Quantification of pancreatic iron overload and fat infiltration and their correlation with glucose disturbance in pediatric thalassemia major patients.

BACKGROUND: Diabetes mellitus affects more than a quarter of patients with thalassemia major (TM) worldwide, and increases the risk for cardiac complications, contributing to significant morbidity. Pancreatic iron overload (IO) and fat infiltration have been correlated with this endocrinal complication in adult TM patients. It has been shown that in adult TM patients, iron accumulation and fat infiltration are found to be heterogeneous in the pancreatic head, body, and tail region. R2* and a fat fraction (FF) generated by gradient-echo imaging can be used as quantitative parameters to assess the iron and fat contents of the pancreas. This study aimed to determine the pattern of pancreatic iron accumulation and fat infiltration in pediatric TM patients with gradient-echo imaging and evaluate the association between pancreatic IO and fat infiltration and glucose disturbances. METHODS: A total of 90 children with TM (10.7±3.1 years) were included. All patients underwent pancreatic magnetic resonance imaging (MRI) using multi-echo gradient-echo sequences. IO was measured by R2* relaxometry in 90 patients, and FF values were measured using iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) method in 40 patients. R2* and FF were assessed in the pancreatic head, body, and tail. The global R2* and global FF values were obtained by averaging the respective values from the pancreatic head, body, and tail. The correlations between global R2*, global FF, and fasting glucose were determined using Spearman's correlation analysis. The Friedman test was used to compare R2* and FF among different pancreatic regions. Receiver operating characteristic (ROC) analysis was used to determine the performance of global R2* and global FF in discriminating impaired fasting glucose from normal fasting glucose patients. RESULTS: The global R2* was positively correlated with the global FF in the pancreas (r=0.895, P<0.001). No significant differences were found in R2* among the 3 regions of the pancreas (χ2=4.050, P=0.132), but significant differences were found in FF among the 3 pancreatic regions (χ2=16.350, P<0.001). Both global pancreatic R2* (r=0.408, P<0.001) and global FF (r=0.523, P=0.001) were positively correlated with fasting glucose. ROC analysis showed that global pancreatic R2* and global FF had an area under the curve of 0.769 and 0.931 (both P<0.001), respectively, in discriminating between impaired and normal glucose function patients. CONCLUSIONS: Pediatric TM patients can have homogeneous iron siderosis and heterogeneous fat infiltration in the pancreas as measured by gradient-echo imaging, both of which are risk factors for diabetes.

Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses.

H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses require the development of cross-protective vaccine candidates. In this study, a methodology called computationally optimized broadly reactive antigen (COBRA) was used to develop four consensus H7 antigens (CH7-22, CH7-24, CH7-26, and CH7-28). In vitro experiments confirmed the binding of monoclonal antibodies to the head and stem domains of cell surface-expressed consensus HAs, indicating display of their antigenicity. Immunization with DNA vaccines encoding the four antigens was evaluated in a mouse model. Broadly reactive antibodies against H7 viruses from Eurasian and North American lineages were elicited and detected by binding, inhibition, and neutralizing analyses. Further infection with Eurasian H7N9 and North American H7N3 virus strains confirmed that CH7-22 and CH7-24 conferred the most effective protection against hetero-lethal challenge. Our data showed that the consensus H7 vaccines elicit a broadly reactive, protective response against Eurasian and North American lineage H7 viruses, which are suitable for development against other zoonotic influenza viruses.

Comparison of T2, T1rho, and diffusion metrics in assessment of liver fibrosis in rats.

