Xulei Qin

Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer.

Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic.

Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging

Abstract. Early detection of malignant lesions could improve both survival and quality of life of cancer patients. Hyperspectral imaging (HSI) has emerged as a powerful tool for noninvasive cancer detection and diagnosis, with the advantage of avoiding tissue biopsy and providing diagnostic signatures without the need of a contrast agent in real time. We developed a spectral-spatial classification method to distinguish cancer from normal tissue on hyperspectral images. We acquire hyperspectral reflectance images from 450 to 900 nm with a 2-nm increment from tumor-bearing mice. In our animal experiments, the HSI and classification method achieved a sensitivity of 93.7% and a specificity of 91.3%. The preliminary study demonstrated that HSI has the potential to be applied in vivo for noninvasive detection of tumors.

Characterization of the homogeneous tissue mixture approximation in breast imaging dosimetry

PURPOSE To compare the estimate of normalized glandular dose in mammography and breast CT imaging obtained using the actual glandular tissue distribution in the breast to that obtained using the homogeneous tissue mixture approximation. METHODS Twenty volumetric images of patient breasts were acquired with a dedicated breast CT prototype system and the voxels in the breast CT images were automatically classified into skin, adipose, and glandular tissue. The breasts in the classified images underwent simulated mechanical compression to mimic the conditions present during mammographic acquisition. The compressed thickness for each breast was set to that achieved during each patients last screening cranio-caudal (CC) acquisition. The volumetric glandular density of each breast was computed using both the compressed and uncompressed classified images, and additional images were created in which all voxels representing adipose and glandular tissue were replaced by a homogeneous mixture of these two tissues in a proportion corresponding to each breasts volumetric glandular density. All four breast images (compressed and uncompressed; heterogeneous and homogeneous tissue) were input into Monte Carlo simulations to estimate the normalized glandular dose during mammography (compressed breasts) and dedicated breast CT (uncompressed breasts). For the mammography simulations the x-ray spectra used was that used during each patients last screening CC acquisition. For the breast CT simulations, two x-ray spectra were used, corresponding to the x-ray spectra with the lowest and highest energies currently being used in dedicated breast CT prototype systems under clinical investigation. The resulting normalized glandular dose for the heterogeneous and homogeneous versions of each breast for each modality was compared. RESULTS For mammography, the normalized glandular dose based on the homogeneous tissue approximation was, on average, 27% higher than that estimated using the true heterogeneous glandular tissue distribution (Wilcoxon Signed Rank Test p = 0.00046). For dedicated breast CT, the overestimation of normalized glandular dose was, on average, 8% (49 kVp spectrum, p = 0.00045) and 4% (80 kVp spectrum, p = 0.000089). Only two cases in mammography and two cases in dedicated breast CT with a tube voltage of 49 kVp resulted in lower dose estimates for the homogeneous tissue approximation compared to the heterogeneous tissue distribution. CONCLUSIONS The normalized glandular dose based on the homogeneous tissue mixture approximation results in a significant overestimation of dose to the imaged breast. This overestimation impacts the use of dose estimates in absolute terms, such as for risk estimates, and may impact some comparative studies, such as when modalities or techniques with different x-ray energies are used. The error introduced by the homogeneous tissue mixture approximation in higher energy x-ray modalities, such as dedicated breast CT, although statistically significant, may not be of clinical concern. Further work is required to better characterize this overestimation and potentially develop new metrics or correction factors to better estimate the true glandular dose to breasts undergoing imaging with ionizing radiation.

Improving Reliability and Accuracy of Vibration Parameters of Vocal Folds Based on High-Speed Video and Electroglottography

Quantified vibration parameters of vocal folds, including parameters directly extracted from high-speed video (HSV) and electroglottography (EGG), and inverse parameters based on models, can accurately describe the mechanism of phonation and also classify the abnormal in clinics. In order to improve the reliability and accuracy of these parameters, this paper provides a method based on an integrated recording system. This system includes two parts: HSV and EGG, which can record vibration information of vocal folds simultaneously. An image processing approach that bases on Zernike moments operator and an improved level set algorithm is proposed to detect glottal edges at subpixel-level aiming at image series recorded by HSV. An approach is also introduced for EGG data to extract three kinds of characteristic points for special vibration instants. Finally, inverse parameters of vocal folds can be optimized by a genetic algorithm based on the experimental vibration behaviors synthesized with these parameters and the simulations of a two-mass model. The results of a normal phonation experiment indicate that the parameters extracted by this method are more accurate and reliable than those extracted by general methods, which were only on the basis of HSV data and with pixel-level processing approaches in former studies.

Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery

Abstract. Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, and spectral derivatives for improved accuracy. The experimental results demonstrated the feasibility of the hyperspectral image processing and quantification framework for cancer detection during animal tumor surgery, in a challenging setting where sensitivity can be low due to a modest number of features present, but potential for fast image classification can be high. This HSI approach may have potential application in tumor margin assessment during image-guided surgery, where speed of assessment may be the dominant factor.

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

Summary The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm3. A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm3 and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking.

Measuring myofiber orientations from high-frequency ultrasound images using multiscale decompositions

High-frequency ultrasound (HFU) has the ability to image both skeletal and cardiac muscles. The quantitative assessment of these myofiber orientations has a number of applications in both research and clinical examinations; however, difficulties arise due to the severe speckle noise contained in the HFU images. Thus, for the purpose of automatically measuring myofiber orientations from two-dimensional HFU images, we propose a two-step multiscale image decomposition method. It combines a nonlinear anisotropic diffusion filter and a coherence enhancing diffusion filter to extract myofibers. This method has been verified by ultrasound data from simulated phantoms, excised fiber phantoms, specimens of porcine hearts, and human skeletal muscles in vivo. The quantitative evaluations of both phantoms indicated that the myofiber measurements of our proposed method were more accurate than other methods. The myofiber orientations extracted from different layers of the porcine hearts matched the prediction of an established cardiac mode and demonstrated the feasibility of extracting cardiac myofiber orientations from HFU images ex vivo. Moreover, HFU also demonstrated the ability to measure myofiber orientations in vivo.

Measuring Body-Cover Vibration of Vocal Folds Based on High-Frame-Rate Ultrasonic Imaging and High-Speed Video

Vibration of vocal folds is a body-cover layered vibration pattern due to the two-layer tissue structures of vocal folds. A method based on a synchronal imaging system is proposed in order to image and measure the body-cover vibration pattern of vocal folds. This imaging system contains two parts: high-frame-rate ultrasonic imaging part and high-speed video part, which can synchronously image the vibration of the body and cover layers at high speed. Then, image analysis methods are applied to measure the body-cover vibration of vocal folds from both recorded image sequences. We analyze characteristics of body-layer vibration based on the measurements from designed experiments. Moreover, these results meet simulations of a body-cover model.

Comparison of Non‐Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell‐ versus Induced Pluripotent Stem Cell‐Derived Cardiomyocytes

Both human embryonic stem cell‐derived cardiomyocytes (ESC‐CMs) and human induced pluripotent stem cell‐derived CMs (iPSC‐CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC‐CMs and iPSC‐CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head‐to‐head comparison of ESC‐CMs and iPSC‐CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence‐activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single‐cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub‐acute transplantation of ESC‐CMs and iPSC‐CMs into nude rats post‐MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non‐coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC‐CMs and iPSC‐CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC‐CMs used in therapy, autologous iPSC‐CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. Stem Cells 2017;35:2138–2149

Measuring body layer vibration of vocal folds by high-frame-rate ultrasound synchronized with a modified electroglottograph.

The body-cover concept suggests that the vibration of body layer is an indispensable component of vocal fold vibration. To quantify this vibration, a synchronized system composed of a high-frame-rate ultrasound and a modified electroglottograph (EGG) was employed in this paper to simultaneously image the body layer vibration and record the vocal fold vibration phase information during natural phonations. After data acquisition, the displacements of in vivo body layer vibrations were measured from the ultrasonic radio frequency data, and the temporal reconstruction method was used to enhance the measurement accuracy. Results showed that the modified EGG, the waveform and characteristic points of which were identical to the conventional EGG, resolved the position conflict between the ultrasound transducer and EGG electrodes. The location and range of the vibrating body layer in the estimated displacement image were more clear and discernible than in the ultrasonic B-mode image. Quantitative analysis for vibration features of the body layer demonstrated that the body layer moved as a unit in the superior-inferior direction during the phonation of normal chest registers.