Rui-Meng Yang

Differentiation of Central Lung Cancer from Atelectasis: Comparison of Diffusion-Weighted MRI with PET/CT

Objective Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis. Materials and Methods 38 consecutive lung cancer patients (26 males, 12 females; age range: 28–71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm2. Results PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm2/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both). Conclusions DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer.

Glycosaminoglycan-targeted iron oxide nanoparticles for magnetic resonance imaging of liver carcinoma

To develop an efficient probe for targeted magnetic resonance (MR) imaging of liver carcinoma, the surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) was carried out by conjugating a naturally-occurring glycosaminoglycan with specific biological recognition to human hepatocellular liver carcinoma (HepG2) cells. These modified SPIOs have good water dispersibility, superparamagnetic property, cytocompatibility and high magnetic relaxivity for MR imaging. When incubated with HepG2 cells, they demonstrated significant cellular uptake and specific accumulation, as confirmed by Prussian blue staining and confocal microscopy. The in vitro MR imaging of HepG2 cells and in vivo MR imaging of HepG2 tumors confirmed their effectiveness for targeted MR imaging of liver carcinoma.

Hyaluronan-modified superparamagnetic iron oxide nanoparticles for bimodal breast cancer imaging and photothermal therapy

Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA)-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs), which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs. When incubated with CD44 HA receptor-overexpressing MDA-MB-231 cells in vitro, HA-SPIONs exhibited significant specific cellular uptake and specific accumulation confirmed by Prussian blue staining. The in vitro and in vivo results of magnetic resonance imaging and photothermal ablation demonstrated that HA-SPIONs exhibited significant negative contrast enhancement on T2-weighted magnetic resonance imaging and photothermal effect targeted CD44 HA receptor-overexpressing breast cancer. All these results indicated that HA-SPIONs have great potential for effective diagnosis and treatment of cancer.

Differentiation of true-progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide by GLCM texture analysis of conventional MRI

Twenty-two patients with pathologically confirmed glioblastoma who had received concurrent CCRT with TMZ underwent conventional MRI including T1-weighted imaging(T1WI), T2-weighted imaging(T2WI), fluid attenuated inversion recovery(FLAIR)and contrast-enhanced T1WI(T1Ce). Five GLCM texture maps of contrast, energy, entropy, correlation and homogeneity were generated for each MRI series. Of the aforementioned 5 texture features, the most significant features were contrast and correlation on T2WI with areas under ROC curve of 0.883 and 0.892, respectively, and they had the same sensitivity of 75%, specificity of 100%, accuracy of 86.4%, PPV of 100% and NPV of 76.9% in differentiation true progression from pseudoprogression.

Altered resting-state connectivity in college students with nonclinical depressive symptoms.

Background The underlying brain basis of nonclinical depressive symptoms (nCDSs) is largely unknown. Recently, the seed-based functional connectivity (FC) approach for analyzing resting-state fMRI (rs-fMRI) data has been increasingly used to explore the neural basis of depressive disorders. Other than common seed-based FC method using an a priori seed region, we conducted FC analysis based on regions with altered spontaneous activity revealed by the fractional amplitude of low-frequency fluctuations (fALFF) approach. The aim of the present study was to provide novel insight in the underlying mechanism of nCDSs in college students. Methodology/Principal Findings A total number of 1105 college students were recruited to participant in a survey for assessing depressive symptoms. Subsequently, 17 individuals with nCDSs and 20 healthy controls (HCs) were enrolled to perform MR studies. Alternations of fALFF were identified in the right superior parietal lobule (SPL) and left lingual gyrus, both of which were used as ROIs for further FC analysis. With right SPL, compare with HCs, subjects with nCDSs showed reduced FCs in the bilateral dorsal lateral prefrontal cortex (DLPFC), left inferior frontal gurus (IFG), left premotor cortex (PMC), DMN network [i.e., bilateral precuneus, posterior cingulate cortex (PCC), right supramarginal gyrus (SMG), right parahippocampal gyrus (PHG), bilateral inferior temporal gurus (ITG)] and left cerebellum posterior lobe (CPL). In addition, increased FCs were observed between the left lingual gyrus and right fusiform gyrus as well as in the left precuneus. Conclusion/Significance Our results indicate the abnormalities of spontaneous activity in the right SPL and left lingual gyrus and their corresponding dysfunction of the brain circuits might be related to the pathophysiology of nCDSs.

