Accuracy of multiparametric magnetic resonance imaging for detecting extracapsular extension in prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of multiparametric MRI (mpMRI) for detecting extracapsular extension (ECE) in patients with prostate cancer (PCa). METHODS AND MATERIALS: We searched MEDLINE, PubMed, Embase and the Cochrane library up to December 2018. We included studies that used mpMRI to differentiate ECE from organ-confined PCa with a combination of T2 weighted imaging (T2WI), diffusion-weighted imaging, and dynamic contrast-enhanced MRI. All studies included had pathological diagnosis with radical prostatectomy. Two reviewers independently assessed the methodological quality of included studies by using Quality Assessment of Diagnostic Accuracy Studies 2 tool. We calculated pooled sensitivity, specificity, positive and negative predictive values, diagnostic odds ratios and receiver operating characteristic curve for mpMRI from 2 × 2 tables. RESULTS: A total of 17 studies that comprised 3374 participants were included. The pooled data showed a sensitivity of 0.55 (95% confidence interval 0.43, 0.66]) and specificity of 0.87 (95% confidence interval 0.82, 0.91) for extracapsular extension detection in PCa. CONCLUSION: First, our meta-analysis shows moderate sensitivity and high specificity for mpMRI to differentiate ECE from organ-confined prostate cancer before surgery. Second, our meta-analysis shows that mpMRI had no significant differences in performance compared with the former meta-analysis with use of T2WI alone or with additional functional MRI. ADVANCES IN KNOWLEDGE: It is the first meta-analysis to evaluate the accuracy of mpMRI in combination of TWI, diffusion-weightedimaging and dynamiccontrast-enhanced-MRI for extracapsular extension detection.

Both Wnt/ß-catenin and ERK5 signaling pathways are involved in BDNF-induced differentiation of pluripotent stem cells into neural stem cells.

Although brain-derived neurotrophic factor (BDNF) induces the differentiation of induced pluripotent stem cells (iPSCs) into neural stem cells (NSCs), its exact mechanism remains unelucidated. Wnt/ß-catenin and ERK5 are two important signalling pathways of the Wnt and MAPK signalling cascades and are speculated to be closely related to the differentiation of cells. In this study, we reported the role of the Wnt/ß-catenin and ERK5 signalling pathways on the BDNF-induced differentiation of iPSCs into NSCs. We examined the expression of ß-catenin and p-ERK5 using small interfering RNA (siRNA)-induced silencing of ß-catenin and ERK genes. We found that BDNF significantly improved the efficiency of iPSC differentiation and that the expression of ß-catenin and p-ERK5 in the BDNF culture medium was significantly upregulated. Furthermore, we found that the expression of the ß-catenin component was downregulated by siRNA-ß-catenin, and the expression of the p-ERK5 component was downregulated by siRNA-ERK5. Flow cytometry showed that the differentiation rate of iPSCs was also significantly decreased by RNA interference. The results suggested that the Wnt/ß-catenin and ERK5 signalling pathways are activated in the process of BDNF-induced iPSC differentiation. Interestingly, our study showed that siRNA-ERK5 not only inhibits the activity of the ERK5 signalling pathway but also partially controls the activity of the Wnt/ß-catenin signalling pathway. The results suggested that the Wnt/ß-catenin and ERK5 signalling pathways are not independently involved in the process of BDNF-induced iPSC differentiation. Our study showed that BDNF promotes the differentiation of iPSCs into NSCs by activating the Wnt/ß-catenin and ERK5 signalling pathways, and an interconnected relationship may exist between the Wnt/ß-catenin and ERK5 signalling pathways.

Contrast analysis of the relationship between the HRCT sign and new pathologic classification in small ground glass nodule-like lung adenocarcinoma.

