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      1. Author :
        Li, Rui; Zheng, Ke; Yuan, Cai; Chen, Zhuo; Huang, Mingdong
      2. Title :
        Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting of Nanomaterials
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        nanomaterial; nanoparticle; enhanced permeability and retention effect; receptor-mediated tumor targeting; urokinase-type plasminogen activator receptor; amino-terminal fragment; FMT
      12. Abstract :
        Malignant tumor (cancer) remains as one of the deadliest diseases throughout the world, despite its overall mortality drops. Nanomaterials (NMs) have been widely studied as diagnostic and/or therapeutic agents for tumors. A feature of NMs, compared to small molecules, is that NMs can be concentrated passively in tumors through enhanced permeability and retention (EPR) effect. In the meantime, NMs can be engineered to target toward tumor specific markers in an active manner, e.g., receptor-mediated targeting. The relative contribution of the EPR effect and the receptor-mediated targeting to NM accumulation in tumor tissues has not been clearly defined yet. Here, we tackle this fundamental issue by reviewing previous studies. First, we summarize the current knowledge on these two tumor targeting strategies of NMs, and on how NMs arrive to tumors from blood circulation. We then demonstrate that contribution of the active and passive effects to total accumulation of NMs in tumors varies with time. Over time, the receptor-mediated targeting contributes more than the EPR effect with a ratio of 3 in the case of urokinase-type plasminogen activator receptor (uPAR)-mediated targeting and human serum albumin (HSA)-mediated EPR effect. Therefore, this review highlights the dynamics of active and passive targeting of NMs on their accumulation at tumor sites, and is valuable for future design of NMs in cancer diagnosis and treatment.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14137
      15. Serial :
        13391
      1. Author :
        Zhu, Yansong; Jha, Abhinav K.; Dreyer, Jakob K.; Le, Hanh N. D.; Kang, Jin U.; Roland, Per E.; Wong, Dean F.; Rahmim, Arman
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        10059
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Fmt
      12. Abstract :
        Fluorescence molecular tomography (FMT) is a promising tool for real time in vivo quantification of neurotransmission (NT) as we pursue in our BRAIN initiative effort. However, the acquired image data are noisy and the reconstruction problem is ill-posed. Further, while spatial sparsity of the NT effects could be exploited, traditional compressive-sensing methods cannot be directly applied as the system matrix in FMT is highly coherent. To overcome these issues, we propose and assess a three-step reconstruction method. First, truncated singular value decomposition is applied on the data to reduce matrix coherence. The resultant image data are input to a homotopy-based reconstruction strategy that exploits sparsity via ℓ1 regularization. The reconstructed image is then input to a maximum-likelihood expectation maximization (MLEM) algorithm that retains the sparseness of the input estimate and improves upon the quantitation by accurate Poisson noise modeling. The proposed reconstruction method was evaluated in a three-dimensional simulated setup with fluorescent sources in a cuboidal scattering medium with optical properties simulating human brain cortex (reduced scattering coefficient: 9.2 cm−1, absorption coefficient: 0.1 cm−1 and tomographic measurements made using pixelated detectors. In different experiments, fluorescent sources of varying size and intensity were simulated. The proposed reconstruction method provided accurate estimates of the fluorescent source intensity, with a 20% lower root mean square error on average compared to the pure-homotopy method for all considered source intensities and sizes. Further, compared with conventional ℓ2 regularized algorithm, overall, the proposed method reconstructed substantially more accurate fluorescence distribution. The proposed method shows considerable promise and will be tested using more realistic simulations and experimental setups.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13370
      15. Serial :
        13366
      1. Author :
        Zhao, Yue; Baikejiang, Reheman; Li, Changqing
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        10057
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Luminescence ;; Tomography ;; Matrices ;; Microcomputed tomography ;; Modeling ;; Numerical simulations ;; Machine learning ;; Finite element methods ;; Inverse problems; FMT
      12. Abstract :
        Reconstruction of fluorescence molecular tomography (FMT) is an ill-posed inverse problem. Anatomical guidance in the FMT reconstruction can improve FMT reconstruction efficiently. We have developed a kernel method to introduce the anatomical guidance into FMT robustly and easily. The kernel method is from machine learning for pattern analysis and is an efficient way to represent anatomical features. For the finite element method based FMT reconstruction, we calculate a kernel function for each finite element node from an anatomical image, such as a micro-CT image. Then the fluorophore concentration at each node is represented by a kernel coefficient vector and the corresponding kernel function. In the FMT forward model, we have a new system matrix by multiplying the sensitivity matrix with the kernel matrix. Thus, the kernel coefficient vector is the unknown to be reconstructed following a standard iterative reconstruction process. We convert the FMT reconstruction problem into the kernel coefficient reconstruction problem. The desired fluorophore concentration at each node can be calculated accordingly. Numerical simulation studies have demonstrated that the proposed kernel-based algorithm can improve the spatial resolution of the reconstructed FMT images. In the proposed kernel method, the anatomical guidance can be obtained directly from the anatomical image and is included in the forward modeling. One of the advantages is that we do not need to segment the anatomical image for the targets and background.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13366
      15. Serial :
        13367
      1. Author :
        Wang, Ge
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        10057
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Fmt
      12. Abstract :
        Due to its penetrating power, fine resolution, unique contrast, high-speed, and cost-effectiveness, x-ray imaging is one of the earliest and most popular imaging modalities in biomedical applications. Current x-ray radiographs and CT images are mostly on gray-scale, since they reflect overall energy attenuation. Recent advances in x-ray detection, contrast agent, and image reconstruction technologies have changed our perception and expectation of x-ray imaging capabilities, and generated an increasing interest in imaging biological soft tissues in terms of energy-sensitive material decomposition, phase-contrast, small angle scattering (also referred to as dark-field), x-ray fluorescence and luminescence properties. These are especially relevant to preclinical and mesoscopic studies, and potentially mendable for hybridization with optical molecular tomography. In this article, we review new x-ray imaging techniques as related to optical imaging, suggest some combined x-ray and optical imaging schemes, and discuss our ideas on micro-modulated x-ray luminescence tomography (MXLT) and x-ray modulated opto-genetics (X-Optogenetics).