Alteration of spontaneous neuronal activity in young adults with non-clinical depressive symptoms

Non-clinical depressive symptoms (nCDSs) are highly prevalent in young adults and may be associated with the risk of developing full-fledged depressive disorders. However, the neural basis underlying nCDSs remains unknown. To explore the alteration of spontaneous brain activity in individuals with nCDSs compared with healthy controls (HCs), we investigated resting-state brain activity using the amplitude of low-frequency fluctuations (ALFF) in subjects with nCDSs (n=17) and HCs (n=20). All subjects were drawn from a sample of 1105 college students participating in a survey assessing depressive symptoms. We determined that nCDSs can lead to reduced ALFF in the right ventral lateral prefrontal cortex (VLPFC) and right dorsolateral prefrontal cortex (DLPFC) and to increased ALFF in the left fusiform, left posterior cerebellum, right cuneus, left inferior parietal lobule, right supramarginal gyrus and bilateral precuneus. In addition, with respect to Beck Depression Inventory (BDI) scores and ALFF values in subjects with nCDSs, a positive correlation was discovered in the right DLPFC, while a negative correlation was identified in left posterior cerebellum and bilateral precuneus after correction. These results indicate that nCDSs are characterized by altered spontaneous activity in several important functional regions. We suggest that altered ALFFs in the right DLPFC, left posterior cerebellum and bilateral precuneus may be biomarkers that are related to the pathophysiology of nCDSs in young adults.

Reduction-sensitive amphiphilic dextran derivatives as theranostic nanocarriers for chemotherapy and MR imaging

Reduction-sensitive, amphiphilic dextran derivatives were developed from disulfide-linked dextran-g-poly-(N-e-carbobenzyloxy-L-lysine) graft polymer (Dex-g-SS-PZLL), and used as theranostic nanocarriers for chemotherapy and MR imaging. Dex-g-SS-PZLLs were synthesized by click conjugation between azidized dextran (Dex-N3, 40 kD) and α-alkyne-SS-PZLL (degree of polymerization = 10, 15 and 25). The chemical structures of dextran derivatives were characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to their amphiphilic nature, these copolymers can self-assemble into spherical nanosized micelles in an aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. Interestingly, the hydrodynamic radii of the micelles (65–100 nm in diameter) were dependent on the block length of PZLL, and their critical micelle concentrations were in the range of 0.020–0.007 mg mL−1, which decreased as the length of PZLL increased. The anticancer drug doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), as the magnetic resonance imaging (MRI) contrast agent, were simultaneously encapsulated in the hydrophobic core of the micelles by the dialysis method. The release profiles of encapsulated DOX from SPIO/DOX-loaded micelles were shown to be rapid in the presence of 10 mM glutathione (GSH) within 24 h, whereas less than 30% DOX was released from reduction insensitive Dex-g-PZLL micelles in 48 h. Only about 35% DOX was released from Dex-g-SS-PZLL micelles in the same timeframe. According to the in vitro cytotoxicity test, it was found that reduction-sensitive micelles showed higher toxicity to HepG2 cancer cells than the reduction-insensitive micelles incubated with equivalent DOX concentration. Flow cytometry and fluorescence microscopy analyses further demonstrated that the reduction-sensitive micelles exhibited faster drug release behavior than reduction-insensitive micelles, which also led to higher cytotoxicity. The SPIO/DOX-loaded micelles demonstrated excellent MRI contrast enhancement, and the r2 relaxivity values of the SPIO/DOX-loaded micelles were up to 261.3 Fe mM−1 s−1. Consequently, these reduction-sensitive amphiphilic dextran derivatives are promising theranostic nanocarriers for MR imaging and chemotherapy.

