Objective To compare the success rate, time of tumor formation and number of tumors in three methods of tumor transplantation, in order to seek an ideal animal model for molecular imaging study. Methods Forty-eight BALB/C-nu/nu nude mice were randomly divided into three groups (each n=16). Tumor tissue mass of 2 mm3 was injected into subcutaneous of nude mice in experiment group. Tumor tissue mass of 1 mm3 was applied in control group 1. Tumor cells suspension liquid was injected into subcutaneous of nude mice in control group 2. The tumor formation rate, the time of tumor formation and the number of tumors were observed. MRI scanning were performed 3-6 weeks after implantation. Results The rate of tumor formation of three groups was 93.75%, 75.00% and 43.75%, respectively. The time of tumor formation was (21.7±2.4), (29.8±2.9) and (34.6±3.9) days, respectively. The rate of solitary nodule implanted tumor was 93.33% in experiment group, higher than that in control group 1 (75.00%) and control group 2 (14.29%). The tumors were hypointense on T1WI and hyperintense on T2WI. Conclusion Transplantation 2 mm3 tumor tissue mass is effective to set up the subcutaneous implanted tumor models with a high success rate of tumor formation, a short time of tumor formation and high rate of solitary tumors, being suitable for the study of molecular imaging. The models can undertake conventional T1WI, T2WI and T2-mapping imaging, and the imaging qualities are good.

Objective To evaluate the diagnostic values of diffusion tensor imaging(DTI)in early radiation-induced brain injury of the temporal lobes.Methods Conventional and MR diffusion tensor imaging examinations were performed in 23 patients following radiotherapy for nasopharyngeal carcinoma(NPC)and in 28 age-matched healthy controls.Isotropic apparent diffusion coefficient(ADCiso)and anisotropic index were measured in the white matter on both of the temporal lobes.Results The value of ADCiso,fractional anisotropy(FA),relative anisotropy(RA)and 1 minus volume ratio(1-VR)were(644.08?56.80)?10-6 mm2/s,0.394?0.074,0.344?0.075 and 0.182?0.072 respectively.In comparison with control group,these values were significant decreased(P

Objeetive To evaluate the diagnostic value of axially loaded MR imaging with supine position in patients with degenerative disorders of lumbar spine.Methods Thirty asymptomatic volunteers and 89 patients were examined in psoas-relaxed position(PRP)and axially compressed supine position(ACE)of the lumbar spine.Sixty-one patients with low back pain,19 with sciatica and 9 with neurogenic claudication were included in the symptomatic study group.The disc levels from L3 to S1 were examined.Results In 30 asymptomatie volunteers,a significant decrease in dural sac cross-sectional area(DSCA)was found at 14 disc levels(15.6%)in 10 individuals(33.3%)during ACE(>15 mm2).In 89 patients.a significant decrease in DSCA was found at 55 disc levels(20.6%)in 38 patients(42.7%)during ACE(>15 mm2),and the mean decrease was 28 mm2.During ACE,32 disc levels with an increasing severity of disc herniation were noted in 26 patients.16 disc levels with neural foramen stenosis were found in 12 patients,11 disc levels with ligamentum flavum thickening were observed in 10 patients,3 cases facet dislocation and 3 cases lumbar spondylolisthesis were also seen.In 22 of the 89 patients(24.7%).additional valuable information(AVI)was found during ACE,including 7 patients(7/9)with neurogenic claudication,8 patients(8/19)with sciatica,and 11.5%(7/61)of the patients with low back pain.Conclusion As compared with conventional imaging methods,axially loaded imaging provides AVI,and more occult lesions can be found during ACE.ACE MRI is a valuable tool in diagnosing degenerative disorders of lumbar spine.

