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Author: Yun-Sheng Chen Publisher: ISBN: Category : Languages : en Pages : 370
Book Description
Molecular imaging is an emerging imaging principle which can visually represent the biological processes both spatially and temporally down to the sub-cellular level in vivo. The outcome of this research is expected to have a profound impact on facilitating the early diagnosis of diseases, accelerating the development of new drugs, and improving the efficacy of therapy. In general, molecular imaging highly relies on probes to sense the occurrence of molecular biological events, and to generate signals which could be picked up by diagnostic imaging modalities. The advances in the design of molecular probes not only have equipped traditional anatomical medical imaging with new capabilities but also, in some cases, stimulated developments of new imaging modalities and renaissance of existing medical imaging modalities. One of these is photoacoustic imaging, which as an emerging medical imaging modality, unites the merits from both optical imaging and ultrasound imaging. It shares with optical imaging, that it uses non-ionizing radiation and provides higher contrast and higher sensitivity than ultrasound imaging. Unlike optical imaging, which requires ballistic photons for imaging, photoacoustic imaging requires only diffusive photons to excite the ultrasound signal from the imaging target; therefore, it is capable of imaging much deeper into the tissue. In combination with molecular probes, photoacoustic molecular imaging has been demonstrated by several research groups using various photoacoustic molecular probes. However, the molecular probes used for most of these studies were contrast agents simply adopted from other optical imaging modalities. Our research on photoacoustic contrast agents indicated that the mechanism of photoacoustic signal generation from nanometer-sized contrast agents is distinct from that of optically homogeneous materials, such as tissue. We have discovered that, the amplitude of the photoacoustic signal generated from nano-contrast agents depends not only on the optical absorption of the particles, but more importantly, on the dynamic process of the heat conduction from the nanoparticles to the ambient, and the thermal properties of the surrounding materials. Based on our finding, we explored and further improved the photoacoustic response of the nanoparticles by exploiting the heat conduction process between the nanoparticle and its surrounding materials and by manipulating the excitations. This research allows to create optimized molecular specific contrast enhanced photothermal stable probes which can aid photoacoustic imaging and image guided photothermal cancer therapy.
Author: Yun-Sheng Chen Publisher: ISBN: Category : Languages : en Pages : 370
Book Description
Molecular imaging is an emerging imaging principle which can visually represent the biological processes both spatially and temporally down to the sub-cellular level in vivo. The outcome of this research is expected to have a profound impact on facilitating the early diagnosis of diseases, accelerating the development of new drugs, and improving the efficacy of therapy. In general, molecular imaging highly relies on probes to sense the occurrence of molecular biological events, and to generate signals which could be picked up by diagnostic imaging modalities. The advances in the design of molecular probes not only have equipped traditional anatomical medical imaging with new capabilities but also, in some cases, stimulated developments of new imaging modalities and renaissance of existing medical imaging modalities. One of these is photoacoustic imaging, which as an emerging medical imaging modality, unites the merits from both optical imaging and ultrasound imaging. It shares with optical imaging, that it uses non-ionizing radiation and provides higher contrast and higher sensitivity than ultrasound imaging. Unlike optical imaging, which requires ballistic photons for imaging, photoacoustic imaging requires only diffusive photons to excite the ultrasound signal from the imaging target; therefore, it is capable of imaging much deeper into the tissue. In combination with molecular probes, photoacoustic molecular imaging has been demonstrated by several research groups using various photoacoustic molecular probes. However, the molecular probes used for most of these studies were contrast agents simply adopted from other optical imaging modalities. Our research on photoacoustic contrast agents indicated that the mechanism of photoacoustic signal generation from nanometer-sized contrast agents is distinct from that of optically homogeneous materials, such as tissue. We have discovered that, the amplitude of the photoacoustic signal generated from nano-contrast agents depends not only on the optical absorption of the particles, but more importantly, on the dynamic process of the heat conduction from the nanoparticles to the ambient, and the thermal properties of the surrounding materials. Based on our finding, we explored and further improved the photoacoustic response of the nanoparticles by exploiting the heat conduction process between the nanoparticle and its surrounding materials and by manipulating the excitations. This research allows to create optimized molecular specific contrast enhanced photothermal stable probes which can aid photoacoustic imaging and image guided photothermal cancer therapy.