PURPOSE: To evaluate the value of T2 , T1 rho, and diffusion metrics in assessment of liver fibrosis in rats. MATERIALS AND METHODS: Liver fibrosis in a rat model (n = 72) was induced by injection of carbon tetrachloride (CCl4 ) at 3T. T2 , T1 rho, and diffusion parameters (apparent diffusion coefficient (ADC), Dtrue ) via spin echo (SE) diffusion-weighted imaging (DWI) and stimulated echo acquisition mode (STEAM) DWI with three diffusion times (DT: 80, 106, 186 msec) were obtained in surviving rats with hepatic fibrosis (n = 52) and controls (n = 8). Liver fibrosis stage (F0-F6) was identified based on pathological results using the traditional liver fibrosis staging method for rodents. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analysis were employed to determine the diagnostic accuracy. RESULTS: Mean T2 , T1 rho, ADC, and Dtrue with DT = 186 msec correlated with the severity of fibrosis with r = 0.73, 0.83, -0.83, and -0.85 (all P < 0.001), respectively. The average areas under the ROC curve at different stages for T1 rho and diffusion parameters (DT = 186 msec) were larger than those of T2 and SE DWI (0.92, 0.92, and 0.92 vs. 0.86, 0.82, and 0.83). The corresponding average sensitivity and specificity for T1 rho and diffusion parameters with a long DT were larger (89.35 and 88.90, 88.36 and 89.97, 90.16 and 87.13) than T2 and SE DWI (90.28 and 79.93, 85.30 and 77.64, 78.21 and 82.41). The performances of T1 rho and Dtrue (DT = 186 msec) were comparable (average AUC: 0.92 and 0.92). CONCLUSION: Among the evaluated sequences, T1 rho and STEAM DWI with a long DT may serve as superior imaging biomarkers for assessing liver fibrosis and monitoring disease severity. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:741-750.

Regulated pH-Responsive Polymeric Micelles for Doxorubicin Delivery to the Nucleus of Liver Cancer Cells.

A diblock copolymer of poly(ethylene glycol) (PEG) and poly(γ-benzyl L-glutamate) (PBLG), PEG-PBLG, was synthesized via the ring-opening polymerization of γ-benzyl L-glutamate N-carboxyanhydride (BLG-NCA) using allyl-PEG-NH2 as a macroinitiator. After deprotection of the benzyl groups, N,N-diisopropyl ethylenediamine (DIP) was conjugated to poly(L-glutamic acid) (PGA) blocks as side groups. The pendant DIP groups on the PGA blocks greatly enhance the pH-sensitivity of poly(ethylene glycol)-block-poly[N-(N',N'-diisopropylaminoethyl) glutamide] [PEG-PGA(DIP)] micelles, and a higher grafting percentage of DIP favors a faster acid-response. In neutral aqueous solution, the PEG-PGA(DIP) can self-assemble into stable micelles featuring an acid-responsive PGA(DIP) core with the encapsulated anticancer drug doxorubicin (DOX). In an acidic environment, the hydrophobic-hydrophilic transition of the PGA block leads to the gradual expansion and disassembly of these micelles and, consequently, an accelerated release of DOX. Thus, DOX transported by PEG-PGA(DIP) micelles can be entrapped more efficiently into the nuclei of hepatoma Bel 7402 cells.

Intravoxel incoherent motion MRI in differentiation between recurrent carcinoma and postchemoradiation fibrosis of the skull base in patients with nasopharyngeal carcinoma.

PURPOSE: To determine the capacity of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in differential diagnosis between recurrent carcinoma and postchemoradiation fibrosis of skull base in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Eleven patients with recurrent NPC and 21 patients with postchemoradiation fibrosis in the skull base were enrolled. All the diagnoses were proved by endoscopic biopsy or imaging follow-up. IVIM MRI was performed to obtain quantitative parameters including D (pure diffusion), f (perfusion fraction), and D* (pseudodiffusion). D, f, and D* were compared between two groups; the diagnostic performances of D and f were evaluated using the receiver operating characteristic (ROC) analysis. RESULTS: D and f values were significantly lower in recurrent carcinoma than that in fibrosis (P < 0.001; P = 0.001). No significant difference was found in D* values between recurrent carcinoma and fibrosis (P = 0.229). ROC curve analysis showed that the area under the curve of D and f values were 0.996 and 0.838, respectively. Respective cutoff values with sensitivity, specificity, and accuracy were: D = 1.161 × 10-3 mm2 /s (sensitivity 100.0%, specificity 95.2%, accuracy 96.9%), f = 0.109 (sensitivity 81.8%, specificity 71.4%, accuracy 75.0%). CONCLUSION: Recurrent NPC and postchemoradiation fibrosis in the skull base have distinctive D and f values. IVIM MRI could be used to differentiate between recurrent carcinoma and postchemoradiation fibrosis in patients with NPC. J. Magn. Reson. Imaging 2016;44:1556-1564.

