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Objective To explore the CT dominant phase and optimal classification model in differenting clear cell renal cell carcinoma (ccRCC) from fat‐poor angiomyolipoma (fpAML) through quantitative multiple‐phase CT radiomic features analysis. Methods Clinical and imaging data of 195 cases pathologically confirmed ccRCC (n=131) and fpAML (n=64) were retrospectively studied. All the patients underwent non‐contrast enhanced CT scans and dynamic multi‐phase (corticomedullary phase, medullary phase and excretion phase) contrast‐enhanced CT scans. Regions of interest (ROIs) were manually delineated based on the selected image slices with the maximal diameter of the lesion using ITK‐SNAP software, followed by the acquisition of candidate CT radiomic feature sets from each phase with statistically significant differences by using Mann‐Whitney U test. Then, using the synthetic minority oversampling technique (SMOTE), 232 classification models which are composed of 29 different feature selection algorithms (top 10 features were chosen by the backward elimination method) and 8 different classifiers were constructed. Employing the 5‐fold cross‐validation method, the performance of each classification models for each phase was evaluated using accuracy (ACC), sensitivity (SEN), specificity (SPE) and area under receiver operating characteristic curve (AUC), to acquire dominant CT phases and the optimal classification models for distingushing ccRCC and fpAML, along with the key imaging radiomic features. Results In this study, the mean maximal diameter of ccRCC and fpAML lesions were (3.9±1.4) cm, and (3.5±1.7) cm, respectively, and there was no statistically significant difference in the size of the tumor between two groups (P>0.05). From 102 initial imaging feature sets, the total number of candidate imaging feature sets (P<0.05) were:non‐enhanced phase (n=26), corticomedullary phase (n=71), medullary phase (n=68), excretion phase (n=62). Among the 232 classification models through different combination of classifiers and feature selectors, the amount of classification models which achieved the maximum of AUC value (AUCmax) from different CT phases were: non‐enhanced phase (n=106, 45.7%), corticomedullary phase (n=94, 40.5%), medullary phase (n=23, 9.9%), excretion phase (n=9, 3.9%). Imaging features from non‐enhanced phase and corticomedullary phase yielded higher performance compared with medullary phase and excretion phase, with the corresponding optimal prediction models were SVM‐fisher_score (AUC: 0.897, ACC: 83%, SEN: 84%, SPE:80%) and Logistic Regression‐RFS (AUC: 0.891, ACC: 83%, SEN: 81%, SPE: 89%), respectively. Conclusions The quantitative imaging features from non‐enhanced and corticomedullary phase have better performance among proposed classification models than that from medullary phase and excretion phase. Furthermore, it is feasible to acquire proper combination of feature selection and classifiers to achieve high performance in identifying ccRCC and fpAML.
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[Objective]To explore the MRI features of the mucinous breast carcinoma and the correlation with biological prognos?tic factors.[Methods]MRI features of 35 pure and 15 mixed mucinous carcinomas were retrospectively analyzed. MR images were reviewed for shape,margin,the signal intensity,enhancement patterns of tumors and DWI features. All the patients were detected by immunohistochemical staining with expression of ER,PR,CerbB-2,Ki-67 and Her-2. Correlations between the pure and mixed mucinous breast carcinoma and prognostic factors were analyzed.[Results]16 oval masses(16/35,45.7%)and 10 circular masses (10/35,28.6%)were found in 35 pure mucinous breast carcinomas with clear boundary(26/35,74.3%)and lobulated shape(31/35,88.6%);9 irregular masses(9/15,60%)were found in mixed mucinous breast carcinomas with unclear boundary(13/15, 86.7%). Very high signal intensity on T2-weighted images was found in 33 pure mucinous carcinomas(33/35,94.3%)and 11 mixed mucinous carcinomas showed mixed signal intensity(11/15,73.3%). Early enhancement rate was(114.7 ± 9.1)% for pure muci?nous carcinomas and(165.6 ± 14.3)%for mixed mucinous carcinomas. 28 pure mucinous tumors demonstrated persistent enhancing pattern on time-signal intensity curve ,7 pure mucinous tumors demonstrated plateau pattern and 7 mixed mucinous carcinomas showed plateau pattern and washout pattern respectively. Mean ADC value was(1.91 ± 0.06)×10-3 mm2/s for pure mucinous carcino?mas and(1.13±0.08)×10-3mm2/s for mixed mucinous carcinomas. There was significant difference with morphology,boundary,T2WI signal,early enhancement rate,time-signal intensity curve,ADC value between pure and mixed mucinous breast carcinoma(P <0.05). There was significant difference between pure and mixed mucinous breast carcinoma with Her-2 and Ki-67 expression(P <0.05).[Conclusion]MRI could identify PMBC and MMBC from the shape,the signal intensity,dynamic enhancement and ADC val?ue,and PMBC had distinctive MRI features. The prognosis of MMBC is worse than that of PMBC form correlation between biological prognostic factors and mucinous breast carcinoma.
