-
[show abstract]
[hide abstract]
ABSTRACT: Magnetic resonance imaging (MRI) is a useful tool for non-invasive identification and characterization of atherosclerotic
plaques in both basic science and clinical practice. To date, the reported studies on in vivo vascular MRI of small animals,
such as mice and rats, are mainly performed on high-field micro-MR scanners, which are not always available in many academic
institutions and basic research units. This study aimed to explore the possibility of generating high-resolution MR images
of the atherosclerotic aortic walls/plaques of mice using a clinical 3.0T MR scanner with a dedicated solenoid mouse coil.
An atherosclerotic mouse model was first generated by feeding 8 ApoE−/− mice an atherogenic diet. MR images of the ascending aortas of these mice were then achieved using a three-dimensional black-blood
turbo spin-echo sequence (repetition time TR = 4 heart echo time TE=10ms). The MRI displayed a clear view of the aortic
lumens and the atherosclerotic lesions, which correlated significantly well with subsequent histological confirmations (linear
regression analysis, r=0.73, P=0.04). This study demonstrated that a clinical 3.0T MR scanner can be used for high-resolution imaging of mouse atherosclerotic
lesions to some extent.
Applied Magnetic Resonance 04/2012; 39(4):401-407. · 0.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To develop a small animal model of controlled aortic intimal injury with ultrasound (US) imaging guidance.
Via carotid artery cutdown, a custom-made microcatheter/angled metal device system was advanced to damage the intima of the ascending aortas of 20 Sprague-Dawley rats and 10 JCR atherosclerotic rats. This minimally invasive endovascular procedure was monitored by a clinical US imaging system. Injured aortas were harvested for histologic confirmation via a grading system: grade I, intima injury; grade II, injury to media; and grade III, injury through the entire aortic wall. Neointimal reactions at the injury site were compared by calculating the ratio of intimal to medial thickness among different animal groups at various survival times (week 1, weeks 2-3, and weeks 4-7).
Clear visualization of the architecture of the heart and great vessels and the exact location of the angled metal device by US imaging ensured consistent intimal damage of the aorta. Histopathologic analysis confirmed that most of the aortic injures were classified as grade I. There was no significant difference between the two rat groups. Analysis of pathophysiologic reactions at the injury sites revealed increased thickening of neointimal hyperplasia as animal survival times extended from week 1 to weeks 4-7 after the aortic interventions.
This study demonstrates the feasibility of clinical US imaging to precisely guide the creation of controlled aortic intimal injury in rats, which may become a useful tool to facilitate research involving the prevention and treatment of atherosclerotic cardiovascular disease.
Journal of vascular and interventional radiology: JVIR 05/2011; 22(8):1193-7. · 1.81 Impact Factor
-
Jihong Sun, Xubin Li,
Hongqing Feng,
Huidong Gu,
Tiffany Blair,
Jiakai Li,
Stephanie Soriano,
Yanfeng Meng,
Feng Zhang,
Qinghua Feng,
Xiaoming Yang
[show abstract]
[hide abstract]
ABSTRACT: A characteristic feature of atherosclerosis is its diffuse involvement of arteries across the entire human body. Bone marrow cells (BMC) can be simultaneously transferred with therapeutic genes and magnetic resonance (MR) contrast agents prior to their transplantation. Via systemic transplantation, these dual-transferred BMCs can circulate through the entire body and thus function as vehicles to carry genes/contrast agents to multiple atherosclerosis. This study was to evaluate the feasibility of using in vivo MR imaging (MRI) to monitor BMC-mediated interleukin-10 (IL-10) gene therapy of atherosclerosis.
For in vitro confirmation, donor mouse BMCs were transduced by IL-10/lentivirus, and then labeled with a T2-MR contrast agent (Feridex). For in vivo validation, atherosclerotic apoE(-/-) mice were intravenously transplanted with IL-10/Feridex-BMCs (Group I, n = 5) and Feridex-BMCs (Group II, n = 5), compared to controls without BMC transplantation (Group III, n = 5). The cell migration to aortic atherosclerotic lesions was monitored in vivo using 3.0T MRI with subsequent histology correlation. To evaluate the therapeutic effect of BMC-mediated IL-10 gene therapy, we statistically compared the normalized wall indexes (NWI) of ascending aortas amongst different mouse groups with various treatments.