Comparison of multislice breath-hold and 3D respiratory triggered T1 ρ imaging of liver in healthy volunteers and liver cirrhosis patients in 3.0 T MRI.

PURPOSE: To compare visual quality and quantitative measurements of multislice (MS) breath-hold and 3D respiratory-triggered T1 ρ sequences. MATERIALS AND METHODS: T1 ρ scans including MS BLOCK T1 ρ, MS HS8 T1 ρ, and 3D BLOCK T1 ρ were performed on 40 healthy volunteers and 17 liver cirrhosis patients on 3.0T magnetic resonance imaging (MRI). The MS breath-hold methods scanned three slices while the 3D method covered 26 slices. Visual scores of image quality, T1 ρ measurements of the three sequences, and T1 ρ values of healthy volunteers and cirrhosis patients were compared using parametric tests. RESULTS: Average visual scores for volunteers and patients of the three sequences were 3.19 and 2.82 for MS BLOCK T1 ρ; 3.71 and 3.59 for MS HS8 T1 ρ; 3.29 and 3.59 for 3D BLOCK T1 ρ, respectively. Difference of visual scores among the three groups was significant (P < 0.001). Differences in T1 ρ values among the three methods were significant (P < 0.001). Difference of T1 ρ between MS BLOCK T1 ρ and 3D BLOCK T1 ρ was not significant (volunteer: P = 0.82, patient: 0.92) while the difference of T1 ρ between MS BLOCK T1 ρ and MS HS8 T1 ρ, MS HS8 T1 ρ and 3D BLOCK T1 ρ was significant in both volunteers and patients (P < 0.01). Differences of T1 ρ between healthy volunteers and patients were all significant in three T1 ρ sequences (P = 0.04, 0.004, 0.03). CONCLUSION: Of the tested sequences, the image quality of MS HS8 T1 ρ was best, but 3D BLOCK T1 ρ with respiratory triggering should also be considered as an alternative sequence for clinical diagnosis of liver cirrhosis due to its superior coverage. J. MAGN. RESON. IMAGING 2016;44:906-913.

Value of severe liver iron overload for assessing heart iron levels in thalassemia major patients.

PURPOSE: The relationship between severe liver iron overload (LIO) and heart iron overload (HIO) in transfusion-dependent patients with thalassemia major (TM) is uncertain. Whether severe LIO can serve as an index for assessing heart iron deposition has vital clinical significance. Therefore, our aim is to determine if a close relationship exists between severe LIO and HIO. MATERIALS AND METHODS: We examined 110 TM patients who underwent T2* measurement in the liver and heart on a 1.5 Tesla MRI scanner. Various statistical analysis methods were used to assess the relationship. RESULTS: Most of these patients suffered from severe LIO (58.18%, liver T2* < 1.4 ms). Both Pearson's and Spearman's tests showed a significant correlation between liver T2* and heart T2* values (with a correlation coefficient of 0.408 and 0.550, respectively, both P < 0.0001). A nonlinear model, with the equation of Heart T2* = 37.974-17.684 / Liver T2*, was found to be the best model to indicate the relationship between liver T2* and heart T2*. Receiver operating characteristic (ROC) analysis showed the area under the ROC curve of liver T2* and serum ferritin for predicting HIO was 0.812 (95% confidence interval [CI]: 0.731-0.892; P < 0.0001) and 0.69 (95% CI: 0.585-0.795; P = 0.001), respectively. CONCLUSION: Our preliminary data suggest the existence of a close relationship between severe LIO and HIO. High liver iron levels appear to increase the risk of heart iron deposition. This further supports the concept of critical liver iron concentration, above which elevated heart iron is present. J. MAGN. RESON. IMAGING 2016;44:880-889.

MRI assessment of excess cardiac iron in thalassemia major: When to initiate?