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Objective To explore a novel long-circulating dual-receptor targeting and dual-modal molecular probe and investigate its physicochemical properties and targeting effect on breast cancer cells in vitro. Methods Dual-receptor targeting and dual-modal molecular probe RGD@BBN-lipo(QDs)-SPIO was synthesized in the following steps: long-circulating liposome was prepared by film dispersion method;water-soluble superparamagnetic iron oxide (SPIO) nanoparticles and Quantum dots (QDs) were loaded in the hydrophilic and hydrophobic layer of liposome, respectively;RGD and BBN polypeptides were coupled on the former functional magnetic/fluorescent liposomes. Stability of the probe in different physiological solutions was investigated. Transmission electron microscopy (TEM) and particle size analyzer were used to measure nanoparticle sizes and the Zeta potential. Characterization of RGD and BBN was investigated through 1H-NMR and elemental analysis. The MRI T2 relaxivities (1/T2) of RGD@BBN-lipo(QDs)-SPIO was measured through T2 map scanning on 3.0 T MR system. HUV-EC-C cells were used for assessment of cells viability by MTS assay. Prussian blue staining and fluorescence imaging were carried out to determine the targeted breast cellular uptake of RGD@BBN-lipo(QDs)-SPIO nanoparticles. Results The targeting magnetic/fluorescent dual-model molecular probes appeared spherical or para-spherical,with a mean diameter of(118.2±3.9)nm,Zeta potential of (-24.78±1.68) mV,MR T2 magnetic relaxation rate of 0.498 1× 106 M-1 · s-1.RGD and BBN polypeptides were successfully coupled on the former functionally magnetic/fluorescent liposomes with the bind rates of 33.05%and 45.06%, respectively. There was low cytotoxity of the molecular probe on human umbilical vein endothelical cells(HUV-EC-C)by MTS study. Prussian blue staining and fluorescence imaging studies showed that the RGD@BBN-lipo(QDs)-SPIO nanoparticles could target any αvβ3 or gastrin releasing peptide receptor overexpression breast cancer. Conclusions RGD@BBN-lipo(QDs)-SPIO is a novel long-circulating dual-receptor targeting and dual-modal molecular probe and has excellent physicochemical properties and stability, high T2 relaxivities and strong targeting effect on cancer cells and has laid a solid foundation for early diagnosis of breast cancer.
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Objective To investigate the diagnostic value of the texture analysis derived from conventional MR imaging in differentiating glioblastomas from solitary brain metastases. Methods Thirty-four patients with pathological diagnoses of glioblastomas and 34 patients with pathological diagnoses of solitary brain metastases were enrolled in our study. All patients underwent conventional MR imaging including axial T1WI, T2WI, fluid attenuated inversion recovery (FLAIR) and contrast-enhanced T1WI before surgery. Texture features were calculated from manually drawn ROIs by using MaZda software. The feature selection methods included mutual information (MI), Fishers coefficient, classification error probability combined with average correlation coefficients (POE+ACC) and the combination of the above three methods. These methods were used to identify the most significant texture features in discriminating glioblastomas from metastases. Then the statistical methods including raw data analysis (RDA), principal component analysis (PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA) were used to distinguish glioblastomas from metastases. The results were shown by misclassification rate. Meanwhile, two senior radiologists (who had 5 and 9 years of experience in neuroimaging diagnosis, respectively) analysed the data of the 68 patients. Chi-square test was used to compare the differences in the results between the radiologists' analysis and the texture analysis. Results In the four kinds of sequences, the texture features for differentiating glioblastomas from solitary brain metastases were mainly from T2WI which had the lowest misclassification rate, 8.82% (6/68). The misclassification rates of the feature selection methods were similar in MI, Fisher's coefficient and POE + ACC (10.29%-27.94% for MI;11.76%-44.12% for Fisher's coefficientand 8.82%-38.24% for POE+ACC). However, the misclassification rate of the combination of the three methods (8.82%-33.83% for FPM) was lower than that of any other kind of method. In the statistical methods, NDA (8.82%-11.76% ) had lower misclassification rate than RDA (26.47%-39.71% ), PCA (27.94%-39.71%) and LDA (13.24%-44.12%). Misclassification rate of the radiologists' analysis 14.71%(10/68) was higher than that of the texture analysis, but there was no statistically difference between them (χ2= 10.993, P=0.287). Conclusion Texture analysis of conventional MR imaging can provide reliably objective basis for differentiating glioblastoma from solitary brain metastasis.
