Non-Invasive Prediction of Survival Time of Midline Glioma Patients Using Machine Learning on Multiparametric MRI Radiomics Features.

Objectives: To explore the feasibility of predicting overall survival (OS) of patients with midline glioma using multi-parameter magnetic resonance imaging (MRI) features. Methods: Data of 84 patients with midline gliomas were retrospectively collected, including 40 patients with OS > 12 months (28 cases were adults, 14 cases were H3 K27M-mutation) and 44 patients with OS < 12 months (29 cases were adults, 31 cases were H3 K27M-mutation). Features were extracted from the largest slice of tumors, which were manually segmented on T2-weighted (T2w), T2 fluid-attenuated inversion recovery (T2 FLAIR), and contrast-enhanced T1-weighted (T1c) images. Data were randomly divided into training (70%) and test cohorts (30%) and normalized and standardized using Z-scores. Feature dimensionality reduction was performed using the variance method and maximum relevance and minimum redundancy (mRMR) algorithm. We used the logistic regression algorithm to construct three models for T2w, T2 FLAIR, and T1c images as well as one combined model. The test cohort was used to evaluate the models, and receiver operating characteristic (ROC) curves, areas under the curve (AUCs), sensitivity, specificity, and accuracy were calculated. The nomogram of the combined model was built and evaluated using a calibration curve. Decision curve analysis (DCA) was used to evaluate the clinical application value of the four models. Results: A total of 1,316 features were extracted from T2w, T2 FLAIR, and T1c images, respectively. And then the best non-redundant features were selected from the extracted features using the variance method and mRMR. Finally, five features were extracted each from T2w, T2 FLAIR, and T1c images, and 12 features were extracted for the combined model. Four models were established using the optimal features. In the test cohort, the combined model performed the best out of all models. The AUCs of the T2w, T2 FLAIR, T1c, and combined models were 0.73, 0.78, 0.74, and 0.87, respectively, and accuracies were 0.72, 0.76, 0.72, and 0.84, respectively. The ROC curves and DCA showed that the combined model had the highest efficiency and most favorable clinical benefits. Conclusion: The combined radiomics model based on multi-parameter MRI features provided a reliable non-invasive method for the prognostic prediction of midline gliomas.

Long non-coding RNA CRNDE promotes cell apoptosis by suppressing miR-495 in inflammatory bowel disease.

OBJECTIVE: This article aims to investigate the mechanism of microRNA-495 (miR-495) and long non-coding RNA CRNDE on the apoptosis of colonic epithelial cells in inflammatory bowel diseases (IBDs). METHODS: The mouse model of IBD was induced by dextran sulfate sodium (DSS), and human colonic epithelial cell lines (HT-29, LOVO, and Caco-2) were treated with DSS, and received cell transfection. RNA interference was used to down-regulate CRNDE expression. RESULTS: CRNDE and SOCS1 were highly expressed, but miR-495 was lowly expressed in the DSS-induced colitis tissues and colonic epithelial cell lines. Interference of CRNDE inhibited cell apoptosis of DSS-induced colonic epithelial cells. The interaction between CRNDE and miR-495 was confirmed by RNA immunoprecipitation and RNA pull-down assay. The target relationship between miR-495 and SOCS1 was confirmed by the luciferase reporter assay. CRNDE promoted DSS-induced colonic epithelial cell apoptosis via miR-495/SOCS1. CRNDE interference in DSS-induced colitis mouse model alleviated clinical manifestations of IBD. CONCLUSIONS: Our findings demonstrated that CRNDE promoted DSS-induced colonic epithelial cell apoptosis via suppressing miR-495 and increasing SOCS1, indicating CRNDE as a novel target of treating IBD.

[Value of diffusion-weighted imaging, 1H-magnetic resonance spectroscopy and 3D whole-brain arterial spin labeling in the diagnosis of medulloblastoma].