BACKGROUND: To determine optimal initial age of cardiac iron screening with magnetic resonance imaging (MRI) T2* in patients with thalassemia major (TM). METHODS: We retrospectively reviewed black blood cardiac T2* assessments from 102 TM patients from the ages of 3 to 32 years. Cases of patients under and above 7 years old with detectable cardiac iron overload were analyzed separately. Associations between cardiac T2* and various factors, such as serum ferritin (SF), patient age and hepatic T2*, were assessed using either scatterplots or regression. Images were evaluated by two independent radiologists. RESULTS: With a T2* cut-off value of 20 ms, no patient under 5 years old showed cardiac iron overload. Three of 19 (15.8%) patients under 7 years of age had a cardiac T2* ≤ 20 ms (5.5 to 7 years) but none had ≤10 ms, while 35 of 83 (42.2%) patients above 7 years old had a cardiac T2* ≤ 20 ms (8 to 32 years) and 18 of them ≤10 ms. Cardiac T2* correlated weakly with serum ferritin and liver T2* (r = -0.39 and 0.41, respectively, both P < 0.001), but not with patient age (P > 0.05). CONCLUSION: Cardiac iron overload can occur in young TM patients, even as young as 5.5 years old. Assessment of cardiac iron with T2* might need to begin as early as 5 years old if suboptimal chelation therapy is administered.

Magnetic resonance imaging-visible and pH-sensitive polymeric micelles for tumor targeted drug delivery.

Folate-functionalized copolymers of poly(ethylene glycol) and 2-(diisopropylamino) ethylamine grafted poly(L-aspartic acid) are synthesized. The copolymers can self-assemble into nanoscaled micelles encapsulated with hydrophobic model drug Fluorescein Diacetate (FDA) and MRI diagnostic agents superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution of a neutral pH resembling physiological environment, whereas disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. In vitro drug release study showed that FDA release from the pH-sensitive micelles was much faster at pH 5.0 than at pH 7.4. Clustering of SPIONs inside the hydrophobic core of the micelles resulted in a high spin-spin (T2,) relaxivity for a super MRI sensitivity. Cell culture studies showed that the FDA-SPION-loaded micelles were effectively internalized by human hepatic Bel-7402 cancer cells following a folate receptor-mediated targeting mechanism, and then FDA was rapidly release from micelles inside lysosomal compartments. Micelles encapsulating paclitaxel (PTX) studies showed it can induce more effective cell toxicity. This study demonstrated the great potential of the pH-sensitive micelles as an effective multifunctional nanomedician platform for cancer therapy due to their active tumor targeting, pH-triggered drug release and ultrasensitive MRI responsiveness.

Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs: a 20-week clinical trial.

Our objective was to evaluate the feasibility, safety, and efficacy of intravenous (IV) infusion of allogenic mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) patients who are refractory to or cannot tolerate the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). AS patients enrolled in this study received four IV infusions of MSCs on days 0, 7, 14, and 21. The percentage of ASAS20 responders (the primary endpoint) at the fourth week and the mean ASAS20 response duration (the secondary endpoint) were used to assess treatment response to MSC infusion and duration of the therapeutic effects. Ankylosing Spondylitis Disease Activity Score Containing C-reactive Protein (ASDAS-CRP) and other preestablished evaluation indices were also adopted to evaluate the clinical effects. Magnetic resonance imaging (MRI) was performed to detect changes of bone marrow edema in the spine. The safety of this treatment was also evaluated. Thirty-one patients were included, and the percentage of ASAS20 responders reached 77.4% at the fourth week, and the mean ASAS20 response duration was 7.1 weeks. The mean ASDAS-CRP score decreased from 3.6 ± 0.6 to 2.4 ± 0.5 at the fourth week and then increased to 3.2 ± 0.8 at the 20th week. The average total inflammation extent (TIE) detected by MRI decreased from 533,482.5 at baseline to 480,692.3 at the fourth week (p > 0.05) and 400,547.2 at the 20th week (p < 0.05). No adverse effects were noted. IV infusion of MSCs is a feasible, safe, and promising treatment for patients with AS.

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells.

PURPOSE: To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N',N'-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. METHODS: As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. RESULTS: To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks' cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. CONCLUSION: Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors.

Clinical manifestations and MRI features of vaginal endodermal sinus tumors in four children.

