Liguang Zou

MR imaging of tumor angiogenesis using sterically stabilized Gd-DTPA liposomes targeted to CD105

AIM To depict tumor angiogenesis via the expression of CD105 in tumor-bearing rats using Gd-DTPA liposomes targeted to CD105 (CD105-Gd-SLs) on MR imaging. MATERIALS AND METHODS Three Gd-DTPA liposomal nanoparticles were prepared in our trial: liposomes entrapping Gd-DTPA (Gd-SLs), Gd-SLs conjugated to immunoglobulins (IgG-Gd-SLs) and CD105-Gd-SLs. Forty glioma-bearing rats were randomized into four groups: (a) Gd-DTPA; (b) Gd-SLs; (c) IgG-Gd-SLs; (d) CD105-Gd-SLs. Axial T1WI MRI images were collected at baseline and repeated at 5, 30, 60 and 120 min post-intravenous injection of Gd-DTPA or liposome. Enhancement features and contrast-to-noise ratio of each group were analyzed. After imaging, tumors were resected for immunohistochemistry and immunofluorescence staining to assess vascularity and angiogenesis. RESULTS The four groups showed different enhancement features. The enhancement area was restricted for group CD105-Gd-SLs, while diffused for the other three. The degree of enhancement over time varied: group Gd-DTPA showed an early contrast enhancement at instant after injection with a peak at 30 min and a decline to baseline values at 60 min. In group CD105-Gd-SLs, the signal intensity (SI) continuously increased over 120 min. In groups IgG-Gd-SLs and Gd-SLs the SI peaked at 60 min, followed by a minor decrease for IgG-Gd-SLs and a rapid decrease for Gd-SLs almost to baseline. Immunohistochemistry and immunofluorescence showed that the enhancement in the CD105-Gd-SLs group resulted mainly from new microvessels. While in the other three groups, mature microvessels and new microvasculature resulted in the enhancement of the tumor. CONCLUSION CD105-Gd-SLs can be used to detect early tumor angiogenesis on MR images. This might provide a means to non-invasively reveal a malignant phenotype of extracerebral F98 tumor and evaluate its progression.

Rathke's cleft cyst: clinicopathological and MRI findings in 22 patients

AIM To evaluate clinical findings and magnetic resonance imaging (MRI) characteristics of Rathkes cleft cyst (RCC) in 22 patients. MATERIALS AND METHODS Twenty-two patients were imaged using non-enhanced MRI and 17 underwent an additional contrast-enhanced MRI examination. Fifteen patients received an additional non-enhanced computed tomography (CT) examination, and amongst these, two underwent contrast-enhanced CT. Two radiologists read the images retrospectively. The imaging data were studied with regards to location, size, margin, signal intensity, enhancement characteristics, haemorrhage, and presence of calcifications. Clinical data, such as presenting signs and symptoms, physical findings, and medical histories, were collected. Histopathological studies were performed and analysed by two pathologists. RESULTS Nine lesions were located in the intrasellar region, 12 in both the intra- and suprasellar regions and one in the suprasellar region. The maximum diameter of the RCCs varied from 0.7 to 4 cm, with an average size of 1.7+/-0.7 cm. MRI features of RCC were divided into three groups based on T1-weighted imaging (T1WI): hypo- (n=6), iso- (n=9), and hyperintensity group (n=7). Patients in the latter two groups were statistically younger than that in the former group. The lesion size in the iso- and hyperintensity groups was significantly less than that in the hypointensity group (F=6.421, p=0.007). Only two cases showed enhancement after contrast injection in the cohort. One lesion with haemorrhage was found as were two cases with intracystic nodules. CONCLUSION Although MRI features of RCCs are variable, RCCs should be suspected when the following conditions occur: lesions located in the intrasellar region or involving both intra and suprasellar regions, less than 1.5 cm in diameter, iso- or hyperdense on T1WI and no signal enhancement after contrast injection. In addition, the first case of a RCC with a markedly enhanced intracystic nodule is reported.

MRI findings of intracranial cystic meningiomas

AIM To report the magnetic resonance imaging (MRI) features of intracranial cystic meningiomas and compare these features in intra- and peritumoural cyst groups. MATERIALS AND METHODS Fourteen cases of peritumoural cystic meningiomas were compared with 18 cases of intratumoural cystic meningiomas. All patients were examined using non-enhanced and contrast-enhanced MRI. Tumour location, tumour size, signal intensity, enhancement characteristics, and cystic changes were assessed. The MRI features were compared between the intra- and peritumoural cyst groups. RESULTS Most cystic meningiomas comprised two or more cysts. The solid parts of the tumours showed moderate or marked enhancement after the injection of contrast material. An enhanced cyst wall was found in six out of 14 cases in the peritumoural cyst group, but not in the intratumoural cyst group. Peritumoural cystic meningiomas were predominately located in the cerebral falx, whereas the intratumoural cystic meningiomas were predominantly found in frontal convexity (X(2)=7.434, p=0.024). The cysts were larger in the peritumoural cyst group than in the intratumoural cyst group (t=5.274, p=0.0258). Peritumoural oedema was more commonly found in the intratumoural cyst group (X(2)=6.863, p=0.008). Cystic meningiomas with solid parts located inside the cyst are reported for the first time. CONCLUSION Cystic meningiomas, although uncommon, should be differentiated from other cystic intracranial lesions. Peri- and intratumoural cystic meningiomas have distinct MRI features. The present study provides the first report of two lesions with solid parts located inside the cyst, as well as one lesion with a calcified solid nodule and haemorrhage within the cyst.