Objective To explore the value of Gadofluorine M,a novel M RI enhancement agent,in the diagnosis the early radiation brain injury.Methods Seventy-two Wistar rats were randomly divided into 5 equal groups.To establish the radiation injury model,the rat's posterior brain was irradiated with 0(blank controls),25,35,45,55,and 65 Gy,respectively.After irradiation MR plain scanning and Gadofluorine M enhancement scanning (after the T1WI and T2WI scanning Gf at the dosage of 0.1 mmol/kg was injected intravenously and scanning was performed again 12 h later) were performed once a week for 8 weeks.Another 12 rats were randomly divided into 2 equal groups to exposure to 55 and 65Gy,respectively,and MR scanning was performed once a week for 8 weeks since the third week after MR.After T1WI and T2WI scanning Gd-DTPA was injected intravenously,MR was conducted again 30 min later,and Gf was injected intravenously (Gd-DTPAenhancement and Gf enhancement contrast).The MR image and the pixel count were compared.Since the third week 2 rats from the Gf enhancement scanning group and 1 rat from the Gd-DTPA enhancement and Gf enhancement contrast were killed after MR with their brains taken out to undergo pathological examination.Results No abnormal signal changes were found in MRI in 25 and 35 Gy groups within 2 months after irradiation.A high signal in the Gf enhancement T1 WI image was found in 45,55,and 65 Gy groups within the period of 4-6 weeks after radiation.The signal intensity was significantly higher than that of the control,25,and 35 Gy groups(F =2.15,P <0.05).The emerge time of this signal was negatively correlated with the dose of radiation(r =-0.62,P < 0.05).When there was no obvious change was found by Gd-DTPA enhancement,a high signal representing change of injury could be found in Gf enhancement in the same rat.The signal intensity was significantly enhanced in Gf enhancement compared to the Gd-DTPA enhancement (F = 2.74,P <0.01).Histopathology examination of the 65 Gy group showed frosted degeneration in part of the region,however,no obvious necrotic damage was found in other groups.Conclusions The Gf enhancement change appears before histopathological changes,it helps discover early radiation injury in brain.Compared to the regular MRI and Gd-DTPA enhancement,Gadofluorine M enhancement has obvious advantage and is worth further research and application.

Objective To discuss the value of MR T2 mapping in the research of the biomechanics and function of cartilage of knee joint.Methods Knees of 20 healthy adults before and after jogging and 19 osteoarthritis patients were examined with sagittal 8-echo SE sequence.The T2 value of cartilage was selected and calculated.The T2 values in the superficial and deep cartilage of femoral and tibial joint before and after jogging were compared,so did between the osteoarthritis patients and healthy adults.The source images were sent to the workstation to get T2 mappings.The T2 value of cartilage between before and after jogging was compared with paired-samples t test.The T2 value between superficial and deep cartilage before jogging was compared with independent-samples t test,so did between the osteoarthritis patients and healthy adults.Results The T2 values in the superficial and the deep tibial cartilage were(48.8±6.3)ms,(44.3±5.7)ms before jogging and(43.4±5.0)ms,(40.3±6.1)ms after jogging.The T2 values were significantly different between before and after jogging(t=6.004 and t=5.037,P＜0.05).There was a significant difference between superficial and deep tibial cartilage before jogging(t=3.148,P＜0.01).The T2 Values in the superficial and deep femoral cartilage were(52.1±5.7)ms,(47.7±5.3)ms before jogging and(47.2±4.5)ms,(43.6±4.1)ms after jogging.The T2 values were significantly different between before and after jogging(t=6.169 and t=5.957,P＜0.05).There was a significant difference between superficial and deep femoral cartilage before jogging(t=3.384,P＜0.01).The T2 mapping showed those changes.The mean T2 value in the tibial cartilage of osteoarthritis patients was(56.0±9.1)ms and was higher than that of healthy adults.There was a significent difference between osteoarthritis patients and healthy adults(t=-3.446,P＜0.01).Conclusion T2 mapping can be used in the research of biomechanics and function of cartilage and has a prelimilary value in the diagnosis of cartilage degeneration.