PURPOSE: To perform contrast analysis of the relationship between high-resolution computed tomography (HRCT) signs and new pathologic classification of small GGNs-like lung adenocarcinoma. MATERIALS AND METHODS: The HRCT data from 145 pathologically confirmed cases of small GGNs of lung adenocarcinoma were analysed retrospectively. The 145 cases of GGNs were divided into pre-invasive (PI) group (n = 46), micro-invasive adenocarcinoma (MIA) group (n = 48), and invasive adenocarcinoma (IAC) group (n = 51). HRCT imaging sign of GGNs in each group was assessed and compared. RESULTS: Significant differences in GGN size were found among the three groups (P < 0.05). The presence of a tumour-lung interface in the MIA and IAC groups was significantly higher than that in the PI group (P < 0.05), but no significant difference was found between the MIA and IAC groups. The presence of a pleural indentation sign in the IAC group was significantly higher than that in the other two groups (P < 0.05), but no significant difference was noted between the latter two groups. Significant differences were found in the lobulated and spicule signs among the three groups (P < 0.05). The presence of a microvascular sign in the MIA and IAC groups was significantly higher than that in the PI group (P < 0.05). No significant difference was found in the GGN density, vacuole sign, air bronchus sign and notch sign among the three groups. CONCLUSIONS: The HRCT signs of GGNs could be used to differentiate among pre-invasive lesions, micro-invasive lesions and invasive lung adenocarcinoma.

Establishment of a Predictive Model for Surgical Resection of Ground-Glass Nodules.

PURPOSE: To establish a predictive model for surgical resection of invasive pulmonary adenocarcinoma (IPA) presenting as ground-glass nodules (GGNs) based on a radiomics nomogram. METHODS: The CT images of 239 patients with GGNs were collected, of which 160 cases were included in the training set to construct the predictive model and 79 cases were included in the validation set to verify the established predictive model. The least absolute shrinkage and selection operator algorithm was used to select the radiomic features and construct the radiomics tagging. The predictive model for the surgical resection of IPA was constructed using the radiomics nomogram. RESULTS: The presence of IPA showed significant correlations with seven radiomics features (P < .01), which were the independent predictors. The predictive model constructed using the radiomics features performed well on the training set (area under the curve [AUC] 0.792, 95% confidence interval [CI]: 0.720-0.864) and the validation set (AUC 0.773, 95% CI: 0.668-0.877). The predictive model constructed using the clinical information alone was relatively less effective (AUC 0.711, 95% CI: 0.634-0.787). The predictive model constructed by integrating the radiomics features into the clinical information using the radiomics nomogram showed the best predictive ability and calibration in the training set (AUC 0.831, 95% CI: 0.765-0.897) and the validation set (AUC 0.816, 95% CI: 0.724-0.909). Decision curve analysis showed that radiomics nomogram has a certain clinical value. CONCLUSION: The predictive model for surgical resection of IPA constructed by integrating the radiomics features and the clinical information based on the radiomics nomogram can help clinicians control the operative node and reduce the occurrence of overtreatment.

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.

Abbreviated MRI Protocols for Detecting Breast Cancer in Women with Dense Breasts.

OBJECTIVE: To evaluate the validity of two abbreviated protocols (AP) of MRI in breast cancer screening of dense breast tissue. MATERIALS AND METHODS: This was a retrospective study in 356 participants with dense breast tissue and negative mammography results. The study was approved by the Nanjing Medical University Ethics Committee. Patients were imaged with a full diagnostic protocol (FDP) of MRI. Two APs (AP-1 consisting of the first post-contrast subtracted [FAST] and maximum-intensity projection [MIP] images, and AP-2 consisting of AP-1 combined with diffusion-weighted imaging [DWI]) and FDP images were analyzed separately, and the sensitivities and specificities of breast cancer detection were calculated. RESULTS: Of the 356 women, 67 lesions were detected in 67 women (18.8%) by standard MR protocol, and histological examination revealed 14 malignant lesions and 53 benign lesions. The average interpretation time of AP-1 and AP-2 were 37 seconds and 54 seconds, respectively, while the average interpretation time of the FDP was 3 minutes and 25 seconds. The sensitivities of the AP-1, AP-2, and FDP were 92.9, 100, and 100%, respectively, and the specificities of the three MR protocols were 86.5, 95.0, and 96.8%, respectively. There was no significant difference among the three MR protocols in the diagnosis of breast cancer (p > 0.05). However, the specificity of AP-1 was significantly lower than that of AP-2 (p = 0.031) and FDP (p = 0.035), while there was no difference between AP-2 and FDP (p > 0.05). CONCLUSION: The AP may be efficient in the breast cancer screening of dense breast tissue. FAST and MIP images combined with DWI of MRI are helpful to improve the specificity of breast cancer detection.

Application of Abbreviated Protocol of Magnetic Resonance Imaging for Breast Cancer Screening in Dense Breast Tissue.