OBJECTIVE: To explore the value of diffusion-weighted imaging (DWI), 1H-magnetic resonance spectroscopy (1H-MRS) and 3D whole-brain arterial spin labeling (3D ASL) in the diagnosis of medulloblastoma in the posterior cranial fossa. METHODS: The magnetic resonance imaging (MRI) findings of 16 patients with pathologically confirmed medulloblastoma in the posterior cranial fossa were analyzed retrospectively. All the patients were examined with plane and enhanced brain MRI scans; 5 patients also underwent examinations with DWI, 12 with MRS, and 5 with 3D ASL. RESULTS: Medulloblastomas were found in the vermis and the fourth ventricle in 9 cases, in the cerebellar hemisphere in 5 cases, and in the cerebellopontine angle in 1 case; in 1 case multiple lesions were detected. The tumors showed iso-intense or slightly hypo-intense signals on T1WI, and iso-intense or hyper-intense signals on T2WI and FLAIR. The lesions showed high signals in DWI and low signals in ADC. Intra-lesion cysts were common (n=12), and calcification and bleeding were rarely seen. Mild patchy enhancement (n=6) or significant enhancement (n=10) was seen after contrast agent administration. Obstructive hydrocephalus was found in 12 cases and the subarachnoid space was involved in 3 cases. In all the 12 patients receiving MRS examination, high Cho and low NAA were found with significantly increased Cho/Cr (≥3.5) and Cho/NAA (≥4.0) ratios; Tau peak was seen in 8 cases, and Lip peak was found in 4 cases. All the 5 patients receiving 3D ASL examination showed decreased cerebral blood flow (CBF). CONCLUSION: The characteristic features of medulloblastomas in DWI, MRS and 3D ASL offer assistance to the diagnosis of atypical medulloblastoma.

In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation.

OBJECTIVE: To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI. MATERIALS AND METHODS: 1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5×10(5) MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals. RESULTS: Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration. CONCLUSION: MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves.

Cobalt-doped cadmium selenide colloidal nanowires.

Co(2+)-doped CdSe colloidal nanowires with tunable size and dopant concentration have been prepared by a solution-liquid-solid (SLS) approach for the first time. These doped nanowires exhibit anomalous photoluminescence temperature dependence in comparison with undoped nanowires.

Transplanted neural stem cells promote nerve regeneration in acute peripheral nerve traction injury: assessment using MRI.

OBJECTIVE: The purpose of our study was to monitor neural stem cells (NSCs) transplanted in acute peripheral nerve traction injury and to use MRI to assess the ability of NSCs to promote nerve regeneration. MATERIALS AND METHODS: After labeling with gadolinium-diethylene triamine pentaacetic acid (gadopentetate dimeglumine) and fluorescent dye (PKH26), 5 × 10(5) NSCs were grafted to acutely distracted sciatic nerves in 21 New Zealand White rabbits. In addition, 5 × 10(5) unlabeled NSCs (n = 21) and vehicle alone (n = 21) subjects were injected as a control. Serial MRI was performed with a 1.5-T scanner to determine the distribution of grafted cells. Sequential T1 and T2 values of the nerves and functional recovery were measured over a 70-day follow-up period, with histologic assessments performed at regular intervals. RESULTS: The distribution and migration of labeled NSCs could be tracked with MRI until 10 days after transplantation. Compared with vehicle control, nerves grafted with labeled or unlabeled NSCs had better functional recovery and showed improved nerve regeneration but exhibited a sustained increase of T1 and T2 values during the phase of regeneration. CONCLUSION: Gadopentetate dimeglumine-based labeling allowed short-term in vivo MRI tracking of NSCs grafted in injured nerves. NSCs transplantation could promote nerve regeneration in acute peripheral nerve traction injury as shown by a prolonged increase of nerve T1 and T2 values.

Significant fluorescence enhancement by supramolecular complex formation between berberine chloride and cucurbit(n=7)uril and its analytical application.

The supramolecular interaction of cucurbit(n=7)uril (Q[7]) with berberine chloride (BER) has been studied in aqueous solution at pH 2.0 and room temperature by spectro-fluorimetry. The association constant of the complex was 2.07 × 10(6) L mol(-1) calculated by using a nonlinear least squares method. (1)H NMR spectra confirmed that a 1:1 stable complex is formed between Q[7] and BER. This work proposes a possible interaction mode, in which the guest BER is incorporated inside the hydrophobic cavity of the host Q[7] via the isoquinoline ring part of the guest molecule. Based on a significant enhancement of the fluorescence intensity of this supramolecular complex, a spectrofluorimetric method with high sensitivity and selectivity has been developed for the determination of BER in aqueous solution in the presence of Q[7]. The linear range of the method was from 7.43 to 11.2 × 10(3) ng mL(-1)with the detection limit 4.2 ng mL(-1). There was no interference from the compounds normally used in tablets, serum or urine constituents. The proposed method was applied to the determination of BER in tablets, serum and urine samples with satisfactory results and good consistency with those obtained by the pharmacopoeia method. This shows that it has promising potential for therapeutic drug monitoring and pharmacokinetics and for clinical application.

