Meiwei Chen

A novel polymeric micelle used for in vivo MR imaging tracking of neural stem cells in acute ischemic stroke

Transplantation of neural stem cells (NSCs) is a promising treatment strategy for acute ischemic stroke. In vivo tracking of the therapeutic stem cells in the host brain after transplantation is essential not only to ensure the safety and efficacy of the treatment, but also to better understand their migrational dynamics and regeneration potential. Many polymeric nanoparticles have been developed to label stem cells for in vivo tracking by magnetic resonance imaging (MRI), optical imaging (OI) or other imaging modalities. However, the non-degradability and presence of cellular toxicity of the nanoparticles restrict their clinical applications. In this study, we developed a novel cationic polymeric micelles based on amphipathic polymer of biodegradable hydrophilic poly(aspartic acid-dimethylethanediamine) (PAsp(DMA)) that were conjugated with two molecules of hydrophobic cholic acid (CA) by lysine. Image labels, superparamagnetic iron oxide nanoparticles (SPIONs) and fluorescent nile red were simultaneously loaded into the micelles to label NSCs. The labeling capacity, efficiency and cytotoxicity of the cationic micelles were determined. The in vivo MRI tracking of the therapeutic NSCs in acute ischemic stroke was also explored. Our results showed that this type of cationic polymeric micelles achieved a high efficient and safe labeling of NSCs and resulted in reliable in vivo MRI tracking of therapeutic stem cells in acute ischemic stroke, but without detrimental effect. The cationic, biodegradable polymeric micelles are highly translatable for clinical application and can be used as a versatile nanoplatform for stem cell labeling and subsequently in vivo tracking in regenerative medicine.

DTI metrics can be used as biomarkers to determine the therapeutic effect of stem cells in acute peripheral nerve injury

To determine the role of diffusion tensor imaging (DTI) metrics as biomarkers for the therapeutic effects of mesenchymal stem cells (MSCs) in acute peripheral nerve injury.

In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke

Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs in stroke. Previously, we have successfully realized in vivo targeted MR imaging of endogenous NSCs in normal adult mice brains by using anti-CD15 antibody-conjugated superparamagnetic iron oxide nanoparticles (anti-CD15-SPIONs) as the molecular probe. Herein, we explore the performance of this molecular probe in targeted in vivo tracking of activated endogenous NSCs in ischemic stroke. Our study showed that intraventricular injection of anti-CD15-SPIONs could label activated endogenous NSCs in situ seven days after ischemic stroke, which were detected as enlarged areas of hypo-intense signals on MR imaging at 7.0 T. The treatment of cytosine arabinosine could inhibit the activation of endogenous NSCs, which was featured by the disappearance of areas of hypo-intense signals on MR imaging. Using anti-CD15-SPIONs as imaging probes, the dynamic process of activation of endogenous NSCs could be readily monitored by in vivo MR imaging. This targeted imaging strategy would be of great benefit to develop a new therapeutic strategy utilizing endogenous NSCs for ischemic stroke.

In Vivo Long-Term Tracking of Neural Stem Cells Transplanted into an Acute Ischemic Stroke model with Reporter Gene-Based Bimodal MR and Optical Imaging

Transplantation of neural stem cells (NSCs) is emerging as a new therapeutic approach for stroke. Real-time imaging of transplanted NSCs is essential for successful cell delivery, safety monitoring, tracking cell fate and function, and understanding the interactions of transplanted cells with the host environment. Magnetic resonance imaging (MRI) of magnetic nanoparticle-labeled cells has been the most widely used means to track stem cells in vivo. Nevertheless, it does not allow for the reliable discrimination between live and dead cells. Reporter gene-based MRI was considered as an alternative strategy to overcome this shortcoming. In this work, a class of lentiviral vector-encoding ferritin heavy chain (FTH) and enhanced green fluorescent protein (EGFP) was constructed to deliver reporter genes into NSCs. After these transgenic NSCs were transplanted into the contralateral hemisphere of rats with acute ischemic stroke, MRI and fluorescence imaging (FLI) were performed in vivo for tracking the fate of transplanted cells over a long period of 6 wk. The results demonstrated that the FTH and EGFP can be effectively and safely delivered to NSCs via the designed lentiviral vector. The distribution and migration of grafted stem cells could be monitored by bimodal MRI and FLI. FTH can be used as a robust MRI reporter for reliable reporting of the short-term viability of cell grafts, whereas its capacity for tracking the long-term viability of stem cells remains dependent on several confounding factors such as cell death and the concomitant reactive inflammation.

CT and MRI findings of radiation-induced external auditory canal carcinoma in patients with nasopharyngeal carcinoma after radiotherapy

