Radiomics of Preoperative Multi-Sequence Magnetic Resonance Imaging Can Improve the Predictive Performance of Microvascular Invasion in Hepatocellular Carcinoma.

Background: The aim of the study is to demonstrate that radiomics of preoperative multi-sequence magnetic resonance imaging (MRI) can indeed improve the predictive performance of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 206 patients with pathologically confirmed HCC who underwent preoperative enhanced MRI were retrospectively recruited. Univariate and multivariate logistic regression analysis identified the independent clinicoradiologic predictors of MVI present and constituted the clinicoradiologic model. Recursive feature elimination (RFE) was applied to select radiomics features (extracted from six sequence images) and constructed the radiomics model. Clinicoradiologic model plus radiomics model formed the clinicoradiomics model. Five-fold cross-validation was used to validate the three models. Discrimination, calibration, and clinical utility were used to evaluate the performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the prediction accuracy between models. Results: The clinicoradiologic model contained alpha-fetoprotein (AFP)_lg10, radiological capsule enhancement, enhancement pattern and arterial peritumoral enhancement, which were independent risk factors of MVI. There were 18 radiomics features related to MVI constructed the radiomics model. The mean area under the receiver operating curve (AUC) of clinicoradiologic, radiomics and clinicoradiomics model were 0.849, 0.925 and 0.950 in the training cohort and 0.846, 0.907 and 0.933 in the validation cohort, respectively. The three models' calibration curves fitted well, and decision curve analysis (DCA) confirmed the clinical usefulness. Compared with the clinicoradiologic model, the NRI of radiomics and clinicoradiomics model increased significantly by 0.575 and 0.825, respectively, and the IDI increased significantly by 0.280 and 0.398, respectively. Conclusions: Radiomics of preoperative multi-sequence MRI can improve the predictive performance of MVI in HCC.

The Value of Amide Proton Transfer MRI in the Diagnosis of Malignant and Benign Urinary Bladder Lesions: Comparison With Diffusion-Weighted Imaging.

BACKGROUND: Conventional magnetic resonance imaging (MRI) has certain limitations in distinguishing between malignant and benign urinary bladder (UB) lesions. Amide proton transfer (APT) imaging may provide more diagnostic information than diffusion-weighted imaging (DWI) to distinguish between malignant and benign UB. PURPOSE: To investigate the potential of APT imaging in the diagnosis of malignant and benign UB lesions and to compare its diagnostic efficacy with that of conventional DWI. STUDY TYPE: Prospective. SUBJECTS: Eighty patients with UB lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T/turbo spin echo (TSE) T1-weighted and T2-weighted imaging, single-shot echo planar DWI, and three-dimensional TSE APT imaging. ASSESSMENT: Patients underwent radical cystectomy or transurethral resection of the bladder lesions within 2 weeks after CT urography and MRI examination. APT signal intensity in UB lesions was quantified by the asymmetric magnetization transfer ratio (MTRasym ). MTRasym and apparent diffusion coefficient (ADC) values were measured and compared between malignant and benign UB lesions. STATISTICAL TESTS: Kolmogorov-Smirnov test, Student's t test or Mann-Whitney U test, Spearman rank correlation coefficient, area under the receiver operating characteristic (ROC) curve (AUC), Delong test, and intraclass correlation coefficient (ICC). The significance threshold was set at P < 0.05. RESULTS: Thirty-two patients had pathologically confirmed benign UB lesions, including 2 bladder leiomyomas, 1 submucosal amyloidosis, 1 inflammatory myofibroblastic tumor, and 28 inflammatory lesions, and 48 patients had pathologically confirmed urothelial carcinoma. Urothelial carcinomas showed significantly higher MTRasym values (1.53% [0.74%] vs. 0.85% [0.23%]) and significantly lower ADC values (1.24 ± 0.34 × 10-3 mm2 /s vs. 1.43 ± 0.22 × 10-3 mm2 /s) than benign UB lesions. The MTRasym value (AUC = 0.928) was significantly better in differentiating urothelial carcinoma from benign UB lesions than the ADC value (AUC = 0.722). DATA CONCLUSION: APT imaging may have value in discriminating malignant from benign UB lesions and has better diagnostic performance than DWI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Evaluation of amide proton transfer imaging for bladder cancer histopathologic features: A comparative study with diffusion- weighted imaging.

