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In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy.

ABSTRACT: BACKGROUND:The cervix must undergo significant biochemical remodeling to allow for successful parturition. This process is not fully understood, especially in instances of spontaneous preterm birth. In vivo Raman spectroscopy is an optical technique that can be used to investigate the biochemical composition of tissue longitudinally and noninvasively in human beings, and has been utilized to measure physiology and disease states in a variety of medical applications. OBJECTIVE:The purpose of this study is to measure in vivo Raman spectra of the cervix throughout pregnancy in women, and to identify biochemical markers that change with the preparation for delivery and postpartum repair. STUDY DESIGN:In all, 68 healthy pregnant women were recruited. Raman spectra were measured from the cervix of each patient monthly in the first and second trimesters, weekly in the third trimester, and at the 6-week postpartum visit. Raman spectra were measured using an in vivo Raman system with an optical fiber probe to excite the tissue with 785 nm light. A spectral model was developed to highlight spectral regions that undergo the most changes throughout pregnancy, which were subsequently used for identifying Raman peaks for further analysis. These peaks were analyzed longitudinally to determine if they underwent significant changes over the course of pregnancy (P < .05). Finally, 6 individual components that comprise key biochemical constituents of the human cervix were measured to extract their contributions in spectral changes throughout pregnancy using a linear combination method. Patient factors including body mass index and parity were included as variables in these analyses. RESULTS:Raman peaks indicative of extracellular matrix proteins (1248 and 1254 cm-1) significantly decreased (P < .05), while peaks corresponding to blood (1233 and 1563 cm-1) significantly increased (P < .0005) in a linear manner throughout pregnancy. In the postpartum cervix, significant increases in peaks corresponding to actin (1003, 1339, and 1657 cm-1) and cholesterol (1447 cm-1) were observed when compared to late gestation, while signatures from blood significantly decreased. Postpartum actin signals were significantly higher than early pregnancy, whereas extracellular matrix proteins and water signals were significantly lower than early weeks of gestation. Parity had a significant effect on blood and extracellular matrix protein signals, with nulliparous patients having significant increases in blood signals throughout pregnancy, and higher extracellular matrix protein signals in early pregnancy compared to patients with prior pregnancies. Body mass index significantly affected actin signal contribution, with low body mass index patients showing decreasing actin contribution throughout pregnancy and high body mass index patients demonstrating increasing actin signals. CONCLUSION:Raman spectroscopy was successfully used to biochemically monitor cervical remodeling in pregnant women during prenatal visits. This foundational study has demonstrated sensitivity to known biochemical dynamics that occur during cervical remodeling, and identified patient variables that have significant effects on Raman spectra throughout pregnancy. Raman spectroscopy has the potential to improve our understanding of cervical maturation, and be used as a noninvasive preterm birth risk assessment tool to reduce the incidence, morbidity, and mortality caused by preterm birth.

SUBMITTER: O'Brien CM

PROVIDER: S-EPMC5916496 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy.

O'Brien Christine M CM Vargis Elizabeth E Rudin Amy A Slaughter James C JC Thomas Giju G Newton J Michael JM Reese Jeff J Bennett Kelly A KA Mahadevan-Jansen Anita A

American journal of obstetrics and gynecology 20180202 5

<h4>Background</h4>The cervix must undergo significant biochemical remodeling to allow for successful parturition. This process is not fully understood, especially in instances of spontaneous preterm birth. In vivo Raman spectroscopy is an optical technique that can be used to investigate the biochemical composition of tissue longitudinally and noninvasively in human beings, and has been utilized to measure physiology and disease states in a variety of medical applications.<h4>Objective</h4>The ...[more]

PMID: 29410109

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Project description:Tumour cells exhibit altered metabolic pathways that lead to radiation resistance and disease progression. Raman spectroscopy (RS) is a label-free optical modality that can monitor post-irradiation biomolecular signatures in tumour cells and tissues. Convolutional Neural Networks (CNN) perform automated feature extraction directly from data, with classification accuracy exceeding that of traditional machine learning, in cases where data is abundant and feature extraction is challenging. We are interested in developing a CNN-based predictive model to characterize clinical tumour response to radiation therapy based on their degree of radiosensitivity or radioresistance. In this work, a CNN architecture is built for identifying post-irradiation spectral changes in Raman spectra of tumour tissue. The model was trained to classify irradiated versus non-irradiated tissue using Raman spectra of breast tumour xenografts. The CNN effectively classified the tissue spectra, with accuracies exceeding 92.1% for data collected 3 days post-irradiation, and 85.0% at day 1 post-irradiation. Furthermore, the CNN was evaluated using a leave-one-out- (mouse, section or Raman map) validation approach to investigate its generalization to new test subjects. The CNN retained good predictive accuracy (average accuracies 83.7%, 91.4%, and 92.7%, respectively) when little to no information for a specific subject was given during training. Finally, the classification performance of the CNN was compared to that of a previously developed model based on group and basis restricted non-negative matrix factorization and random forest (GBR-NMF-RF) classification. We found that CNN yielded higher classification accuracy, sensitivity, and specificity in mice assessed 3 days post-irradiation, as compared with the GBR-NMF-RF approach. Overall, the CNN can detect biochemical spectral changes in tumour tissue at an early time point following irradiation, without the need for previous manual feature extraction. This study lays the foundation for developing a predictive framework for patient radiation response monitoring.

Project description:BackgroundBiochemical cervical change during labor is not well understood, in part, because of a dearth of technologies capable of safely probing the pregnant cervix in vivo. The need for such a technology is 2-fold: (1) to gain a mechanistic understanding of the cervical ripening and dilation process and (2) to provide an objective method for evaluating the cervical state to guide clinical decision-making. Raman spectroscopy demonstrates the potential to meet this need, as it is a noninvasive optical technique that can sensitively detect alterations in tissue components, such as extracellular matrix proteins, lipids, nucleic acids, and blood, which have been previously established to change during the cervical remodeling process.ObjectiveWe sought to demonstrate that Raman spectroscopy can longitudinally monitor biochemical changes in the laboring cervix to identify spectral markers of impending parturition.Study designOverall, 30 pregnant participants undergoing either spontaneous or induced labor were recruited. The Raman spectra were acquired in vivo at 4-hour intervals throughout labor until rupture of membranes using a Raman system with a fiber-optic probe. Linear mixed-effects models were used to determine significant (P<.05) changes in peak intensities or peak ratios as a function of time to delivery in the study population. A nonnegative least-squares biochemical model was used to extract the changing contributions of specific molecule classes over time.ResultsWe detected multiple biochemical changes during labor, including (1) significant decreases in Raman spectral features associated with collagen and other extracellular matrix proteins (P=.0054) attributed to collagen dispersion, (2) an increase in spectral features associated with blood (P=.0372), and (3) an increase in features indicative of lipid-based molecules (P=.0273). The nonnegative least-squares model revealed a decrease in collagen contribution with time to delivery, an increase in blood contribution, and a change in lipid contribution.ConclusionOur findings have demonstrated that in vivo Raman spectroscopy is sensitive to multiple biochemical remodeling changes in the cervix during labor. Furthermore, in vivo Raman spectroscopy may be a valuable noninvasive tool for objectively evaluating the cervix to potentially guide clinical management of labor.

Project description:There is continued focus on the development of new biomaterials and associated biological testing methods needed to reduce the time taken for their entry to clinical use. The application of Raman spectroscopy to the study of individual cells that have been in contact with biomaterials offers enhanced in vitro information in a potentially non-destructive testing regime. The work presented here reports the Raman spectral analysis of discreet U-2 OS bone cells after exposure to hydroxyapatite (HA) coated titanium (Ti) substrates in both the as-deposited and thermally annealed states. These data show that cells that were in contact with the bioactive HA surface for 7 days had spectral markers similar to those cultured on the Ti substrate control for the same period. However, the spectral features for those cells that were in contact with the annealed HA surface had indicators of significant differentiation at day 21 while cells on the as-deposited surface did not show these Raman changes until day 28. The cells adhered to pristine Ti control surface showed no spectral changes at any of the timepoints studied. The validity of these spectroscopic results has been confirmed using data from standard in vitro cell viability, adhesion, and proliferation assays over the same 28-day culture period. In this case, cell maturation was evidenced by the formation of natural bone apatite, which precipitated intracellularly for cells exposed to both types of HA-coated Ti at 21 and 28 days, respectively. The properties of the intracellular apatite were markedly different from that of the synthetic HA used to coat the Ti substrate with an average particle size of 230 nm, a crystalline-like shape and Ca/P ratio of 1.63 ± 0.5 as determined by SEM-EDX analysis. By comparison, the synthetic HA particles used as a control had an average size of 372 nm and were more-rounded in shape with a Ca/P ratio of 0.8 by XPS analysis and 1.28 by SEM-EDX analysis. This study shows that Raman spectroscopy can be employed to monitor single U-2 OS cell response to biomaterials that promote cell maturation towards de novo bone thereby offering a label-free in vitro testing method that allows for non-destructive analyses.

Dataset Information

In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy.

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In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy.

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