OBJECTIVE To summarize the radiological and clinical features of radiation-induced external auditory canal carcinomas (RIEACCs) in patients with nasopharyngeal carcinomas (NPCs) after radiation therapy. METHODS CT, MRI and clinical features in 16 patients with histologically proven RIEACCs were retrospectively reviewed. There were 2 females and 14 males, with a median age of 52.5 years at the time of diagnosis of RIEACC. Imaging parameters including lesion extent, size, margin, shape, bone destruction, adjacent structure invasion, density/signal intensity, and pattern and degree of enhancement were assessed. Clinical features including clinical staging, histological type, treatment and radiation dose (RD) of primary NPC as well as the histological type, staging of radiation-induced tumour and the latent period between NPC and RIT were recorded. RESULTS All patients had a single RIEACC. The lesions had a size of 3.5 ± 1.4 cm and were localized (n = 7) or extensive (n = 9). Most of the lesions were partially or ill defined with an irregular shape and had an intermediate density/signal pattern and moderate homogeneous enhancement. The latent period of RIEACCs ranged from 10 to 20 years in nine patients with a RD of 68-70 Gy; from 2 to 10 years in five patients with a RD of 68-74 Gy; and more than 20 years in two patients with a RD of 70 or 72 Gy. CONCLUSION An external auditory canal (EAC) mass with homogeneous, intermediate CT density or signal intensity in patients with NPC after radiotherapy is highly suggestive of RIEACC, which should be included in the routine surveillance for patients with NPC after radiotherapy. ADVANCES IN KNOWLEDGE RIEACCs could occur as short as 2 years after radiotherapy in patients with NPC and have distinct features from otitis media and sarcomas. This EAC malignancy should be included in routine surveillance for patients with NPC after radiotherapy.

Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging

The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis.

Monitoring of macrophage recruitment enhanced by Toll-like receptor 4 activation with MR imaging in nerve injury: MRI of Enhanced Macrophage Recruitment in Nerve Injury

Introduction: Macrophage recruitment is critical for nerve regeneration after an injury. The aim of this study was to investigate whether ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle‐based MRI could be used to monitor the enhanced macrophage recruitment by Toll‐like receptor 4 (TLR4) activation in nerve injury. Methods: Rats received intraperitoneal injections of either lipopolysaccharide (LPS) or phosphate buffered saline (PBS) or no injection (controls) after a sciatic nerve crush injury. After intravenous injection of the USPIOs (LPS and PBS groups) or PBS (control group), MRI was performed and correlated with histological findings. Results: LPS group showed more remarkable hypointense signals on T2*‐weighted imaging and lower T2 values in the crushed nerves than PBS group. The hypointense signal areas were associated with an enhanced recruitment of iron‐loaded macrophages to the injured nerves. Discussion: USPIO‐enhanced MRI can be used to monitor the enhanced macrophage recruitment by means of TLR4 signal pathway activation in nerve injury. Muscle Nerve 58: 123–132, 2018

In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas using reporter gene‐based MR imaging

Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth. Therefore, a robust surveillance system with a capacity for noninvasive monitoring of the homing, distribution and fate of stem cells in vivo is highly desired for developing stem cell‐based gene therapies for tumors. In this study, we used ferritin gene‐based magnetic resonance imaging (MRI) to track the tumor tropism of MSCs in a rat orthotopic xenograft model of malignant glioma. MSCs were transduced with lentiviral vectors expressing ferritin heavy chain (FTH) and enhanced green fluorescent protein (eGFP). Intra‐arterial, intravenous and intertumoral injections of these FTH transgenic MSCs (FTH‐MSCs) were performed in rats bearing intracranial orthotopic C6 gliomas. The FTH‐MSCs were detected as hypointense signals on T2‐ and T2*‐weighted images on a 3.0 T clinical MRI. After intra‐arterial injection, 17% of FTH‐MSCs migrated toward the tumor and gradually diffused throughout the orthotopic glioma. This dynamic process could be tracked in vivo by MRI up to 10 days of follow‐up, as confirmed by histology. Moreover, the tumor tropism of MSCs showed no appreciable impact on the progression of the tumor. These results suggest that FTH reporter gene‐based MRI can be used to reliably track the tropism and fate of MSCs after their systemic transplantation in orthotopic gliomas. This real‐time in vivo tracking system will facilitate the future development of stem cell‐based therapies for malignant gliomas.

Axillary Sentinel Lymph Nodes in Breast Cancer: Quantitative Evaluation at Dual-Energy CT

Purpose To evaluate the diagnostic performance of quantitative parameters derived from dual-energy CT for the preoperative diagnosis of metastatic sentinel lymph nodes (SLNs) in participants with breast cancer. Materials and Methods For this prospective study, dual-phase contrast agent-enhanced CT was performed in female participants with breast cancer from June 2015 to December 2017. Quantitative dual-energy CT parameters and morphologic parameters were compared between metastatic and nonmetastatic SLNs. The quantitative parameters were fitted to univariable and multivariable logistic regression models. The diagnostic role of morphologic and quantitative parameters was analyzed by receiver operating characteristic curves and compared by using the McNemar test. Results This study included 193 female participants (mean age, 47.6 years ± 10.1; age range, 22-79 years). Quantitative dual-energy CT parameters including slope of the spectral Hounsfield unit curve (λHu) measured at both arterial and venous phases, normalized iodine concentration at both arterial and venous phase, and normalized effective atomic number at the venous phase were higher in metastatic than in nonmetastatic SLNs (P value range, ≤.001 to .031). Univariable and multivariable logistic regression analyses showed that venous phase λHu (in Hounsfield units per kiloelectron-volt) was the best single parameter for the detection of metastatic SLNs. The accuracy of the venous phase λHu for detecting metastatic SLNs was 90.5% on a per-lymph node basis and 87.0% on a per-patient basis. The accuracy and specificity at venous phase λHu was higher than their counterparts in the morphologic parameters (P < .001). Conclusion Dual-energy CT is a complementary means for the preoperative identification of sentinel lymph nodes metastases in participants with breast cancer.