RATIONALE AND OBJECTIVES: The study aimed to evaluate the usefulness of an abbreviated protocol (AP) of magnetic resonance imaging (MRI) in comparison to a full diagnostic protocol (FDP) of MRI in the breast cancer screening with dense breast tissue. MATERIALS AND METHODS: There are 478 female participants with dense breast tissue and negative mammography results, who were imaged with MRI using AP and FDP. The AP and FDP images were analyzed separately, and the sensitivity and specificity of breast cancer detection were calculated. The chi-square test and receiver operating characteristics curves were used to assess the breast cancer diagnostic capabilities of the two protocols. RESULTS: Sixteen cases of breast cancer from 478 patients with dense breasts were detected using the FDP method, with pathologic confirmation of nine cases of ductal carcinoma in situ, six cases of invasive ductal carcinoma, and one case of mucinous carcinoma. Fifteen cases of breast cancer were successfully screened using the AP method. The sensitivity showed no obvious significant difference between AP and FDP (χ2 = 0.592, P = 0.623), but the specificity showed a statistically significant difference (χ2 = 4.619, P = 0.036). The receiver operating characteristics curves showed high efficacy of both methods in the detection of breast cancer in dense breast tissue (the areas under the curve were 0.931 ± 0.025 and 0.947 ± 0.024, respectively), and the ability to diagnose breast cancer was not statistically significantly different between the two methods. CONCLUSIONS: The AP of MRI may improve the detection rate of breast cancer in dense breast tissue, and it may be useful in efficient breast cancer screening.

Hydrogen Proton Magnetic Resonance Spectroscopy in Multidomain Amnestic Mild Cognitive Impairment and Vascular Cognitive Impairment Without Dementia.

To investigate the value of hydrogen proton magnet resonance spectroscopy ((1)H-MRS) in the differential diagnosis of multiple-domain amnestic mild cognitive impairment (M-aMCI) and vascular cognitive impairment with no dementia (VCIND); (1)H-MRS was performed in patients with M-aMCI and VCIND. The level was determined for N-acetylaspartate (NAA), glutamate (Glu), inositol (mI), choline (Cho), and creatine (Cr). Compared with the normal control group, the NAA-Cr ratio in all regions studied was significantly lower in the M-aMCI and VCIND groups. The Glu-Cr ratio in the posterior cingulate gyrus of the M-aMCI group was significantly lower than in the VCIND. The mI-Cr ratio in the frontal white matter of the VCIND was significantly higher than in the M-aMCI group. In the white matter adjacent to the lateral ventricles, the Cho-Cr ratio was significantly higher in the VCIND than the M-aMCI. Our results suggested (1)H-MRS is an effective method in the differential diagnosis of M-aMCI and VCIND.

Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of neural stem cells in vitro.

Neurotrophic factors can promote the proliferation and differentiation of neural stem cells (NSCs). Here we report that the possibility of using bFGF in combination with BDNF and NGF to promote proliferation and differentiation of NSCs in vitro. C57BL/6 mouse NSCs were cultured, passaged and stained by immunofluorescence for nestin and GFP. According to different neurotrophic factors added to NSCs, seven experiment groups (NGF, BDNF, bFGF, bFGF+NGF, bFGF+BDNF, NGF+BDNF and NGF+BDNF+bFGF) and a blank control group were established. One week after induction and differentiation, results showed that there was significant difference in the percentage of NSCs differentiating into neurons among the experiment groups. The percentage in the multi-factor groups was significantly higher than that in the single-factor groups (p<0.05), among which the percentage was the highest in NGF+BDNF+bFGF group. In the two-factor groups, the percentage in bFGF+NGF and bFGF+BDNF groups was significantly higher than that in NGF+BDNF group (p<0.05). The NSCs growth curves showed that cells proliferated continuously with the time of culture prolonging, but there was significant difference between the group containing bFGF and that without bFGF. Our results demonstrate that combined use of NGF/BDNF/bFGF significantly improved the ability of NSCs proliferation and differentiation.

Neural stem cell transplantation improves spatial learning and memory via neuronal regeneration in amyloid-ß precursor protein/presenilin 1/tau triple transgenic mice.