Objective To evaluate the tumor targeting characteristic of the Folate-SPIO-DOX-Micelles by in vitro studies,and to test the feasibility of monitor tumor targeting using it and clinical MRI.Methods The polymeric micelles,Folate-SPIO-DOXO-Micelles were prepared.The in vitro tumor cell targeting efficacy of these folate modified and DOX or SPIO-loaded micelles (Folate-SPIO-DOX-Micelles)was evaluated by observing the cellular uptake of micelles by human hepatic carcinoma cells(Bel 7402 cells) which overexpressed folate surface receptors. Cell suspensions were incubated with Folate-SPIO-DOXO-Micelles for 1 h.Prussian blue staining was performed to show intracellular irons.Flow cytometry was used to further quantify the cellular uptake of the nanoparticles into Bel 7402 cells.MRl was performed to show the signal intensity changes by using T2 WI sequences at a clinical 1.5 T MR system.Results Prussian blue staining showed much more intracellular iron in cells incubated with Folate-SPIO-DOX-Micelles than the cells incubated with the non-targeting SPIO-DOX-Micelles.As revealed by flow cytometry,the mean fluorescence intensity of cells in the folate group and the non-folate group were 117.88 and 46.33,respectively.The T2 signal intensity in MRI of cells treated with the folate targeting micelles decreased significantly (when the concentration of SPIO in cell culture medium was 5,10,20,40,and 80 μg/ml,respectively,T2 signal intensity decreased by -5.02%,-23.58%,-45.89%,-70.34%,and -92.41%,respectively).In contrast,T2 signal intensity did not show obvious decrease for cells treated with the folate-free micelles (when the concentration of SPIO in cell culture medium was at 5,10,20,40,and 80 μg/ml,respectively,T2 signal intensity decreased by -3.77%,-2.16%,-2.18%,-2.74% and -19.77%,respectively).Conclusion The polymeric micelles,Folate-SPIO-DOX-Micelles has good targeting ability to the hepatic carcinoma cells in vitro,and the cell targeting events of the micelles can be monitored by using a clinical MR scanner.

Objective To determine the feasibility of magnetically labeling and tracking mesenchymal stem cells(MSCs)in vitro by using a gadolinium and fluorescent bi-functionally transfection agent of polyethylenimine.Methods A gadolinium bifunctional transfection reagent complex was obtained after the linear polyethylenimine derivative(JetPEI-FluoR)was incubated with Gd-DTPA.Mesenchymal stem cells isolated from the bone marrows of SD rats were cultured and expanded.The mesenchymal stem cells were incubated with the bi-functional labeling agents.After labeling,the MSCs were examined with fluoroscope and electron microscope and the biological characters were detected including trypan blue exclusion test,MTT,and apoptosis detection.On a 1.5 T MR system,the labeled MSCs were examined with spin echo T1 WI and T2 WI and T1 measurement with mixed sequence.After labeling,the cells were cultured and undergone routine passage.Prior MR examinations were repeated for each passage of labeled cells.All data was statistically prolessed with SPSS for Windows.Results Of 5×105 MSCs incubated with the bi-functional agents,4.25×105 MSCs were successfully labeled,the percentage of labeled MSCs was 85% fluoroscopically.The high density electron particles of gadolinium observed electron microscopically existed around cellular apparatuses,especially around Golgi apparatus.In trypan blue exclusion test,the exclusion rate of labeled MSCs with incubation duration of 3,6,12,24 h was(96.55±2.90)%,(94.17±2.56)%,(97.16±3.12)% and(94.23±2.67)%,respectively.The corresponding exclusion rate of unlabeled MSCs was(95.86±2.67)%,(92.04±2.21)%,(93.38±3.64)%and(92.12±2.53)%,respectively.There was no statistical difference of trypan blue exclusion rate between labeled cells and control unlabeled cells within 24 hours of incubation(F=4.523,P＞0.05).In the proliferation test,the optical absorption value of labeled MSC with 2.5,5.0,10.0,20.0,30.0 and 40.0 μl bi-functional labeling agent was(0.1884±0.0151),(0.1878±0.0190),(0.1741±0.0160),(0.1135±0.0215),(0.1079±0.0145)and(0.0811±0.0079),respectively.The corresponding optical absorption value of unlabeled MSCs was(0.1940±0.0116).The optical absorption value of labeled cells was not affected in case of less than 30.0 μl of Gd-DTPA(q'=0.2225-0.9458,P＞0.05).The apoptosis index for labeled cells and unlabeled cells were 5.08% and 3.86%,respectively.On T1 WI,the signal intensity and T1 relaxation time of unlabeled cells and labeled cells were 240.3±24.7 and(2457±56)ms,336.2±20.7 and(1102±64)ms,respectively,and there were significant statistical difference(t=12.656,17.889,P＜0.01).The minimal amount of cells which was detectable for T1 WI was 5×103.After routine passage,the gadolinium in the cells gradually decreased and could be tracked by MRI until the fifth passage.Conclusions The gadolinium and fluorescent bi-functionally labeling rat bone marrow mesenchymal stem cell by using the transfection agent of polyethylenimine is feasible,efficient and safe.The labeled cells could be tracked in vitro on MR imaging.

