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Aggregation-induced emission (AIE) refers to an uncommon phenomenon that some fluorogens are weakly emissive in solution but become intensely florescent in aggregated state. Fluorogens with the characteristics of AIE are called AIEgens. Traditional dyes often suffer from a common photophysical phenomenon named aggregation-caused quenching (ACQ). As an anti-ACQ phenomenon, AIE shows great potential in biomedical applications. In this paper, the flurescence mechanism and characteristics of AIE are summarized, and the recent advances of aggregation-induced emission in tumor diagnosis and therapy is reviewed.
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Objective To preliminarily explore the anti?cancer efficiency of disulfide?bonded hyaluronic acid?functionalized targeted sodium?meter probe for hepatocellular carcinoma and the feasibility of MRI. Methods Twenty?one nude mice models of subcutaneous liver cancer transplantation were randomly divided into saline, hyaluronic acid?poly ε?caprolactone@ doxorubicin/superparamagnetic iron oxide (HA?PCL@DOX/SPIO) and HA?disulfide?bonded?PCL@DOX/SPIO (HA?SS?PCL@DOX/SPIO) groups, with 7 mice in each group. The experimental groups were injected with micelles at a dose of Fe 5 mg/kg through the tail vein, and the control group was injected with the same amount of saline via the tail vein. MRI was performed before and after injection (2 h, 4 h, 8 h). The T2 value of the region of interest (tumor) was measured and its decline rate was calculated. Twenty?one nude mice models of orthotopic liver cancer transplantation were randomly divided into saline group,HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups, with 7 mice in each group. The experimental groups were injected with micelles at a dose of DOX 2 mg/kg through the tail vein by three consecutive times a day apart, and the control group was injected with the same amount of saline through the tail vein. Continuous observation for 15 days to calculate tumor inhibition rate. One way ANOVA test was used. Results The T2 value of HA?SS?PCL@DOX/SPIO group decreased significantly after 2, 4 and 8 hours (P<0.05) than initial time, which was distinct compared with HA?PCL@DOX/SPIO group. The growth rate of tumor in HA?SS?PCL@DOX/SPIO and HA?PCL@DOX/SPIO groups was significantly lower than that in the control group (F=21.513,P<0.05). The former had the most obvious inhibitory effect on orthotopic liver cancer (47.7% and 28.2%). Conclusion Disulfide?bonded hyaluronic acid?functionalized targeted sodium?meter probe for hepatocellular carcinoma(HA?SS?PCL@DOX/SPIO) has high anti?cancer efficiency and imaging function at the animal level in vivo, and can be used to monitor the early therapeutic effect of tumor at the molecular imaging level.
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Objective To explore the construction method and physicochemical properties of disulfide?bonded hyaluronic acid?functionalized sodium?meter probe for hepatocellular carcinoma, and its biological evaluation in vitro and feasibility of MRI. Methods Synthesis of hyaluronic acid?disulfide?bonded?poly ε?caprolactone (HA?SS?PCL) by disulfide?bonded alkynyl?terminated polycaprolacton (alkyne?SS?PCL) and azido?terminated hyaluronic acid (HA?N3) by clicking chemical reaction, then doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) were encapsulated in HA?SS?PCL core by dialysis method.HA?SS?PCL@DOX/SPIO was prepared and its particle size,DOX and SPIO loading rate were measured. With PBS as control group, the safety of HA?SS?PCL on human hepatocellular carcinoma cells HepG2 and normal liver cells LO2 was evaluated by the methylthiazolyl tetrazolium (MTT) assay, and the cytotoxicity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO on human hepatocellular carcinoma cells HepG2 was evaluated. Immunofluorescence and flow cytometry were used to observe the expression of CD44 receptor on the surface of HepG2 cells in HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups. Through in vitro MRI, PBS was used as the control group to observe the changes of T2 signal intensity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups when SPIO concentration was 10, 20, 40, 80 μg / ml. One way ANOVA test and t test were used. Results HA?SS?PCL@DOX / SPIO sodium?meter probes were successfully constructed. The particle size of HA?SS?PCL@DOX/SPIO was (126.9±6.3) nm,and they were spherical with uniform size. The loading rates of DOX and SPIO were 61.4% and 58.7%. MTT assay showed that the survival rate of HepG2 and LO2 cells was more than 80% even at 500 μg/ml of HA?SS?PCL, 66.6% in HA?PCL@DOX/SPIO group and 55.2% in HA?SS?PCL@DOX/SPIO group. Immunofluorescence and flow cytometry showed that HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups all have strong fluorescence, and the latter has stronger fluorescence intensity the former fluorescence intensity was 139.70±8.52,less than the latter 245.06±13.21. In vitro MRI showed that the T2 signal intensity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO was significantly lower than that of the control group (F values were 613.591 and 569.234,P=0.000), the latter decline rate was more significant. Conclusion The disulfide?bonded hyaluronic acid?functionalized sodium?meter probe for hepatocellular carcinoma has excellent physicochemical properties, good targeting and MRI functions on human hepatoma cell HepG2 at the cellular level in vitro.