PURPOSE: To assess the ability of amide proton transfer (APT) imaging, in comparison with diffusion-weighted imaging (DWI), to differentiate low-grade from high-grade bladder tumors and predict the aggressiveness of bladder cancer (BCa). METHODS: Forty-eight patients diagnosed with BCa confirmed by histopathological findings who underwent magnetic resonance (MR) imaging, including APT imaging and DWI (b = 0, 1000 sec/mm2), were enrolled in this study. The asymmetric magnetization transfer ratio (MTRasym) was defined as the magnetization transfer asymmetry at 3.5 ppm. MTRasym and apparent diffusion coefficients (ADCs) were compared between the low- and high-grade groups and between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) in terms of the areas under the receiver operating characteristic curves (AUCs). RESULTS: The MTRasym values were significantly higher in patients with high-grade bladder tumors than in those with low-grade tumors (1.61 % [0.76 %], 1.12 ± 0.3 %; P = 0.000) and in MIBC than in NMIBC (2.53 ± 0.67 %, 1.38 % [0.35 %]; P = 0.000). The AUCs of MTRasym were significantly larger than those of ADC for differentiating MIBC from NMIBC (0.973, 0.771; P = 0.016). Adding APT imaging to DWI significantly improved the diagnostic accuracy for differentiating MIBC from NMIBC versus DWI alone (0.985, 0.876; P = 0.013). CONCLUSIONS: APT imaging can predict tumor grade and aggressiveness in BCa. The diagnostic performance of APT imaging in predicting tumor aggressiveness was better than that of DWI, and adding APT imaging to DWI significantly improved the diagnostic accuracy of predicting tumor aggressiveness versus DWI alone.

Brain hemodynamic changes in amnestic mild cognitive impairment measured by pulsed arterial spin labeling.

We used pulsed arterial spin labeling (PASL) to investigate differences in cerebral blood flow (CBF) between 26 patients with amnestic mild cognitive impairment (aMCI) and 27 controls with normal cognition (NC). Hypoperfusion was observed in the right temporal pole of the middle temporal gyrus and the right inferior temporal gyrus in the aMCI compared with NC group. Interestingly, hyperperfusion was observed in the left temporal pole of the middle temporal gyrus, left superior temporal gyrus, bilateral precuneus, postcentral gyrus, right inferior parietal lobule, and right angular gyrus in the aMCI group, which likely resulted from a compensatory mechanism to maintain advanced neural activities. We found that mean CBF in the right inferior temporal gyrus, precuneus, and postcentral gyrus was positively correlated with cognitive ability in the aMCI but not NC group. Collectively, our data indicate that PASL is a useful noninvasive technique for monitoring changes in CBF and predicting cognitive decline in aMCI.

Prognostic Value of Pre-Autologous Stem Cell Transplantation PET/CT in Diffuse Large B-Cell Lymphoma: The Deauville Score Is Prognostically Superior to ΔSUVmax.