BACKGROUND: Vaginal endodermal sinus tumor is a rare entity. OBJECTIVE: The purpose of this study was to report the clinical manifestations and MRI features in a case series. MATERIALS AND METHODS: Children with vaginal endodermal sinus tumor admitted to our hospitals between January 2008 and August 2012 were included. MRI was performed in all four children and diffusion-weighted imaging was performed in two children. RESULTS: Four children, mean age 14 months, were included. All had a history of vaginal bleeding. Serum alpha-fetoprotein was significantly elevated on admission. Relative to muscle, the vaginal masses were uniformly isointense on T1-weighted images, heterogeneously hyperintense on T2-weighted images and heterogeneously enhancing on contrast-enhanced images. The vaginal masses were obviously hyperintense on diffusion-weighted images (b value, 800 s/mm(2)). Extravaginal invasion was observed in three children. Pelvic lymphadenopathy was noted in two children and pulmonary metastasis was found in one child. CONCLUSION: MRI may contribute in the evaluation of vaginal endodermal sinus tumors.

MRI manifestations of adult choledochal cysts associated with biliary malignancy: a report of ten cases.

BACKGROUND: To retrospectively review the MRI imaging features of adult choledochal cysts associated with biliary malignancy. PATIENTS AND METHODS: Ten out of 72 cases of adult choledochal cysts were found to be associated with biliary malignancy between January 1, 2003 and April 1, 2011 in our hospital database. The following MRI findings of these ten patients were retrospectively reviewed: the type of choledochal cysts, the presence of anomalous union of the pancreaticobiliary duct (AUPBD), manifestations of biliary malignancy, and concomitant findings. RESULTS: Among the ten patients, there were five type I and five type IVA choledochal cysts. AUPBD was noted in four cases. The biliary malignancy was diagnosed as cholangiocarcinoma in seven cases (70.0%) and as gallbladder cancer in three cases. Cholangiocarcinoma manifested with irregularly thickened cyst wall (n = 2), mass with irregularly thickened cyst wall (n = 4), or multiple papillary nodules without thickened cyst wall (n = 1). Most of them showed mark enhancement (n = 4) after contrast administration. Gallbladder cancer appeared as mass with irregular thickening of the gallbladder wall with inhomogeneous enhancement. Concomitant findings included liver invasion or metastases in five cases, lymph node metastases in two cases, cholangitis and/or hepatic abscess in two cases, biliary stones in three cases. The type of choledochal cysts and the extent of malignant tumor invasion revealed by MRI were consistent with the surgical findings. CONCLUSION: Most malignancies associated with choledochal cysts are cholangiocarcinoma and gallbladder cancer. MRI is a reliable method for the detection of choledochal cysts with biliary malignant changes. MR features such as irregular thickening of the gallbladder wall or cyst wall, mass or papillary nodules are suggestive of biliary malignant changes.

Development of an MRI-visible nonviral vector for siRNA delivery targeting gastric cancer.

An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFv(CD44v6),-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFv(CD44v6)-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFv(CD44v6)-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.

[Value of magnetic resonance imaging in preoperative staging of endometrial carcinoma according to International Federation of Gynecology and Obstetrics (2009) staging criteria].

OBJECTIVE: To analyze the magnetic resonance imaging (MRI) features of endometrial carcinoma and their value in endometrial carcinoma staging according to the International Federation of Gynecology and Obstetrics (FIGO 2009) staging criteria. METHODS: Fifty-four patients with pathologically confirmed endometrial carcinoma and complete clinical data underwent preoperative MRI examination. According to FIGO 2009 staging criteria of endometrial carcinoma, the MRI features of the tumor lesions were evaluated for assessment of myometrial invasion and cervical involvement and preoperative staging. RESULTS: The 54 cases included 27 stage Ia cases, 9 stage Ib cases, 10 stage II cases, 5 stage III cases, and 3 stage IV cases. The total lesion display rate by MRI was 94% (51/54). With an isointensity or hypo-intensity on T1WI, the tumor lesions showed a moderate hyper-intensity on T2WI. In enhanced MRI scanning, the lesions showed a moderate heterogeneous enhancement, which had a lower intensity than the marked enhancement of the myometrium. Combination of T2WI and T1WI in fat suppression sequence enhanced scan had a diagnostic accuracy of 91% (49/54) for myometrial invasion, and the sensitivity, specificity and accuracy of MRI for detecting cervical involvement were 77%, 89%, and 83%, respectively. The accuracy of preoperative MRI-based staging of endometrial carcinoma was 89% (48/54), showing no significant difference from the results of postoperative FIGO 2009 staging and pathological examination (P>0.05). CONCLUSION: MRI has a high accuracy in the diagnosis, evaluation of myometrial and cervical invasion depth, and preoperative staging of endometrial carcinoma, and serves as an important modality in assisting clinical decisions on the optimal therapeutic protocols and in prognostic estimation.