Author: Soon Joon Yoon Publisher: ISBN: Category : Languages : en Pages : 216
Book Description
Advances in novel imaging techniques and molecular probes are now extending the opportunity of visualizing molecular targets of disease. Molecular imaging provides anatomic as well as functional and pathological information to sense the expression of molecular biological events. In general, molecular imaging aims to target a specific cell type or tissue and visualize biological events in vivo at the molecular or cellular levels through specific probes. Molecular imaging is usually performed in conjunction with probes for specific targets. The objective of this dissertation is to explore molecular imaging by providing highly efficient photoacoustic nanocluster contrast agents to further validate in vivo molecular imaging, improve the therapeutic procedure, and study fundamental photoacoustic signal processes from cluster of nanoparticles. Initially, a photothermal stimuli-responsive photoacoustic nanocluster was designed and synthesized to provide highly sensitive dynamic contrast within tissue samples. The photoacoustic signal enhancement from clustering of nanoparticles was demonstrated by characterizing the photoacoustic signal from photothermal stimuli-responsive nanoclusters. After characterization, photothermal stimuli-responsive nanoclusters were injected into a mouse tissue and the dynamic photoacoustic response from the nanoclusters activated by an external laser source was observed. This activation can be repeatedly turned on by modulating input laser signals, suggesting a new route for dynamic photoacoustic contrast imaging that will further improve the imaging contrast and more accurately guide the drug release process. Despite tremendous advantages of using these nanoparticles, their safety in a biological environment could be a major hurdle for their in vivo utilization. In order to avoid accumulation and long-term toxicity of nanoparticles, biodegradable nanoclusters consisting of sub-5 nm primary gold particles stabilized by a weakly adsorbed biodegradable polymer were introduced. The photoacoustic signal from biodegradable nanoclusters was quantitatively characterized. In addition, photothermal stability of different sizes of biodegradable nanoclusters was investigated. These nanoclusters were then intravenously injected into mice and biodistribution of nanoparticles was observed. Finally, in vivo spectroscopic photoacoustic imaging was performed on tumor-bearing mice with antibody conjugated biodegradable nanoclusters. This research may provide a new opportunity for molecular imaging to help diagnose tumors at an early stage and promote clinical translation of these techniques.
Author: Adam De la Zerda Publisher: ISBN: Category : Languages : en Pages :
Book Description
Biomedical imaging has seen a tremendous shift over the past decades, moving to non-invasive and high spatial-resolution imaging, spanning multiple imaging modalities and applications. However, one common limitation of traditional medical imaging is its intrinsic inability to provide information on the molecular levels of various biomarkers. Molecular Imaging solves this limitation by introducing an exogenous imaging agent that upon administration to the subject, binds to or interacts with the molecular target(s) and produces an imaging signal. The agent can be designed to produce the imaging signal in the form of visible fluorescent light, gamma rays, ultrasound waves and other forms of energy. In this thesis, we summarize our work on Photoacoustic Molecular Imaging, a technique where short laser light pulses are converted into ultrasound waves by a nanoparticle that was molecularly targeted to a diseased site. We summarize the physical basis for the technique and its first demonstration -- highlighting angiogenesis markers in living subjects (Chapter 2). We then summarize the development of second generation photoacoustic imaging agents and demonstrate their utility in ultrahigh sensitivity molecular imaging of tumors (Chapter 3) as well as in multiplexing studies (Chapter 4). Next, we describe a novel application for Photoacoustic Imaging in visualizing the retina and the posterior eye segment with unprecedented depth of penetration, giving hope for early diagnosis of age-related macular degeneration and other retinal diseases (Chapter 5). We then describe a novel molecular imaging technology called Optical Coherence Contrast Imaging, and demonstrate it provides ultrahigh resolution and sensitivity images of gold nanoparticles in living mice eyes (Chapter 6). Finally, we conclude with various therapeutic and theranostic (therapy and diagnostic combined) concepts and highlight the synergy between them and the imaging methods presented in earlier chapters (Chapter 7).