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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 investigate the application value of functional MRI in the differential diagnosis between breast mucinous carcinoma and phyllodes tumor(≥ 3 cm). Methods 55 cases of breast mucinous adeno-carcinoma and phyllodes tumors(≥ 3 cm)from January 2012 to December 2017 were retrospectively analyzed. MRI features of 20 mucinous carcinomas and 35 phyllodes tumors were analyzed,compared with pathology. Re-sults There were 20 cases of breast mucinous carcinoma in current study,including 14 cases of pure mucinous carcinoma and 6 cases of mixed mucinous carcinoma. There were 35 cases of phyllodes tumors,including 9 be-nign,18 borderline and 8 malignant cases. There was no significant difference in T1WI signal and enhancement mode between breast mucinous carcinoma and phyllodes tumors. There were significant differences in age,long di-ameter,morphology,lobulation,border,ADC value,EER,T2WI signal and TIC curve pattern(P < 0.05). The area under ROC(AUC)of ADC value and EER for breast mucinous adenocarcinoma and phyllodes tumor was 0.7036 and 0.8029,respectively. Conclusions Multi-model functional MRI can effectively distinguish breast mucinous adenocarcinoma from phyllodes tumor(≥ 3 cm),and EER is more accurate than ADC value.
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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 investigate the CT findings and its pathological basis of gastrointestinal neuroendocrine tumors (GEP-NETs ). Methods The CT findings of 23 patients with GEP-NETs confirmed by pathology were analyzed retrospectively and compared with the pathological results.Results The GEP-NETs were found on CT in 20 patients,including focal gastrointestinal wall thickening in 4,mass formation in 6,and both in 10.The tumor diameter ranged from 0.9 cm to 5.2 cm with a mean value of (2.6±0.6)cm. Plain CT showed homogenous isodensity in 15 lesions,little necrosis with low density in 4,and hemorrhage with high density in 1. The dynamic contrast-enhanced CT showed the tumors with obvious enhancement in 16 cases and mild enhancement in 4 in arterial phase.In addition,serosa invasion was found in 7,enlargement of mesentery lymph node in 7,and liver metastases in 2.The pathol-ogy showed the location of submucosa and invasion of the tumors.Most small tumors had intact gastrointestinal mucosa,and some large ones had surface or infiltrated ulcer.Conclusion Some specific CT findings of GEP-NETs depend on its pathological character-istics.CT plays an important role in assessment of invasion extent and metastasis of the tumor.