Synergistic anticancer effect of rAd/P53 combined with 5-fluorouracil or iodized oil in the early therapeutic response of human colon cancer in vivo.

Exogenous wild-type p53 (wt-p53) tumor suppression increases the sensitivity of tumor cells to radiotherapy and chemotherapy. An iodized oil emulsion was used as a p53 vector for intra-arterial gene delivery to treat hepatic tumors. Whether the chemotherapeutic agent or the iodized oil affects exogenous wt-p53 activity remains poorly understood. In the present study, the early therapeutic response of rAd/p53, combined with 5-fluorouracil (5-FU) or with iodized oil, was observed in a human colon cancer model. Allograft models in 82 nude mice with human colon carcinoma SW480 were divided randomly into four groups and administered with physiologic saline, rAd/p53, rAd/p53+5-FU, and rAd/p53+iodized oil by intratumoral injection. At 24, 48, 72, 120, and 168 h after treatment, p53 expression, the Ki-67 index (KI), and the degree of tumor necrosis were assessed. The p53 expression and tumor necrosis in the therapeutic groups were higher than those in the control group. p53 expression reached its peak at 120 h in the rAd/p53 group, at 72 h in the rAd/p53+5-FU group, and at 48 h in the rAd/p53+iodized oil group. The p53 expression in the rAd/P53+5-FU group and the iodized oil group was significantly higher than those in the rAd/P53 group at 24 and 48 h. The results revealed that tumor necrosis is positively correlated with p53 expression. The KI of the rAd/p53+5-FU group increased significantly at 24 h. 5-FU and iodized oil increase the anticancer effect of rAd/p53, and 5-FU combined with rAd/p53 has a synergistic anticancer effect.

Juxta-adrenal schwannoma: dynamic multi-slice CT and MRI findings.

BACKGROUND: We retrospectively analyzed the MSCT and MRI findings of three cases of juxta-adrenal schwannoma and reviewed literature. METHODS AND RESULTS: Three patients were male, and showed no signs for endocrine activity. The three cases of juxta-adrenal schwannoma were all well-circumscribed, oval masses with cystic components, and one case with hemorrhage. Hypointense signal capsules were observed on T2-weighted images in two cases, and the capsule in one case showed rim enhancement. The tumors displayed mild enhancement in the arterial phase and progressive enhancement during the portal venous phase and equilibrium phase. Computed tomography angiography clearly showed the tumor feeding vessels arising from the abdominal aorta. CONCLUSIONS: MSCT and MRI are valuable imaging modalities for diagnosis of juxta-adrenal schwannoma.

Optimal technique of three-dimensional MRI of the lumbar nerve root and its radicular vein in normal and lumbar disc herniation patients.

BACKGROUND: Although three-dimensional MRI (3D-MRI) of short T1 inversion recovery turbo spin-echo (STIR TSE) has showed superior to two-dimensional MRI (2D-MRI) in showing the spinal cord and lumbar nerve roots, it remains difficult in demonstrating radicular vein at present. We have found that short T1 inversion recovery long time echo (STIR LONG TE) was better in showing radicular vein. To further study the methods and character of the 3D-MRI of lumbar nerve root, ganglions and radicular vein in normal and lumbar disc herniation (LDH) adults, in the present study, we evaluated two 3D-MRI techniques, STIR TSE and STIR LONG TE for demonstrating lumbar nerve roots and especial radicular vein in normal and LDH adults. METHODS: Twelve normal adult persons and 19 LDH patients were included in this study; special oblique coronal location was adopted. STIR TSE and STIR LONG TE were performed in all participants, and the detection rates of radicular vein and nerve root of L3, L4, L5, S1 were calculated. The grading system was used in grading compromise of the intraspinal extradural lumbar nerve root, ganglion and radicular vein in LDH patients, and all the grading injury of nerve root, ganglion and radicular vein had been evaluated. RESULTS: The definite rate of radicular vein (DRRV) of 3D-MRI of STIR LONG TE was significantly different from that of STIR TSE. DRRV of STIR LONG TE was L3, 91.7%, L4, 100%, L5, 100%, S1, 100% and that of STIR TSE was L3, 33.3%, L4, 37.5%, L5, 58.3%, S1, 45.8% in normal adults. It showed no difference between STIR LONG TE and STIR TSE in the detection rate of nerve root. The different patho-injuries of nerve root, ganglion and radicular vein could be seen in all LDH patients by the 3D-MRI of STIR LONG TE. The mean score of Japanese Orthopaedic Association (JOA) was 16.16, and 29 nerve roots were calculated in all the study. The mean grading injury of nerve root was 2.17, that of nerve root ganglion was 1.28, that of radicular vein was 1.83, and the mean co-grading injury of nerve root, ganglion and radicular vein was 5.31. The correlation coefficient was 0.478 (P = 0.010) between the score of JOA and that of radicular vein. CONCLUSION: The 3D-MRI of STIR LONG TE is superior to STIR TSE for not only detecting the lumbar nerve root, ganglion and especial radicular vein in normal adults, but also displaying their patho-injuries degree in LDH patients.