Of in vitro experiments, simultaneous IL-10 transduction and Feridex labeling of BMCs were successfully achieved, with high cell viability and cell labeling efficiency, as well as IL-10 expression efficiency (≥90%). Of in vivo experiments, MRI of animal groups I and II showed signal voids within the aortic walls due to Feridex-created artifacts from the migrated BMCs in the atherosclerotic plaques, which were confirmed by histology. Histological quantification showed that the mean NWI of group I was significantly lower than those of group II and group III (P<0.05).
This study has confirmed the possibility of using MRI to track, in vivo, IL-10/Feridex-BMCs recruited to atherosclerotic lesions, where IL-10 genes function to prevent the progression of atherosclerosis.
PLoS ONE 01/2011; 6(9):e24529. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was designed to develop a novel magnetic resonance (MR) probe for the antigen OC183B2 in ovarian cancer cells and investigate its imaging features in vitro and in vivo.
Molecular probes were achieved through ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) conjugated to ovarian cancer monoclonal antibodies 183B2 (OCMab183B2) using a chemical method. In the control group, USPIOs were coupled with murine immunoglobulin G (mIgG) and conjugated the same way. Native polyacrylamide gel electrophoresis was used to evaluate the conjugation reaction. The cytotoxicity of the probe was measured using the methyl thiazolyl tetrazolium assay, and its cell-labeling efficiency was evaluated by Prussian blue staining. In vitro cell MR imaging was performed to evaluate the targeting of the probe to the cells. After that, the OCMab183B2 USPIOs and mIgG USPIOs were injected intravenously into nude mice implanted with ovarian cancer xenograft tumors, respectively. T2-weighted imaging and T2 mapping were then performed on a 3.0-T MR imaging system equipped with an animal birdcage coil at different times. Finally, the nude mice were sacrificed for histologic examination to confirm the imaging results.
Native polyacrylamide gel electrophoresis displayed an optimal conjugation of USPIOs to OCMab183B2 and mIgG. Various blue-staining particles were found in the cells labeled with the molecular probe at different iron concentrations, and the density of particles was positively related to the iron concentration. Its labeling rate was 96.06%, which was higher than that of USPIOs (62.5%) at the same iron concentration (20 μg/mL). The methyl thiazolyl tetrazolium assay showed that there was no difference in cellular bioactivity between OCMab183B2 USPIO-labeled and nonlabeled cells (P > .05). In vitro cell MR imaging showed that there was an obvious decrease in signal intensity for the probe-labeled cells compared to mIgG USPIO-labeled cells. For in vivo MR imaging, distinct changes of signal intensities and T2 values of ovarian cancers were detected after the injection of OCMab183B2 USPIOs compared to mIgG USPIOs. The histologic analysis showed that iron depositions were visualized in the experimental group but not in the control group.
OCMab183B2 USPIO conjugates have the potential to be useful as OC183B2-targeted MR imaging agents for the early detection of ovarian cancers.
Academic radiology 12/2010; 17(12):1468-76. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aggressive angiomyxoma is a rare tumor that affects the pelvis and perineum in women of reproductive age. Here we present the typical CT and MRI appearances of a 36-year old young woman with an aggressive angiomyxoma of the pelvis and perineum that was proved by postoperative pathology. We also review the CT and MRI features of this disease in the current literature.
Abdominal Imaging 12/2010; 36(6):739-41. · 1.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to develop an instant MR cell labeling technique, called magnetosonoporation. First, a magnetosonoporation apparatus was successfully established for MR labeling of stem cells. Then, the safety of this new cell labeling approach was confirmed by evaluation of cell viability, proliferation, and differentiation of magnetosonoporation-labeled and unlabeled C17.2 neural stem cells. Subsequently, the feasibility of using in vivo MRI to detect magnetosonoporation/Feridex-labeled stem cells was validated in living animals and confirmed by histologic correlation. The magnetosonoporation technique is expected to be convenient, efficient, and safe for future clinical application of MRI-guided cell therapies.
