Inhibition of Notch1 Signaling at the Subacute Stage of Stroke Promotes Endogenous Neurogenesis and Motor Recovery After Stroke.

Background and Purpose: It is still not clear whether Notch1 signaling inhibition can promote functional outcomes after stroke, given that it plays time-dependent roles in the sequential process of endogenous neurogenesis. The purpose of this study was to identify the appropriate time frame for Notch1 signaling inhibition according to the temporal evolution of Notch1 signaling activation and the responses of neural stem cells (NSCs), in order to target it for therapeutic intervention and stimulate neurorestorative strategies after stroke. Methods: Sprague-Dawley (SD) rats were subjected to 90-min of middle cerebral artery occlusion (MCAO). Rats were sacrificed before, and at day 1, day 2, day 3, day 4, and day 7 after ischemia for immunohistochemical analysis of the Notch intracellular domain (NICD), Nestin and doublecortin (Dcx). Next, MCAO rats were treated with the γ-secretase inhibitor N-[N-(3,5-di uorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT) or with saline at day 4 after ischemia, and subsequently evaluated with behavioral test analysis and magnetic resonance imaging (MRI). The rat brains were then harvested for immunohistochemical analysis of Dcx, NeuN and myelin basic protein (MBP) at 2, 3, 4, and 8 weeks. Results: Notch1 signaling was maximally activated at day 3 after ischemia in parallel with the temporal evolution of NSCs. Inhibiting Notch1 signaling at day 4 after reperfusion with DAPT further promoted recovery of MRI parameters of the corticospinal tract (CST) and the functional outcomes, concomitantly with an increase in neuroblasts, their migration to the ischemic boundary, and potential differentiation to mature neurons, as well as the amelioration of axonal bundle integrity. Conclusion: Inhibition of Notch1 signaling at the subacute stage of stroke could maximally promote endogenous neurogenesis and axonal reorganization.

Dynamic Evaluation of Notch Signaling-Mediated Angiogenesis in Ischemic Rats Using Magnetic Resonance Imaging.

OBJECTIVE: The Notch signaling pathway is involved in angiogenesis induced by brain ischemia and can be efficiently inhibited by the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). The aim of the present study was to noninvasively investigate the effect of DAPT treatment on angiogenesis in brain repair after stroke using magnetic resonance imaging (MRI). METHODS: Sprague-Dawley rats (n = 40) were subjected to 90 minutes of transient middle cerebral artery (MCA) occlusion and treated with PBS (n = 20) or DAPT (n = 20) at 72 hours after the onset of ischemia. MRI measurements including T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and cerebral blood flow (CBF) were performed at 24 hours after reperfusion and weekly up to 4 weeks using a 3-Tesla system. Histological measurements were obtained at each time point after MRI scans. RESULTS: SWI showed that DAPT treatment significantly enhanced angiogenesis in the ischemic boundary zone (IBZ) with respect to the control group, with local CBF in the angiogenic area elevated, along with increases in vascular density confirmed by histology. CONCLUSION: Treatment of ischemic stroke with DAPT significantly augments angiogenesis, which promotes poststroke brain remodeling by elevating CBF level, and these processes can be dynamically monitored and evaluated by MRI.

Small-worldness of brain networks after brachial plexus injury: A resting-state functional magnetic resonance imaging study.

Research on brain function after brachial plexus injury focuses on local cortical functional reorganization, and few studies have focused on brain networks after brachial plexus injury. Changes in brain networks may help understanding of brain plasticity at the global level. We hypothesized that topology of the global cerebral resting-state functional network changes after unilateral brachial plexus injury. Thus, in this cross-sectional study, we recruited eight male patients with unilateral brachial plexus injury (right handedness, mean age of 27.9 ± 5.4 years old) and eight male healthy controls (right handedness, mean age of 28.6 ± 3.2). After acquiring and preprocessing resting-state magnetic resonance imaging data, the cerebrum was divided into 90 regions and Pearson's correlation coefficient calculated between regions. These correlation matrices were then converted into a binary matrix with affixed sparsity values of 0.1-0.46. Under sparsity conditions, both groups satisfied this small-world property. The clustering coefficient was markedly lower, while average shortest path remarkably higher in patients compared with healthy controls. These findings confirm that cerebral functional networks in patients still show small-world characteristics, which are highly effective in information transmission in the brain, as well as normal controls. Alternatively, varied small-worldness suggests that capacity of information transmission and integration in different brain regions in brachial plexus injury patients is damaged.