OBJECTIVE: The predictive value of pre-autologous stem cell transplantation (pre-ASCT) positron emission tomography/computed tomography (PET/CT) scans according to different criteria remains elusive in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 46 DLBCL patients treated with pre-ASCT were enrolled in the present study, and two methods, Deauville score and maximal standardized uptake value reduction (ΔSUVmax), were used to evaluate the PET/CT scans before transplantation. RESULTS: In patients with Deauville 1-3 and ≥4, the 2-year progression-free survival (PFS) rates were 82.8 and 11.8% (p < 0.001), respectively, while the 2-year overall survival (OS) rates were 89.7 and 41.2%, respectively (p < 0.001). When using the ΔSUVmax cut-off of 66% criterion, in patients with a ΔSUVmax of >66 and ≤66%, the 2-year PFS rates were 78.1 and 7.1%, respectively (p < 0.001), while the 2-year OS rates were 87.5 and 35.7%, respectively (p < 0.001). In the univariate analysis, the ΔSUVmax, Deauville score, NCCN-IPI and serum lactate dehydrogenase levels were significantly correlated with the 2-year PFS/OS. Furthermore, the multivariate analysis revealed that the Deauville score was an independent prognostic factor for 2-year PFS. CONCLUSION: The present results indicate that PET/CT scans at pre-ASCT can predict the survival of DLBCL patients, and the Deauville score is better than ΔSUVmax in prognostic prediction.

Predictive ability of DWI/ADC and DCE-MRI kinetic parameters in differentiating benign from malignant breast lesions and in building a prediction model.

OBJECTIVES: To analyze DWI/ADC and DCE-MRI kinetic parameters on breast MRI between benign and malignant lesions, to obtain independent predictors of malignancy, and to build a possible future predictive model. METHODS: 121 patients (151 breast lesions) were evaluated by 3.0T breast MRI. Based on their post-operative histopathology, we divided them into two groups, benign and malignant. We processed their DCE-MRI images to obtain size of lesions and several kinetic parameters like Time Intensity Curve (TIC), Time To Peak (TTP), Area Under Curve (AUC), Maximum Enhancement, Wash-In (WI), and Wash-Out (WO). We also processed their DWI/ADC maps to obtain their Signal Intensity (SI) ADC values. These parameters were compared between the two groups. RESULTS: The age of the patients was higher in the malignant group as compared to the benign group (mean=55.9 years and 47.3 years, respectively, P<0.001). Malignant lesions were of greater size than benign ones (mean 2.55 cm and 1.82 cm, respectively, P<0.01). On DCE-MRI, parameters such as TIC, AUC, WI, and WO were statistically significantly different (all P values <0.05). On DWI/ADC, malignant lesions had statistically significant lower ADC values than benign lesions (mean of 1.02x0.001 and 1.72x0.001 mm2/s, respectively, P<0.001). We obtained a cutoff ADC value of 1.18x0.001 mm2/s to differentiate between benign and malignant lesions. Our predictive model results showed ADCmean and TIC as independent predictors of malignancy with an excellent combined model of fit (P=0.000). CONCLUSION: Kinetic DCE-MRI and DWI parameters are significantly different between benign and malignant breast lesions. ADCmean and TIC are reliable independent predictors of malignancy in our prediction model, with excellent goodness of fit to predict cancer with a sensitivity of 94.2%.

Prediction and prognosis of biologically aggressive breast cancers by the combination of DWI/DCE-MRI and immunohistochemical tumor markers.

Breast cancer (BC) research has been evolving tremendously on all fronts, whether it being for imaging, pathology, oncology, pharmacology, or genetics. Regarding medical imaging, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) are now both universally recognized and widely used modalities in multiparametric MRI (mp-MRI) to diagnose and stage BC, to assess post-chemotherapy response, and to differentiate between scar tissue and recurrent tumor. Meanwhile, pathologists have provided evidence of BC being heterogeneous and having several subtypes, which in turn might affect its prognostic and therapeutic outcomes. Immunohistochemical testing for estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor factor-2 (HER-2), and Ki-67 proliferation index is performed daily to categorize breast tumors into different molecular subtypes. Since then, a number of studies have evaluated whether there is any inter-relationship between them and mp-MRI parameters, the nature of their relationship if any, and the predictive ability of mp-MRI to diagnose biologically aggressive tumors. This review aims to summarize published literature where the data of DCE-MRI/DWI and immunohistochemical markers have been combined for BC studies in order to observe what conclusions have been reached so far, how our understanding of BC has changed because of them, and what are the future implications of these for the diagnosis of breast tumors. We also give our suggestions on what other relevant areas should be investigated.

