Author: Sun Kuk Kwon Publisher: ISBN: Category : Languages : en Pages :
Book Description
Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electronmultiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual-wavelength fluorescence images were acquired using a targeted 111In- DTPA-K(IRDye800)-c(KRGDf) to selectively detect tumor angiogenesis and an untargeted Cy5.5 to image lymphatics. After acquiring the experimental data, fluorescence image-guided surgery was performed. Dynamic, multi-wavelength fluorescence imaging was accomplished using a liquid crystal tunable filter (LCTF). Excitation light was used for reflectance images with a LCTF transmitting a shorter wavelength than the peak in the excitation light spectrum. Therefore, images can be dynamically acquired alternating frame by frame between emission and excitation light, which should enable image-guided surgery.
Author: Mikhail Gurfinkel Publisher: ISBN: Category : Languages : en Pages :
Book Description
A new optical imaging modality has been developed for small animal in vivo imaging of near-infrared fluorescence resulting from fluorescent contrast agents specifically targeted to molecular markers of cancer. The imaging system is comprised of an intensified charge-coupled device (ICCD) for the detection of ultra-low levels of re-emitted fluorescence following the delivery of an expanded beam of excitation light. The design of the ICCD detection system allows for both continuous wave (CW) and frequency-domain modes of operation. Since the accurate acquisition of frequency-domain photon migration (FDPM) data is important for tomographic imaging, the imaging system was also validated using experimentally obtained FDPM measurements of homogenous turbid media and diffusion theory to obtain estimates of the optical properties characteristic of the media. The experiments demonstrated that the absorption and reduced scattering coefficients are determined least accurately when relative measurements of average light intensity I rel [over] DC are employed either alone or in a combination with relative modulation amplitude data I rel [over] AC and/or relative phase shift data [theta] [superscript]rel. However, when FDPM measurements of [theta] [superscript]rel are employed either alone or in combination with I rel [over] AC data, the absorption and reduced scattering coefficients may be found accurate to within 15% and 11%, respectively, of the values obtained from standard single-pixel measurements; a result that suggests that FDPM data obtained from an ICCD detection system may in fact be useful in tomographic imaging. Furthermore, intensified-detection allows for sub-second exposure times, permitting the acquisition of dynamic fluorescence images immediately following administration of the contrast agent. Experimental results demonstrate that when coupled with a suitable pharmacokinetic model describing targeted dye distribution throughout the body, dynamic fluorescence imaging may be used to discriminate spontaneous canine adenocarcinoma from normal mammary tissue. A separate experiment demonstrates that pharmacokinetic analysis of dynamic fluorescence images enables one to estimate the rate constant governing Kaposi's sarcoma tumor uptake of an [alpha subscriptV beta]3 integrin-targeted dye and integrin receptor turnover rate. The rate constant for uptake was calculated to be 0.16-sec−1 while the turnover rate of the integrin receptor was estimated to occur within 24-hours.
Author: Metasebya Solomon Publisher: ISBN: Category : Electronic dissertations Languages : en Pages : 146
Book Description
In the United States, cancer is the second leading cause of death following heart disease. Although, a variety of treatment regimens are available, cancer management is complicated by the complexity of the disease and the variability, between people, of disease progression and response to therapy. Therefore, advancements in the methods and technologies for cancer diagnosis, prognosis and therapeutic monitoring are critical to improving the treatment of cancer patients. The development of improved imaging methods for early diagnosis of cancer and of near real-time monitoring of tumor response to therapy may improve outcomes as well as the quality of life of cancer patients. In the last decade, imaging methods including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), have revolutionized oncology. More recently optical techniques, that have access to unique molecular reporting strategies and functional contrasts, show promise for oncologic imaging. This dissertation focuses on the development and optimization of a fiber-based, video-rate fluorescence molecular tomography (FMT) instrument. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established to depths of>10 mm. In vivo accumulation of indocyanine green dye was imaged in the region of the sentinel lymph node (SLN) following intradermal injection into the forepaw of rats. These results suggest that video-rate FMT has potential as a clinical tool for noninvasive mapping of SLN. Spatial and temporal co-registration of nuclear and optical images can enable the fusion of the information from these complementary molecular imaging modalities. A critical challenge is in integrating the optical and nuclear imaging hardware. Flexible fiber-based FMT systems provide a viable solution. The various imaging bore sizes of small animal nuclear imaging systems can potentially accommodate the FMT fiber imaging arrays. In addition FMT imaging facilitates co-registering