Increased interhemispheric functional connectivity in college students with non-clinical depressive symptoms in resting state

The underlying neural basis of non-clinical depressive symptoms (nCDSs) remains unclear. Interhemispheric functional connectivity has been suggested as one of the most robust characteristics of brains intrinsic functional architecture. Here, we investigated the functional connectivity between homotopic points in the brain using the voxel-mirrored homotopic connectivity (VMHC) approach. We performed VMHC analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 17 individuals with nCDSs and 20 healthy controls (HCs) who were enrolled from a sample of 1105 college students. We found increased VMHCs in the bilateral posterior cerebellum and fusiform gyrus in nCDSs subjects compared with HCs. Furthermore, receiver operating characteristic (ROC) curves indicated that VMHC values in the posterior cerebellum lobes could use to differente nCDSs from HCs [area under the curve (AUC), 0.756; p<0.01]. We suggest increased VMHCs indicate a possible compensatory mechanism involved in the pathophysiology of nCDSs. VMHC values of the posterior cerebellum lobes might serve as a reliable biomarker for identifying nCDSs.

Surface functionalization of superparamagnetic nanoparticles by an acid-liable polysaccharide-based prodrug for combinatorial monitoring and chemotherapy of hepatocellular carcinoma

For combinatorial monitoring and chemotherapy of hepatocellular carcinoma, the macromolecular prodrug based on hyaluronic acid and doxorubicin hydrochloride was prepared by an acid-labile hydrazone linkage, and then conjugated with amine-modified iron oxide nanoparticles by a carbodiimide mediated coupling reaction. The resultant hybrid nanoparticles have the characteristics of good water dispersibility, superparamagnetic property and high magnetic relaxivity for magnetic resonance imaging. In particular, they demonstrated significant cellular uptake and specific accumulation in human hepatocellular liver carcinoma HepG2 cells due to specific biological recognition of hyaluronic acid. In addition, in vitro cumulative release of doxorubicin hydrochloride from the resultant hybrid nanoparticles was significantly accelerated at a mildly acidic pH of 5.0–6.0 when compared to its release at the physiological pH of 7.4, suggesting the pH-responsive feature of this conjugated prodrug for effective chemotherapy of hepatocellular carcinoma. In vivo antitumor efficacy of the mice further confirmed the effect.

Bioreducible amphiphilic block copolymers based on PCL and glycopolypeptide as multifunctional theranostic nanocarriers for drug delivery and MR imaging

Amphiphilic diblock poly(e-caprolactone)-b-glycopolypeptides (PCL–SS–GPPs) bearing disulfide bonds were synthesized from a clickable poly(e-caprolactone)–SS–poly(2-azidoethyl-L-glutamate) diblock copolymer. Galactosyl and lactosyl sugar units as targeting ligands were conjugated to the polypeptide blocks via an efficient click reaction. The chemical structures of PCL–SS–GPPs were characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis. Owing to their amphiphilic nature, these copolymers could self-assemble into spherical nano-sized micelles in an aqueous medium, as confirmed by fluorometry, transmission electron microscopy, and dynamic light scattering. The hydrophobic anticancer drug doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), as the magnetic resonance imaging (MRI) contrast agent, were simultaneously encapsulated in the hydrophobic core of the micelles via dialysis. The release profiles of encapsulated DOX from the SPIO/DOX-loaded PCL–SS–GPPs micelles were shown to be rapid in the presence of 10 mM glutathione (GSH) within 24 h, whereas in the absence of GSH, there was less than 35% DOX released from the PCL–SS–GPPs micelles in 24 h. Inverted fluorescence microscopy revealed the specific interaction between the sugars units on the PCL–SS–GPPs surface with the FITC-lectin. MTT assay demonstrated that the blank PCL–SS–GPPs micelles were nontoxic to the HepG2 cells, even for concentrations up to 500 μg mL−1, whereas the free DOX and DOX-loaded PCL–SS–GPPs micelles showed significant cytotoxicity against the HepG2 cells. The fluorescence images and flow cytometry tests revealed that DOX could be efficiently transported into HepG2 tumor cells by PCL–SS–GPPs micelles. The PCL–SS–GPPs micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles enabled excellent MRI contrast enhancement, thus confirming their effectiveness for MR imaging.