction using statistical parametric mapping (SPM12) with DPARSF toolbox. The regions of interest including hippocampus, cornu ammonis (CA1), CA2/3/dentate gyrus (DG), and subiculum were defined in the standard MNI space. RESULTS: Patient groups had reduced SUVR, gray matter volume, and functional connectivity compared to NC in CA1, CA2/3/DG, and subiculum (AD < MCI < NC). There was a linear correlation between the left CA2/3DG gray matter volume and 18F-FDG SUVR in AD patients (P < 0.001, r = 0.737). Significant correlation was also found between left CA2/3/DG-superior medial frontal gyrus functional connectivity and left CA2/3/DG hypometabolism in patients with AD. The functional connectivity of right CA1-precuneus in patients with MCI and right subiculum-superior frontal gyrus in patients with AD was positively correlated with mini mental status examination scores (P < 0.05). CONCLUSION: Our findings demonstrate that the associations existed at subregional hippocampal level between the functional connectivity measured by fMRI and neurodegeneration measured by structural MRI and 18F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD.

Homotopic Connectivity in Early Pontine Infarction Predicts Late Motor Recovery.

Connectivity-based methods are essential to explore brain reorganization after a stroke and to provide meaningful predictors for late motor recovery. We aim to investigate the homotopic connectivity alterations during a 180-day follow-up of patients with pontine infarction to find an early biomarker for late motor recovery prediction. In our study, resting-state functional MRI was performed in 15 patients (11 males, 4 females, age: 57.87 ± 6.50) with unilateral pontine infarction and impaired motor function during a period of 6 months (7, 14, 30, 90, and 180 days after stroke onset). Clinical neurological assessments were performed using the Fugl-Meyer scale (FM).15 matched healthy volunteers were also recruited. Whole-brain functional homotopy in each individual scan was measured by voxel-mirrored homotopic connectivity (VMHC) values. Group-level analysis was performed between stroke patients and normal controls. A Pearson correlation was performed to evaluate correlations between early VMHC and the subsequent 4 visits for behavioral measures during day 14 to day 180. We found in early stroke (within 7 days after onset), decreased VMHC was detected in the bilateral precentral and postcentral gyrus and precuneus/posterior cingulate cortex (PCC), while increased VMHC was found in the hippocampus/amygdala and frontal pole (P < 0.01). During follow-up, VMHC in the precentral and postcentral gyrus increased to the normal level from day 90, while VMHC in the precuneus/PCC presented decreased intensity during all time points (P < 0.05). The hippocampus/amygdala and frontal pole presented a higher level of VMHC during all time points (P < 0.05). Negative correlation was found between early VMHC in the hippocampus/amygdala with FM on day 14 (r = -0.59, p = 0.021), day 30 (r = -0.643, p = 0.01), day 90 (r = -0.693, p = 0.004), and day 180 (r = -0.668, p = 0.007). Furthermore, early VMHC in the frontal pole was negatively correlated with FM scores on day 30 (r = -0.662, p = 0.013), day 90 (r = -0.606, p = 0.017), and day 180 (r = -0.552, p = 0.033). Our study demonstrated the potential utility of early homotopic connectivity for prediction of late motor recovery in pontine infarction.

Neuronal Specificity of Acupuncture in Alzheimer's Disease and Mild Cognitive Impairment Patients: A Functional MRI Study.