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Objective To investigate the value of T2WI histogram analysis in differential diagnosis of glioblastoma multiform (GBM) from solitary metastasis.Methods Data of 103 patients with pathologically confirmed GBM (GBM group,n=57) and solitary brain metastasis (solitary brain metastasis group,n =46) were retrospectively reviewed.All patients underwent conventional MR scanning,including axial T1WI,T2WI,FLAIR and contrast-enhanced T1WI before surgery.The histogram metrics,including mean,standard deviation (SD),median,kurtosis and skewness were calculated from ROI,which were manually placed on the maximal section of the solid part of tumors on T2WI by using Image J software.ROCs were generated to evaluate differential diagnostic performance of the histogram metrics with significant difference between both groups.Results The values of mean,SD and median were significantly higher in GMB group than those in solitary brain metastasis group (P＜0.05).The areas under ROC curve of mean,SD and median was 0.772 (95％ CI [0.681,0.862],P＜0.001),0.719 (95％ CI [0.616,0.822],P＜0.001) and 0.767 (95％ CI [0.674,0.860],P＜0.001),respectively;and the diagnosis cutoff value of mean,SD and median was 509.575,58.844 and 550.500,respectively.The sensitivity of the three parameters was 0.719,0.702 and 0.719,and the specificity was 0.783,0.652,and 0.826,respectively.Conclusion The value of mean,SD and median of T2WI histogram analysis can be helpful to differentiating GBM and solitary brain metastasis,of which the mean value is the best for differential diagnosis.
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Objective To improve the diagnostic accuracy of primary renal rare benign tumors by exploring and analyzing the CT/MRI and clinical pathologic features.Methods 9 patients with primary renal rare benign tumors pathologically proven lesions after operation who had CT or MRI exams with contrast were enrolled in our hospital.The radiological and clinical pathological features of all tumors were analyzed respectively.Results The cases were the mixed epithelial and stromal tumor of kidney (MESTK),cystic nephroma(CN),renal leiomyoma(RL)and renal oncocytoma(RO)respectively.Location:6 cases were in left kidney and 3 in right kidney.Size:long diameter 2.5-8.9 cm,mean 5.7 cm;short diameter 2.5-8.4 cm,mean 4.9 cm.The tumor shape included oval(n=7) and irregular(n=2).9 cases protruded from the renal surface.MESTK showed polycystic lesions on preconstrast,various degrees of cystic wall and septum enhancement were detected on enhancement scans.CN showed cystic lesions and calcification on preconstrast, slight septum enhancement were detected on enhancement scans.RL showed heterogeneous density or signal with patchy necrosis and clear border on precontrast,the obvious enhancement was found on cortex and medullary phase and slight washout enhancement was detected on excretory phase.RO showed heterogeneous hypointense on T1 WI,hyperintense on T2 WI and mixed isodensity and hypodensity on CT precontrast.Slight delayed enhancement was found in central scar and washout enhancement was detected in parenchyma on three phases.Conclusion There are some special CT/MRI characteristics for primary renal rare benign tumors,which could improve their diagnosis and differential diagnosis combined with the clinical pathological features.
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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 investigate the MRI features of pleomorphic xanthoastrocytoma (PXA).Methods 1 5 pathologically confirmed PXA cases were analyzed retrospectively.Clinical history and imaging features including location,size,shape,signal intensi-ty,enhancement and surrounding changes of those lesions were analyzed.Results All 1 5 cases were supratentorial and solitary le-sions,of which 9 lesions located in temporal lobe(60%).14 lesions contacted with the leptomeninges,and 1 lesion contacted with lat-eral ventricle wall.All lesions were solid-cystic,with different proportion of solid/cystic components.8 large lesions were predomi-nantly cystic(53.3%),3 small lesions were predominantly solid(20%),and 4 lesions had roughly equal cystic and solid proportions (26.7%).Solid components showed iso-intense or mild hypo-intense on T1 WI,iso-intense or mild hyper-intense on T2 WI,and signif-icant enhancement with contrast.Cyst fluid showed slightly hyper-intense in some cases.Cyst wall or septa enhancement was seen in 7 cases,and leptomeningeal enhancement was seen in 8 cases.Conclusion The MRI features of PXA are the characteristic of suprat-entorial solid-cystic lesions commonly seen in temporal lobe and contacting with leptomeninges.The typical features include “cyst with mural nodule”and “multiple cysts with irregular eccentric nodule”with significant enhancement of solid component and some cyst wall.MRI features of PXA is valuable in diagnosis and differential diagnosis of PXA.