the nuclear and optical contrasts in time. In this dissertation, the feasibility of integrating the fiber-based, video-rate FMT system with a commercial preclinical NanoSPECT/CT platform was established. Feasibility of in vivo imaging is demonstrated by tracking a monomolecular multimodal-imaging agent (MOMIA) during transport from the forepaw to the axillary lymph nodes region of a rat. These co-registered FMT/SPECT/CT imaging results with MOMIAs may facilitate the development of the next generation preclinical and clinical multimodal optical-nuclear platforms for a broad array of imaging applications, and help elucidate the underlying biological processes relevant to cancer diagnosis and therapy monitoring. Finally, I demonstrated that video-rate FMT is sufficiently fast to enable imaging of cardiac, respiratory and pharmacokinetic induced dynamic fluorescent signals. From these measurements, the image-derived input function and the real-time uptake of injected agents can be deduced for pharmacokinetic analysis of fluorescing agents. In a study comparing normal mice against mice liver disease, we developed anatomically guided dynamic FMT in conjunction with tracer kinetic modeling to quantify uptake rates of fluorescing agents. This work establishes fiber-based, video-rate FMT system as a practical and powerful tool that is well suited to a broad array of potential imaging applications, ranging from early disease detection, quantifying physiology and monitoring progression of disease and therapies.
Author: Brian D. Ross Publisher: Academic Press ISBN: 0128163879 Category : Science Languages : en Pages : 1872
Book Description
The detection and measurement of the dynamic regulation and interactions of cells and proteins within the living cell are critical to the understanding of cellular biology and pathophysiology. The multidisciplinary field of molecular imaging of living subjects continues to expand with dramatic advances in chemistry, molecular biology, therapeutics, engineering, medical physics and biomedical applications. Molecular Imaging: Principles and Practice, Volumes 1 and 2, Second Edition provides the first point of entry for physicians, scientists, and practitioners. This authoritative reference book provides a comprehensible overview along with in-depth presentation of molecular imaging concepts, technologies and applications making it the foremost source for both established and new investigators, collaborators, students and anyone interested in this exciting and important field. - The most authoritative and comprehensive resource available in the molecular-imaging field, written by over 170 of the leading scientists from around the world who have evaluated and summarized the most important methods, principles, technologies and data - Concepts illustrated with over 600 color figures and molecular-imaging examples - Chapters/topics include, artificial intelligence and machine learning, use of online social media, virtual and augmented reality, optogenetics, FDA regulatory process of imaging agents and devices, emerging instrumentation, MR elastography, MR fingerprinting, operational radiation safety, multiscale imaging and uses in drug development - This edition is packed with innovative science, including theranostics, light sheet fluorescence microscopy, (LSFM), mass spectrometry imaging, combining in vitro and in vivo diagnostics, Raman imaging, along with molecular and functional imaging applications - Valuable applications of molecular imaging in pediatrics, oncology, autoimmune, cardiovascular and CNS diseases are also presented - This resource helps integrate diverse multidisciplinary concepts associated with molecular imaging to provide readers with an improved understanding of current and future applications
Author: E. Edmund Kim Publisher: Springer Science & Business Media ISBN: 9780387950280 Category : Medical Languages : en Pages : 322
Book Description
Cancer cells dedifferentiate with repect to cell function; their vascularity is more leaky, but perfusion is heterogenerously reduced, and interstitial fluid pressure is high, severely retarding delivery of agents from the blood. Targeted imaging is designed to produce a detectable difference between tissue that is visualized with single photon and positron emission tomography, magnetic resonance imaging, computed tomography, or ultrasonography. This book uniquely reports strategies for the application of molecular targeted imaging agents such as antibodies, peptides, receptors and contrast agents in the biologic grading of tumors, differential diagnosis of tumors, prediction of therapeutic response and monitoring tumor response to treatment. This book also describes updated information about the imaging of tumor angiogenesis, hypoxia, apoptosis and gene delivery as well as expression in the understanding and utility of tumor molecular biology for better cancer management.
Author: Raquel Seruca Publisher: CRC Press ISBN: 1498737056 Category : Medical Languages : en Pages : 328
Book Description
This comprehensive reference work details the latest developments in fluorescence imaging and related biological quantification. It explores the most recent techniques in this imaging technology through the utilization and incorporation of quantification analysis which makes this book unique. It also covers super resolution microscopy with the introduction of 3D imaging and high resolution fluorescence. Many of the chapter authors are world class experts in this medical imaging technology.