Low-density point eating algorithm for surface reconstruction from dense scans.

We present a low-density point eating algorithm for surface reconstruction from dense scans. First, the density map for each scan is estimated and the boundary densities are down-weighted. Subsequently, the poorly scanned low-density overlapping points are eaten up based on a user-specified threshold. Finally, the overlapping areas are thinned by using the moving least-squares operator and the homogeneous points are weighted averaged. The new algorithm can extract smooth but detailed point set surfaces that are as close as possible to the ground truth. The good performance of the new algorithm is demonstrated by comparison with several advanced surface reconstruction algorithms.

Predictors of short-term outcome in patients with acute middle cerebral artery occlusion: unsuitability of fluid-attenuated inversion recovery vascular hyperintensity scores.

Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days (National Institutes of Health Stroke Scale) and 90 days (modified Rankin Scale) to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome.

Characterization of Free, Conjugated, and Bound Phenolic Acids in Seven Commonly Consumed Vegetables.

Phenolic acids are thought to be beneficial for human health and responsible for vegetables' health-promoting properties. Free, conjugated, and bound phenolic acids of seven commonly consumed vegetables, including kidney bean, cow pea, snow pea, hyacinth bean, green soy bean, soybean sprouts and daylily, from the regions of Beijing, Hangzhou, and Guangzhou, were identified and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Three vegetables, namely green soy bean, soybean sprouts, and daylily (Hemerocallisfulva L.), from the Beijing region contained higher concentrations of total phenolic acids than those from the Hangzhou and Guangzhou regions. The results indicated that the phenolic acid content in the seven vegetables appeared to be species-dependent. The highest content of phenolic acids was found in daylily, followed by green soy bean, while the least amounts were identified in kidney bean and hyacinth bean. Typically, phenolic acids are predominantly found in conjugated forms. Principle component analysis (PCA) revealed some key compounds that differentiated the seven vegetables. Green soy bean, compared to the other six vegetables, was characterized by higher levels of syringic acid, ferulic acid, vanillic acid, and sinapic acid. Other compounds, particularly p-coumaric acid, neochlorogenic acid, and caffeic acid, exhibited significantly higher concentrations in daylily. In addition, p-coumaric acid was the characteristic substance in cow pea. Results from this study can contribute to the development of vegetables with specific phytochemicals and health benefits.

MRI detects protective effects of DAPT treatment with modulation of microglia/macrophages at subacute and chronic stages following cerebral ischemia.

Notch homolog 1 (Notch 1) signaling is regarded as a potential therapeutic target for modulating the inflammatory response and exhibiting neuroprotective effects in cerebral injury following stroke. N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t­butylester (DAPT) efficiently inhibits activation of the Notch 1 signaling pathway in microglia and may protect brain tissue from ischemic damage. However, the temporal proliferation and morphological alterations of microglia/macrophages throughout progression of the disease, as well as the comprehensive alterations of the whole brain following DAPT treatment, remain to be elucidated. The present study evaluated the temporal proliferation and the morphological alterations of microglia/macrophages over the period of the subacute and chronic stages, in addition to dynamic alterations of brain tissue, using the magnetic resonance imaging (MRI) method, following DAPT treatment. Sprague­Dawley rats (n=40) were subjected to 90 min of middle cerebral artery occlusion and were treated with DAPT (n=20) or acted as controls with no treatment (n=20). The two groups of rats underwent MRI scans prior to the induction of stroke symptoms and at 24 h, 7, 14, 21 and 28 days following the stroke. A total of five rats from each group were sacrificed at 7, 14, 21 and 28 days following induction of stroke. Compared with control rats, the MRI data of the ipsilateral striatum in treated rats revealed ameliorated brain edema at the subacute stage and recovered brain tissue at the chronic stage. In addition to this, treatment attenuated the round­shape and promoted a ramified­shape of microglia/macrophages. The present study confirmed the protective effect of DAPT treatment by dynamically monitoring the cerebral alterations and indicated the possibility of DAPT treatment to alter microglial characteristics to induce a protective effect, via inhibition of the Notch signaling pathway.

