Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis

Jo, Javier A.; Park, Jesung; Pande, Paritosh; Shrestha, Sebina; Serafino, Michael J.; Rico-Jimenez, Jose J.; Clubb, Fred J.; Walton, Brian; Buja, L. Maximilian; Phipps, Jennifer E.; Feldman, Marc D.; Adame, Jessie; Applegate, Brian E.

doi:10.1093/ehjci/jev018

Cited by 23 publications

(14 citation statements)

References 32 publications

(18 reference statements)

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“…Especially, the corresponding histopathological sections showed that the fluorescence lifetime changes are closely related to the compositional changes, such as collagen density, lipid deposition, and macrophage infiltration. The fluorescence lifetime distribution might result from compositions located on the surface of the tissue since the FLIm subsystem is based on ultraviolet excitation with a penetration depth of around 200 µm [33]. Nevertheless, since thin cap fibroatheroma, a high-risk plaque, has a fibrous cap with a thickness of <65 µm [66], and macrophages are often distributed at the boundary between a fibrous cap and a necrotic core [64], the shallow penetration depth is sufficient for atherosclerosis imaging, especially for evaluating inflamed high-risk plaques.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the vulnerability of atherosclerotic plaques is closely related to changes in biochemical compositions, which contain the endogenous fluorophores. Previous FLIm imaging studies of atherosclerosis [10, 16-18, 33,34] have demonstrated the feasibility of FLIm as a method for characterizing the vulnerability of atherosclerotic plaques and have shown the potential to improve the diagnostic accuracy and sensitivity of imaging modalities to detect vulnerable plaques.…”

Section: Introductionmentioning

confidence: 99%

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Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography

Nam

Kang

Lee

et al. 2018

Biomed. Opt. Express

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The pathophysiological progression of chronic diseases, including atherosclerosis and cancer, is closely related to compositional changes in biological tissues containing endogenous fluorophores such as collagen, elastin, and NADH, which exhibit strong autofluorescence under ultraviolet excitation. Fluorescence lifetime imaging (FLIm) provides robust detection of the compositional changes by measuring fluorescence lifetime, which is an inherent property of a fluorophore. In this paper, we present a dual-modality system combining a multispectral analog-mean-delay (AMD) FLIm and a high-speed swept-source optical coherence tomography (OCT) to simultaneously visualize the cross-sectional morphology and biochemical compositional information of a biological tissue. Experiments using standard fluorescent solutions showed that the fluorescence lifetime could be measured with a precision of less than 40 psec using the multispectral AMD-FLIm without averaging. In addition, we performed imaging on rabbit iliac normal-looking and atherosclerotic specimens to demonstrate the feasibility of the combined FLIm-OCT system for atherosclerosis imaging. We expect that the combined FLIm-OCT will be a promising next-generation imaging technique for diagnosing atherosclerosis and cancer due to the advantages of the proposed label-free high-precision multispectral lifetime measurement.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography

Nam

Kang

Lee

et al. 2018

Biomed. Opt. Express

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“…The lifetime is related to molecular properties including the pH of its surroundings, the concentration of oxygen near the molecule, and the molecule’s bonds to other molecules [6]. FLIM has been used to image atherosclerotic plaques, helping characterize the plaque composition [30, 51]. FLIM may have uses in cardiac myopathy, where the ratio of collagen I and III fibers matters.…”

Section: Cellular–scale Imagingmentioning

confidence: 99%

Imaging the Cardiac Extracellular Matrix

Pinkert

Hortensius

Ogle

et al. 2018

Advances in Experimental Medicine and Biology

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Cardiovascular disease is the global leading cause of death. One route to address this problem is using biomedical imaging to measure the molecules and structures that surround cardiac cells. This cellular microenvironment, known as the cardiac extracellular matrix, changes in composition and organization during most cardiac diseases and in response to many cardiac treatments. Measuring these changes with biomedical imaging can aid in understanding, diagnosing, and treating heart disease. This chapter supports those efforts by reviewing representative methods for imaging the cardiac extracellular matrix. It first describes the major biological targets of ECM imaging, including the primary imaging target of fibrillar collagen. Then it discusses the imaging methods, describing their current capabilities and limitations. It categorizes the imaging methods into two main categories: organ-scale noninvasive methods and cellular-scale invasive methods. Noninvasive methods can be used on patients, but only a few are clinically available, and others require further development to be used in the clinic. Invasive methods are the most established and can measure a variety of properties, but they cannot be used on live patients. Finally, the chapter concludes with a perspective on future directions and applications of biomedical imaging technologies.

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“…As a combined system, such multi-modal diagnostic tools are capable of interrogating the morphology as well as the biochemistry of tissue. The collective information generated with multi-modal systems has been shown to improve sensitivity and specificity in the analysis of diseased tissues [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Our group has been investigating multi-modal systems that incorporate OCT and FLIM for the detection of oral cancer and characterization of atherosclerotic plaques [2,13]. Optical Coherence Tomography (OCT) uses low-coherence interferometry to measure the depthresolved intensity of light backscattered from the tissue up to a depth of ~2 mm.…”

Section: Introductionmentioning

confidence: 99%

Multimodal optical coherence tomography and fluorescence lifetime imaging with interleaved excitation sources for simultaneous endogenous and exogenous fluorescence

Shrestha¹,

Serafino²,

Rico-Jimenez³

et al. 2016

Biomed. Opt. Express

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Abstract:Multimodal imaging probes a variety of tissue properties in a single image acquisition by merging complimentary imaging technologies. Exploiting synergies amongst the data, algorithms can be developed that lead to better tissue characterization than could be accomplished by the constituent imaging modalities taken alone. The combination of optical coherence tomography (OCT) with fluorescence lifetime imaging microscopy (FLIM) provides access to detailed tissue morphology and local biochemistry. The optical system described here merges 1310 nm swept-source OCT with time-domain FLIM having excitation at 355 and 532 nm. The pulses from 355 and 532 nm lasers have been interleaved to enable simultaneous acquisition of endogenous and exogenous fluorescence signals, respectively. The multimodal imaging system was validated using tissue phantoms. Nonspecific tagging with Alexa Flour 532 in a Watanbe rabbit aorta and active tagging of the LOX-1 receptor in human coronary artery, demonstrate the capacity of the system for simultaneous acquisition of OCT, endogenous FLIM, and exogenous FLIM in tissues.

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Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis

Cited by 23 publications

References 32 publications

Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography

Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography

Imaging the Cardiac Extracellular Matrix

Multimodal optical coherence tomography and fluorescence lifetime imaging with interleaved excitation sources for simultaneous endogenous and exogenous fluorescence

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