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Objective To explore a promising system for tumor CD 44 receptor-targeted imaging and to investigate their physic-chemical properties and targeting effect on CD 44 abundant cancer cells in vitro.Methods The superparamagnetic iron oxide ( SPIO) nanoparticles were prepared by a coprecipitation in alkaline media starting from a mixed of the ferrous and ferric solution.And then the surface of the SPIO nanoparticles were modified with APTMS by a reaction with the hydroxyl groups.Finally, the hyaluronan-modified SPIO ( SPIO-HA) nanoparticles were prepared.Control and experimental groups were established after adding SPIO or SPIO-HA as agents respectively.Transmission electron microscopy ( TEM) and particle size analyzer were used to measure these nanoparticle sizes and the hydrodynamic diameters.Thermogravimetric analysis ( TGA) was carried out to evaluate the HA-content on the surface of SPIO-HA.The MRI T2 ralaxivities (1/T2 ) of the two groups at different Fe concentrations (0.09, 0.18, 0.27, 0.36, 0.45 mmol/L ) were measured on a 3.0T MR system.HepG2 cells and HL7702 cells were used for assessment of cells viability by methyl thiazolyl tetrazolium ( MTT ) assay.Prussian blue staining , immunoassay fluorescence image and flow cytometry were carried out to determine the targeted cellular uptake of SPIO-HA nanoparticles.MRI were performed to show the MR T 2 value changes after incubating with HepG2 cancer cells by using T 2 WI sequences at a clinical 3.0 T MR system.One-way analysis of variance was performed to determine significant changes in MR T 2 values of blank control , SPIO-HA and SPIO groups.Results The SPIO-HA and SPIO NPs were fairly homogeneous with an average core size of 18.2 and 22.4 nm, hydrodynamic diameter of 91.1 and 103.2 nm, Zeta potential of (-45.00 ±0.86) mV and (-18.50 ±0.73) mV, and magnetic relaxivity of 0.212 ×106 M-1 · s-1 and 0.191 ×106 M-1 · s-1.Based on the TGA data , HA accounted for 24%weight of each SPIO-HA.The internalization of the SPIO-HA was confirmed by prussian blue staining , while the cells showed no obvious blue stains with SPIO , incubation of SPIO-HA with tumor cells led to blue color inside the cells.After that, we examined cancer cell binding of FITC-SPIO-HA by immunoassay fluorescence image and flow cytometry.The green fluorescence resulting from FITC-SPIO-HA was observed inside the cells in both the cytoplasm and the plasmalemma.Tumor cells treated with SPIO-HA exhibited higher fluorescence signals with 7.97-fold enhancement observed for HepG 2 cells over control particles.In vitro MR, mean T2 values of blank control , SPIO and SPIO-HA groups were ( 115.20 ±0.36 ), ( 115.07 ±0.81 ) and ( 21.67 ±0.21 ) ms, respectively.There was significant difference among those three groups (F=31 703.339,P<0.01), MR T2 values of HepG2 cells treated with the SPIO-HA NPs were lower than blank and SPIO group.In comparison, SPIO did not generate any MRI signal changes compared with blank group.Conclusion The tumor CD44 receptor-targeted MR molecular probe SPIO-HA had a good physic-chemical property and well targeted HepG2 cells.
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As a carrier for MRI contrast agent,active targeting liposome demonstrates distinct advantages in tumor diagnosis and treatment due to its characteristics of biocompatibility,non-toxicity and targeting ability.Tumor targeting imaging with liposome labeled with molecular recognition system,or liposome sensitive to pH value or temperature is a popular research topic.The application of various types of active targeting liposome for tumor magnetic resonance imaging is reviewed in this review.