Imaging the Transformation of Ipsilateral Internal Capsule Following Focal Cerebral Ischemia in Rat by Diffusion Kurtosis Imaging.

BACKGROUND: The purpose of our study is to explore the relationship between recovery of neural function and transformation of the internal capsule (IC) after transient middle cerebral artery occlusion (MCAO) by using diffusion kurtosis imaging (DKI). METHODS: Six male adult Sprague-Dawley rats implemented with transient MCAO were used in this study. Sensorimotor function was assessed according to repetitive behavioral testing on day 1, 3, 7, 14, and 28 after cerebral ischemia. Metrics of DKI were acquired, and the time course of the region-to-normal ratio was evaluated in IC. RESULTS: After cerebral ischemia, relative fractional anisotropy in IC decreased on day 3 (P < .01). Relative mean diffusivity (rMD) increased on day 28 (P < .05). Relative mean diffusional kurtosis (rMK) increased on day 3 (P < .01) and decreased on day 7 (P < .05). Relative axial diffusional kurtosis (rKa) increased on day 3 (P < .01) and declined on day 7 (P < .05). Relative radial diffusional kurtosis (rKr) was reduced on day 7 (P < .05). Changes in rMK were larger than changes in rMD on day 3 (P < .05). The factor of rKa and rKr revealed marked difference on day 7 (P < .05) and day 14 (P < .05). Neurological function score showed that rats exhibited functional recovery from day 7 (P < .01) post stroke. CONCLUSIONS: This longitudinal multiparametric magnetic resonance imaging study suggested that K metrics offers information complimentary to conventional diffusion metrics and revealed the procedure during the structural modification in the ipsilateral IC following focal cerebral ischemia. After transient MCAO, the neural transformation occurred in a time-dependent procedure.

Comparison of the Outcomes of Modified Artificial Chordae Technique for Mitral Regurgitation through Right Minithoracotomy or Median Sternotomy.

BACKGROUND: Right minithoracotomy (RM) has been proven to be a safe and effective approach for mitral valve surgery, but the differences of artificial chordae technique between RM and median sternotomy (MS) were seldom reported. Here, we compared the outcomes of modified artificial chordae technique for mitral regurgitation (MR) through RM or MS approaches. METHODS: One hundred and eighteen consecutive adult patients who received mitral valve repair with artificial chordae and annuloplasty for MR through RM (n = 58) or MS (n = 60) from January 2006 to January 2015 were analyzed. RESULTS: All of the selected patients underwent mitral valve repair successfully without any complication during the surgery. There was no significant difference between RM group and MS group in cardiopulmonary bypass time, aortic cross-clamp time, and early postoperative complications. However, compared with the MS group, the RM group had shorter hospital stay and faster surgical recovery. At a mean follow-up of 44.8 ± 25.0 months, the freedom from more than moderate MR was 93.9% ± 3.5% in RM group and 94.8% ± 2.9% in MS group at 3 years postoperatively. Log-rank test showed that there was no significant difference in the freedom from recurrent significant MR between the two groups (χ2 = 0.247, P = 0.619). Multivariate analysis revealed that the presence of mild MR at discharge was the independent risk factor for the recurrent significant MR. CONCLUSION: Right minithoracotomy can achieve the similar therapeutic effects with MS for the patients who received modified artificial chordae technique for treating MR.

Combining systemic and stereotactic MEMRI to detect the correlation between gliosis and neuronal connective pathway at the chronic stage after stroke.