Although acupuncture is considered to be effective and safe for Alzheimer's disease (AD) and mild cognitive impairment (MCI), the mechanism underlying its therapeutic effect is still unknown. Most studies clarifying the neuronal pathway produced by acupuncture were still applied to healthy subjects with limited single acupuncture point stimulation, which was inconsistency with clinical practice. Thus, in our present study, we investigate the differences between brain activity changes in AD and MCI patients caused by multi-acupuncture point Siguan (four gates), in order to provide visualized evidence for neuronal specificity of clinical acupuncture. Forty-nine subjects were recruited, including 21 AD patients, 14 MCI patients, and 14 healthy controls (HC). AD and MCI patients were randomly divided into two groups, respectively: real acupuncture point group (14 AD and 8 MCI) and sham acupuncture point group (7 AD and 6 MCI). We adopted a 16-minute, single-block, experimental design for acquiring functional MRI images. We found, in AD and MCI patients, Siguan (four gates) elicited extensive activations and deactivations in cognitive-related areas, visual-related areas, the sensorimotor-related area, basal ganglia, and cerebellum. Compared with HC, AD and MCI patients showed similar activations in cognitive-related brain areas (inferior frontal gyrus, supramarginal gyrus, and rolandic operculum) as well as deactivations in cognitive-related areas, visual-related areas, basal ganglia, and cerebellum, which were not found in HC. Compared with sham acupuncture points, real acupuncture points produced more specific brain changes with both activated and deactivated brain activities in AD and MCI. The preliminary results in our study verified the objective evidence for neuronal specificity of acupuncture in AD and MCI patients.

Correlation of Longitudinal Gray Matter Volume Changes and Motor Recovery in Patients After Pontine Infarction.

The mechanisms of motor functional recovery after pontine infarction (PI) remain unclear. Here, we assessed longitudinal changes in gray matter volume (GMV) and examined the relationship between GMV and clinical outcome. Fifteen patients with unilateral PI underwent magnetic resonance imaging and neurological exams five times during a period of 6 months. Another 15 healthy participants were enrolled as the normal control (NC) group and were examined with the same protocol. The MR exam included routine protocol and a 3D T1-weighted magnetization-prepared rapid acquisition gradient echo scan. Changes in GMV were assessed using voxel-based morphometry. Furthermore, the correlations between GMV changes in regions of interest and clinical scores were assessed. Compared with NCs, the decreased GMVs in the contralateral uvula of cerebellum and the ipsilateral tuber of cerebellum were detected at third month after stroke onset. At the sixth month after stroke onset, the decreased GMVs were detected in the contralateral culmen of cerebellum, putamen, as well as in the ipsilateral tuber/tonsil of cerebellum. Compared with NC, the PI group exhibited significant increases in GMV at each follow-up time point relative to stroke onset. Specifically, the significant GMV increase was found in the ipsilateral middle frontal gyrus and ventral anterior nucleus of thalamus at second week after stroke onset. At first month after stroke onset, the increased GMVs in the ipsilateral middle temporal gyrus were detected. The significant GMV increase in the ipsilateral mediodorsal thalamus was noted at third month after stroke onset. At the end of sixth month after stroke onset, the GMV increase was found in the ipsilateral mediodorsal thalamus, superior frontal gyrus, and the contralateral precuneus. Across five times during a period of 6-month, a negative correlation was observed between mean GMV in the contralateral uvula, culmen, putamen, and ipsilateral tuber/tonsil and mean Fugl-Meyer (FM) score. However, mean GMV in the ipsilateral mediodorsal thalamus was positively correlated with mean FM score. Our findings suggest that structural reorganization of the ipsilateral mediodorsal thalamus might contribute to motor functional recovery after PI.

Local-to-remote cortical connectivity in amnestic mild cognitive impairment.

Alterations in both local and remote connectivity were reported in amnestic mild cognitive impairment (aMCI) patients but rarely in the same group of patients. In the present study, we employed a novel resting-state functional magnetic resonance imaging (rfMRI) connectome index, regional functional homogeneity on the 2-dimensional cortical surface, to detect full-cortex vertex-wise changes of the local rfMRI connectivity in 32 aMCI patients compared with 40 healthy controls. We further used the seed-based functional connectivity to explore the remote rfMRI connectivity in aMCI. The results revealed significantly lower local connectivity in the default network and higher local connectivity in the somatomotor network in aMCI patients. Abnormal remote connectivity relevant to local connectivity was primarily detectable within the default network (decrease) and in the somatomotor and attention networks (increase). The abnormalities in the remote (not local) default network connectivity were significantly associated with episodic memory performance in patients. These distance-related connectivity profiles illustrated a dysfunctional pattern in aMCI, which extended our knowledge of this pathological aging process.

White Matter Abnormalities in Two Different Subtypes of Amnestic Mild Cognitive Impairment.