7.0 tesla high resolution MRI study on intracerebral migration of magnet-labeled neural stem cells in a mouse model of Alzheimer's disease.

OBJECTIVE: To observe the migration characteristics of neural stem cells (NSCs) labeled with the MRI contrast agent superparamagnetic iron oxide (SPIO) in the brain of APP/PS1 transgenic mice with Alzheimer's disease (AD) by 7.0 T high resolution MRI. METHODS: C57BL/6 mouse NSCs were cultured, amplified, labeled with Feridex and Poly-l-lysine (FE-PLL) and evaluated by transmission electron microscopy (TEM). Using the random number table method, 24 APP/PS1 transgenic AD mice aged 12 months were equally assigned to two groups: animals in group A were transplanted with FE-PLL labeled NSCs and those in group B were transplanted with non-labeled NSCs in the right hippocampus. Twelve wild-type mice of the same age and born from the same litter were used as the control group (group C) and transplanted with FE-PLL labeled NSCs. Using the 7.0 T high resolution MR scanner, the transplanted NSCs were traced in vivo at 1 day, 1 and 2 weeks after cell transplantation. The MRI findings were compared with the histopathological findings. RESULTS: C57BL/6 mouse NSCs were cultured and amplified successfully. TEM showed large amounts of iron-containing particles in the cytoplasm of transplanted cells. MRI in group A showed the presence of spheroid low signals at the injection point of the hippocampus on T2*WI one day after transplantation; one weeks later, the low signals were seen diffusing to the surroundings along the injection point, and covering almost the whole hippocampal area but the intensity of the low signals became weaker gradually; two weeks after transplantation, almost all low signals disappeared. In group B, no significant change in low signals was observed in the transplantation area at all designated time points. Although low signals were also observed in the hippocampus after transplantation of FE-PLL labeled NSCs in group C, their size and location remained almost unchanged. Prussian blue staining showed that migration of the FE-PLL labeled NSCs in the hippocampus of the AD mice was consistent with the MRI findings at all designated time points. CONCLUSION: NSCs underwent diffuse and non-directional migration to the surroundings after they were transplanted to the hippocampus of APP/PS1 transgenic AD mice, and this migration pattern could be traced in vivo by MRI when they were labeled with magnet.

An Intracranial Gliosis Mimicking Neoplasm: A Dilemma.

Intracranial gliosis has no typical clinical signals or imaging characteristics. Therefore, it can be easily misdiagnosed as neoplasm. Hereby, we report a unique case of gliosis that grew outward from the surface of the brain. MRI depicted its signal and enhancement pattern similar to the cerebral gray matter. The diagnosis was confirmed by pathology and immunohistochemistry. Although it was difficult to reach a diagnosis, correlating its origin, growing pattern and MR features and knowing that gliosis can present this way may help in differentiating it from other diseases.

Prenatal exposure to ultrasound affects learning and memory in young rats.

Prenatal exposure to ultrasound may cause cognitive impairments in experimental animals; however, the exact mechanisms remain unknown. In this study, we exposed pregnant rats (or sham-exposed controls) to different intensities of ultrasound repeatedly on days 6, 12 and 18 of pregnancy for 4 min (3.5 MHz, spatial peak time average intensity = 7.6 mW/cm(2), mechanical index = 0.1, thermal index bone = 0.1: 4-min group) or 20 min (3.5 MHz, spatial peak time average intensity = 106 mW/cm(2), mechanical index = 1.4, thermal index bone = 1.0: 20-min group). The Morris water maze was used to assess learning and memory function in pups at 2 mo of age. Noticeable deficits in behavior occurred in the group exposed to ultrasound for 20 min. Using real-time polymerase chain reaction and Western blot, we also determined that both the mRNA and protein expression levels of hippocampal N-methyl-D-aspartate (NMDA) receptor units 1 (NR1) and 2B (NR2B) and brain-derived neurotrophic factor (BDNF) were significantly lower in pups exposed to ultrasound for 20 min than in controls. Furthermore, the morphology of the synapses in the hippocampus was partially damaged. Compared with the control group, the 4-min group had better spatial learning and memory abilities, as well as higher mRNA and protein levels of NR1, NR2B and BDNF. Our study suggests that high-intensity ultrasound irradiation can decrease learning and memory abilities by reducing the expression of NR1, NR2B and BDNF in the hippocampal regions and damaging the structure of synapses. In contrast, low-intensity ultrasound irradiation can enhance the learning and memory abilities of the offspring rats by increasing the expression of NR1, NR2B and BDNF receptor in the hippocampal regions.

Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease-like pathology.

Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an early and prominent feature of Alzheimer's disease (AD). Previous studies demonstrated that the number of mitochondria is significantly reduced in susceptible hippocampal neurons from AD patients. Neural stem cell (NSC) transplantation in AD-like mice can compensate for the neuronal loss resulting from amyloid-beta protein deposition. The effects of NSC transplantation on mitochondrial biogenesis and cognitive function in AD-like mice, however, are poorly understood. In this study, we injected NSCs or vehicle into 12-month-old amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like pathology. The effects of NSC transplantation on cognitive function, the amount of mitochondrial DNA, the expression of mitochondrial biogenesis factors and mitochondria-related proteins, and mitochondrial morphology were investigated. Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive function, number of mitochondria, and expression of mitochondria-related proteins, specifically the mitochondrial fission factors (dynamin-related protein 1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy 1 (OPA1), were significantly increased compared with those in age-matched vehicle-injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data indicate that NSC transplantation may enhance mitochondria biogenesis and further rescue cognitive deficits in AD-like mice.

Contrast-enhanced ultrasonography of skeletal muscles for type 2 diabetes mellitus patients with microvascular complications.

PURPOSE: To explore the applicability of contrast-enhanced ultrasound (CEUS) as a new method to detect impaired microcirculation in type 2 diabetes mellitus patients with microvascular complications (DM+MC). METHODS: Ultrasound contrast agent was injected into peripheral vein of 28 patients with DM+MC, 30 uncomplicated type 2 diabetes mellitus (DM) patients, and 30 control subjects. Its appearance in the calf muscle was detected by contrast-enhanced ultrasound. Time-intensity curves were established based on mathematical modeling, particularly in small artery, muscular tissue and small vein. Times to peak intensity (TTPs), arrival times (ATs) and contrast transit times (CTTs) were analyzed. CTTs were calculated as the differences between arrival times. With patients under fasting conditions, plasma glucose and rheologic parameters of erythrocyte deformability and plasma viscosity were measured. RESULTS: DM and DM+MC groups tended to have longer TTPs than the control group, but without significant differences between DM group and DM+MC group. The median artery-vein and muscle-vein CTTs were statistically significantly highest in the DM+MC group (P < 0.05). Blood viscosity in the DM+MC group was higher than two other groups (P < 0.05). Blood viscosity correlated positively with both blood glucose and C-reactive peptide (P < 0.01). CONCLUSION: CEUS is potentially reliable to detect changes in the microvascular bed. Abnormalities in capillary recruitment may be related to abnormal hemorheology.

Neural stem cell transplants improve cognitive function without altering amyloid pathology in an APP/PS1 double transgenic model of Alzheimer's disease.

Neural stem cells (NSCs) are capable of self-renewal and are multipotent. Transplantation of NSCs may represent a promising approach for treating neurodegenerative disorders associated with cognitive decline, such as Alzheimer disease (AD) characterized by extensive loss of neurons. In this study, we investigated the effect of NSC transplantation on cognitive function in the amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mouse, an AD mouse model with age-dependent cognitive deficits. We found that NSCs bilaterally transplanted into hippocampal regions improved spatial learning and memory function in these mice, but did not alter Aß pathology. Immunohistochemical analyses determined that NSCs proliferated, migrated, and differentiated into three neuronal cell types. The improvement in cognitive function was correlated with enhanced long-term potentiation (LTP) and an increase in the neuron expression of proteins related to cognitive function: N-methyl-D-aspartate (NMDA) 2B unit, synaptophysin (SYP), protein kinase C ζ subtypes (PKCζ), tyrosine receptor kinase B (TrkB), and brain-derived neurotrophic factor (BDNF). Taken together, our data indicated that injected NSCs can rescue cognitive deficits in APP/PS1 transgenic mice by replacing neuronal cell types expressing multiple cognition-related proteins that enhance LTP.