BACKGROUND: The early dysfunction and subsequent recovery after stroke, characterized by the destruction and remodeling of connective pathways between cortex and subcortical regions, is associated with neuroinflammation. As major components of the inflammatory process, reactive astrocytes have double-edged effects on pathological progression. The temporal patterns of astrocyte and neuronal pathway activity can be revealed by systemic and stereotactic manganese-enhanced magnetic resonance imaging (MEMRI), respectively. In the present study, we aimed to detect an association between astrocyte activity and recovery of neuronal connective pathways by combining systemic with stereotactic MEMRI. METHODS: Fifty adult rats, divided into two groups, underwent a 60-min occlusion of the middle cerebral artery. The groups were given either a systemic administration or stereotactic injection of MnCl2 at 1, 3, 7, and 14 days after stroke and underwent MRI 4 and 2 days later, respectively. Immunofluorescence (IF) of group 1 was conducted to corroborate the results. Repetitive behavioral testing was also performed with all rats at 1, 3, 7, and 14 days to obtain a functional score. RESULTS: Ring- or crescent-shaped enhancements formed in the striatal peri-infarct regions (STR) at 11 and 18 days. This was concurrent with the activity of glial fibrillary acidic protein (GFAP)-positive astrocytes, which mainly localized at the peri-infarct region and significantly increased in number at 11 and 18 days after stroke. Microglia/macrophages, detected by IF, mainly localized in the lesion core, rather than in the region of enhancement. The ipsilateral substantia nigra (SN) revealed Mn-related signal enhancement reduction and subsequent signs of the recovery process at 3 to 5 days and 9 to 16 days, respectively. Behavioral testing showed that sensorimotor functions were initially disturbed, but subsequently recovered at 7 and 14 days. CONCLUSIONS: We found a positive temporal correlation between astrogliosis and the recovery of neuronal connective pathways at the chronic stage by using the in vivo method of MEMRI. Our results highlighted the potential contribution of astrocytes to the neuronal recovery of these connective pathways.

The Initial Exploration of Adamkiewicz Artery Computed Tomographic Angiography With Monochromatic Reconstruction of Gemstone Spectral Imaging.

OBJECTIVE: The study aimed to explore whether optimal monochromatic reconstruction can improve the depiction of the Adamkiewicz artery (AKA) on gemstone spectral computed tomographic angiography (GSCTA) compared with the polychromatic reconstruction protocol. METHODS: The prospective study was approved by the ethics committee, and written informed consent was obtained from each patient. The 58 consecutive patients suspected of aortic aneurysm or dissection underwent aortic GSCTA. All images were reconstructed with both polychromatic (group A) and optimal monochromatic (group B) protocol. The CT values of the descending aorta and muscle, background noise, and the contrast-to-noise ratio were measured and calculated. With the criterion standard display of AKA, characteristic hairpin curve sign, 2 blinded radiologists analyzed data independently with the paired samples t, χ, and Mann-Whitney U test. RESULTS: The CT value of the descending aorta and the contrast-to-noise ratio of group B were significantly superior to group A (t = 12.7, P < 0.01; t = 15.2, P < 0.01). The visual rate of AKA (94.8%) in group B was significantly higher (χ = 4.2, P = 0.04) than group A (82.8%). Using a 5-point scale to assess, the score of the visualization efficiency of group B (226) was significantly higher (Z = -2.4, P = 0.02) than group A (192). CONCLUSIONS: The optimal monochromatic reconstruction for GSCTA can improve the visualization efficiency and quality of the AKA compared with the polychromatic reconstruction protocol.

Cross-modality PET/CT and contrast-enhanced CT imaging for pancreatic cancer.

AIM: To explore the diagnostic value of the cross-modality fusion images provided by positron emission tomography/computed tomography (PET/CT) and contrast-enhanced CT (CECT) for pancreatic cancer (PC). METHODS: Data from 70 patients with pancreatic lesions who underwent CECT and PET/CT examinations at our hospital from August 2010 to October 2012 were analyzed. PET/CECT for the cross-modality image fusion was obtained using TureD software. The diagnostic efficiencies of PET/CT, CECT and PET/CECT were calculated and compared with each other using a χ(2) test. P < 0.05 was considered to indicate statistical significance. RESULTS: Of the total 70 patients, 50 had PC and 20 had benign lesions. The differences in the sensitivity, negative predictive value (NPV), and accuracy between CECT and PET/CECT in detecting PC were statistically significant (P < 0.05 for each). In 15 of the 31 patients with PC who underwent a surgical operation, peripancreatic vessel invasion was verified. The differences in the sensitivity, positive predictive value, NPV, and accuracy of CECT vs PET/CT and PET/CECT vs PET/CT in diagnosing peripancreatic vessel invasion were statistically significant (P < 0.05 for each). In 19 of the 31 patients with PC who underwent a surgical operation, regional lymph node metastasis was verified by postsurgical histology. There was no statistically significant difference among the three methods in detecting regional lymph node metastasis (P > 0.05 for each). In 17 of the 50 patients with PC confirmed by histology or clinical follow-up, distant metastasis was confirmed. The differences in the sensitivity and NPV between CECT and PET/CECT in detecting distant metastasis were statistically significant (P < 0.05 for each). CONCLUSION: Cross-modality image fusion of PET/CT and CECT is a convenient and effective method that can be used to diagnose and stage PC, compensating for the defects of PET/CT and CECT when they are conducted individually.