White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study. Neuropsychological measures and diffusion tensor imaging (DTI) data were acquired from each subject and tract-based spatial statistics (TBSS) was implemented. It was found that both aMCI groups showed significantly reduced fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) than NC. It was also identified that, as compared to aMCI-m, aMCI-s showed significantly decreased FA in the left SLF, left uncinate fasciculus (UF) and left inferior longitudinal fasciculus (ILF), while significantly increased FA in the left anterior thalamic radiation (ATR). The correlation analysis showed that FA values in the regions with group difference were significantly correlated with cognitive functions as measured by Boston naming test and trail making test. These results suggested that the variations of aMCI may be differentiated by FA indexes and DTI may help to understand why specific signs and symptoms occur in patients.

Wnt/ß-Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy.

Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR. Kidney biopsies of DN patients and health individuals were stained by immunofluorescence (IF) method. The morphological and functional changes of podocytes were tested by F-actin staining and cell migration assay. Results demonstrated that HG induced upregulation of UCH-L1 and activation of the Wnt/ß-catenin signaling pathway in podocytes. However, blocking of the Wnt pathway by dickkopf related protein 1 (DKK1) eliminated the above changes. Furthermore, IF staining confirmed that, compared with healthy individuals, the expression of UCH-L1 and ß-catenin were obviously increased in kidney biopsy of DN patients. Overexpression of UCH-L1 remodeled its actin cytoskeleton, increased its cell migration and impacted its important proteins. All the findings manifested that Wnt/ß-catenin/UCH-L1 may be a new potential therapy method in the treatment of DN in future.

Pontine infarction: diffusion-tensor imaging of motor pathways-a longitudinal study.

PURPOSE: To investigate the dynamic evolution of diffusion indexes in the corticospinal tract (CST) distal to a pontine infarct by using diffusion-tensor imaging, to determine the relationship of these indexes with clinical prognosis, and to explore the structural changes in the motor pathway during recovery. MATERIALS AND METHODS: This study was approved by the institutional ethics committee, and written informed consent was obtained from each participant. Seventeen patients with pontine infarct underwent five diffusion-tensor imaging examinations during a period of 6 months (within 7 days of onset, 14, 30, 90, and 180 after onset). Fractional anisotropic values were measured in the medulla, cerebral peduncle, internal capsule, and centrum semiovale. Fractional anisotropic values of the CST in the ipsilateral side of the infarct were compared with those in the contralateral sides and those in control subjects by using the Student t test and one-way analysis of variance, and their relationships with clinical scores were analyzed by using Pearson correlation analysis. Reconstructions of the CST were performed. Structural changes of the damaged CST were followed up. RESULTS: Fractional anisotropic ratios in the CST above the pons decreased significantly compared with those in the contralateral side and those in control subjects within 7 days, on day 14, and on day 30 after onset (P < .001). Fractional anisotropic ratios above the pons on day 14 correlated positively with Fugl-Meyer scores on day 90 (r = 0.771, P < .001) and day 180 (r = 0.730, P = .001). Follow-up diffusion-tensor tractographic images showed regeneration and reorganization of the motor pathways. CONCLUSION: Secondary degeneration of the CST can be detected at diffusion-tensor imaging in the early stages after pontine infarction, which could help predict the motor outcomes. Diffusion-tensor tractography can allow detection of regeneration and reorganization of the motor pathways during recovery.

Changes of gray matter volume and amplitude of low-frequency oscillations in amnestic MCI: An integrative multi-modal MRI study.

