Browsing by Subject "Photoacoustic"
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Item Clinical photoacoustic imaging for detection and characterization of metal implants(2011-08) Su, Jimmy Li-Shin; Emelianov, Stanislav Y.; Dunn, Andrew; Karpiouk, Andrei; Smalling, Richard; Sokolov, KonstantinAccurate insertion and monitoring of metal implants in-vivo is essential for clinical diagnosis and therapy of various diseases. Clinical studies and examples have demonstrated that the misplacement errors of these metal devices can have dramatic consequences. This thesis focuses on three main metal devices that are in widespread use today: needles, coronary stents and brachytherapy seeds. Each application requires proper image-guidance for correct usage. For needles, image guidance is required to ensure correct local injection delivery or needle aspiration biopsy. Fine needle aspiration biopsies are performed in order to avoid major surgical excisions when obtaining tissue biopsy procedures. However, because of the small biopsy sample, the risk is that the sample is collected outside of the tumorigenic region, resulting in a false negative result. Implantation of stents requires that confirmation that proper stent apposition has been achieved due to balloon inflation. Furthermore, it is important to guide the stent to shield the vulnerable region of an atherosclerotic plaque. With prostate brachytherapy seeds, the ability to monitor seed placement is crucial because needle deflections or tissue deformation can result in seed misplacement errors, decreasing the efficacy of the pre-established treatment plan. For the described applications and other possible clinical practices involving the use of metallic implants, an imaging technology that can accurately depict the location of the metal objects, relative to their respective backgrounds, in real-time, is necessary to improve the safety and the efficacy of these procedures. Currently, ultrasound is used because of its real-time capabilities, non-ionizing radiation, and soft tissue contrast. However, due to high acoustic scattering from tissue, the contrast of metal implants can be low. Photoacoustic imaging can be used as an alternative, or complementary, imaging method to ultrasound for imaging metal. This thesis focuses on the benefits and the pitfalls of using photoacoustic imaging for detecting three different metal implants, each having unique requirements. Overall, the goal of this work is to develop a framework for clinical applications using combined ultrasound and photoacoustic imaging to help guide, detect and follow-up on clinical metal implants introduced in-vivo.Item Intravascular photoacoustics as a theranostic platform for atherosclerosis(2014-08) Yeager, Douglas Edward; Emelianov, Stanislav Y.; Baker, Aaron; Sessler, Jonathan; Smalling, Richard; Sokolov, KonstantinThe persistence of high global mortality rates directly attributable to cardiovascular disease drives ongoing research into novel approaches for improved diagnosis and treatment of its primary underlying cause, atherosclerosis. Combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging is one such modality, actively being developed as a tool for improved characterization of high-risk atherosclerotic plaques. The pathophysiology associated with progression and destabilization of atherosclerotic plaques leads to characteristic changes in arterial morphology and composition. IVUS/IVPA imaging seeks to expand upon the ability of clinically utilized intravascular ultrasound (IVUS) imaging to assess vessel anatomy by adding improved sensitivity to image the underlying cellular and molecular composition through intravascular photoacoustic (IVPA) imaging of either endogenous chromophores (e.g. lipid) or exogenously delivered contrast agents. This dissertation focuses on the expansion of IVUS/IVPA imaging using exogenous contrast agents to enable the detection and subsequent optically-triggered therapy of atherosclerotic plaques. The passive extravasation and aggregation of systemically injected plasmonic gold nanorods absorbing within the near infrared tissue optical window within plaques of atherosclerotic rabbit models is first demonstrated, along with the ability to localize the contrast agents using ex vivo IVUS/IVPA imaging. The motivation for nanoparticle labeling of atherosclerosis is then expanded from that of purely image contrast agents to vehicles for image-guided, dual-modality phototherapy. The integrated IVUS/IVPA imaging catheter is utilized for photothermal delivery with simultaneous IVPA temperature monitoring using the high optical absorption of gold nanorod contrast agents to enable localized heating. Subsequently, the potential role for IVUS/IVPA-guided phototherapy is further expanded through the characterization and in vitro assessment of novel multifunctional theranostic nanoparticles comprised of a gold nanorod core with a degradable, photosensitizer-doped silica shell. Together, the results presented within this dissertation provide a framework for ongoing research into the expansion of IVUS/IVPA imaging as a platform for complimentary diagnosis and local treatment of atherosclerotic plaques using multifunctional theranostic nanoparticle contrast agents.Item Photoacoustic image guidance and tissue characterization in cardiovascular applications(2016-12) Dana, Nicholas Pacheco; Suggs, Laura J.; Emelianov, Stanislav Y.; Dunn, Andrew; Tunnell, James; Bouchard, RichardCollectively, cardiovascular