Abstract
Understanding the viability of the ischemic myocardial tissue is a critical issue in determining the appropriate surgical procedure for patients with chronic heart failure after myocardial infarction (MI). Conventional MI evaluation methods are; however, preoperatively performed and/or give an indirect information of myocardial viability such as shape, color, and blood flow. In this study, we realize the evaluation of MI in patients undergoing cardiac surgery by Raman spectroscopy under label-free conditions, which is based on intrinsic molecular constituents related to myocardial viability. We identify key signatures of Raman spectra for the evaluation of myocardial viability by evaluating the infarct border zone myocardium that were excised from five patients under surgical ventricular restoration. We also obtain a prediction model to differentiate the infarcted myocardium from the non-infarcted myocardium by applying partial least squares regression-discriminant analysis (PLS-DA) to the Raman spectra. Our prediction model enables identification of the infarcted tissues and the non-infarcted tissues with sensitivities of 99.98% and 99.92%, respectively. Furthermore, the prediction model of the Raman images of the infarct border zone enabled us to visualize boundaries between these distinct regions. Our novel application of Raman spectroscopy to the human heart would be a useful means for the detection of myocardial viability during surgery.
Highlights
Staining[7,8,9,10,11,12,13]
In all the specimens excised from 5 patients, the non-infarcted myocardium, which predominantly consists of cardiomyocytes, exhibited four evident Raman peaks at 755, 1133, 1318, and 1590 cm−1 that were all assigned to heme proteins[23] with no obvious differences among the patients (Fig. 1b)
The infarcted myocardium had a spectral peak at 2942 cm−1, which is distinct from the peak at 2934 cm−1 in the non-infarcted myocardium
Summary
Staining[7,8,9,10,11,12,13]. For over two decades, this modality has been applied experimentally to a variety of human tissues, e.g., the brain[14], coronary artery[15], skin[16], breast[17,18], and peripheral nerves[19,20,21]. We previously reported Raman spectroscopic analysis of old myocardial infarct of rats created by coronary artery ligation by resonant scattering of cytochromes[22,23,24], which provides higher sensitivity and selectivity for the Raman signals as compared with the conventional Raman spectroscopy. In contrast to the rat experimental model, where infarcted tissues are distinctly replaced by fibrosis consisting mainly of type I collagen with no other major components[26], accurate Raman spectroscopic evaluation is quite difficult in human old MI because of the spectral complexity of the tissue constituents and lack of relevant characteristic molecules exhibiting the resonant Raman scattering in the infarcted tissues. To elucidate definitive Raman spectral fingerprints and a reliable prediction model for the evaluation of myocardial viability under the presence of noise in Raman spectrum, we employed a multivariate spectral analysis method, partial least squares regression-discriminant analysis (PLS-DA). Our novel application of Raman spectroscopy to the human heart would be a useful means for the detection of myocardial viability during surgery
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