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Fluorescence spectroscopy of tissue is a promising technique for early detection of precancerous changes in the human body. Investigation of the microscopic origin of the clinically observed tissue fluorescence can provide valuable information about the tissue's histology. The objective of this study was the development of a morphological model of colon tissue fluorescence which connects the clinically observed spectra with their underlying microscopic origins. Clinical colon tissue fluorescence which connects the clinically observed spectra with their underlying microscopic origins. Clinical colon tissue fluorescence spectra were modeled by measuring the intrinsic fluorescence properties of colon tissue on a microscopic level and by simulating light propagation in tissue using the Monte-Carlo method. The computed spectra were in good agreement with the clinical spectra acquired during colonoscopy, and exhibited the characteristic spectral features of the in vivo collected spectra. Our analysis quantitated these spectral features in terms of the intrinsic fluorescence properties of tissue and its general histological characteristics. The fluorescence intensity difference between normal and adenoma observed in vivo was found to be due to the increased hemoglobin absorption, the reduced mucosal fluorescence intensity, and the absence of submucosal fluorescence in adenomatous polyps. The increased red fluorescence in adenoma was found to be associated with the dysplastic crypt cell fluorescence.

Objective-Foam cells perform critical functions in atherosclerosis. We hypothesize that coronary segments with superficial foam cells (SFCs) situated in a region of interest with a depth of 200 m can be identified using intrinsic fluorescence spectroscopy (IFS) and diffuse reflectance spectroscopy (DRS). This is a key step in our ongoing program to develop a spectroscopic technique for real-time in vivo diagnosis of vulnerable atherosclerotic plaque. Methods and Results-We subjected 132 human coronary segments to in vitro IFS and DRS. We detected SFCs in 13 thick fibrous cap atheromas and 8 pathologic intimal thickening (PIT) lesions. SFCs colocalized with accumulations of smooth muscle cells and proteoglycans, including hyaluronan (PϽ0.001). Two spectroscopic parameters were generated from analysis of IFS at 480 nm excitation and DRS. A discriminatory algorithm using these parameters identified specimens with SFC area Ͼ40%, 20%, 10%, 5%, 2.5%, and 0% of the region of interest with 98%, 98%, 93%, 94%, 93%, and 90% accuracy, respectively. Key Words: foam cells Ⅲ spectroscopy Ⅲ atherosclerosis Ⅲ coronary artery disease Ⅲ human A s a continuation of our work of arterial fluorescence and Raman spectroscopy, 1 we developed an ongoing program targeting the diagnosis of vulnerable atherosclerotic plaques. The main objective of the current study was to demonstrate that a combination of intrinsic fluorescence spectroscopy (IFS) and diffuse reflectance spectroscopy (DRS) can accurately detect human coronary superficial foam cells (SFCs), a potential marker of vulnerable atherosclerotic plaques. Conclusion-Our combined IFS and DRS technique accurately detectsFibrous cap rupture and plaque erosion are the 2 main causes of coronary thrombosis. 2 Eroded plaques are responsible for at least a third of sudden cardiac deaths, with increased prevalence among young subjects. 2,3 Several studies have demonstrated the presence of macrophages and foam cells in ruptured and eroded vulnerable plaques. [3][4][5] Eroded plaques accumulate in their superficial layers macrophages, proteoglycans, smooth muscle cells (SMCs), and extracellular lipids. 2-7 However, whereas ruptured plaques feature a necrotic core and thin fibrous cap, these 2 structures are not necessarily present in eroded plaques. 2,3,6,7 Hence, an ideal technique for diagnosis of vulnerable plaques prone to rupture or erosion should be able to accurately identify macrophages and macrophage-derived foam cells.Although existing invasive diagnostic techniques such as intravascular ultrasound, elastography, and intravascular MRI can identify subsurface plaque features such as fibrous cap and necrotic core, it is only thermography and more recently optical coherence tomography that can identify areas of increased macrophage density. 8 However, none of these methods have focused specifically on foam cells, which, through their interaction with oxidized low-density lipoprotein (LDL) particles and complex inflammatory and plaque degrading functions, play a critical role in the vuln...

Objectives-The protein components of low-density lipoprotein (LDL), oxidized LDL and proteoglycans such as versican contain tryptophan, an amino acid with characteristic fluorescence features at 308 nm excitation wavelength. We hypothesize that intrinsic fluorescence spectroscopy at 308 nm excitation wavelength (IFS 308 ), a method suitable for clinical use, can identify coronary artery lesions with superficial foam cells (SFCs) and/or proteoglycans.Methods-We subjected 119 human coronary artery specimens to in vitro fluorescence and reflectance spectroscopy. We used 5 basis spectra to model IFS 308 , and extracted their contributions to each individual IFS 308 spectrum. A diagnostic algorithm using the contributions of total tryptophan and fibrous cap to IFS 308 was built to identify specimens with SFCs and/or proteoglycans in their top 50 µm.Results-We detected SFCs and/or proteoglycans, such as versican or the glycosaminoglycan hyaluronan, in 24 fibrous cap atheromas or pathologic intimal thickening (PIT) lesions. An algorithm using the contributions of total tryptophan and fibrous cap to IFS 308 was able to identify these segments with 92% sensitivity and 80% specificity. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-WeThere are no conflicts of interest for any of the authors listed. NIH Public Access