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13372
      15. Serial :
        13376
      1. Author :
        Seth, Arjun
      2. Title :
        Development of nanovaccines against Influenza A and Group A Streptococcus
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Fmt
      12. Abstract :
        Modern vaccine development has focused on developing effective vaccines without compromising vaccine safety and tolerability. This has prompted the rational design of modern subunit vaccines, which are safe and well-characterized, by incorporating key immunogenic elements of pathogen properties to induce tailored responses of appropriate strength, quality and specificity. Based on this strategy, Virus-like particles (VLPs) and their subunit capsomeres have been utilized as a platform to present a variety of foreign epitopes from targeted pathogens. Promising vaccine candidates based on the modular murine polyomavirus (MPyV) VLP or capsomere platform have been developed to target influenza A and Group A streptococcus (GAS), which are microbially-produced rapidly at low-cost and are easily scalable. However, the understanding of their effectiveness in inducing specific immune response is limited. Building on the previous successful outcomes with these vaccine candidates, different strategies were investigated to improve their immunogenicity and protective efficacy. This involved the refinement of vaccine at formulation level (e.g. adjuvants) or administration route (e.g. parenteral or non-parenteral). This work utilizes a fluorescence optical imaging approach for in vivo tracking of vaccine components after immunization to correlate the immune responses with their biodistribution. The main objectives of this thesis are: (i) demonstrating the non-carrier adjuvanting efficacy of PLGA and silica nanoparticles for modular capsomeres presenting influenza M2e antigen; (ii) visualizing the in vivo trafficking of silica nanoparticle-adjuvanted modular capsomere formulation by fluorescence imaging to understand their ability to induce effective antibody-biased immune response, even though these components are not attached prior to immunization; (iii) determining the potential of sublingual delivery of modular VLPs presenting GAS J8 antigen; and (iv) evaluating the in vivo trafficking of sublingually-administered modular VLPs to comprehend their ability to raise systemic as well as mucosal response. This work confirms that a simple ‘mix and inject’ formulation of nanoparticles and modular capsomeres can lead to effective adjuvanting of antigenic modular capsomeres by nanoparticles, with level of antibody response reliant on physicochemical properties of nanoparticles. The non-carrier adjuvanting effect of silica nanoparticles on modular capsomere was observed despite independent in vivo trafficking of nanoparticles and capsomeres, as visualized by fluorescence imaging. To the best of my knowledge, this work is the first to demonstrate the efficacy of sublingually-administered modular VLPs-based GAS vaccine and visualize their in vivo trafficking. These sublingually-administered modular VLPs induced high mucosal and systemic responses, which was aided by the observed draining of VLPs into submandibular lymph nodes and iii in parallel with rapid absorption into systemic circulation. More importantly, the induced salivary antibodies opsonized GAS in vitro. This work also reports the potential of a freeze-dried formulation of modular VLPs as a cold-chain free, cost-effective GAS vaccine especially for poor remote regions which are most affected by GAS diseases. The outcomes of this thesis foster the development of modular VLPs and capsomeres targeting GAS and influenza A, respectively, and highlights the flexibility of MPyV VP1 based microbial vaccine platform to cater to the need for low-cost, rapid response and safe and efficacious vaccines.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13616
      15. Serial :
        13382
      1. Author :
        Lo, Pei-An; Cho, Jaedu; Nouizi, Farouk; Chiang, Huihua Kenny; Gulsen, Gultekin
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        10056
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Diffuse optical tomography; Luminescence; Lasers; Reconstruction algorithms; Animal testing; Absorption; Computed tomography; Fluorescence tomography; Imaging systems; Indocyanine green; FMT
      12. Abstract :
        Fluorescence diffuse optical tomography (FDOT) has been widely used for in vivo small animal studies and the illposed problem in reconstruction can be eased by utilizing structural a priori obtained from an anatomic imaging modality. In this study, a multispectral fluorescence tomography (FT) is used, which has shown the ability to detect subtle shifts in the ICG absorption spectrum in our previous study. The imaging system is in trans-illumination mode with a swept-wavelength laser and a CCD on a rotation gantry and the structural image from the X-ray computed tomography is used to guide and constrain the FT reconstruction algorithm. In this work, a phantom with two inclusions filled with different fluorophores is utilized to evaluate whether the spectral information obtained using sweptwavelength laser can distinguish these two inclusions. The images are captured from 8 different views with three different wavelengths.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13510