diseases continue to be the leading cause of death, across nations and across decades. Improved diagnostic imaging methods offer promise to alleviate the morbidity associated with these diseases. Photoacoustic (PA) imaging is one such method, poised to make a significant impact on cardiovascular imaging, both as a research tool, as well as a clinical imaging modality. Offering the potential of molecular imaging in real-time, PA methods have been demonstrated in proof-of-concept studies tracking myocyte calcium dynamics. These results open the door to non-invasive longitudinal assessment of cardiac electrophysiological function, with implications for drug and contrast agent development. PA image guidance has also been extended to the characterization of cardiac radiofrequency ablation lesions. This method has been demonstrated to utilize endogenous chromophore changes resulting from ablation for the generation of depth-resolved tissue characterization maps, capable of assessing lesion extent. The technique has been subsequently validated by assessing high-intensity focused ultrasound ablation lesions in myocardium, with the hope for offering thermographic capabilities as well. While PA imaging offers such promise in cardiac ablation procedures, it is also in the process of clinical translation for image guidance and characterization in coronary artery disease applications. Research has shown, using Monte Carlo optical modeling, that using a simple dual-wavelength PA imaging technique has great potential for successful visualization of atherosclerotic plaques across multiple tissue types and at clinically relevant multiple millimeters of depth. Collectively these results offer a suite of PA imaging tools with the potential for molecular and thermographic imaging across a broad range of cardiovascular applications.Item Photoacoustic imaging for temperature monitoring and photothermal therapy guidance(2015-08) Dumani Jarquin, Diego Sayed; Emelianov, Stanislav Y.; Aglyamov, Salavat; Cook, JasonCancer is among the leading causes of death in the United States and the world. Using combined ultrasound (US) and photoacoustic (PA) imaging can provide both anatomical and molecular information of cancerous cells for both diagnostic and therapeutic purposes. This thesis is focused on combining these two modalities, in conjunction with nanoparticles, to treat cancerous tumors and monitor the progress of the therapy. Specifically, the work evaluates the use of photoacoustic imaging as a temperature monitoring tool during photothermal therapy. In this study, the mathematical relationship between photoacoustic signal and temperature is presented and validated with a glass tube phantom using gold nanoparticles. Then in vitro and ex vivo studies were performed to validate the effect of photothermal therapy and the monitoring capability of photoacoustic imaging. The results show that photoacoustic imaging can be used to monitor temperature during photothermal therapy. Future directions include in vivo studies of image guided photothermal therapy and survival studies.Item Photoacoustic imaging using nanoclusters(2014-08) Yoon, Soon Joon; Emelianov, Stanislav Y.; Sokolov, Konstantin; Johnston, Keith; Pearce, John; Yu, EdwardAdvances 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.Item Ultrasound and photoacoustic imaging for cancer detection and therapy guidance(2011-08) Kim, Seungsoo; Emelianov, Stanislav Y.; Aglyamov, Salavat R.; Sokolov, Konstantin V.; Hamilton, Mark F.; Pearce, John A.Cancer has been one of main causes of human deaths for many years. Early detection of cancer is essential to provide definitive treatment. Among many cancer treatment methods, nanoparticle-mediated photothermal therapy is considered as one of the promising cancer treatment methods because of its non-invasiveness and cancer-specific therapy. Ultrasound and photoacoustic imaging can be utilized for both cancer detection and photothermal therapy guidance. Ultrasound elasticity imaging can detect cancer using tissue elastic properties. Once cancer is diagnosed, spectroscopic photoacoustic imaging can be used to monitor nanoparticle delivery before photothermal therapy. When nanoparticles are well accumulated at the tumor, ultrasound and photoacoustic-based thermal imaging can be utilized for estimating temperature distribution during photothermal therapy to guide therapeutic procedure. In this dissertation, ultrasound beamforming, elasticity imaging, and spectroscopic photoacoustic imaging methods were developed to improve cancer detection and therapy guidance. Firstly, a display pixel based synthetic aperture focusing method was developed to fundamentally improve ultrasound image qualities. Secondly, an autocorrelation based sub-pixel displacement estimation method was developed to enhance signal-to-noise ratio of elasticity images. The developed elasticity imaging method was utilized to clinically evaluate the feasibility of using ultrasound elasticity imaging for prostate cancer detection. Lastly, a minimum mean square error based spectral separation method was developed to robustly utilize spectroscopic photoacoustic imaging. The developed spectroscopic photoacoustic imaging method was utilized to demonstrate ultrasound and photoacoustic image-guided photothermal cancer therapy using in-vivo tumor-bearing mouse models. The results of these studies suggest that ultrasound and photoacoustic imaging can assist both cancer detection and therapy guidance.