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OBJECTIVE@#To evaluate signal intensity-time (SI-Time) curve and quantitative dynamic contrast-enhanced 3.0T magnetic resonance imaging in diagnosis and differentiating neoplasm of uterus. @*METHODS@#A total of 42 cases of uterine neoplasm (20 were malignant and 22 were benign) were evaluated in our study. All cases received dynamic contrast-enhanced scanning on 3.0T MRI. The raw data was processed by Siemens Tissue 4D software and the SI-Time curve was obtained and analyzed. Pharmacokinetic modeling of Tofts with a modeled vascular input function was used for calculating volume parameters: volume transfer constant (Ktrans), reverse volume transfer constant (Kep), the extravascular extracellular space volume per unit volume of tissue (Ve). The correlation of these parameters at each groups were investigated. The SI-Time curve and the data of perfusion parameters between the 2 groups were compared by T test. @*RESULTS@#Among 20 malignant tumors, 12 were cervical carcinoma and 8 were endometrial cancer. Among the benign tumors, 13 were leiomyomas, 3 were endometrial polyp, 3 were endometrial hyperplasia, and 3 were adenomyosis. 59.1% cases of benign tumors belong to Type I curve and 65% cases of malignant tumors belong to Type II curve. There was significant difference in SI-Time curve between benign and malignant tumors (P=0.011). If Type I curve was used as diagnostic criteria for benign tumors, and Type II and III curve were for malignant tumors, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value were 90.0%, 59.1%, 66.7%, and 86.7%, respectively. Ve was 0.477 ± 0.143 in malignant and 0.614 ± 0.146 in control group with significant difference (P=0.004). Ve was 0.477 ± 0.143 in malignant and 0.589 0.176 in benign group with significant difference (P=0.004). Ktrans was (0.178 ± 0.067) min⁻¹ in malignant and (0.263 ± 0.111) min⁻¹ in control group with significant difference (P=0.003). Ktrans was (0.182 ± 0.096) min⁻¹ in benign and (0.263 ± 0.111) min⁻¹ in control group with significant difference (P=0.011). @*CONCLUSION@#The type of SI-Time curve and perfusion parameters were important for differentiating benign and malignant uterine tumors in dynamic enhanced MRI. These parameters provide a supplement for conventional morphological MR diagnosis.
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Female , Humans , Contrast Media , Magnetic Resonance Imaging , Sensitivity and Specificity , Uterine Neoplasms , Diagnosis , Uterus , PathologyABSTRACT
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 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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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 detect radiation-induced changes of temporal lobe normal-appearing white matter on conventional MRI following radiation therapy (RT) for nasopharyngeal carcinoma (NPC).Methods The clinical and imaging features of 75 patients with nasopharyngeal carcinoma were retrospectively analyzed,all patients were confirmed by biopsy.All patients performed conventional MRI and Diffusion-tensor imaging (DTI) examinations,and there was no abnormal finding on conventional MRI.Eighteen patients without radiotherapy were selected as the control group and fifty-seven patients with radiotherapy were as the experimental group.We divided the experimental group into five subgroups based on completion time of RT:group 1 (less than 3 months,n =16),group 2 (3 to 6 months,n =12),group 3 (6 to 9 months; n =10),group 4 (9 to12 months,n =8),and group 5 ( more than 12 months,n =11 ).The mean diffusivity ( MD),apparent diffusion coefficient ( ADC ),fractional anisotropy ( FA),radial diffusivity ( λ⊥ ) and axial diffusivity ( k ‖ ) were calculated in bilateral temporal lobe.One-way analysis of variance (one-way ANOVA) test was