CT perfusion with acetazolamide challenge in C6 gliomas and angiogenesis.

BACKGROUND: This study was performed to investigate the correlation between CT perfusion with acetazolamide challenge and angiogenesis in C6 gliomas. METHODS: Thirty-two male Sprague-Dawley rats were evaluated. The rats were divided randomly to four groups: eight rats with orthotopically implanted C6 gliomas at 10-days old (Group A), eight rats with gliomas at 14-days old (Group B), eight rats with gliomas at 18-days old (Group C), eight rats with orthotopically injected normal saline served as controls. CT perfusion was performed before and after administration of acetazolamide. Changes in perfusion parameters due to acetazolamide administration were calculated and analyzed. RESULTS: Elevated carbon dioxide partial pressure and decreased pH were found in all 32 rats post acetazolamide challenge (P<0.01). Cerebral blood flow(pre-challenge) was increased in group C (95.0±2.5 ml/100 g/min), as compared to group B (80.1±11.3 ml/100 g/min) and group A (63.1±2.1 ml/100 g/min). Cerebral blood flow percentage changes were detected with a reduction in group C (54.2±4.8%) as compared to controls (111.3±22.2%). Cerebral blood volume(pre-challenge) was increased in group C (50.8±1.7 ml/100 g), as compared to group B (45.7±1.9 ml/100 g) and group A (38.2±0.8 ml/100 g). Cerebral blood volume percentage changes were decreased in group C (23.5±4.6%) as compared to controls (113.5±30.4%). Angiogenesis ratio = [(CD105-MVD) / (FVIII-MVD)] ×100%. Positive correlations were observed between CD105-microvessel density, angiogenesis ratio, vascular endothelial growth factor, proliferation marker and cerebral blood flow(pre-challenge), cerebral blood volume(pre-challenge). Negative correlations were observed between CD105-microvessel density and cerebral blood flow percentage changes (P<0.01, correlation coefficient r=-0.788), cerebral blood volume percentage changes (P<0.01, r=-0.703). Negative correlations were observed between angiogenesis ratio, vascular endothelial growth factor, proliferation marker and cerebral blood flow percentage changes, cerebral blood volume percentage changes. CONCLUSION: Our findings suggest that CT perfusion with challenge can provide new insight into non-invasive assessment of rat C6 glioma angiogenesis.

Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat model with endoglin-targeted paramagnetic liposomes using 3T MRI.

PURPOSE: To evaluate the use of endoglin-targeted paramagnetic liposomes in delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging in a rat model. MATERIALS AND METHODS: Four liposome preparations, including nontargeted paramagnetic liposomes (Gd-SLs), isotype control IgG-coupled paramagnetic liposomes (IgG-Gd-SLs), endoglin monoclonal antibody coupled paramagnetic liposomes (MAb-Gd-SLs), and biotinylated antibodies (Bio-MAb)/streptavidin-coupled paramagnetic liposomes (SAv-Gd-SLs) for two-step pretargeting imaging, were formulated. All animal experiments were carried out with the approval of the Shanghai Animal Care. C6 glioma-bearing Sprague-Dawley rats were intravenously injected with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) or the previously mentioned liposomes (n = 5) and imaged with MR. T1 -weighted MRI was performed before and dynamically repeated after different contrast agents were injected. The enhancement features of the tumors were compared. RESULTS: The signal enhancement of the tumor in the two-step pretargeting group increased by 117.9 ± 5.3% at the periphery and 109.2 ± 3.5% in the center (P = 0.032) at the 8-hour timepoint after SAv-Gd-SLs injection. Ring-like enhancement margins were demonstrated at the periphery of the tumor in the two-step targeted group. The specificity of the targeted liposomes was supported by the competitive study. The signal of peak enhancement using MAb-Gd-SLs was 59% less than that of the two-step group and only slightly higher than the non-targeted groups. CONCLUSION: The two-step endoglin-targeted imaging using biotin-streptavidin interaction was demonstrated to induce intense enhancement of the tumor periphery, which implies that this advanced MR molecular contrast agent may be suitable for accurately delineating glioma tumor margins. J. Magn. Reson. Imaging 2015;41:1056-1064. © 2014 Wiley Periodicals, Inc.