Abnormal intrinsic brain activity in amnestic mild cognitive impairment revealed by amplitude of low-frequency fluctuation: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Previous studies have shown that brain functional activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, alterations in intrinsic brain activity patterns in mild cognitive impairment (MCI) patients are poorly understood. This study aimed to explore the differences in regional intrinsic activities throughout the whole brain between aMCI patients and controls. METHODS: In the present study, resting-state functional magnetic resonance imaging (fMRI) was performed on 18 amnestic MCI (aMCI) patients, 18 mild AD patients and 20 healthy elderly subjects. And amplitude of low-frequency fluctuation (ALFF) method was used. RESULTS: Compared with healthy elderly subjects, aMCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex, left lateral temporal cortex, and right ventral medial prefrontal cortex (vMPFC) and increased ALFF in the left temporal-parietal junction (TPJ) and inferior parietal lobule (IPL). Mild AD patients showed decreased ALFF in the left TPJ, posterior IPL (pIPL), and dorsolateral prefrontal cortex compared with aMCI patients. Mild AD patients also had decreased ALFF in the right posterior cingulate cortex, right vMPFC and bilateral dorsal MPFC (dMPFC) compared with healthy elderly subjects. CONCLUSIONS: Decreased intrinsic activities in brain regions closely related to episodic memory were found in aMCI and AD patients. Increased TPJ and IPL activity may indicate compensatory mechanisms for loss of memory function in aMCI patients. These findings suggest that the fMRI based on ALFF analysis may provide a useful tool in the study of aMCI patients.

[In vivo labeling of rat neural progenitor cells in subventricular zone with superparamagnetic iron oxide for tracking of magnetic resonance imaging].

OBJECTIVE: To explore the feasibility of in vivo labeling of adult rat neural progenitor cells (NPCs) in subventricular zone (SVZ) with superparamagnetic iron oxide particles (SPIOs) for tracking of magnetic resonance imaging (MRI). METHODS: A total of 7 SD rats were stereotactically injected with 3 µl SPIOs (7 mg Fe/ml) into anterior horn of right lateral ventricle and then 5-bromo-2'-deoxyuridine (BrdU) was injected intraperitoneally once daily for 1 week. MRI was performed at 1, 3, 7 and 14 days post-injection. After the final MRI scan, all rats were transcardially perfused and their brains removed and fixed. The sections were processed for Prussian blue iron staining and Prussian blue plus BrdU immunohistochemical staining. RESULTS: In all experimental animals, SPIOs were predominantly located in the anterior horn of right lateral ventricle and partial SPIOs entered the ventricular system. A needle path and a distribution of SPIOs along rostral migratory stream (RMS) towards olfactory bulb (OB) were depicted at the sagittal view of T2(*)WI, moderate MR artifact was visible and SPIOs tracking NPCs were successful (success rate of 100%). The result of staining showed SPIOs labeling NPCs were effective. And the labeling rates were 75.5%, 42.3%, 23.6% in SVZ, RMS and OB respectively. CONCLUSION: Effective in vivo labeling of adult rat NPCs in SVZ with SPIOs is feasible. And dynamical migration of labeling NPCs along RMS towards OB may be visualized on MRI.

[Values of ocular hemodynamics and serum endothelin-1 in the early diagnosis of diabetic retinopathy].

