This dissertation presents work towards novel optical techniques for detecting markers of plaque vulnerability. The rupture of vulnerable atherosclerotic plaque continues to be a major contributor to the cardiovascular death toll every year and currently there are no clinical methods to detect the risk of plaque rupture. Chapter one provides an overview of atherosclerosis, current and in-progress diagnostic methods, and an introduction to fluorescence and time-resolved fluorescence techniques. At the end of this chapter, the overall objectives of the thesis are outlined: (1) Further characterize the ability of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) to determine the functional composition of the arterial wall without the use of contrast agents by studying the relationship between matrix metalloproteinase (MMP) -2 and -9 expression and TR-LIFS parameters (chapter 3). (2) Show that results achieved with the TR-LIFS system could be expanded to an imaging technique, fluorescence lifetime imaging (FLIM), and that this technique could provide maps of the distribution of critical molecular markers of plaque instability (chapter 4). (3) Develop an automated method of assessing biochemical composition and risk of plaque rupture based on FLIM images to advance the potential for clinical translation of this technique (chapter 5). (4) Demonstrate how the results from these studies will aid in clinical translation of time-resolved fluorescence techniques for label-free intravascular assessment of atherosclerotic plaque in patients (chapter 6). Rather than describe the methods in detail in each chapter, chapter 2 is devoted to describing the time-resolved techniques investigated in this work and the methods involved with each. This chapter provides the most details about FLIM because the majority of this work was focused on experiments utilizing this technique; it also discusses TR-LIFS and simultaneous time and wavelength resolved fluorescence spectroscopy (STWRFS). Chapter 2 also gives an example of how FLIM is capable of distinguishing between the main biochemical constituents that determine the stability vs. instability of atherosclerotic plaque (collagen, elastin, and lipids), proving that it is feasible to assess these features in tissue. The next three chapters depict the specific methods, results and conclusions for the three most important aspects of this work that address the specific objectives of the thesis. Chapter 6 summarizes the implications of this work, provides some future directions and in particular shows how conclusions from this work will be utilized in a scanning STWRFS technique to allow for clinical implementation.
|Commitee:||Chiamvimonvat, Nipavan, Ferrara, Katherine W., Qi, Jinyi, Simon, Scott S.|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||DAI-B 72/08, Dissertation Abstracts International|
|Keywords:||Atherosclerosis, Cardiovascular disease, Fluorescence lifetime imaging, Matrix metalloproteinases|
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