Infective severe acute pancreatitis: a comparison of 99mTc-ciprofloxacin scintigraphy and computed tomography.

AIM: To evaluate (99m)Tc-ciprofloxacin scintigraphy compared with computed tomography (CT) for detecting secondary infections associated with severe acute pancreatitis (SAP) in swine. METHODS: Six healthy swine were assigned to a normal control group (group A, n = 6). SAP was induced in group B (n = 9) and C (n = 18), followed by inoculation of the resulting pancreatic necroses with inactive Escherichia coli (E. coli) (group B) and active E. coli (group C), respectively. At 7 d after inoculation, a CT scan and a series of analyses using infecton imaging (at 0.5, 1, 2, 3, 4 and 6 h after the administration of 370 MBq of intravenous infecton) were performed. The scintigrams were visually evaluated and semi-quantitatively analyzed using region of interest assignments. The differences in infecton uptake and changes in the lesion-background radioactive count ratios (L/B) in the 3 groups were recorded and compared. After imaging detection, histopathology and bacterial examinations were performed, and infected SAP was regarded as positive. The imaging findings were compared with histopathological and bacteriological results. RESULTS: In group A, 6 animals survived without infection in the pancreas. In group B, 7/9 swine survived and one suffered from infection. In group C, 15/18 animals survived with infection. Hence, the number of normal, non-infected and infected SAP swine was 6, 6 and 16, respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the infecton method were 93.8% (15/16), 91.7% (11/12), 92.9% (26/28), 93.8% (15/16) and 91.7% (11/12), whereas these values for CT were 12.5% (2/16), 100.0% (12/12), 50.0% (14/28), 100.0% (2/2) and 46.2% (12/26), respectively. The changes in L/B for the infected SAP were significantly different from those of the non-infected and normal swine (P < 0.001). The mean L/B of the infectious foci at 0.5, 1, 2, 3, 4 and 6 h was 1.17 ± 0.10, 1.71 ± 0.30, 2.46 ± 0.45, 3.36 ± 0.33, 2.04 ± 0.37 and 1.1988 ± 0.09, respectively. At 3 h, the radioactive counts (2350.25 ± 602.35 k) and the mean L/B of the infectious foci were significantly higher than that at 0.5 h (P = 0.000), 1 h (P = 0.000), 2 h (P = 0.04), 4 h (P = 0.000) and 6 h (P = 0.000). CONCLUSION: (99m)Tc-ciprofloxacin scintigraphy may be an effective procedure for detecting SAP secondary infections with higher sensitivity and accuracy than CT.

Discriminative analysis of early-stage Alzheimer's disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study.