[Expressional changes of Th1 and Th2 cells in retina of a rat glaucoma model vaccinated by Cop-1].

OBJECTIVE: To explore the morphological and expressional changes of Th1 cells and Th2 cells in retina of a rat model of glaucoma vaccinated by Cop-1 (Copolymer-1) and elucidate the possible neuroprotection roles played by Th1/Th2. METHODS: After modeling, the aqueous outflow from the right eyes was blocked by a ligation of three of four episcleral veins. There were 48 rats with elevated IOP (intraocular pressure) immunized by Cop-1 (Cop-1 group), 48 rats with elevated IOP immunized by PBS (phosphate-buffered saline) (PBS group) and 10 rats without any treatment (normal group). The experimental rats were immunized with Cop-1/PBS emulsified in a total volume of 0.4 ml complete Freund's adjuvant. The immunization was administered subcutaneously at the base of tail. Immunofluorescence was employed to test the distribution and activation of Th1 and Th2 cells in retina at Days 3, 7, 10, 17, 24 and 31 post-immunization respectively for each group. Western blot was selectively performed according to the results of immunofluorescence to verify if there was a similar variation of the retinal expression of IL-4 protein. RESULTS: The results of immunofluorescence showed the numbers of Th1 cells peaked at Day 7 in both Cop-1 ((216 ± 21)/mm(2)) and PBS groups ((194 ± 27)/mm(2)). And no statistical significance existed between two groups (P > 0.05). The numbers of Th2 cells in the experimental groups peaked at Day 7 with statistical significance (Cop-1 group: 300 ± 28/mm(2) vs PBS group: 129 ± 27/mm(2)) (P < 0.01). With the prolongation of experimental period, the number of Th2 cells decreased gradually in the Cop-1 group but remained greater than that of the PBS group afterward (P < 0.05). The Western blot results showed that the expression of IL-4 in the Cop-1 group (1.91 ± 0.05) was significantly higher than that of the PBS group (0.51 ± 0.04) from Day 3 and peaked at Day 7 (2.11 ± 0.06 vs 0.57 ± 0.05). Then the IL-4 expression decreased gradually in the COP-1 group but still represented statistical significance versus the PBS group until Day 31 post-immunization (P < 0.001). CONCLUSION: The retinal activation and accumulation of IL-4 are found in a rat model of chronic glaucoma immunized by Cop-1. Thus Th2 cells may play vital roles in the Cop-1-induced neuroprotective autoimmune responses.

In vivo MR imaging tracking of transplanted mesenchymal stem cells in a rabbit model of acute peripheral nerve traction injury.

PURPOSE: To investigate in vivo MRI tracking mesenchymal stem cells (MSCs) in peripheral nerve injures using a clinically available paramagnetic contrast agent (Gd-DTPA) and commercially available rhodamine-incorporated transfection reagents (PEI-FluoR). MATERIALS AND METHODS: After bone marrow MSCs were labeled with Gd-DTPA and PEI-FluoR complex, the labeling efficacy and longevity of Gd-DTPA maintenance were measured and cell viability, proliferation, and apoptosis were assessed. Thirty-six rabbits with acute sciatic nerve traction injury randomly received 1 × 10(6) labeled (n = 12) or unlabeled MSCs (n = 12) or vehicle alone injection. The distribution and migration of implanted cells was followed by MRI and correlated with histology. The relative signal intensity (RSL) of the grafts was measured. RESULTS: The labeling efficiency was 76 ± 4.7% and the labeling procedure did not influence cell viability, proliferation, and apoptosis. A persistent higher RSL in grafts was found in the labeled group compared with the unlabeled and vehicle groups until 10 days after transplantation (P < 0.05). The distribution and migration of labeled cells could be tracked by MRI until 10 days after transplantation. Transplanted MSCs were not found to transdifferentiate into Schwann-like cells within 14-day follow-up. CONCLUSION: Labeling MSCs with the dual agents may enable cellular MRI of the engraftment in the experimental peripheral nerve injury.

MR neurography: T1 and T2 measurements in acute peripheral nerve traction injury in rabbits.

