Photoacoustic imaging of the uterine cervix to assess collagen and water content changes in murine pregnancy

Abstract

The uterine cervix plays a central role in the maintenance of pregnancy and in the process of parturition. Cervical remodeling involves dramatic changes in extracellular matrix composition and, in particular, of collagen and water content during cervical ripening (a term that describes the anatomical, biochemical, and physiologic changes in preparation for labor). Untimely cervical ripening in early gestation predisposes to preterm labor and delivery, the leading cause of infant death worldwide. Inadequate ripening of the cervix is associated with failure of induction or prolonged labor. The current approach to evaluate the state of the cervix relies on digital examination and sonographic examination. Herein, we present a novel imaging method that combines ultrasound (US) and photoacoustic (PA) techniques to evaluate cervical remodeling by assessing the relative collagen and water content of this organ. The method was tested in vitro in extracted collagen phantoms and ex vivo in murine cervical tissues that were collected in mid-pregnancy and at term. We report, for the first time, that our imaging approach provides information about the molecular changes in the cervix at different gestational ages. There was a strong correlation between the results of PA imaging and the histological assessment of the uterine cervix over the course of gestation. These findings suggest that PA imaging is a powerful method to assess the biochemical composition of the cervix and open avenues to non-invasively investigate the composition of this organ, which is essential for reproductive success.

Effective photoacoustic absorption spectrum for collagen-based tissue imaging

“…At 1560 nm, that was up to five times over what is possible with wavelengths of 1200 and 1310 nm, which are commonly used in collagen PAI. 18,19 This confirms the utility of the effective PA absorption spectrum and optimal wavelength for PAI of collagen-based tissues, thereby contributing to an improvement in the PA image sensitivity.…”

“…Recently, the imaging of collagen and collagen-based tissues using the PAI method was reported. 18,19 Even though the optical absorption by collagen is relatively high in the VIS and NIR-I wavelength ranges, it still requires precise optical alignment and a complex acoustic capturing process to measure the PA signals of collagen in biological tissue due to the dominant concentration of oxy-/deoxyhemoglobin (Hb) in whole blood and its morphological proximity to the blood vessels. Therefore, one solution involves looking for an effective collagen absorption spectrum in the SWIR band, which presents two main benefits: (1) avoiding the interference from whole blood and (2) achieving almost an order of magnitude higher absorption by collagen than with the NIR-I band.…”

Immunobiology of Cervix Ripening

“…Moreover, further study using non-invasive image analyses would strengthen the accepted conclusion that reduced alignment and less anisotropy, as determined by, directly reflect a decline in extracellular cross-linked mature collagen with remodeling. By example, photoacoustic imaging was recently used to identify that increased water content accompanied collagen disorganization in the ripened vs. unripe cervix (37). The relationship of edema, cellular hypertrophy, cell nuclei density, and cross-linked collagen in the stroma could clarify if heterogeneity within and along subregions may be extrapolated from a biopsy of one area to a broader conclusion about the entire cervix.…”

Dual-Illumination Ultrasound/ Photoacoustic System for Cervical Cancer Imaging

“…PA imaging can be easily integrated with a US imaging system because the same US transducer can be used for acquiring the PA signals, and minimal modification is required in the imaging sequence as US/ PA images are naturally co-registered. PA imaging can also provide spatial distribution of the tissue's optical absorption components [9][10][11][12]. The dependence of the PA signal on the optical absorption properties can be exploited to distinguish between different chromophores, including melanin, hemoglobin, fat occurring within a tissue or organ.…”