OBJECTIVE: To evaluate the values of ocular hemodynamics and serum endothelin-1 (ET-1) in the early diagnosis of diabetic retinopathy (DRP). METHODS: A total of 85 DRP patients were examined by ophthalmoscope and fluorescein angiography and divided into 3 groups: no obvious retinopathy (n = 20), non-proliferative diabetic retinopathy (n = 35) and proliferative diabetic retinopathy (n = 30). Control group included 15 healthy volunteers. The peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of ophthalmic artery (OA) and central retinal artery (CRA) were measured by color Doppler energy imaging. The level of endothelin-1 was measured by radioimmunoassay. Then plasma ET-1 levels and eye vascular hemodynamic parameters were compared with correlation and diagnostic specificity after data analysis. RESULTS: Compared with the control group, DRP, EDV and PSV decreased progressively while RI increased gradually (P < 0.05). EDV and RI were more sensitive than PSV in diagnosis. The plasma level of ET-1 was significantly higher than that of control group (P < 0.05). And it was correlated positively with RI and negatively with PSV and EDV of CRA. The diagnostic value of EDV was higher than that of ET-1 level. CONCLUSION: Ocular hemodynamics become abnormal during the early stage of DRP and worsen with the progress of DRP. An elevated plasma level of ET-1 may lead to the abnormal of retinal hemodynamics. The test of plasma ET-1 and the examination of ocular hemodynamics may play an important role in the early diagnosis of DRP.

1H-MRS assessment of the therapeutic effect of bilateral intraventricular BDNF infusion into APP/PS1 double transgenic mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid deposits. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor whose levels have been shown to be decreased in AD brains. BDNF supplementation can offer improvement in the course of AD. However, the means of assessment are still relatively limited. In the present study, 1H-MRS was used to evaluate the therapeutic effects of bilateral intraventricular BDNF infusion into Alzheimer's disease APP/PS1 double transgenic mice. For comparison to the 1H-MRS observations, Fluoro-Jade B staining and immunofluorescence for beta amyloid peptides (Aß), glial fibrillary acidic protein, and tropomyosin-related kinase B (TrkB) were also performed. Our results showed that N-acetylaspartate (NAA) levels increased and myoinositol levels decreased in the BDNF group compared with the PBS group. However, the BDNF group NAA level was still lower than the control group at 6 weeks after infusion. These changes correlated with increased immunoreactivity for TrkB, decreased compact Aß peptide containing plaques, and decreased Fluoro-Jade B-positive cells in the BDNF-infused mice compared to vehicle controls. These findings demonstrate that 1H-MRS may be a promising means of evaluating the therapeutic effects of BDNF on AD.

[Effects of neural stem cells transplanted into an animal model of Alzheimer disease on Aß plaques].

OBJECTIVE: To explore the effects on Aß plaques of neural stem cells transplanted into an Alzheimer disease mouse model. METHODS: A total of twenty 12-months-old APP+PS1 double transgenic AD mice were randomly divided into two groups.One group received neural stem cells transplantation, that was NSC group, another mice received an equal quantity 0.01 mol/L PBS, as positive control group. After 5 weeks transplantation, the total number of Aß plaques examined by immunohistochemistry, the ratio of compact of Aß plaques by TS staining, and whether NSCs migrate into Aß plaques by immunofluorescence monitoring. RESULTS: There was no difference in total number of Aß plaques between NSC group (181 ± 12) and PBS (179 ± 14) group after transplantation (P > 0.05). There was no difference in the number of TS+ plaques between NSC group (54.9%) and PBS (55.7%) group after eight weeks NSCs transplantation (P > 0.05). (2) However, engrafted NSCs showed partial chemotaxis toward Aß plaques. CONCLUSION: NSCs transplantation did not have a significant impact on Aß plaques of AD mice, but the tropism of engrafted NSCs may be capable of replacing lost or damaged cells and reverse the course of AD mice in some extent.

Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice.

Proton magnetic resonance spectroscopy ((1)H-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether (1)H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. (1)H-MRS was performed in 20 tg mice and 15 wild-type mice at 3, 5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The (1)H-MRS revealed that mI levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p<0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that (1)H-MRS is a more sensitive biomarker for assessing early AD.