PURPOSE: To prospectively evaluate magnetic resonance (MR) signal abnormalities and the time course of T1 and T2 values in a rabbit model of acute nerve traction injury with histologic and functional recovery correlation. MATERIALS AND METHODS: All experimental protocols were approved by the institutional animal use and care committee. Acute traction injury was produced in the sciatic nerve of one hind limb in each of 28 rabbits. The contralateral sham-operated nerves served as controls. Sequential MR imaging and T1 and T2 measurements, as well as measurements of functional changes, were obtained over a 70-day follow-up period, with histologic assessments performed at regular intervals. Signal abnormalities and the time course of T1 and T2 values were observed in the proximal, traction, and distal portions of the injured nerves and the sham-operated nerves, and were compared with each other. RESULTS: Nerves with acute traction injury showed visible hyperintense signals on T2-weighted images and had prolonged T1 and T2 values. Differences of T1 and T2 values were dependent on the sites along the same injured nerve, with the most pronounced and prolonged phase of T1 and T2 increases (peak values of 1333 msec +/- 46 and 79 msec +/- 3.7, respectively) observed in the most severely damaged portion of the injured nerve. T1 and T2 values and functional changes after nerve injury showed a similar time course. A return of T1 and T2 signals to normal values correlated with functional improvement. CONCLUSION: MR imaging could be used to help predict the degree of nerve damage and monitor the process of nerve recovery in acute peripheral nerve traction injury. (c) RSNA, 2010.

Efficient in vitro labeling rabbit neural stem cell with paramagnetic Gd-DTPA and fluorescent substance.

OBJECTIVES: The aim of this study is to label rabbit neural stem cells (NSCs) by using standard contrast agents (Gd-DTPA) in combination with PKH26 and in vitro track them with MR imaging. MATERIALS AND METHODS: NSCs from prenatal brains of rabbits were cultured and propagated. Intracellular uptake of Gd-DTPA was achieved by using a non-liposomal lipid transfection reagent (Effectene) as the transfection agent. After labeling with Gd-DTPA, cells were incubated with cellular membrane fluorescent dye PKH26. The labeling effectiveness and the longevity of Gd-DTPA maintenance were measured on a 1.5T MR scanner. The influence of labeling on the cellular biological behaviors was assessed by cellular viability, proliferation and differentiation assessment. RESULTS: The labeling efficiency of Gd-DTPA was up to 90%. The signal intensity on T1-weighted imaging and T1 values of labeled cells were significantly higher than those of unlabeled cells (P<0.05). The minimal number of detectable cells for T1-weighted imaging was 5×10(3). Cellular uptake of Gd-DTPA was maintained until 15 days after initially labeling. There was no significant difference in the cellular viability and proliferation between the labeled and unlabeled NSCs (P>0.05). Normal glial and neuronal differentiation remained in labeled NSCs like unlabeled NSCs. CONCLUSION: Highly efficient labeling NSCs with Gd-DTPA could be achieved by using Effectene. This method of labeling NSCs allows for tracking cells with MR imaging, and without alterations of cellular biological behaviors.

Magnetic resonance imaging of mesenchymal stem cells labeled with dual (MR and fluorescence) agents in rat spinal cord injury.

RATIONALE AND OBJECTIVES: In vivo tracking cells using gadolinium-based contrast agents have the important advantage of providing a positive contrast on T1-weighted images, which is less likely to be confused with artifacts because of postoperative local signal voids such as metal, hemorrhage, or air. The aim of this study is to paramagnetically and fluorescently label marrow with dual agents (gadolinium-diethylene triamine penta-acetic acid [Gd-DTPA] and PEI-FluoR) and track them after transplantation into spinal cord injury (SCI) with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Marrow mesenchymal stem cells (MSCs) from Sprague-Dawley rats were incubated with PEI-FluoR (rhodamine-conjugated PEI-FluoR) and Gd-DTPA complex for labeling. After labeling, cellular viability, proliferation, and apoptosis were evaluated. T1 value and longevity of intracellular Gd-DTPA retention were measured on a 1.5 T MRI scanner. Thirty-six SCI rats were implanted with labeled and unlabeled MSCs and phosphate-buffered saline. Then, serial MRI and Basso-Beattie-Bresnehan (BBB) locomotor tests were performed and correlated with fluorescent microscopy. The relative signal intensity (RSL) of the engraftment in relation to normal cord was measured and the linear mixed model followed by post-hoc Bonferroni test was used to identify significant differences in RSL as well as BBB score. RESULTS: MSCs could be paramagnetically and fluorescently labeled by the dual agents. The labeling did not influence the cellular viability, proliferation, and apoptosis. The longevity of Gd-DTPA retention in labeled MSCs was up to 21 days. The distribution and migration of labeled MSCs in SCI lesions could be tracked until 7 days after implantation on MRI. The relative signal intensities of SCI rats treated with labeled cells at 1 day and 3 days (1.34 +/- 0.02, 1.27 +/- 0.03) were significantly higher than rats treated with unlabeled cells (0.94 +/- 0.01, 0.99 +/- 0.02) and phosphate-buffered saline (0.91 +/- 0.01, 0.95 +/- 0.01) (P < .05). Rats treated with labeled MSCs or unlabeled MSCs achieved significantly higher BBB scores than controls at 14, 21, 28, and 35 days after injury (P < .05). CONCLUSIONS: Labeling MSCs with the dual agents may enable cellular MRI and tracking in experimental spinal cord injury.