Thiol-PEG-carboxyl-stabilized Fe2O3/Au nanoparticles targeted to CD105: Synthesis, characterization and application in MR imaging of tumor angiogenesis

OBJECTIVE To detect tumor angiogenesis in tumor-bearing mice using thiol-PEG-carboxyl-stabilized Fe2O3/Au nanoparticles targeted to CD105 on magnetic resonance imaging (MRI). METHODS Fe2O3/Au nanoparticles (hybrids) were prepared by reducing Au(3+) on the surface of Fe2O3 nanoparticles. Hybrids were stabilized with thiol-PEG-carboxyl via the Au-S covalent bond, and further conjugated with anti-CD105 antibodies through amide linkages. Characteristics of the hybrid-PEG-CD105 nanoparticles were evaluated. Using these nanoparticles, the labeling specificity of human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. MRI T2-weighted images were obtained at different time points after intravenous administration of the hybrid-PEG-CD105 nanoparticles in the tumor-bearing mice. After MR imaging, the breast cancer xenografts were immediately resected for immunohistochemistry staining and Prussian blue staining to measure the tumor microvessel density (MVD) and evaluate the labeling of blood microvessels by the hybrid-PEG-CD105 nanoparticles in vivo. RESULTS The mean diameter of the hybrid-PEG-CD105 nanoparticles was 56.6 ± 8.0 nm, as measured by transmission electron microscopy (TEM). Immune activity of the hybrid-PEG-CD105 nanoparticles was 53% of that of the anti-CD105 antibody, as detected by enzyme-linked immunosorbent assay (ELISA). The specific binding of HUVECs with the hybrid-PEG-CD105 nanoparticles was proved by immunostaining and Prussian blue staining in vitro. For breast cancer xenografts, the combination of the hybrid-PEG-CD105 nanoparticles with blood microvessels was detectable by MRI after 60 min administration of the contrast agent. The T2* relative signal intensity (SIR) was positively correlated with the tumor MVD (R(2)=0.8972). CONCLUSION Anti-CD105 antibody-coupled, thiol-PEG-carboxyl-stabilized core-shell Fe2O3/Au nanoparticles can efficiently target CD105 expressed by HUVECs. Furthermore, the hybrid-PEG-CD105 nanoparticles can be used to detect tumor angiogenesis in vivo.

Cantrell syndrome with complex cardiac malformations: a case report.

Cantrell syndrome is a rare condition of congenital defects of 5 developmentally associated structures: the abdominal wall, sternum, diaphragm, pericardium, and heart. Few patients survive, and even fewer survive with good outcomes of quality of life. We present a case with the pentalogy and profound cardiac malformations. Despite repeated life-threatening conditions, the boy survived to have his first operation at 5 months old. The operation reduced the heart within the thoracoabdominal area, repaired the abdominal wall defect, and released multiple stenoses of the heart and great vessels. The patient recovered uneventfully. At 4.5 years old, he is healthy and developed normally.

Superparamagnetic core/shell GoldMag nanoparticles: size-, concentration- and time-dependent cellular nanotoxicity on human umbilical vein endothelial cells and the suitable conditions for magnetic resonance imaging

BackgroundGoldMag nanoparticles (GMNPs) possess the properties of colloid gold and superparamagnetic iron oxide nanoparticles, which make them useful for delivery, separation and molecular imaging. However, because of the nanometer effect, GMNPs are highly toxic. Thus, the biosafety of GMNPs should be fully studied prior to their use in biomedicine. The main purpose of this study was to evaluate the nanotoxicity of GMNPs on human umbilical vein endothelial cells (HUVECs) and determine a suitable size, concentration and time for magnetic resonance imaging (MRI).ResultsTransmission electron microscopy showed that GMNPs had a typical shell/core structure, and the shell was confirmed to be gold using energy dispersive spectrometer analysis. The average sizes of the 30 and 50 nm GMNPs were 30.65 ± 3.15 and 49.23 ± 5.01 nm, respectively, and the shell thickness were 6.8 ± 0.65 and 8.5 ± 1.36 nm, respectively. Dynamic light scattering showed that the hydrodynamic diameter of the 30 and 50 nm GMNPs were 33.2 ± 2.68 and 53.12 ± 4.56 nm, respectively. The r2 relaxivity of the 50 nm GMNPs was 98.65 mM−1 s−1, whereas it was 80.18 mM−1 s−1 for the 30 nm GMNPs. The proliferation, cytoskeleton, migration, tube formation, apoptosis and ROS generation of labeled HUVECs depended on the size and concentration of GMNPs and the time of exposure. Because of the higher labeling rate, the 50 nm GMNPs exhibited a significant increase in nanotoxicity compared with the 30 nm GMNPs at the same concentration and time. At no more than 25 μg/mL and 12 hours, the 50 nm GMNPs exhibited no significant nanotoxicity in HUVECs, whereas no toxicity was observed at 50 μg/mL and 24 hours for the 30 nm GMNPs.ConclusionsThese results demonstrated that the nanotoxicity of GMNPs in HUVECs depended on size, concentration and time. Exposure to larger GMNPs with a higher concentration for a longer period of time resulted in a higher labeling rate and ROS level for HUVECs. Coupled with r2 relaxivity, it was suggested that the 50 nm GMNPs are more suitable for HUVEC labeling and MRI, and the suitable concentration and time were 25 μg/mL and 12 hours.

High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer

BackgroundLymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients’ survival are still uncertain.MethodsDatabases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer.ResultsNineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69–2.40) for disease-free survival and 2.88 (2.07–4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57–2.08) for disease-free survival and 1.64 (1.43–1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total.ConclusionsOur study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed.

Targeting T1 and T2 dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles.

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM−1 s−1, which was much higher than that of MnFe2O4 nanoparticles (67.5 mM 1 s−1). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn2+ ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.