BACKGROUND: Previous studies have revealed that amyloid depositions exist in not only the hippocampus but in other subcortical gray matter structures as well. Diffusion-tensor imaging (DTI) parameters might be more sensitive measures of early degeneration in Alzheimer's disease (AD) than conventional magnetic resonance imaging (MRI) techniques. PURPOSE: To evaluate the significance of the volumes and the mean diffusivity (MD) values of subcortical gray matter structures in discrimination between early-stage AD and normal subjects using the Integrated Registration and Segmentation Tool in FMRIB's Software Library. MATERIAL AND METHODS: Fifty-three cases of early-stage AD and 30 normal aging volunteers from two hospitals were scanned with 3D-FSPGRIR and SSSE-EPI sequences using two similar 1.5T MR systems. The mean relative volumes and mean MD values of subcortical gray matter structures were compared between early-stage AD and control groups. Binary logistic regression analysis and receiver-operating characteristic (ROC) curves were applied to assess the diagnostic significance of every structure's relative volume, MD value, and combination of both. RESULTS: The relative volumes of the left hippocampus, right amygdala, bilateral thalamus, right caudate, left putamen, and bilateral pallidum were significantly lower in the early-stage AD group than in the control group (P < 0.05). The MD values of the bilateral hippocampus and pallidum, and of the right thalamus and caudate were significantly elevated in the early-stage AD group (P < 0.05). In binary logistic regression analysis, the relative volume of left hippocampus and age entered the final model of volumetric analysis. The MD values of bilateral hippocampi and pallidums entered the final model of MD analysis. The MD values of bilateral hippocampi and pallidums, and the relative volume of left pallidum, entered the final model of combination analysis. The accuracy of three models was 84.7%, 88.9%, and 93.1%, respectively. CONCLUSION: Pathological changes takes place in the hippocampus and other subcortical gray matter structures in early-stage AD. Diffusive imaging has great diagnostic significance in early-stage AD. The combination of both imaging modalities can lead to better discrimination between early-stage AD and normal aging.

Reprogramming of adult human neural stem cells into induced pluripotent stem cells.

BACKGROUND: Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors. METHODS: NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors (OCT3/4, SOX2, KLF4, and c-MYC), iPSCs colonies were successfully obtained. RESULTS: Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo. CONCLUSION: Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

MRI features of atypical teratoid/rhabdoid tumors in children.

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, highly malignant tumors of the central nervous system, usually occurring in young children. OBJECTIVE: To investigate the MRI features of AT/RT, with special emphasis on diffusion-weighted imaging (DWI) and MR spectroscopy (MRS). MATERIALS AND METHODS: MRI findings of 11 children with AT/RT were reviewed retrospectively, including DWI in 9 AT/RT children and MRS in 6 children. RESULTS: The neoplasms were infratentorial in 4 children and supratentorial in 5 children, both infra- and supratentorial in 1 child and multifocal in 1 child. AT/RT produced heterogeneous signal intensity from peripheral cysts in 7/11 (63%) and hemorrhage in 7/11 (63%). All lesions showed contrast enhancement of varying degrees. Seven (63%) had peritumoral edema. Nine (82%) were hyperintense on DWI with a mean ± SD ADC of 0.60 ± 0.13 × 10(-3) mm(2) s(-1). Six lesions (55%) exhibited elevated levels of choline and decreased NAA, and three had lipid peaks. CONCLUSIONS: A childhood intracranial tumor with off-midline location, peripheral cystic components, hemorrhage, low ADC, and lipid peaks on MRS suggests AT/RT to be considered a differential diagnosis.

In vivo USPIO-enhanced MR signal characteristics of secondary degeneration in the ipsilateral substantia nigra after middle cerebral artery occlusion at 3T.

BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide (USPIO) particles to enhance MRI have been used to study neuroinflammation in vivo. Our purpose was to observe the USPIO-enhanced MR signal alterations in the primary ischemic lesion and ipsilateral substantia nigra after middle cerebral artery occlusion (MCAO) to verify the subsequent sequelae of neuroinflammation seen in the primary ischemic focus and secondary degeneration region. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to transient MCAO. In addition to conventional T2-, T1-weighted imaging, USPIO-enhanced MRI was performed in USPIO-injected stroke rats, while Gd-enhanced imaging was acquired in control stroke rats, on days 3, 6 using a 3-T MR scanner. The MR signal characteristics in the primary ischemic striatum, ipsilateral substantia nigra were noted, compared on histopathological H&E, Prussian blue (PB) staining. RESULTS: After MCAO, USPIO-induced T2 hypointensity changes were observed in the primary ischemic region with BBB impairment at both time points. In the substantia nigra ipsilateral to the primary ischemic lesion, there was no evidence of USPIO accumulation detected by MRI and PB staining, and no BBB leakage reflected by Gd-enhanced imaging on days 3 and 6. CONCLUSION: USPIO-enhanced MR signals have variable characteristics in both primary and remote sites after focal cerebral ischemia. This suggests that the neuroinflammatory response to brain ischemia in the primary ischemic focus and secondary degeneration region have different temporal patterns and pathophysiological mechanisms.