The leading global cause of death in children under the age of five is due to complications arising from Preterm Birth (PTB). Although it is not fully understood why PTB can happen spontaneously, it is known that the cervix’s collagen rich extracellular matrix remodels prior to both term and preterm labor. In vitro Polarization-Sensitive Optical Coherence Tomography (PS-OCT) has successfully imaged the distribution and 3D alignment of collagen in the cervix, as well as determined birefringence and measured cervical tissue depolarization in healthy tissue samples. The present investigation aims to expand on this research, by implementing in silico design, optimization, and simulation techniques for a PS-OCT probe to be used for human in vivo cervical scanning. The design considers patient comfort and clinical access as key parameters; ensuring the components are suitable for a colposcope-like probe and commercially available for quick and cost-effective manufacturing. To achieve these aims, the design benefits from using as few components as possible and limiting optical surface reflections. In this paper we demonstrate that with the use of a cemented Gradient Index (GRIN) relay system, a Field of View (FOV) of up to 6 mm can be achieved, with a back-coupling efficiency of over 73%, on-axis and at up to a 2° scanning angle. Although Huygens Point Spread Function (PSF) lateral resolution reached 81 μm, this paper demonstrates that manual adjustment and optimization of the components can increase this resolution to 12 μm, although at the expense of FOV width reduction. The simulated probe design was verified in preliminary experiments using an in-house built fiber-based OCT engine where high-quality OCT images with wide FOV were obtained from various samples, including healthy human skin.
Babies born before they reach full-term are at an increased risk of long-term complications. Currently, there are no accurate ways to predict when preterm birth (PTB) will occur. The cervix, which plays an essential role in maintaining a pregnancy to term, has to remain closed throughout gestation. However, for birth to occur, it has to shorten, soften and dilate. This crucial remodeling process appears to be linked to variations in the arrangement of collagen. Previous in vitro work using X-ray diffraction suggests that collagen fibers exhibit a preferential orientation in the non-gravid cervix: adjacent to the endocervical canal and in the outermost areas, fibers are mainly arranged in a longitudinal fashion whereas in the middle area they are circumferentially organized. We proposed using a potentially non-invasive imaging technique, polarization-sensitive optical coherence tomography (PS-OCT), to detect the changes in the collagen arrangement of human non-gravid cervix (n=10). Qualitatively, we found that PS-OCT is capable of discriminating between the three cervical regions. Quantitatively, the apparent birefringence of these areas is significantly different across all samples (p<0.05). As expected, apparent birefringence is much lower adjacent to the endocervical canal and in the outermost areas. PS-OCT also seems to be capable of estimating the thickness of the cervical epithelium. Our study, therefore, shows that PS-OCT can assess the microstructure of the human cervical collagen in vitro and holds the potential to help us better understand cervical remodeling prior to birth and develop more timely identification and prevention of PTB pending the development of an in vivo probe.
Spontaneous preterm birth (sPTB) is one of the most serious causes of neonatal death. However, sPTB is unpredictable at present due to simplistic research. That cervix remodels progressively through collagen alterations plays an important role during gestation, but the study of cervical collagen structure has been limited by the lack of suitable observational method. Polarization-sensitive optical coherence tomography (PSOCT) is a functional extension of intensity-based OCT, which can noninvasively offer additional information, i.e., the light’s polarization state. Thus, the collagen properties of birefringence and depolarization can be obtained by a PSOCT in vivo. A PSOCT has been developed from our in-house swept-source (SS) OCT. In the PS-SS-OCT, a circularly polarized light is used to interact tissue and the backscattered light which carries sample’s polarization information is detected by two channels for measuring the horizontal and vertical polarization state respectively. Several human cervix tissues have been investigated by the PS-SS-OCT in vitro. The birefringence and depolarization information of cervical collagen can be obtained by processing the intensity and phase value of the two channels. Besides the birefringence and depolarization information, a conical beam scan strategy has been applied for exploring orientation of the collagen structure of human cervix. In the conical scan, the illumination beam streams into sample at a 45° of incidence angle, and the sample is imaged by acquiring successive B-scan over sample-rotation spans of 0-360°. Since probe of PSOCT can be easily integrated into a catheter or a hand-held probe, PSSS-OCT with a conical beam scan is an excellent candidate to identify cervical structure in clinical practice.
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