OBJECTIVETo investigate the effect of CCM3 gene defection on lead induced cell genotoxicity in mouse embryonic fibroblasts.

METHODSC57 female mice were mated with CCM3 gene heterozygous male mice. E13.5 embryos were taken to isolate primary mouse embryonic fibroblasts. After genotyping, wild type and heterozygous cells were treated with different doses of lead acetate. Cell viability, genotoxicity and protein expression were detected by MTS assay, CB micronucleus method and Western blot, respectively.

RESULTSMouse embryonic fibroblasts with lead acetate treatment for 24 h, wild-type cells 100.00 µmol/L lead acetate-treated group (69.16±1.36) and the control group (100.00±2.33) compared to cells decreased by 30%, CCM3 heterozygous type cell 100.00 µmol/L lead acetate-treated group (87.16±5.50) and the control group (100.00±2.06) compared to cells decreased by 13%, the difference was statistically significant (F values were 98.59, 82.63, P<0.001). Lead acetate treatment after 48 h, wild-type cells 100.00 µmol/L lead acetate-treated group (51.99±5.62) and the control group (100.00±3.11) compared to cells decreased by 50%, heterozygous type cells 100.00 µmol/L lead acetate treatment group (66.33±4.06) and the control group (100.00±5.72) compared to cells decreased by 35%, the differences were statistically significant (F values were 82.63, 36.86, P < 0.001). The results of CBMN test showed that with increased dose, micronucleus cell rate of two genotypes showed an increasing trend, in the wild-type cells, the micronucleus cell rate (/1 000) for the control group, 29.6±2.2, 6.25 µmol/L dose group 47.3±6.6, 25 µmol/L dose group 55.5±9.1, 100.00 µmol/L dose group 66.8±3.5; heterozygous cells micronucleus cell rate (/1 000) for the control group, 35.3±5.6, 6.25 µmol/L dose of 50.0±8.3, 25.00 µmol/L dose group 57.0±8.5, 100.00 µmol/L dose group 58.8±2.1. Micronucleus cell rates (/1 000) were significant differences, in 100.00 µmol/L dose groups of two genotypes. Western blot results showed that wild-type cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.70±0.03) was 1.32 times higher than the control group (0.53±0.07), heterozygous cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.48±0.02) was 1.77 times higher than control group that of 0.27±0.04, there was statistically significant difference (F values were 14.77, 25.74, P < 0.001); wild-type cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.69±0.03) was 1.06 times higher than the control group (0.65±0.07), heterozygous cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.99±0.04) was 1.55 times higher than the control group CCM3 expression levels (0.64±0.06), there was statistically significant difference (wild-type cells: F = 7.08, P = 0.012, heterozygous type cell: F = 13.49, P = 0.002).

CONCLUSIONCCM3 gene may play a role in lead-induced genetic toxicity of mouse embryonic fibroblasts, CCM3 gene-lead interactions effects on mouse embryonic fibroblasts cell toxicity.

Animals ; Apoptosis Regulatory Proteins ; DNA Damage ; Embryo, Mammalian ; Female ; Fibroblasts ; Genotype ; Male ; Membrane Proteins ; Mice ; Mice, Inbred Strains ; Micronuclei, Chromosome-Defective ; Organometallic Compounds ; Proto-Oncogene Proteins

In recent years, osteoporosis (OP) has become one of the main diseases affecting the health of middle-aged and elderly people in China, and the prevalence of OP has increased significantly. The clinical diagnosis and treatment guidelines for this disease are also constantly updated. The overall principles speciallyemphasise that doctors and patients need to work together to negotiate the details of the diagnosis and treatment guidelines, in order to improve the OP clinical diagnosis and treatment rate. Therefore, patients′ knowledge of the disease, understanding of clinical guidelines, and cooperation with doctors to implement diagnosis and treatment plans are very important. In this study, from the most concerned issues of the patients, we established the OP patient practice guideline working group. 14 recommendations, as the OP patient practice guidelines, are proposed in accordance with the relevant principles of the "World Health Organization guidelines development manual" and the international normative process.