Neural stem cell (NSC) transplantation has recently become a main research target for Alzheimer's disease (AD) treatment. In the present study, we transplanted NSCs from C57BL/6 mice into the hippocampus in the 12-month-old triple transgenic model of AD (3 × Tg) and determined whether NSC transplantation can alleviate impairments in spatial learning and memory via neuronal regeneration in AD mice. Two months after transplantation, Morris water maze tests suggested that spatial learning and memory in the 3 × Tg mice receiving NSCs was significantly improved compared to 3 × Tg mice not receiving NSCs. Furthermore, quantification of Nissl staining revealed that the number of neurons in the hippocampus of 3 × Tg mice receiving NSCs was significantly greater than that in 3 × Tg mice not receiving NSCs, indicating that new neurons were generated. These results may demonstrate that NSC transplantation can improve spatial learning and memory via neuronal regeneration in amyloid-ß precursor protein/presenilin 1/tau 3 × Tg mice.

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.

(1)H-MRS evaluation of therapeutic effect of neural stem cell transplantation on Alzheimer's disease in AßPP/PS1 double transgenic mice.

The aim of this work was to explore the applicable value of (1)H-MRS evaluation on the treatment of Alzheimer's disease (AD) with neural stem cell (NSC) transplantation by quantitative analysis of metabolite changes in the hippocampal area in AßPP/PS1 transgenic (tg) mice. The tg mice (n = 30) aged 12 months were randomized into two subgroups: One receiving NSCs and the other receiving PBS transplantation in the bilateral hippocampal CA1 region. The wild-type mice (n = 15) were used as the control group. (1)H-MRS was performed before transplantation and 6 weeks after transplantation to measure the change of N-acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), choline (Cho), and creatine (Cr) in the hippocampus. Results showed NAA and Glu levels were increased and mI level was decreased in NSC group compared with the PBS group at six weeks after transplantation (p < 0.05). There was no significant difference in NAA and Glu (p > 0.05), and there was significant difference in mI (p < 0.05) between NSC and control groups. However, there was no significant difference in Cho before and after transplantation among the three groups (p > 0.05). Histology showed the number of neurons in the hippocampal CA1 region increased significantly in the NSC group than those in the PBS group (p < 0.05), and the number of astrocytes significantly decreased in the NSC group compared with the PBS group. Ultrastructure showed that the neurons in the NSC group were morphologically normal. In conclusion, (1)H-MRS can display intracranial metabolite changes before and after NSC transplantation in tg mice and has a applicable value in evaluating the therapeutic effect of NSCs on AD.

[The comparative study on high field MRI and pathology of Alzheimer's disease transgenic mice].

OBJECTIVE: To observe and investigate the neuroimaging characters in early progression of transgenic Alzheimer's disease (AD) mice model, and make sure the diagnosis value of 7.0 T high field magnetic resonance microimaging (MRMI). METHODS: APP/PS-1 transgenic mice aged 3, 6, 9 months and the same aged wild type mice were each divided into 6 groups (6 mice in every groups) based on age. The mice brains were scaned with 7.0T high magnetic field MR. Then the mice were killed. The Aß immunohistochemistry examination was analyzed in the mice brains specimens, and pathological changes were in comparison with the T(2) weighted imaging in the mice brains. RESULTS: There were a few Aß plaques in the brains of 6 months APP/PS-1 transgenic mice, while Aß plaques were increased both in number and volume in the cerebral cortex and hippocampus of 9 months AD mice. The brains of APP/PS-1 double transgenic mice of 3, 6 months and the control group mice were not showed intensity loss on T(2) weighted MR images, while the signal intensity loss was visualized in the cerebral cortex and hippocampus of 9 months AD mice. CONCLUSION: 7.0T high magnetic field MR could display Aß plaques in the brains of APP/PS-1 double transgenic mice of 9 months and it is helpful to diagnosis early AD.

[The effect of continuous low doses X-ray on the proliferation of pyramidal cell in hippocampus CA1 in prenatal rats].