Author: Xiaoyuan Chen Publisher: John Wiley & Sons ISBN: 1118110021 Category : Technology & Engineering Languages : en Pages : 848
Book Description
The cutting-edge guide on advancing the science of molecular imaging using nanoparticles Nanoplathform-Based Molecular Imaging provides rationale for using nanoparticle-based probes for molecular imaging, then discusses general strategies for this underutilized, yet promising, technology. It addresses general strategies of particle synthesis and surface chemistry, applications in computed tomography optical imaging, magnetic resonance imaging, ultrasound, multimodality imaging, theranostics, and finally, the clinical perspectives of nanoimaging. This comprehensive volume summarizes the opinions of those in the forefront of research and describes the latest developments by emphasizing fundamentals and initiating hands-on application.
Author: Lihong V. Wang Publisher: CRC Press ISBN: 1420059920 Category : Science Languages : en Pages : 518
Book Description
Photoacoustics promises to revolutionize medical imaging and may well make as dramatic a contribution to modern medicine as the discovery of the x-ray itself once did. Combining electromagnetic and ultrasonic waves synergistically, photoacoustics can provide deep speckle-free imaging with high electromagnetic contrast at high ultrasonic resolution and without any health risk. While photoacoustic imaging is probably the fastest growing biomedical imaging technology, this book is the first comprehensive volume in this emerging field covering both the physics and the remarkable noninvasive applications that are changing diagnostic medicine. Bringing together the leading pioneers in this field to write about their own work, Photoacoustic Imaging and Spectroscopy is the first to provide a full account of the latest research and developing applications in the area of biomedical photoacoustics. Photoacoustics can provide functional sensing of physiological parameters such as the oxygen saturation of hemoglobin. It can also provide high-contrast functional imaging of angiogenesis and hypermetabolism in tumors in vivo. Discussing these remarkable noninvasive applications and so much more, this reference is essential reading for all researchers in medical imaging and those clinicians working at the cutting-edge of modern biotechnology to develop diagnostic techniques that can save many lives and just as importantly do no harm.
Author: Pratixa Paritosh Joshi Publisher: ISBN: Category : Languages : en Pages : 254
Book Description
Gold nanoparticles attain an intense focus in biomedical imaging applications due to their unique optical properties, facile conjugation with biomolecules, and biocompatibility. Although a considerable amount of work towards the development of gold nanoparticles has been completed, these promising contrast agents have not yet reached the clinic due to several challenges including efficient accumulation at the diseased site, sensitivity of detection in vivo, potential adverse effects, and clearance from the body. High signal-to-background ratio is required to enhance sensitivity of detection. Because near infrared (near-IR) light has the best tissue penetration, contrast agents designed to work in this range can significantly increase imaging sensitivity. Moreover, efficient targeting of the molecular biomarkers on diseased cells can decrease the required dosage, increase the site-specific accumulation, and enhance the imaging sensitivity. Molecular-specific contrast agents developed in this project use directional attachment of antibody molecules to the nanoparticle surface, enhancing the targeting efficacy. Additionally, cell-based delivery of diagnostic and therapeutic agents is gaining much interest due to the immune cells' special access to the avascular, diseased regions. The contrast agents developed in this project enable detection of just a few cells per unit of imaging volume, enable multiplex imaging, and open up a possibility for tracking different cell populations with noninvasive photoacoustic and ultrasound imaging. Finally, the clearance of nanoparticles from the body dictates their clinical translation. The in vivo pharmacokinetics study along with the proposed in vitro model explored in this project will enable fast, reliable, and cost-efficient screening of promising agents and facilitate quick optimization of nanoparticles for their potential use in the clinic.