      15. Serial :
        13387
      1. Author :
        Liu, Yuhao; Liu, Jie; An, Yu; Jiang, Shixin; Ye, Jinzuo; Mao, Yamin; He, Kunshan; Zhang, Guanglei; Chi, Chongwei; Tian, Jie
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        10047
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Luminescence ;; Tomography ;; Algorithms ;; Matrices ;; Molecular imaging ;; Simulations ;; Tissues; FMT
      12. Abstract :
        Fluorescence molecular tomography (FMT) is developing rapidly in the field of molecular imaging. FMT has been used in surgical navigation for tumor resection and has many potential applications at the physiological, metabolic, and molecular levels in tissues. Due to the ill-posed nature of the problem, many regularized methods are generally adopted. In this paper, we propose a region reconstruction method for FMT in which the trace norm regularization. The trace norm penalty was defined as the sum of the singular values of the matrix. The proposed method adopts a priori information which is the structured sparsity of the fluorescent regions for FMT reconstruction. In order to improve the solution efficiency, the accelerated proximal gradient algorithms was used to accelerate the computation. The numerical phantom experiment was conducted to evaluate the performance of the proposed trace norm regularization method. The simulation study shows that the proposed method achieves accurate and is able to reconstruct image effectively.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13325
      15. Serial :
        13388
      1. Author :
        Zhou, Yuan; Guang, Huizhi; Pu, Huangsheng; Zhang, Jiulou; Bai, Jing; Luo, Jianwen
      2. Title :
        Multispectral excitation based multiple fluorescent targets resolving in fluorescence molecular tomography
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Luminescence; Tomography; Metabolism; Animals; Simulations; Independent component analysis; Inverse problems; FMT
      12. Abstract :
        Fluorescence molecular tomography (FMT) can visualize biological activities at cellular and molecular levels in vivo, and has been extensively used in drug delivery and tumor detection research of small animals. The ill-posedness of the FMT inverse problem makes it difficult to reconstruct and resolve multiple adjacent fluorescent targets that have different functional features but are labeled with the same fluorochrome. An algorithm based on independent component analysis (ICA) for multispectral excited FMT is proposed to resolve multiple fluorescent targets in this study. Fluorescent targets are excited by multispectral excitation, and the three-dimensional distribution of fluorescent yields under the excitation spectrum is reconstructed by an iterative Tikhonov regularization algorithm. Subsequently, multiple fluorescent targets are resolved from mixed fluorescence signals by employing ICA. Simulations were performed and the results demonstrate that multiple adjacent fluorescent targets can be resolved if the number of excitation wavelengths is not smaller than that of fluorescent targets with different concentrations. The algorithm obtains both independent components that provide spatial information of different fluorescent targets and spectral courses that reflect variation trends of fluorescent yields along with the excitation spectrum. By using this method, it is possible to visualize the metabolism status of drugs in different structure organs, and quantitatively depict the variation trends of fluorescent yields of each functional organ under the excitation spectrum. This method may provide a pattern for tumor detection, drug delivery and treatment monitoring in vivo. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 11390
      15. Serial :
        13412
      1. Author :
        Zhao, Yue; Zhang, Wei; Zhu, Dianwen; Li, Changqing
      2. Title :
        Optimization and performance evaluation of a conical mirror based fluorescence molecular tomography imaging system
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Luminescence ;; Mirrors ;; Imaging systems ;; Tomography ;; Lasers ;; Reflection ;; Numerical simulations ;; Optical filtering ;; Photons ;; Ray tracing; FMT
      12. Abstract :
        We performed numerical simulations and phantom experiments with a conical mirror based fluorescence molecular tomography (FMT) imaging system to optimize its performance. With phantom experiments, we have compared three measurement modes in FMT: the whole surface measurement mode, the transmission mode, and the reflection mode. Our results indicated that the whole surface measurement mode performed the best. Then, we applied two different neutral density (ND) filters to improve the measurement's dynamic range. The benefits from ND filters are not as much as predicted. Finally, with numerical simulations, we have compared two laser excitation patterns: line and point. With the same excitation position number, we found that the line laser excitation had slightly better FMT reconstruction results than the point laser excitation. In the future, we will implement Monte Carlo ray tracing simulations to calculate multiple reflection photons, and create a look-up table accordingly for calibration. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 11346
      15. Serial :
        13413
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