used for comparison among groups.Results The mean λ⊥ values of the control group and experimental groups ( group1-5 ) after radiotherapy were ( 6.075 ± 0.341 ) × 10 -4 (6.700±0.379) × 10-4,(6.976 ±0.527) ×10-4,(6.621 ±0.388) ×10-4,(6.751 ±0.460) ×10-4,(6.222 ±0.256) × 10-4 mm2/s,respectively.The mean λ ‖ values of the control group and experimental groups were (12.524±0.713) ×10-4,(11.764 ±0.574) ×l0-4,(11.842±0.471) ×10-4,(11.569 ± 0.552) × 10-4,( 12.050 ±0.614) × 10-4,( 12.100 ±0.529) × 10-4 mm2/s,respectively.The mean FA values of the control group and experimental groups were 0.452 ± 0.030,0.379 ± 0.028,0.382 ± 0.028,0.389 ± 0.032,0.388 ± 0.022,0.423 ± 0.232,respectively.The three indicators were significantly different among groups ( F =10.485,4.625,16.539,respectively,P ＜ 0.05 ). Multiple comparisons showed that λ⊥ increased significantly in group 1-4 compared with that in the control group.In group 5,λ ⊥ was not significantly different from that in the control group,λ ‖ decreased in group 1-3 compared with that in the control group,but was not significantly different in the control group and group 4-5. In all experimental groups,FA decreased significantly. MD and ADC values in experimental groups were not significantly different from those in the control group. Conclusion Diffusion tensor imaging is a noninvasive and quantitative method to detect the structural changes in WM after RT and can provide scientific evidence for the early diagnosis and intervention treatment of radiation-induced changes.
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Objective To investigate the differential diagnostic features of subtypes of renal cell carcinoma(RCC) using dynamic contrast-enhanced MRI(DCE-MRI).Methods The MRI appearances of 77 RCCs, including 55 clear cell RCCs(CCRCC),14 papillary RCCs(PRCC) and 8 chromophobe RCCs(CRCC), were retrospectively analyzed and compared with findings of pathology. DCE-MRI was conducted in each case after intravenous administration of contrast agent. Region of interest measurements (cortical, nephrographic and delayed Phases) of signals within tumor and uninvolved renal cortex were used to calculate percentage signal intensity change and tumor-to-cortex enhancement index, and the data was analyzed by AVONA and t test. Results On unenhanced and enhanced MRI, most CRCCs showed homogeneous signal(7/8). CCRCC and PRCC often show inhomogenous signal with necrosis(36/55, 7/14). Hemorrhage and cystic degeneration were often found in PRCC (9/14). On the cortical, nephrographic and delayed phase images, CCRCCs showed greater signal intensity change[(296.15±60.27)%, (236.33±58.31)% and (216.83±46.72)%,respectively than PRCCs (79.70±18.84)%, (122.81±27.35)% and (117.55±20.63)%, respectively], and CRCCs showed intermediate change [(119.56±40.76)%, (163.06±33.91)% and (179.72±32.89)%, respectively].A phenomenon of quick staining and quick fainting was observed in CCRCCs. Both of CRCCs and PRCCs showed delayed enhancement. The tumor-to-cortex enhancement index at the cortical, nephrographic and delayed phases was highest for CCRCCs (1.26±0.34, 0.92±0.23 and 0.76±0.14, respectively), lowest for PRCCs (0.33±0.12, 0.41±0.23 and 0.35±0.11, respectively), and intermediate for CRCCs (0.54±0.10, 0.62±0.15 and 0.69±0.12, respectively,P＜0.01). The degree of enhancement was significantly different among the 3 subtypes at the every contrast enhanced phase (F=940.931, 124.515 and 38.194, P＜0.01), so was the tumor-to-cortex enhancement index(F=798.625,78.308 and 73.699, P＜0.01). There was a good consistency between MR appearances of the 3 RCC subtypes and pathological characteristics. Conclusion DCE-MRI could distinctly show imaging features of CCRCC, PRCC and CRCC, which were related to their pathological characteristics, and these features were helpful in predicting a specific subtype of RCC.
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Objective To investigate the imaging characteristic of DWI in rabbit models of hepatic VX2 tumors after three-dimensional stereotactic conformal radiation therapy, and the characteristics of apoptosis after radiotherapy. Methods Sixty hepatic VX2 tumor models were successfully created. After the tumor grew to more than 1 cm in diameter, 40 tumor models were treated with SCRT and then divided into four groups using random number table. The remaining 20 tumor models were used as controls and randomly assigned to each group. MR scanning were performed at different time points ( 1 st day, 5 th day, 10 th day, 15 th day) for each group respectively. ROIs of the VX2 tumor tissues and normal liver tissue were taken and ADC values were measured to calculate their ratios. Cell apoptesis were determined by using TUNEL method. ADC values with their ratios and the apoptotic index were analyzed using one-way analysis of variance and SNK test was used for comparison among different time points of groups, while two sample t test was used for comparison between the groups. Results On the 1 st day, 5 th day, 10 th day, and the 15 th day, the ADC ratios of the radiotherapy groups were 0.74 ±0. 15(n =8), 1.04 ±0.09(n =7), 1.43 ±0. 12 (n = 7 ), 1.25 ± 0. 23 (n = 8 ) (F = 24. 221, P ＜ 0. 01 ), the corresponding ADC ratios of control groups were 0. 78 ±0.07(n =5), 0.79 ±0.07(n=4), 0.83 ±0. 14(n =4), 0.97 ±0. 19(n =4). The ratios of ADC values for radiotherapy groups and control group were compared, and the t value was 0. 569 ( P ＞0.05), 4.417(P＜0.05), 7.259(P ＜0.01), 1.957(P＞0.05) respectively for each time point. On the 1 st day, 5 th day, 10 th day, 15 th day, the apoptotic index of the radiotherapy groups were 0. 39 ±0. 13(n=8), 0.29 ±0.08(n=7), 0.28 ±0.07(n=7), 0.58 ±0. 19(n=8,F=8. 128,P＜0.05), while the corresponding apoptotic index of control groups were 0. 26 ±0. 13(n =5), 0. 18 ±0. 03(n =4), 0. 16 ±0. 06(n =4), 0. 18 ±0. 08(n =4,F= 1. 006,P ＞0. 05). The apoptotic index value for radiotherapy groups and control group were compared, with t value of 1. 716 ( P ＞ 0.05 ), 2. 348 ( P ＜ 0. 05 ), 2. 386 ( P ＜0. 05 ), 3. 756( P ＜0.01 ) respectively. Conclusion DWI ADC values can reflect the dynamic changes of cell apoptosis in hepatic VX2 tumors after radiotherapy at different time points.
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Objective To observe imaging characteristics and changes of vivo two-dimension multi-voxel proton magnetic resonance spectroscopy (~1H-MRS) in the rabbit models of VX2 hepatic carcinoma after high intensity focused ultrasound (HIFU) treatment. Methods VX2 hepatic carcinoma models were established in 20 New Zealand rabbits. Routine MR and 2-dimentional ~1H-MRS scanning were performed before and after HIFU treatment. The central regions of interest (ROI) of the VX2 tumor, tumor border and paratumor normal liver tissues were selected. The Cho/Cr and Lip/Cr of the same ROI before and after HIFU treatment were compared. Results Total 28 satisfied spectrogram diagram of ~1H-MRS were brought into statistical analysis. Of all the spectra, 6 metabolite peaks were detected as lipids (Lip), glutamine and glutamate complex (Glx), choline (Cho), lactate (Lac) and creatine (Cr). Cho and Lac peak in tumor center and tumor border regions after HIFU treatment were higher than those before HIFU treatment. Lip peak was lower than before, and major metabolites of paratumor normal liver tissues did not changed significantly. Statistical differences of Cho/Cr and Lipid/Cr of tumor center and border region were found between before and after HIFU treatment (P＜0.05). Conclusion Two-dimension multi-voxel ~1H-MRS can reflect major changes in the level of metabolites of different ROI for hepatic VX2 carcinoma after HIFU treatment.