Author: Srivalleesha Mallidi Publisher: ISBN: Category : Languages : en Pages : 386
Book Description
Cancer has become one of the leading causes of death today. The early detection of cancer may lead to desired therapeutic management of cancer and to decrease the mortality rate through effective therapeutic strategies. Advances in materials science have enabled the use of nanoparticles for added contrast in various imaging techniques. More recently there has been much interest in the use of gold nanoparticles as optical contrast agents because of their strong absorption and scattering properties at visible and near-infrared wavelengths. Highly proliferative cancer cells overexpress molecular markers such as epidermal growth factor receptor (EGFR). When specifically targeted gold nanoparticles bind to EGFR they tend to cluster thus leading to an optical red-shift of the plasmon resonances and an increase in absorption in the red region. These changes in optical properties provide the foundation for photoacoustic imaging technique to differentiate cancer cells from surrounding benign cells. In photoacoustic imaging, contrast mechanism is based on the optical absorption properties of the tissue constituents. Studies were performed on tissue phantoms, ex-vivo and in-vivo tumor models to evaluate molecular specific photoacoustic imaging technique. The results indicate that highly sensitive and selective detection of cancer cells can be achieved by utilizing the plasmon resonance coupling effect of EGFR targeted gold nanoparticles and photoacoustic imaging. In conclusion, the combined ultrasound and photoacoustic imaging technique has the ability to image molecular signature of cancer using bioconjugated gold nanoparticles.
Author: Wei Shi Publisher: ISBN: Category : Acoustic imaging Languages : en Pages : 142
Book Description
Tumor metastasis is referred to the spread of cancer from one to another unadjacent part of the body, which results in more than 90% of tumor deaths, and however is still poorly understood. Circulating tumor cells (CTCs) have been proposed as an important biomarker of tumor metastasis. Many approaches have been developed for detection of CTCs, but each has its own advantages and disadvantages. With the aid of nanoparticles (NPs), photoacoustic detection along with efficient magnetic enrichment of CTCs demonstrated high sensitivity. However, differentiation of photoacoustic signals is non-trivial hence specificity can be poor. Surface-enhanced-Raman-scattering (SERS) NPs were used for detection of CTCs with high multiplexing capability. However, the lack of enrichment of CTCs limits its application for in vivo detection. High sensitivity and high specificity in vivo methods of detecting CTCs are in urgent need. A hallmark signature of metastasis is angiogenesis, the proliferation of vessel networks growing from pre-existing vasculature. Imaging angiogenesis is important for cancer research since angiogenesis is regarded as a necessity for tumor growth and tumor metastasis. Photoacoustic imaging (PAM) is a promising technique for imaging angiogenesis due to intrinsic high optical contrast between blood and tissues, and high spatial resolution at adequate penetration depth. Optical-resolution photoacoustic imaging (OR-PAM) pushed the lateral resolution limit of PAM to micron or submicron level, which enables imaging of single capillaries, the finest vasculature elements. However, the low imaging speed of OR-PAM may limit its application in the clinic, and for practical pre-clinical imaging of animal models. A single modality tool for studies on tumor metastasis is unlikely to be able to fullfill these needs. Therefore, the long term goal of this dissertation is to develop a multimodality imaging tool for imaging tumor metastasis and detecting of CTCs with high specificity and high sensitivity. Specially, we focused on the approach of combing PAM with a Raman imaging technology for this purpose. For the task of detecting CTCs, the photoacoustic subsystem could aid in placement of a magnet for trapping of such CTCs and gaging the flow rate for optimal optical and multiplexed detection with the Raman sub-system. The photoacoustic sub-system could also be used for detecting absorption signatures from nanoparticles on tumor cells. For detecting metastases, the Raman imaging subsystem could be used to detect multiple flavors of nanoparticles targeted to (non-circulating) tumor cells and the photoacoustic sub-system could be used to detect neoplasm angiogenesis. We aimed to push limits of