Annually, about 15 million preterm infants are born in the world. Of these, due to complications resulting from their premature birth, about 1 million would die before the age of five. Since the high incidence of preterm birth (PTB) is partially due to the lack of effective diagnostic modalities, methodologies are needed to determine risk of PTB. We propose a noninvasive tool based on polarized light imaging aimed at measuring the organization of collagen in the cervix. Cervical collagen has been shown to remodel with the approach of parturition. We used a full-field Mueller matrix polarimetric colposcope to assess and compare cervical collagen content and structure in nonpregnant and pregnant women in vivo. Local collagen directional azimuth was used and a total of eight cervices were imaged.
Preterm birth (PTB) presents a serious medical health concern throughout the world. There is a high incidence of PTB in both developed and developing countries ranging from 11% to 15%, respectively. Recent research has shown that cervical collagen orientation and distribution changes during pregnancy may be useful in predicting PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent materials, such as the cervix’s extracellular matrix. Noninvasive, full-field Mueller matrix polarimetry (MMP) imaging methodologies, and optical coherence tomography (OCT) imaging were used to assess cervical collagen content and structure in nonpregnant porcine cervices. We demonstrate that the highly ordered structure of the nonpregnant porcine cervix can be observed with MMP. Furthermore, when utilized ex vivo, OCT and MMP yield very similar results with a mean error of 3.46% between the two modalities.
Scars can be debilitating and cause serious functional limitations, significantly reduced physical function and loss of ability to perform normal daily activities. Scar formation is not fully understood and the treatment options have been hampered by the lack of an objective diagnostic tool to assess scars. Presently, assessment of hypertrophic scars has been based on subjective clinician rankings using a four-parameter scale called the Vancouver Scar Scale (VSS) or the Patient Observer Scar Assessment Scale (POSAS) but no objective, standardized tool for quantifying scar severity is available, despite known inadequacies of the subjective scales. We have developed a hand-held multi modal system consisting of a combined Spatial Frequency Domain Imager (SFDI) used for the assessment of tissue molecular components and a polarimeter for structural measurements. The SFDI capability is provided by an Arduino board controlled spectrally and polarimetric diverse Light Emitting Diodes (LED) ring illuminator. For SFDI imagery, the LEDs are combined with sinusoidal patterns. A single pattern snapshot SFDI approach is used to observe and quantify the biological components in the scar tissue including: oxygenated and de oxygenated hemoglobin, water, and melanin. The SFDI system is integrated with a reduced Mueller Matrix polarimetric system, whose illumination is also included in the LED’s ring, and providing for the assessment of collagen orientation through Mueller Matrix decomposition. The design of the system and experimental work on phantoms will be presented.
Preterm birth (PTB) presents a serious medical heath concern throughout the world. There is a high incidence of
PTB in both developed and developing countries ranging from 11%-15%, respectively. Studies have shown there
may be numerous precursors to PTB including infections, genetic predisposition, nutrition and various other
morbidities which all lead to a premature disorganization in the cervical collagen resulting in the weakening of the
structure designed to keep the fetus in utero. The changes in cervical collagen orientation and distribution may prove
to be a predictor of PTB. Polarization imaging is an effective means to measure optical anisotropy in birefringent
materials such as those rich in collagen as the cervix is. Non-invasive, full-field Mueller Matrix polarimetry (MMP)
imaging methodologies and ex-vivo second harmonic generation (SHG) imaging were used to assess cervical
collagen content and structure in non-pregnant porcine cervices. The SHG microscopy was used to verify the
efficacy of the MMP in assessing changes in collagen orientation.
Preterm birth (PTB) presents a serious medical heath concern in both economically developed
and developing nations, with incidence rate from 15%-11% respectively. Changes in cervical
collagen bundle orientation and distribution may prove to be a predictor of PTB. Polarization
imaging is an effective means to measure optical anisotropy in birefringent biological tissue such
as those rich in collagen. Non-invasive, full-field Mueller Matrix polarimetry (MMP) imaging
methodologies, optical coherence tomography (OCT), and second harmonic generation (SHG)
microscopy were used to assess cervical collagen content and structure in non-pregnant cervices.
In vivo studies using a Mueller Matrix colposcope are underway. Further studies of cervical
collagen orientation throughout pregnancy are needed to understand if Mueller matrix
polarimetry can effectively identify at-risk conditions for PTB.
The extra-cellular space in connective tissue of animals and humans alike is comprised in large part of collagen. Monitoring of collagen arrangement and cross-linking has been utilized to diagnose a variety of medical conditions and guide surgical intervention. For example, collagen monitoring is useful in the assessment and treatment of cervical cancer, skin cancer, myocardial infarction, and non-arteritic anterior ischemic optic neuropathy. We have developed a suite of tools and models based on polarized light transfer for the assessment of collagen presence, cross-linking, and orientation in living tissue. Here we will present some example of such approach applied to the human cervix. We will illustrate a novel Mueller Matrix (MM) imaging system for the study of cervical tissue; furthermore we will show how our model of polarized light transfer through cervical tissue compares to the experimental findings. Finally we will show validation of the methodology through histological results and Second Harmonic imaging microscopy.
Preterm birth is a worldwide health issue, as the number one cause of infant mortality and neurological disorders.
Although affecting nearly 10% of all births, an accurate, reliable diagnostic method for preterm birth has, yet, to be
developed. The primary constituent of the cervix, collagen, provides the structural support and mechanical strength
to maintain cervical closure, through specific organization, during fetal gestation. As pregnancy progresses, the
disorganization of the cervical collagen occurs to allow eventual cervical pliability so the baby can be birthed
through the cervical opening. This disorganization of collagen affects the mechanical properties of the cervix and,
if the changes occur prematurely, may be a significant factor leading to preterm birth. The organization of collagen
can be analyzed through the use of Mueller Matrix Polarimetric imaging of the characteristic birefringence of
collagen. In this research, we have built a full Mueller Matrix Polarimetry attachment to a standard colposcope to
enable imaging of human cervixes during standard prenatal exams at various stages of fetal gestation. Analysis of
the polarimetric images provides information of quantity and organization of cervical collagen at specific gestational
stages of pregnancy. This quantitative information may provide an indication of risk of preterm birth.
Mueller matrix polarimetry and polarization-sensitive optical coherence tomography (PS-OCT) are two emerging techniques utilized in the assessment of tissue anisotropy. While PS-OCT can provide cross-sectional images of local tissue birefringence through its polarimetric sensitivity, Mueller matrix polarimetry can be used to measure bulk polarimetric properties such as depolarization, diattenuation, and retardance. To this day true quantification of PS-OCT data can be elusive, partly due to the reliance on inverse models for the characterization of tissue birefringence and the influence of instrumentation noise. Similarly for Mueller matrix polarimetry, calculation of retardance or depolarization may be influenced by tissue heterogeneities that could be monitored with PS-OCT. Here, we propose an instrument that combines Mueller matrix polarimetry and PS-OCT. Through the co-registration of the two systems, we aim at achieving a better understanding of both modalities.
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