Fluorescence lifetime in cardiovascular diagnostics

University of California, Davis, Department of Biomedical Engineering, Davis, California 95616, USA.
Journal of Biomedical Optics (Impact Factor: 2.86). 01/2010; 15(1):011106. DOI: 10.1117/1.3327279
Source: PubMed


We review fluorescence lifetime techniques including time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and fluorescence lifetime imaging microscopy (FLIM) instrumentation and associated methodologies that allow for characterization and diagnosis of atherosclerotic plaques. Emphasis is placed on the translational research potential of TR-LIFS and FLIM and on determining whether intrinsic fluorescence signals can be used to provide useful contrast for the diagnosis of high-risk atherosclerotic plaque. Our results demonstrate that these techniques allow for the discrimination of important biochemical features involved in atherosclerotic plaque instability and rupture and show their potential for future intravascular applications.

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Available from: Laura Marcu, Mar 24, 2014
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    • "In comparison, the lifetime values do not depend on the aforementioned distance, and thus can be used to detect changes in the composition of the plaque. This means that the three-dimensional reconstruction of the luminal surface shown in Fig. 8(a) for the first channel (390/40 nm) and Fig. 8(b) for the second channel (452/45 nm) can become a valuable asset towards the assessment of the composition of the plaque, as has been shown in previous studies of our group [6] [7], that might be difficult to achieve through intensity measurements. Fig. 7. "
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    ABSTRACT: Fluorescence lifetime imaging (FLIM) has demonstrated potential for robust assessment of atherosclerotic plaques biochemical composition and for complementing conventional intravascular ultrasound (IVUS), which provides information on plaque morphology. The success of such a bimodal imaging modality depends on accurate segmentation of the IVUS images and proper angular registration between these two modalities. This paper reports a novel IVUS segmentation methodology addressing this issue. The image preprocessing consisted of denoising, using the Wiener filter, followed by image smoothing, implemented through the application of the alternating sequential filter on the edge separability metric images. Extraction of the lumen/intima and media/adventitia boundaries was achieved by tracing the gray-scale peaks over the A-lines of the IVUS preprocessed images. Cubic spline interpolation, in both cross-sectional and longitudinal directions, ensured boundary smoothness and continuity. The detection of the guide-wire artifact in both modalities is used for angular registration. Intraluminal studies were conducted in 13 ex-vivo segments of human coronaries. The IVUS segmentation accuracy was assessed against independent manual tracings, providing 91.82% sensitivity and 97.55% specificity. The proposed methodology makes the bi-modal FLIM and IVUS approach feasible for comprehensive intravascular diagnosis by providing co-registered biochemical and morphological information of atherosclerotic plaques.
    IEEE Transactions on Medical Imaging 08/2014; 34(1). DOI:10.1109/TMI.2014.2350491 · 3.39 Impact Factor
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    • "Advances in the diagnosis of atherosclerotic cardiovascular disease depend on the availability of tools for the characterization of arterial wall and reliable detection and discrimination of distinct types of plaques [1,2]. Time-resolved (lifetime) fluorescence techniques have demonstrated potential tissue diagnosis including cancer [3–6] and atherosclerotic plaques [7]. Recent reports showed that instrumentation based on either time-resolved fluorescence spectroscopy (TRFS) or fluorescence lifetime imaging (FLIM) techniques can generate useful label-free optical molecular contrast for detection of critical atherosclerotic plaque such as plaques with thin fibrous cap [8], plaques rich in lipids [9,10], and plaques with macrophage infiltration in the fibrotic cap [9]. "
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    ABSTRACT: This study describes a scanning time-resolved fluorescence spectroscopy (TRFS) system designed to continuously acquire fluorescence emission and to reconstruct fluorescence lifetime images (FLIM) from a luminal surface by using a catheter-based optical probe with rotary joint and pull-back device. The ability of the system to temporally and spectrally resolve the fluorescence emission from tissue was validated using standard dyes and tissue phantoms (e.g., ex vivo pig aorta phantom). Current results demonstrate that this system is capable to reliably resolve the fluorescence emission of multiple fluorophores located in the lumen; and suggest its potential for intravascular detection of distinct biochemical features of atherosclerotic plaques.
    Biomedical Optics Express 07/2012; 3(7):1521-33. DOI:10.1364/BOE.3.001521 · 3.65 Impact Factor
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    • "A total of four aorta samples from three patients were measured using STWRFS. In addition, conventional TR-LIFS measurements of diverse arterial beds similar to those we previously reported [11,14,16,20] were conducted at multiple points along the scanning line of STWRFS. Results were analyzed and compared to verify the new method. "
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    ABSTRACT: Simultaneous time- and wavelength-resolved fluorescence spectroscopy (STWRFS) was developed and tested for the dynamic characterization of atherosclerotic tissue ex vivo and arterial vessels in vivo. Autofluorescence, induced by a 337 nm, 700 ps pulsed laser, was split to three wavelength sub-bands using dichroic filters, with each sub-band coupled into a different length of optical fiber for temporal separation. STWRFS allows for fast recording/analysis (few microseconds) of time-resolved fluorescence emission in these sub-bands and rapid scanning. Distinct compositions of excised human atherosclerotic aorta were clearly discriminated over scanning lengths of several centimeters based on fluorescence lifetime and the intensity ratio between 390 and 452 nm. Operation of STWRFS blood flow was further validated in pig femoral arteries in vivo using a single-fiber probe integrated with an ultrasound imaging catheter. Current results demonstrate the potential of STWRFS as a tool for real-time optical characterization of arterial tissue composition and for atherosclerosis research and diagnosis.
    Optics Express 02/2011; 19(5):3890-901. DOI:10.1364/OE.19.003890 · 3.49 Impact Factor
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