[Effects of nuclear factor-kappaB siRNA upon dextran sulphate sodium-induced colitis murine model].

OBJECTIVE: To investigate the effects of nuclear factor-kappaB (NF-kappaB) siRNA upon dextran sulphate sodium (DSS)-induced colitis. METHODS: Thirty-six BALB/C mice were randomly divided into 4 groups: normal control group, NF-kappaB siRNA, scrambled siRNA and DSS group. Colitis was induced by treatment with 5% DSS in drinking water and evaluated by disease activity index (DAI) and histological score. The tumor necrosis factor (TNF-alpha) level of colonic mucosa was measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB p65 expression was determined by immunohistochemical staining. RESULTS: Compared with the scrambled siRNA (DAI 3.42 +/- 0.67, histological score 4.65 +/- 1.53) and DSS group (3.73 +/- 0.55, 4.47 +/- 1.52), a significant decrease was observed in DAI (2.31 +/- 0.26) and histological score (2.19 +/- 0.77) in mice with NF-kappaB p65 siRNA (both P < 0.05). The expression of NF-kappaB p65 and TNF-alpha [(266 +/- 35) pg/ml] in mice with DSS-induced colitis was significantly reduced after treatment with NF-kappaB p65 siRNA (P < 0.05) in comparisons with the scrambled siRNA [(412 +/- 51) pg/ml] and DSS group pg/ml [(449 +/- 44) pg/ml]. CONCLUSION: NF-kappaB p65siRNA shows protective effects upon the mice with DSS-induced colitis. Blockade of NF-kappaB pathway by NF-kappaB p65 siRNA may serve as a novel gene therapy for ulcerative colitis.

Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor -kappaB activation.

BACKGROUND: Activation of nuclear factor (NF)-kappaB has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC), and tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to be a potent inhibitor of NF-kappaB activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of UC. MATERIALS AND METHODS: Tetrandrine was administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. NF-kappaB DNA binding activity was assessed by electrophoretic mobility shift assay. The expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: A significant improvement was observed in DAI and histological score in mice with tetrandrine, and the increase in NF-kappaB DNA binding activity, myeloperoxidase activity, IL-1beta, and TNF-alpha in mice with DSS-induced colitis was significantly reduced following administration of tetrandrine. CONCLUSION: The administration of tetrandrine leads to an amelioration of DSS-induced colitis, suggesting administration of tetrandrine may provide a therapeutic approach for UC.

Bone marrow MR imaging as predictors of outcome in hemopoietic stem cell transplantation.

The purpose of this study is to investigate the role of femoral marrow MR imaging as predictor of outcome for hemopoietic stem cell transplantation (HSCT) in beta-thalassemia major. MR imaging of the proximal femur, including T1- and T2-weighted spin echo and short-tau inversion recovery and in-phase and out-of-phase fast field echo images, was prospectively performed in 27 thalassemia major patients being prepared for HSCT. The area of red marrow and its percentage of the proximal femur were measured, and the presence of marrow hemosiderosis was assessed. Age-adjusted multivariate logistic regression was used to determine the relationship between red marrow area percentage and marrow hemosiderosis and HSCT outcome. Red area percentage were less in patients with successful (90.25 +/- 4.14%) compared to unsuccessful transplants (94.54% +/- 2.93%; p = 0.01). Red marrow area percentage correlated positively with duration of symptoms(r = 0.428, p = 0.026) and serum ferritin (r = 0.511, p = 0.006). In multivariate-adjusted logistic regression analyses, red marrow area percentage was significantly inversely associated with successful HSCT (OR = 1.383, 95% CI: 1.059-1.805, p = 0.005). Marrow hemosidersosis and duration of sympotms and serum ferritin were not associated with HSCT outcome(p = 0.174, 0.974, 0.762, respectively). Red marrow area percentage of proximal femur on MR imaging is a useful predictor of HSCT outcome.