Hepatocellular carcinoma with bile duct tumor thrombus: dynamic computed tomography findings and histopathologic correlation.

PURPOSE: This purpose of this study was to analyze the computed tomography (CT) findings of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) and explore their correlations with pathological manifestations. METHODS: The clinical data, CT findings, and pathological manifestations of the 16 HCC patients with BDTT were retrospectively reviewed. All cases were pathologically proven. RESULTS: Most HCCs showed hyperattenuation at hepatic arterial phase (HAP) (14/16) and hypoattenuation at portal venous phase (PVP) (12/16) and equilibrium phase (9/10), and the presence of rapid washout of contrast material was noted in 11 cases. The BDTT presented as cordlike masses in the dilated bile ducts, and mostly showed hyperattenuation at HAP (12/16) and hypoattenuation at PVP (13/16) and equilibrium phase (10/10), and the presence of rapid washout of contrast material was noted in 10 cases. Four cases of BDTT showed homogeneous enhancement, which were mainly consisted of cancer cells; 9 cases showed heterogeneous enhancement, which were mainly consisted of cancer cells with flakes of necrotic tissues or abundant red blood cells. Bile duct tumor thrombus was composed of 2 different pathological tissues in 3 cases, proximal part of BDTT was composed of tumor tissue, which was uniformly enhanced on dynamic enhanced CT, whereas the distal part was composed of necrotic or debris tissue without enhancement. CONCLUSIONS: Hepatocellular carcinoma lesion and soft-tissue mass in the bile ducts with bilary dilation are usually depicted on dynamic enhanced CT in HCC patients with BDTT. Early enhancement at HAP and rapid washout of contrast material at PVP are the characteristic findings of HCC and BDTT. Dynamic contrast CT examination is very valuable for diagnosing this disease.

Targeting EGFR-overexpressing tumor cells using Cetuximab-immunomicelles loaded with doxorubicin and superparamagnetic iron oxide.

Epidermal growth factor receptor (EGFR), a cellular transmembrane receptor, plays a key role in cell proliferation and is linked to a poor prognosis in various human cancers. In this study, we constructed Cetuximab-immunomicelles in which the anti-EGFR monoclonal antibody was linked to poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-PCL) nanomicelles that were loaded with doxorubicin (DOX) and superparamagnetic iron oxide (SPIO). The specific interactions between EGFR-overexpressing tumor cells (A431) and immunomicelles were observed using confocal laser scanning microscopy (CLSM) and flow cytometry. Furthermore, the capacity of transporting SPIO into tumor cells using these immunomicelles was evaluated with a 1.5 T clinical magnetic resonance imaging (MRI) scanner. It was found that the acquired MRI T2 signal intensity of A431 cells that were treated with the SPIO-loaded and antibody-functionalized micelles decreased significantly. Using the thiazolyl blue tetrazolium bromide (MTT) assay, we also demonstrated that the immunomicelles inhibited cell proliferation more effectively than their nontargeting counterparts. Our results suggest that Cetuximab-immunomicelles are a useful delivery vehicle for DOX and SPIO to EGFR-overexpressing tumor cells in vitro and that Cetuximab-immunomicelles can serve as a MRI-visible and targeted drug delivery agent for better tumor imaging and therapy.