Browsing by Author "Hu, Jingzhe"

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    In Vivo Molecular Magnetic Resonance Imaging via Hyperpolarized Silicon Particles
    (2017-08-11) Hu, Jingzhe; Bhattacharya, Pratip K.; Farach-Carson, Mary C.
    This thesis describes the characterization, development and application of hyperpolarized silicon particles, which can serve as a molecular imaging platform based on magnetic resonance imaging (MRI). Silicon particles are suited for use as biomedical imaging agents due to their biocompatibility, biodegradability, and relatively simple surface chemistry that facilitates drug loading and functionalization for targeting various diseases as well as physiological processes. A method of hyperpolarizing the 29Si nuclei inside silicon particles using dynamic nuclear polarization (DNP) has recently been developed, increasing the MR signal by several orders-of-magnitude through enhanced nuclear spin alignment. At room temperature, enhanced spin polarization of 29Si nuclei lasts on the order of tens of minutes, significantly longer than that of other hyperpolarized species (tens of seconds). In addition to extremely long-lived signal, hyperpolarized silicon particles provide background-free positive contrast, thereby making a wide range of imaging applications possible. For silicon particles on the micrometer scale, we first explored their application for MRI-guided catheter tracking, demonstrating catheter tip tracking in 2D, 3D and in vivo over extended period of time without the use of ionizing radiation. Paving way for potential targeted molecular imaging applications, we characterized silicon particles of various sizes (20 nm to 2µm), whose hyperpolarized signal were found to have characteristic spin relaxation times (T1) ranging from ~10 to 50 mins. The addition of various functional groups to the particle surface had no effect on the hyperpolarized signal buildup or decay rates and allowed in vivo imaging over long time scales. Additional in vivo studies examined a variety of particle administration routes in mice, including intraperitoneal injection, rectal enema, and oral gavage. Targeting moieties such as antibodies were found to be able to retain their functionalities after enduring the harsh DNP condition of low temperature (several Kelvins) and continuous microwave irradiation. As a proof of concept study, we demonstrated targeted imaging of colorectal cancer in genetic models using hyperpolarized silicon particles functionalized with MUC1 antibodies. To better hyperpolarize silicon particles on the nanometer scale, we incorporated external radicals such as TEMPO to eliminate the bottleneck of insufficient surface electrons and calibrated the concentration of radicals needed to achieve better signal enhancement for various particle sizes (20-200 nm). With optimal amounts of the added radicals, 29Si T1 times are ~20 minutes and MR imaging in phantoms can be achieved over an hour after completion of hyperpolarization. Equipped with the unusually long signal decay time and the fact that the signal decay times are not affected by surface functionalization or the in vivo environment, hyperpolarized silicon particles have the potential of becoming the next generation high-impact molecular MR imaging agents.
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    Post-Acquisition Hyperpolarized 29Silicon Magnetic Resonance Image Processing for Visualization of Colorectal Lesions Using a User-Friendly Graphical Interface
    (MDPI, 2022) McCowan, Caitlin V.; Salmon, Duncan; Hu, Jingzhe; Pudakalakatti, Shivanand; Whiting, Nicholas; Davis, Jennifer S.; Carson, Daniel D.; Zacharias, Niki M.; Bhattacharya, Pratip K.; Farach-Carson, Mary C.
    Medical imaging devices often use automated processing that creates and displays a self-normalized image. When improperly executed, normalization can misrepresent information or result in an inaccurate analysis. In the case of diagnostic imaging, a false positive in the absence of disease, or a negative finding when disease is present, can produce a detrimental experience for the patient and diminish their health prospects and prognosis. In many clinical settings, a medical technical specialist is trained to operate an imaging device without sufficient background information or understanding of the fundamental theory and processes involved in image creation and signal processing. Here, we describe a user-friendly image processing algorithm that mitigates user bias and allows for true signal to be distinguished from background. For proof-of-principle, we used antibody-targeted molecular imaging of colorectal cancer (CRC) in a mouse model, expressing human MUC1 at tumor sites. Lesion detection was performed using targeted magnetic resonance imaging (MRI) of hyperpolarized silicon particles. Resulting images containing high background and artifacts were then subjected to individualized image post-processing and comparative analysis. Post-acquisition image processing allowed for co-registration of the targeted silicon signal with the anatomical proton magnetic resonance (MR) image. This new methodology allows users to calibrate a set of images, acquired with MRI, and reliably locate CRC tumors in the lower gastrointestinal tract of living mice. The method is expected to be generally useful for distinguishing true signal from background for other cancer types, improving the reliability of diagnostic MRI.
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    Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell of Interest Using Cell-Derived, Biomimetic Patterning
    (American Chemical Society, 2015) Slater, John H.; Culver, James C.; Long, Byron L.; Hu, Chenyue W.; Hu, Jingzhe; Birk, Taylor F.; Qutub, Amina A.; Dickinson, Mary E.; West, Jennifer L.
    Heterogeneity of cell populations can confound population-averaged measurements and obscure important findings or foster inaccurate conclusions. The ability to generate a homogeneous cell population, at least with respect to a chosen trait, could significantly aid basic biological research and development of high-throughput assays. Accordingly, we developed a high-resolution, image-based patterning strategy to produce arrays of single-cell patterns derived from the morphology or adhesion site arrangement of user-chosen cells of interest (COIs). Cells cultured on both cell-derived patterns displayed a cellular architecture defined by their morphology, adhesive state, cytoskeletal organization, and nuclear properties that quantitatively recapitulated the COIs that defined the patterns. Furthermore, slight modifications to pattern design allowed for suppression of specific actin stress fibers and direct modulation of adhesion site dynamics. This approach to patterning provides a strategy to produce a more homogeneous cell population, decouple the influences of cytoskeletal structure, adhesion dynamics, and intracellular tension on mechanotransduction-mediated processes, and a platform for high-throughput cellular assays.