OR-PAM imaging frame-rate, to develop a novel CTC detection technique with high sensitivity and high specificity, and to further build a multimodality photoacoustic-Raman imaging tool for high sensitivity and high specificity molecular imaging. Our work presented in this dissertation can be divided into three parts. First, we worked on developing realtime OR-PAM using various high pulse repetition rate lasers and combined with a fast optical scanning galvanometer mirror systems. We reported the first near realtime volumetric OR-PAM with 4 frames per second (fps) imaging speed and ~ 6 ?m lateral resolution by employing a fiber laser with up to 600 kHz pulse repetition rate. Further, we demonstrated in vivo near realtime sustained OR-PAM imaging of dynamic process and 30 fps realtime imaging of cardiac-induced mircrohemodynamics in murine microvasculature. In addition, we studied the scanning speed dependence of photoacoustic signals which may lead to a super-resolution technique in the future. Second, we demonstrated for the first time the magnetic enrichment and detection of CTCs in circulating PBS or rat blood with high specificity and high sensitivity by targeting tumor cells with both SERS NPs and magnetic NPs (MNPs). Third, we presented a multimodality imaging system consisting of PAM and SERS imaging which may advance the research of tumor metastasis in the future.
Author: Osasere M. Evbuomwan Publisher: ISBN: Category : Contrast media (Diagnostic imaging) Languages : en Pages : 228
Book Description
Paramagnetic chemical exchange saturation transfer (PARACEST) agents represent a new class of magnetic resonance imaging (MRI) contrast media that offer a considerable number of advantages over conventional gadolinium-based contrast agents. However, these agents are limited by the high concentrations required to produce an observable effect, thus prompting the need to design PARACEST agents that display better sensitivity. In the present work, an attempt to design PARACEST agents with enhanced sensitivity was made by altering some of the factors known to significantly influence the efficiency of the CEST process. Chapter one describes the synthesis and characterization of amphiphilic PARACEST agents capable of micellar self-assembly. The central hypothesis was that micelle formation would increase the number of exchanging groups per agent which when simultaneously saturated, should result in a CEST signal enhancement. Chapter two elucidates an attempt at understanding the effect of pH and functional group position on a series of PARACEST agents bearing carboxylic acid and amine groups with the intention of determining what conditions produce the optimum exchange rates for CEST. In chapter three, the development of a single-molecule dual-modality agent that combines both PARACEST and luminescence properties is reported. The expectation was that the high sensitivity of the optical imaging technique would complement the poor sensitivity but high spatial resolution of the MRI technique thus resulting in a potential molecular imaging probe.
Author: Mikhail Y. Berezin Publisher: John Wiley & Sons ISBN: 1118873149 Category : Technology & Engineering Languages : en Pages : 534
Book Description
Nanotechnology for Biomedical Imaging and Diagnostics: From Nanoparticle Design to Clinical Applications reflects upon the increasing role of nanomaterials in biological and medical imaging, presenting a thorough description of current research as well as future directions. With contributions from experts in nanotechnology and imaging from academia, industry, and healthcare, this book provides a comprehensive coverage of the field, ranging from the architectural design of nanomaterials to their broad imaging applications in medicine. Grouped into three sections, the book: Elucidates all major aspects of nanotechnology and bioimaging Provides comprehensive coverage of the field, ranging from the architectural design of nanomaterials to their broad imaging applications in medicine Written by well-recognized experts in academia, industry, and healthcare, will be an excellence source of reference With a multidisciplinary approach and a balance of research and diagnostic topics, this book will appeal to students, scientiests, and healthcare professionals alike
Author: Yun-Sheng Chen
Author: Yun-Sheng Chen
Author: Soon Joon Yoon
Author: Adam De la Zerda
Author: Xiaoyuan Chen
Author: Lihong V. Wang
Author: Pratixa Paritosh Joshi
Author: Srivalleesha Mallidi
Author: Wei Shi
Author: Osasere M. Evbuomwan
Author: Mikhail Y. Berezin