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Objective To study the characteristics of DWI in nude mice models of hepatic Bel7402 tumors after treatment with adenovirus-mediated cytosine diaminase-thymidine kinase ( Ad.CD-TK) double suicide gene therapy, and then to identify whether DWI can be used for assessing curative effect of postoperative tumors.Methods Thirty nude mice models of hepatic Be17402 tumors were successfully created using cell suspension method,after the tumor grew to more than 1 cm in diameter,20 tumor models were treated by intratumoral administration of Ad.CD-TK for 3 days plus intraperitonea( i.p.) treatment with 5-Fc and GCV for the duration of the study.Then they were randomly divided into three groups during 5-Fc and GCV treatment.The remaining 10 tumor models were used as controls.MR scanning were performed in 10th day before and after tumor implantation in all models by using EPI-SE series and SENSE technology for treatment group. Tumor volumes and ADC values were calculated pretreatment and posttreatment. Cell apoptosis were determined by using TUNEL method.Analyze the change of ADC and apoptosis index (AI) in different times,t test was used for comparison the difference of AI and ADC values respectively. Results After 10 days,the tumor volumes of the treatment groups and controls were respectively (724.16 ±57.45 ) mm3,( 754.57 ± 66.84 ) mm3,with no significant difference ( t =0.488,P ＞ 0.05 ).The ADC values of the treatment groups were (0.98 ±0.11 ) × 10-3 mm2/s,the ones of the control groups were (0.68 ±0.04) × 10 -3mm2/s;AI of the treatment groups were(23.25 ±6.57)％,the ones of the control groups were (2.57 ± 0.58) ％.There were difference in both groups ( t =4.473,5.874 ; P ＜ 0.01 ).Conclusion DWI can be effectively to monitor the early pathological changes of hepatic Bel7402 tumors after Ad.CD-TK double suicide gene therapy,and provide experimental evidences for clinical application.
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Objective To evaluate pharmacodynamics of prepared long-circulating superparamagnetic iron oxide (SPIO) liposomes. Methods Control and experimental groups were established after adding SPIO or long-circulating SPIO liposomes as agents. (1)Macrophages experiment in vitro: the RAW 264.7 macrophage cell strains were recovered, cultured and seeded in the culture plate at a density of 2.5×105 cells/well until they reached 80%-90% confluence. The intracellular Fe uptake of control and experimental group cells were quantified by Ferrozine assay after incubation with different concentrations of drugs. Factorial design analysis of variance was used as statistics method. Prussian blue staining method was used to detect staining of experimental cells.(2)Drug biodistribution in mice: C57BL/6J(n=6) were classified into blank control group (n=2), control group(n=2) and experimental group(n=2).Saline, SPIO and long circulating SPIO were injected via the tail vein in the blank control group, control group and experimental group respectively. Then distribution of drugs in the body was observed by pathological examination.(3) MR imaging of tumor-bearing nude mice: 20 BALB/c nude mice bearing lung cancer models were established and classified into control group and experimental group. After administration of drugs, all animals underwent MR scanning. Signal intensities of livers and tumors were measured, SNR-time dynamic curves were drew. Covariance analysis was used to compare post-enhanced SNR at the 12th hour. (4)Cytotoxicity studies (MTT): cytotoxicity of both drugs on human liver cell line HL-7702 was studied, and statistically analyzed using factorial design analysis of variance. Results (1) Macrophages experiment in vitro: The nanoparticle uptake by macrophage cells evaluated by ferrozine assay showed the uptake of blank SPIO was higher than long-circulating SPIO liposomes. Compared with the blank control group, there was strong blue staining in the macrophages with Prussian staining in the control group and little blue staining in the experimental group. (2) Drug biodistribution in mice: for blue stained cells composed of iron particles, the amounts in the liver, spleen, lung, kidney of the control group were more than those in the experimental group. (3) MR imaging of tumor-bearing nude mice: the non-enhanced SNR of livers and tumors in the control group and experimental group were 31.47 ± 0.56, 30.89 ± 1.41, 58.41 ± 0.61, 58.44 ± 1.08, respectively. After injecting of contrast agents, SNR of livers and tumors in the control group and experimental group were 17.00 ± 0.96, 22.29 ± 0.73, 58.50 ± 0.63, 52.47 ± 1.18, respectively. The covariance analysis showed that SNR of the livers in the control group after 12 hours was significantly lower than the experimental group (F=167.022, P=0.000); while the SNR of the tumors in the experimental group was significantly lower than the control group (F=266.106, P=0.000).(4) Cytotoxicity of nanoparticles by MTT method: the viability of HL-7702 cells tend to decrease with the increase of Fe concentration. Cytotoxicity in the long-circulating SPIO liposomes was lower than the SPIO(F=2256.204,P=0.000). Conclusions Long-circulating SPIO liposomes we prepared reveal suitable sizes, even distribution, and good anti-macrophage ability in vitro and in vivo. They have long circulation characteristic and T2 negative enhancement effect in the transplanted lung cancers, while they still maintain low cytotoxicity.