Determination of Human Coronary Artery Composition by Raman Spectroscopy

Brennan, James F.; Römer, T; Lees, Robert S.; Tercyak, Anna M.; Kramer, John; Feld, Michael S.

doi:10.1161/01.cir.96.1.99

Cited by 148 publications

(115 citation statements)

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“…Details of the model and its validation with standard chemical assays have been described previously. 24,25 In calcified plaques, CS occupied a large part of the tissue volume examined by Raman spectroscopy. To obtain information about the remaining noncalcified tissue, we renormalized the chemical fractions in the NCR, eg,…”

Section: Selected Abbreviations and Acronymsmentioning

confidence: 99%

“…19,20 Recently, we demonstrated that the chemical composition of human coronary artery can be quantified with NIR Raman spectroscopy. [21][22][23][24][25] Raman spectra were obtained from homogenized coronary artery samples and processed to calculate the relative weights (in percent) of FC, CE, TG, and PL, and CS in the examined volume of arterial tissue. These chemical weights agreed with those determined by standard lipid assays and CS assays to within a few percent.…”

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confidence: 99%

“…These chemical weights agreed with those determined by standard lipid assays and CS assays to within a few percent. 24 Furthermore, it has been demonstrated that Raman spectra from arterial wall can be collected in vivo via optical fiber probes in signal collection times of only a few seconds. These studies indicate that spectra obtained in vivo have signal-to-noise ratios sufficiently high to calculate chemical weights.…”

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Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy

et al. 1998

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Background-Lesion composition, rather than size or volume, determines whether an atherosclerotic plaque will progress, regress, or rupture, but current techniques cannot provide precise quantitative information about lesion composition. We have developed a technique to assess the pathological state of human coronary artery samples by quantifying their chemical composition with near-infrared Raman spectroscopy. Methods and Results-Coronary artery samples (nϭ165) obtained from explanted recipient hearts were illuminated with 830-nm infrared light. Raman spectra were collected from the tissue and processed to quantify the relative weights of cholesterol, cholesterol esters, triglycerides and phospholipids, and calcium salts in the examined artery location. The artery locations were then classified by a pathologist and grouped as either nonatherosclerotic tissue, noncalcified plaque, or calcified plaque. Nonatherosclerotic tissue, which included normal artery and intimal fibroplasia, contained an average of Ϸ4Ϯ3% cholesterol, whereas noncalcified plaques had Ϸ26Ϯ10% and calcified plaques Ϸ19Ϯ10% cholesterol in the noncalcified regions. The average relative weight of calcium salts was 1Ϯ2% in noncalcified plaques and 41Ϯ21% in calcified plaques. To make this quantitative chemical information clinically useful, we developed a diagnostic algorithm, based on a first set of 97 samples, that demonstrated a strong correlation of the relative weights of cholesterol and calcium salts with histological diagnoses of the same locations. This algorithm was then prospectively tested on a second set of 68 samples. The algorithm correctly classified 64 of these new samples, thus demonstrating the accuracy and robustness of the method. Conclusions-The pathological state of a given human coronary artery may be assessed by quantifying its chemical composition, which can be done rapidly with Raman spectroscopic techniques. When Raman spectra are obtained clinically via optical fibers, Raman spectroscopy may be useful in monitoring the progression and regression of atherosclerosis, predicting plaque rupture, and selecting proper therapeutic intervention. (Circulation. 1998;97:878-885.)

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Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy

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“…The point-to-point spatial variations in the structure of plaque samples reduce the accuracy of the Raman assay and its applicability for noninvasive quantitative analysis. 13,14 There is currently no method available for the accurate quantification of liquid and liquid-crystalline phases of CEs in a plaque. The best method available, polarized light microscopy, can estimate the relative amounts of CE phases in a thin section (10 m) dissected from a plaque.…”

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Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic-Angle Spinning ¹³ C-NMR

Peng¹,

Guo²,

Morrisett³

et al. 2000

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Abstract-Accumulation of cholesteryl esters (CEs) is a key event in the formation of atherosclerotic plaques. More recent work suggests a role for CEs in plaque rupture leading to thrombosis, which can result in an acute event such as myocardial infarction or stroke. In this study, we present nuclear magnetic resonance (NMR) protocols for quantification of CEs in plaques in situ. Total CEs quantified by 13 C magic-angle spinning (MAS) NMR in excised plaques from human carotid arteries and rabbit aortic arteries were in good agreement with the amounts determined by subsequent standard chemical assays. The latter analysis is disadvantageous because it requires that plaque lipids be extracted from the tissue, resulting in the loss of all phase information of CEs as well as other major plaque components. With our MAS-NMR protocol, the plaque components are preserved in their native phases. Combining MAS and off-MAS NMR, we were able to quantitatively distinguish isotropic (liquid) CEs from anisotropic (liquid-crystalline) CEs in plaque tissues. In a recent study, we applied a different 13 C MAS-NMR protocol to quantify crystalline cholesterol monohydrate in plaques. Together, these 2 studies describe a new, noninvasive MAS-NMR strategy for the identification and quantification of the major lipid components in plaques in situ. This approach will be useful for investigation of the relationship between plaque rupture and specific lipids in their biologically relevant phases. Key Words: NMR Ⅲ cholesteryl esters Ⅲ atherosclerotic plaques Ⅲ plaque rupture Ⅲ lipid phase T he formation of a lipid-rich lesion in the arterial wall is a key event in the initiation and progression of atherosclerosis. The lipid content and composition are important factors in predicting the stability of an atheromatous plaque. 1,2 Cholesteryl esters (CEs) constitute a major fraction of the lipid-rich core in the atherosclerotic plaque, and their abundance is highly associated with rupture of plaques and formation of thrombi. 3 Aortic plaques with a lipid core occupying Ͼ40% of the total plaque volume are at the highest risk of rupture. 4 It is hypothesized that the accumulation of noncrystalline CEs may soften the lipid core, making plaques with a thin, fibrous cap more prone to rupture. 5 A more specific suggestion is that the ratio of CEs to crystalline cholesterol monohydrate is a determinant of plaque "softness." 6 However, only very recently has an accurate quantification of crystalline cholesterol monohydrate in a plaque in situ been achieved. 7 In addition to the chemical abundance of CEs, the physical state of CEs and the proximity of CEs to other plaque components may be important for plaque stability. CE is a nonpolar lipid that does not mix well with polar lipids (eg, phospholipids) but can serve as a weak solvent for weakly polar lipids such as triglycerides and cholesterol. 3 Within plaques, CE is phase-separated from phospholipid/cholesterol bilayers and crystalline cholesterol. In some plaques, the CE pool is enriched with saturat...

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Detection of transplant vasculopathy in a rat aortic allograft model by fluorescence spectroscopic optical analysis

et al. 1999

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Determination of Human Coronary Artery Composition by Raman Spectroscopy

Cited by 148 publications

References 21 publications

Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy

Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy

Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic-Angle Spinning ¹³ C-NMR

Detection of transplant vasculopathy in a rat aortic allograft model by fluorescence spectroscopic optical analysis

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Determination of Human Coronary Artery Composition by Raman Spectroscopy

Cited by 148 publications

References 21 publications

Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy

Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy

Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic-Angle Spinning 13 C-NMR

Detection of transplant vasculopathy in a rat aortic allograft model by fluorescence spectroscopic optical analysis

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Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic-Angle Spinning ¹³ C-NMR