Author: Dolonchampa Maji Publisher: ISBN: Category : Electronic dissertations Languages : en Pages : 149
Book Description
Optical imaging and spectroscopy technologies offer the ability to provide structural and functional information in a fast, low-cost, ionizing radiation free, highly sensitive and high throughput fashion. The diverse contrast mechanisms and complementary imaging platforms form the foundation for the application of optical imaging in pre-clinical studies of pathophysiological development as well as direct clinical application as a tool for diagnosis and therapy. Fluorescence imaging techniques have been one of the most rapidly adopted methods in biology and biomedicine. Visualization of biological processes and pathologic conditions at the cellular and tissue levels largely relies on the use of exogenous fluorophores or their bioconjugates. Some fluorescent molecular probes provide usable contrast for disease diagnosis due to their responsiveness to interactions with other molecular species and/or immediate microenvironment. As a result, understanding exogenous fluorescent contrast mechanisms will allow the development of efficient strategies for biomedical fluorescence imaging. The present work focuses on exploring novel fluorescent molecular probe strategies for imaging cancer and cardiovascular diseases. We have developed a platform for synthesizing activatable fluorescent molecular probes using the fluorescence quenching properties of copper (II) ions. We used these activatable probes for rapid imaging of cancerous tissue in vivo in mice. While developing these molecular probes, we discovered an unexpected molecular interaction that yields stable dimeric molecules. This finding can potentially enable the development of new molecular entities for modifying the signaling properties of fluorescent dyes to minimize background fluorescence. Although planar fluorescence imaging methods using exogenous molecular probes provide rapid information about molecular processes in vivo, extraction of depth information require complex data acquisition and image analysis methods. By designing a dual emission fluorescent probe incorporating two spectrally different fluorophore systems, we developed a method to successfully estimate the depth of fluorescent inclusions from planar imaging data and demonstrated the potential of using this approach to locate a blood vessel and tumorous tissue in mouse in vivo. An important feature of fluorescence methods is the availability of various techniques that provide complementary information. Combining the fluorescence intensity and lifetime properties of a biologically targeted near infrared fluorescent probe, we demonstrate an effective way to distinguish specific from nonspecific uptake mechanisms in cancer cells, an approach that can be translated in vivo. Alternatively, dynamic fluorescence imaging technique expands the scope of applications to include detection and estimation of the size of circulating cancer cells and clusters. The approach developed in this work could allow longitudinal monitoring of these cells, which are implicated in cancer metastases. To circumvent the shallow penetration of light using optical methods, we developed multimodal imaging approaches by incorporating a radionuclide for nuclear imaging into a broad spectrum near infrared fluorescent tumor targeting agent. This molecular construct allows for noninvasive whole body nuclear imaging of tumors, followed by fluorescence image guided resection. In each of these areas, novel fluorescent molecular probes were developed, characterized and applied to solve critical biomedical problems.
Author: Jun Ki Kim Publisher: Springer Nature ISBN: 981336064X Category : Medical Languages : en Pages : 560
Book Description
This book is a wide-ranging guide to advanced imaging techniques and related methods with important applications in translational research or convergence science as progress is made toward a new era in integrative healthcare. Conventional and advanced microscopic imaging techniques, including both non-fluorescent (i.e., label-free) and fluorescent methods, have to date provided researchers with specific and quantitative information about molecules, cells, and tissues. Now, however, the different imaging techniques can be correlated with each other and multimodal methods developed to simultaneously obtain diverse and complementary information. In addition, the latest advanced imaging techniques can be integrated with non-imaging techniques such as mass spectroscopic methods, genome editing, organic/inorganic probe synthesis, nanomedicine, and drug discovery. The book will be of high value for researchers in the biological and biomedical sciences or convergence science who need to use these multidisciplinary and integrated techniques or are involved in developing new analytical methods focused on convergence science.
Author: Sun Kuk Kwon
Author: Mikhail Gurfinkel
Author: Metasebya Solomon
Author: Brian D. Ross
Author: E. Edmund Kim
Author: Raquel Seruca
Author: Dolonchampa Maji
Author: Sanjiv Sam Gambhir
Author: Jun Ki Kim
Author: