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Investigating Preterm Labor using Raman Spectroscopy

10 Apr | By Biophotonics.World
Investigating Preterm Labor using Raman Spectroscopy
Figure- In vivo Raman spectroscopy monitors cervical change in humans throughout pregnancy. A) Computational model of Raman spectra changing throughout pregnancy and postpartum (PP). Spectral bands that exhibited significant changes throughout pregnancy are shaded. B) Schematic of probe design including Raman probe, camera, and illumination fibers; C) Speculum-free probe top-down cross-section, D-E) Speculum-free probe in gloved hand
Image source: Laura Masson


Preterm delivery occurs in over 12% of pregnancies in the United States and is the leading cause of neonatal mortality. Still, little is understood about what causes a woman to go into preterm labor, in part due to a lack of technologies to investigate pregnancy. Dr. Anita Mahadevan-Jansen’s research group at the Vanderbilt Biophotonics Center has pioneered the use of Raman spectroscopy to probe the pregnant cervix for clues to the underlying causes of preterm labor. The cervix plays a crucial role in maintaining pregnancy and undergoes an extensive biochemical remodeling process to prepare for delivery. Raman spectroscopy uses inelastically scattered light to track these biochemical changes without posing any risk to the mother or baby. Dr. Christine O’Brien, whose PhD research centered on this application, said, “Pregnancy is a very delicate state, making it extremely difficult to investigate using the classical methods of taking tissues for study. This is not possible nor ethical for pregnant patients, and thus we have had to be creative in learning about pregnancy without introducing harm. Light-based methods are excellent for this purpose and have incredible potential to improve our understanding of pregnancy and therefore improve patient care.”


Raman spectroscopy of the pregnant human cervix:

The researchers first conducted a pilot study of patients receiving prenatal care at Vanderbilt University’s Center for Women’s Health. Patients underwent Raman spectroscopy measurements at each of their prenatal visitsas well as their postpartum visit. Measurements were taken using a clinical Raman spectroscopy system, including a fiber optic probe to deliver excitation light to the cervix and collect the Raman scattered light. 


Analysis of patient data revealed that the spectral contribution of collagen decreases over the course of pregnancy, which is consistent with previous work showing that the cervix extracellular matrix becomes less dense leading up to delivery. The contribution of blood also increased over the course of pregnancy, suggesting an increase in vasculature which can be observed in the darker pink appearance of the pregnant cervix. Patients who had a previous pregnancy had higher intensities of Raman signatures associated with blood, indicating that there may be a permanent vascular network that is established during a woman’s first pregnancy. In patients with high body mass indices (BMI), who often experience longer labors, spectral features associated with collagen changed less over the course of pregnancy compared to low BMI patients, suggesting that these patients may have disrupted collagen breakdown.


Dr. Mahadevan-Jansen explains, “We’ve shown that Raman spectroscopy has the unique ability to track biochemical cervical changes in vivo throughout the course of pregnancy. This approach has already deepened our knowledge of the cervical remodeling process, and I think our future work will allow Raman spectroscopy to serve as a tool for preterm birth risk assessment.”


Development of a speculum-free Raman spectroscopy probe:

While the pilot study focused on the prenatal and postpartum stages, there was a gap in knowledge regarding how the cervix changes during labor. Therefore, patients undergoing induction of labor at Vanderbilt University Hospital were recruited for Raman spectroscopy measurements. The measurement protocol used in both the prenatal and labor studies required a speculum exam to visualize the cervix and ensure that no blood or mucus would contaminate Raman spectral measurements. Many patients declined participation in the study because of the speculum exam, while others who did choose to participate expressed discomfort. These measurements disrupted the clinical workflow and added extra time for providers, since speculum exams are not routinely performed as part of obstetric care. 


As a solution to these issues, the speculum-free Raman spectroscopy probe was developed. This probe, which is approximately 7 mm in diameter, includes a 1 mm CMOS camera along with ESKA illumination fibers coupled to a white light source, allowing the provider to visualize the cervix without a speculum exam. The new probe integrates with the type of cervical checks that are standard in obstetric care. Measurements using this probe showed the same data quality as the speculum-based approach. Further, the majority of patients and providers surveyed preferred the speculum-free approach. This technology has improved patient recruitment rates and allowed Raman spectroscopy to better integrate into the existing workflow, thus moving this approach one step closer to clinical implementation.


Impact:

The results of this and future work have the potential to deepen our understanding of preterm labor and revolutionize clinical management of this condition. Dr. J Newton, an obstetrician and the director of Labor and Delivery at Vanderbilt University Hospital, said “Raman spectroscopy holds great promise in helping us understand the tissue changes occurring during labor in real-time. In particular, the latest speculum-free probe has allowed for improved ease of use and significantly less patient discomfort.”  The research team envisions that Raman spectroscopy measurements will eventually become a routine part of prenatal care. A baseline measurement will be taken at the patient’s first prenatal visit, and subsequent measurements will inform the provider of the patient’s predicted time to delivery, likelihood of preterm delivery, and underlying causes, thus allowing the provider to tailor care to ensure a healthy, full-term pregnancy. 


Click hereto learn more about the use of Raman spectroscopy to track biochemical changes in the human cervix throughout pregnancy.


O’Brien CM, Vargis E, Rudin A, et al. In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy. Am J Obstet Gynecol 2018;218:528.e1-18.


Click hereto learn more about the development and validation of the visually-guided Raman spectroscopy probe.


O'Brien CM, Cochran KJ, Masson LE, et al. Development of a visually guided Raman spectroscopy probe for cervical assessment during pregnancy. J Biophotonics. 2019:e201800138.


 Author: Laura Masson




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