Magnetic Resonance in Medicine 06/2010; 63(6):1437-41. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to develop an instant MR cell labeling technique, called magnetosonoporation. First, a magnetosonoporation apparatus was successfully established for MR labeling of stem cells. Then, the safety of this new cell labeling approach was confirmed by evaluation of cell viability, proliferation, and differentiation of magnetosonoporation-labeled and unlabeled C17.2 neural stem cells. Subsequently, the feasibility of using in vivo MRI to detect magnetosonoporation/Feridex-labeled stem cells was validated in living animals and confirmed by histologic correlation. The magnetosonoporation technique is expected to be convenient, efficient, and safe for future clinical application of MRI-guided cell therapies. Magn Reson Med 63:1437–1441, 2010. © 2010 Wiley-Liss, Inc.
Magnetic Resonance in Medicine 05/2010; 63(6):1437 - 1441. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent advances in magnetic cell labeling have taken place with the development of a magnetosonoporation (MSP) technique. The aim of this study was to optimize the MSP protocol in order to achieve high cell viability and intracellular uptake of MR contrast agents. First, we determined the sub-optimal MSP parameters by evaluating the viabilities of C17.2 neural stem cells without Feridex using various MSP intensities ranging from 0.1 to 1 w/cm(2), duty cycles at 20%, 50% or 100%, and exposure times from 1-15 min. The sub-optimized MSP parameters with cell viabilities greater than 90% were further optimized by evaluating both cell viability and intracellular iron uptake when Feridex was used. We then used the optimized MSP parameters to determinate the optimal concentration of Feridex for magnetic cell labeling. Subsequently, we validated the feasibility of using MRI to track the migration of neural stem cells from the transplanted sites to glioma masses in four mouse brains when the cells had been labeled with Feridex using the optimized MSP protocol. The MRI findings were confirmed by histological correlations. In vitro experiments demonstrated that the optimal MSP protocol was achieved at 20% duty cycle, 0.3 w/cm(2) ultrasound intensity, 5-min exposure time and 1 mg/mL Feridex. This study demonstrated that the optimized MSP cell labeling technique can achieve both high cell viability and intracellular uptake of MR contrast agents, and has the potential to be a useful cell labeling technique to facilitate future clinical translation of MRI-integrated cell therapy.
NMR in Biomedicine 03/2010; 23(5):480-4. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Targeted magnetic resonance contrast agents have enabled the imaging of biological processes in vivo, and current insights have opened up new perspectives for the monitoring and diagnosis of many diseases.
To develop a contrast agent for targeting somatostatin receptors (SSTRs) expressed on breast cancer cells, and to evaluate the detection capabilities of a molecular probe using magnetic resonance (MR) imaging in an in vivo mouse model of breast carcinoma.
Octreotide (OCT) was conjugated with polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles by an ethyl-3-(dimethylaminopropyl) carbodiimide (EDC)-mediated reaction. Prussian blue staining for intracellular iron, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cellular MR imaging in vitro were performed on labeled MCF-7 breast cancer cells. Twenty-four mice bearing tumors were divided into two groups: 1) study group with injection of OCT-USPIOs (n=12); 2) control group with injection of USPIOs (n=12). Tumors were monitored in vivo using a 3.0-Tesla MR scanner before and after injection of contrast agents, and the findings were correlated with the histopathological findings.
OCT-USPIOs were shown to specifically bind to MCF-7 cells and did not affect proliferation and viability of the cells labeled. T(2) value of the cells labeled with OCT-USPIOs in vitro was 56.465+/-13.147 ms, while those of the cells cultured with USPIOs and gelatin/phosphate-buffered saline (PBS) gel alone were 75.435+/-16.171 ms and 85.950+/-22.352 ms, respectively (P<0.05). Signal intensity of the tumor gradually decreased, and its T(2) value reached a minimum of approximately 24.49% 6 hours after injection of OCT-USPIOs in vivo, compared to a minimum of 21.89% after 2 hours in the control group. Iron depositions were visualized as blue particles in tumor 6 hours after injection of OCT-USPIOs, while no blue particles were observed in the control group.
SSTR expression in vitro and in vivo can be selectively and directly imaged with an MR molecular probe. OCT-conjugated PEG-coated USPIO is potentially suitable to be used as a magnetic resonance contrast agent for MR imaging in vivo and increases the sensitivity for the early detection of breast carcinoma.
Acta Radiologica 06/2009; 50(6):583-94. · 1.37 Impact Factor