BACKGROUND: Numerous studies have reported that the amnestic-type mild cognitive impairment (aMCI) patients have impaired brain structural integrity and functional alterations separately. PURPOSE: To investigate the changes of gray matter and amplitude of low-frequency oscillations in patients with aMCI by combining structural and functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: Thirty-four patients with aMCI and 34 controls were recruited. We adopted optimized voxel-based morphometry to detect regions with gray matter volume (GMV) loss induced by aMCI. Then regional differences in amplitude of slow-4 band (0.027-0.073 Hz) oscillations among these regions between patients and healthy controls were examined. Both slow-4 amplitude of low-frequency fluctuations (ALFF) and slow-4 fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) were employed. RESULTS: Patients with aMCI demonstrated significant GMV loss in the ventral medial prefrontal cortex (vMPFC), posterior cingulate cortex (PCC), bilateral hippocampus, right superior parietal gyrus, left insula and left middle temporal gyrus (P < 0.01). The patients exhibited significant decreases of slow-4 ALFF in the left hippocampus (P = 0.05) and PCC (P = 0.02), while the decreased slow-4 fALFF was detected in PCC (P = 0.01) and increased slow-4 fALFF in vMPFC (P = 0.03). In PCC, aMCI and controls exhibited significant different GMV-fALFF correlation (P < 0.05), with opposite correlation trend. CONCLUSION: The correlates between anatomical deficits and functional alterations in aMCI suggest that anatomical and functional deficits are linked to each other. The differences of GMV-fALFF correlations demonstrated altered anatomical-functional relationship in aMCI.

An FMRI study of neuronal specificity in acupuncture: the multiacupoint siguan and its sham point.

Clarifying the intrinsic mechanisms of acupuncture's clinical effects has recently been gaining popularity. Here, we choose the Siguan acupoint (a combination of bilateral LI4 and Liv3) and its sham point to evaluate multiacupoint specificity. Thirty-one healthy volunteers were randomly divided into real acupoint (21 subjects) and sham acupoint (10 subjects) groups. Our study used a single block experimental design to avoid the influence of posteffects. Functional magnetic resonance imaging data were acquired during acupuncture stimulation. Results showed extensive increase in neuronal activities with Siguan acupuncture and significant differences between stimulation at real and sham points. Brain regions that were activated more by real acupuncture stimulation than by sham point acupuncture included somatosensory cortex (the superior parietal lobule and postcentral gyrus), limbic-paralimbic system (the calcarine gyrus, precuneus, cingulate cortex, and parahippocampal gyrus), visual-related cortex (the fusiform and occipital gyri), basal ganglia, and the cerebellum. In this way, our study suggests Siguan may elicit specific activities in human brain.

Selective changes of resting-state brain oscillations in aMCI: an fMRI study using ALFF.

Mild cognitive impairment (MCI) refers to a transitional state between normal aging and dementia and is a syndrome with cognitive decline greater than expected for an individual's age and educational level. As a subtype of MCI, amnestic mild cognitive impairment (aMCI) most often leads to Alzheimer's disease. This study aims to elucidate the altered brain activation in patients with aMCI using resting-state functional magnetic resonance. We observed Frequency-dependent changes in the amplitude of low-frequency fluctuations in aMCI patients (n = 20), and normal subjects (n = 18). At the same time, we took gray matter volume as a covariate. We found that aMCI patients had decreased amplitude of low-frequency fluctuation signal in left superior temporal gyrus, right middle temporal gyrus, right inferior parietal lobe, and right postcentral gyrus compared to the control group. Specially, aMCI patients showed increased signal in left superior and middle frontal gyrus. Our results suggested that increased activation in frontal lobe of aMCI patients may indicate effective recruitment of compensatory brain resources. This finding and interpretation may lead to the better understanding of cognitive changes of aMCI.

Acupuncture modulates resting state hippocampal functional connectivity in Alzheimer disease.

Our objective is to clarify the effects of acupuncture on hippocampal connectivity in patients with Alzheimer disease (AD) using functional magnetic resonance imaging (fMRI). Twenty-eight right-handed subjects (14 AD patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all subjects. MRI was performed using a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired baseline resting state data during the initial 3 minutes and then performed acupuncture stimulation on the Tai chong and He gu acupoints for 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using statistical parametric mapping (SPM5) software. Two-sample t-tests were performed using data from the two groups in different states. We found that during the resting state, several frontal and temporal regions showed decreased hippocampal connectivity in AD patients relative to control subjects. During the resting state following acupuncture, AD patients showed increased connectivity in most of these hippocampus related regions compared to the first resting state. In conclusion, we investigated the effect of acupuncture on AD patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong and He gu can enhance the hippocampal connectivity in AD patients.