Browsing by Author "Bhattacharya, Pratip K."

Now showing 1 - 4 of 4
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    Beyond Colonoscopy: Exploring New Cell Surface Biomarkers for Detection of Early, Heterogenous Colorectal Lesions
    (Frontiers Media S.A., 2021) Ramezani, Saleh; Parkhideh, Arianna; Bhattacharya, Pratip K.; Farach-Carson, Mary C.; Harrington, Daniel Anton; Bioengineering; Biosciences
    Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women in the United States. Early detection and surgical removal of high-risk lesions in the colon can prevent disease from developing and spreading. Despite implementation of programs aimed at early detection, screening colonoscopies fail to detect a fraction of potentially aggressive colorectal lesions because of their location or nonobvious morphology. Optical colonoscopies, while highly effective, rely on direct visualization to detect changes on the surface mucosa that are consistent with dysplasia. Recent advances in endoscopy techniques and molecular imaging permit microscale visualization of the colonic mucosa. These technologies can be combined with various molecular probes that recognize and target heterogenous lesion surfaces to achieve early, real-time, and potentially non-invasive, detection of pre-cancerous lesions. The primary goal of this review is to contextualize existing and emergent CRC surface biomarkers and assess each’s potential as a candidate marker for early marker-based detection of CRC lesions. CRC markers that we include were stratified by the level of support gleaned from peer-reviewed publications, abstracts, and databases of both CRC and other cancers. The selected biomarkers, accessible on the cell surface and preferably on the luminal surface of the colon tissue, are organized into three categories: (1) established biomarkers (those with considerable data and high confidence), (2) emerging biomarkers (those with increasing research interest but with less supporting data), and (3) novel candidates (those with very recent data, and/or supportive evidence from other tissue systems). We also present an overview of recent advances in imaging techniques useful for visual detection of surface biomarkers, and discuss the ease with which these methods can be combined with microscopic visualization.
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    Dynamic Nuclear Polarization of Silicon for Targeted Molecular Imaging
    (2019-04-17) McCowan, Caitlin; Kemere, Caleb; Bhattacharya, Pratip K.
    Colorectal cancer is the second highest cause of cancer-related deaths and is the third most commonly diagnosed cancer in America. Although there are currently available screening methods such as colonoscopy, many patients remain undiagnosed until the disease has spread and thus likely advanced beyond hope of curative treatment. Also, colonoscopy carries the risk of intestinal perforation and is less apt to identify small or flat lesions. Patients diagnosed after metastasis make up 21% of all colorectal cancer cases, with a 5-year survival rate of only 13.5%. This presents an opportunity to improve screening methods with higher accuracy and safer implementation, namely through magnetic resonance imaging (MRI) of hyperpolarized silicon particles functionalized to specifically target colorectal cancer. MRI is a commonly used imaging modality that does not require ionizing radiation. Nevertheless, sensitivity and specificity are considered to be the major drawbacks regarding MRI. One method to improve the sensitivity is through hyperpolarization, a technique used to increase signal measured with MRI by at least 10,000-fold. Silicon is a promising candidate for in vivo medical applications due to its biocompatibility. Additionally, silicon is compatible with hyperpolarization due to its MR active isotope 29Si making up 4.7% of naturally occurring silicon. I have investigated the ability to functionalize silicon particles for targeted molecular imaging of colorectal cancer in vivo through hyperpolarized MRI. Furthermore, I have explored the feasibility of utilizing hyaluronic acid-based hydrogels to improve particle targeting ability.
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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.; Bioengineering; Biosciences
    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.