OBJECTIVE: To explore the effect of low doses X-ray on proliferation of hippocampal pyramidal cell in the area of CA1 in prenatal rat and its relevant mechanism. METHODS: A total of 25 pregnant rats were randomly divided into four experimental groups and one control group. The experimental groups, in a duration of consistent 18 days, respectively received different doses as follows: 0.015 mGy/d, 0.03 mGy/d, 0.06 mGy/d and 0.09 mGy/d. The control group received sham radiation. To observe the density and width of hippocampal pyramidal cell in the area of CA1 by HE stained and observe the expression of the ERK1/2 by IHM. RESULTS: (1) Except C group, all other groups presented increment in width of the level of hippocampal pyramidal cell, compared with C group; H group, M group, L1 group and L2 group were higher than that (F value respectively were 8.475, 33.42, 14.395, 44.955; P value respectively were 0.002, 0.048, 0.030, 0.012). But the phenomenon of inhomogeneity in width in H group was observed, at the same time, the density of cell in H group became looser (F = 4.466, P = 0.017). (2) The expression of ERK1/2 in the hippocampus CA1 was seen in cytoplasm of every group, the average optical density of positive ERK1/2 protein significantly increased in L1 group and L2 group, compared with control group respectively (F value respectively were 4.561, 4.103, P value respectively were 0.044, 0.035). CONCLUSION: Low doses X-ray could promote proliferation of hippocampus CA1 cell in prenatal. The reason could be the increment of the ERK1/2 protein induced by X-ray. When the doses reached 0.09 mGy/d, the excesses proliferation phenomenon was observed.

[Study of bone mesenchymal stem cells tropism for hepatic tumors and effect on the form of tumor stromal].

OBJECTIVE: To investigate the tropism capacity of the rat bone mesenchymal stem cells (BMSC) for hepatic tumors microenvironment and the effect on the form of tumor stromal. METHODS: Rat BMSC were isolated, cultured and expanded, then incubated with superparamagnetic iron oxide (SPIO) nanoparticles. Prussian blue stain was performed for showing intracellular irons. Walker-256 cells were injected into the rat livers directly to establish hepatic tumor models. The experiment was divided into two experimental groups (the group venous injected with BMSC after tumors becoming mass: tail venous injected with BMSC after MR showed the presence of tumors at 6-8 days after operation and the group venous injected with BMSC before tumors becoming mass: tail venous injected with BMSC when MR showed no presence of tumors at 3 days after operation) and one control group. To the experimental groups animals, MRI was made before venous injection of BMSC and at 5, 10, 15 days after BMSC transplantation. The rats were killed at corresponding period. The pathologic examinations were analyzed, including HE, Prussian blue stain. The expression of vascular endothelial growth factor (VEGF), CD31, von Willebrand factor (vWF) in the specimens harvested at 10 days after BMSC transplantation were detected immunohistochemically. RESULTS: Prussian blue staining of SPIO labeled BMSC demonstrated cells could be effectively labeled and the labeling efficiency was almost 90%. After BMSC transplantation, two experimental groups were showed tuberculous signal intensity loss at the margin of tumors on T(2) weighted MR images at 5, 10 days after transplantation and the signal intensity loss was not visualized at 15 days after transplantation. The control group was not observed signal intensity decrease. Prussian blue staining of histological analysis showed blue-stained iron particles distributed at the margin of tumor at 5, 10, 15 days after transplantation. Immunohistochemical examination showed that the expression of VEGF, CD31, vWF in two experimental groups at 10 days after transplantation were higher than that in the control group (F = 34.03, P < 0.01; F = 84.24, P < 0.01; F = 7.08, P < 0.05). CONCLUSION: Rat BMSC have the ability to migrate towards hepatic tumors in vivo and promote to form vascular endothelium.

Role of myo-inositol by magnetic resonance spectroscopy in early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice.

BACKGROUND/AIMS: To explore the potential value of myo-inositol (mIns), which is regarded as a biomarker for early diagnosis of Alzheimer's disease, in APP/PS1 transgenic (tg) mice detected by (1)H-MRS. METHODS: (1)H-MRS was performed in 30 APP/PS1 tg mice and 20 wild-type (wt) littermates at 3, 5 and 8 months of age. Areas under the peak of N-acetylaspartate (NAA), mIns and creatine (Cr) in the frontal cortex and hippocampus were measured, and the NAA/Cr and mIns/Cr ratios were analyzed quantitatively. RESULTS: Compared with the wt mice, the mIns/Cr ratio of the 3-month-old tg mice was significantly higher (p < 0.05), and pathology showed activation and proliferation of astrocytes in the frontal cortex and hippocampus. The concentration of NAA was significantly lower at 8 and 8 months of age (p < 0.05). According to the threshold of mIns/Cr that was adopted to separate the tg from the wt mice, the rate of correct predictions was 82, 94 and 95%, respectively, for 3, 5 and 8 months. CONCLUSION: Of the early AD metabolites as detected by (1)H-MRS, mIns is the most valuable marker for assessment of AD. Quantitative analysis of mIns may provide important clues for early diagnosis of AD.