Spectroscopy can enable earlier detection of pelvic organ prolapse

Pelvic organ prolapse is a common but often overlooked condition that affects millions of women. It occurs when the tissues that support the pelvic organs weaken, allowing organs such as the bladder, uterus, or rectum to shift from their normal position. Doctors can assess how severe the prolapse is, but existing tools do not provide much information about what's happening inside the tissue itself. 

In a recent study, published in Biophotonics Discovery, researchers from the University of Texas Southwestern’s Pence Lab have shown that a light-based imaging technique called Raman spectroscopy may offer a way to detect those hidden tissue changes without removing or damaging tissue. The study suggests the approach could eventually help doctors monitor tissue health and track disease progression in a much less invasive way. 

To explore the idea, the researchers used a well-established mouse model of prolapse based on fibulin-5 deficiency. Fibulin-5 is a protein required for the formation of healthy elastic fibers, which allow tissues to stretch and recoil. Mice that lack fibulin-5 develop abnormalities similar to those seen in human pelvic organ prolapse, making them a valuable model for studying the condition. The study included twenty-four female mice, consisting of fibulin-5 knockout animals and healthy wildtype controls between 20 and 26 weeks of age. 

To obtain a comprehensive picture of tissue health, the team combined Raman spectroscopy with biomechanical testing and conventional histology. Raman spectroscopy was used to analyze the molecular composition of the vaginal tissue without damaging it. The same samples were then mechanically stretched to assess their ability to withstand forces in different directions. Finally, microscopic examination of stained tissue sections allowed the researchers to directly visualize elastic fibers and other structural components. 

The study revealed clear differences between healthy and prolapsed tissues. Raman spectroscopy showed that optical biomarkers associated with mature, functional elastic fibers were significantly reduced in the fibulin-5 knockout mice. 

In particular, the ratio of crosslinked elastic fibers to extracellular matrix proteins was lower than in healthy controls, indicating impaired formation of the elastic fiber network. Histological analysis confirmed these findings, revealing a substantial decrease in the amount of functional elastic fibers present within the tissue. 

The alterations were not limited to tissue composition. Mechanical testing demonstrated that prolapsed tissues behaved differently when stretched. Compared with healthy tissue, the knockout vagina showed reduced extensibility in the circumferential direction and increased extensibility in the longitudinal direction. 

These findings indicate that prolapse changes not only the tissue's molecular makeup but also the way it responds to physical forces, highlighting increased directional dependence in its mechanical behavior. 

Raman spectroscopy also revealed evidence of metabolic dysregulation. Levels of glycogen, a stored form of energy that supports tissue maintenance and repair, were significantly lower in prolapsed tissues. Histological measurements independently confirmed this decline.  

At the same time, the optical data suggested increases in lipid-related signals, including cholesterol, which may reflect altered metabolism and inflammatory processes associated with tissue remodeling. Together, these results point to a complex interaction among elastic fiber loss, extracellular matrix changes, and disrupted tissue metabolism in pelvic organ prolapse. 

Notably, the researchers found that some of the most important biological changes occurred without significant differences in tissue thickness. This suggests that molecular and functional deterioration can be present even when the tissue appears relatively normal using traditional anatomical assessments. As a result, techniques capable of detecting biochemical changes may provide valuable information that current clinical evaluations miss. 

According to the authors, the work represents an important step toward developing Raman spectroscopy as a practical, noninvasive tool for evaluating pelvic organ prolapse. By measuring the composition and integrity of vaginal tissue without requiring a biopsy, the approach could eventually help clinicians identify early signs of tissue deterioration, monitor disease progression, and assess treatment effectiveness over time. 

While additional studies, particularly in humans, will be needed to validate the technology, the findings establish a foundation for future noninvasive diagnostics and more personalized approaches to care. The study demonstrates how optical measurements can be combined with biomechanical and histological analyses to provide a more complete understanding of pelvic organ prolapse and the tissue changes that drive its progression. 

• This article, first published on spie.org, is part of the special section “Maternal, Reproductive, and Neonatal Health,” edited by Christine P. Hendon (Columbia University), Christine O’Brien (University of California – Davis), Kylie Dunning (University of Adelaide), and Nienke Bosschaart (University of Twente), publishing as a series in Biophotonics Discovery. The articles are collected here: spiedigitallibrary.org/biophotonics-in-maternal-reproductive-and-neonatal-health