Joseph Chue-Sang

Use of combined polarization-sensitive optical coherence tomography and Mueller matrix imaging for the polarimetric characterization of excised biological tissue

Abstract. 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.

Use of Mueller matrix polarimetry and optical coherence tomography in the characterization of cervical collagen anisotropy

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.

Development and characterization of a snapshot Mueller matrix polarimeter for the determination of cervical cancer risk in the low resource setting

Mueller Matrix polarimetry can provide useful information about the function and structure of the extracellular matrix. Mueller Matrix systems are sophisticated and costly optical tools that have been used primarily in the laboratory or in hospital settings. Here we introduce a low-cost snapshot Mueller Matrix polarimeter that that does not require external power, has no moving parts, and can acquire a full Mueller Matrix in less than 50 milliseconds. We utilized this technology in the study of cervical cancer in Mysore India, yet the system could be translated in multiple diagnostic applications.

Optimization of the incident wavelength in Mueller Matrix imaging of cervical collagen

Mueller matrix polarimetry (MMP) can be utilized to determine optical anisotropy in birefringent materials. Many factors must be optimized to improve the quality of information collected from MMP of biological samples. As part of a study of pre-term birth (PTB) that relied on measurement of the orientation and distribution of collagen in the cervix, an optimal wavelength for MMp to allow more accurate characterization of collagen in cervical tissue was sought. To this end, we developed a multispectral Mueller matrix polarimeter and conducted experiments on ex-vivo porcine cervix samples preserved in paraffin. The Mueller matrices obtained with this system were decomposed to generate orientation and retardation images. Initial findings indicate that wavelengths below 560 nm offer a more accurate characterization of collagen anisotropy in the porcine cervix.

Comparison of collagen orientation and distribution in-vivo between non-pregnant and pregnant human cervix using Mueller Matrix polarimetry (Conference Presentation)

Preterm birth (PTB) presents a serious medical heath concern throughout the world and maintains a high incidence rate in both developed and developing countries ranging between 11-15%, respectively. PTB can be caused by many different morbidities and ultimately results in the disorganization of cervical collagen and the premature alteration of the cervix mechanical properties. 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. Non-invasive, in-vivo full-field Mueller Matrix polarimetry (MMP) imaging was conducting using a modified colposcope in a clinical study comparing collagen orientation and distribution between non-pregnant and pregnant patients. Six patients threatening PTB were imaged at the Jackson Memorial Hospital Triage Unit and six non-pregnant patients were image at Florida International University STAR center. In pregnant women collagen distributions changed depending on patient age and number of pregnancies in the non-pregnant population age played an important role in collagen organization.

Quantitative analysis of a scar's pliability, perfusion and metrology

The primary effect of scarring is the loss of function in the affected area. Scarring also leads to physical and psychological problems that could be devastating to the patient’s life. Currently, scar assessment is highly subjective and physician dependent. The examination relies on the expertise of the physician to determine the characteristics of the scar by touch and visual examination using the Vancouver scar scale (VSS), which categorizes scars depending on pigmentation, pliability, height and vascularity. In order to establish diagnostic guidelines for scar formation, a quantitative, accurate assessment method needs to be developed. An instrument capable of measuring all categories was developed; three of the aforementioned parameters will be explored. In order to look at pliability, a durometer which measures the amount of resistance a surface exerts to prevent the permanent indentation of the surface is used due to its simplicity and quantitative output. To look at height and vascularity, a profilometry system that collects the location of the scar in three-dimensions and laser speckle imaging (LSI), which shows the dynamic changes in perfusion, respectively, are used. Gelatin phantoms were utilized to measure pliability. Finally, dynamic changes in skin perfusion of volunteers’ forearms undergoing pressure cuff occlusion were measured, along with incisional scars.

Handheld SFDI/polarimetric imaging device for objective evaluation of hypertrophic scars (Conference Presentation)

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.

Imaging and modeling of collagen architecture in living tissue with polarized light transfer(Conference Presentation)

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.

Cervical collagen imaging for determining preterm labor risks using a colposcope with full Mueller matrix capability

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.

Imaging of skin surface architecture with out of plane polarimetry (Conference Presentation)

Knowledge of skin surface topography is of great importance when establishing environmental and age related skin damage. Furthermore an effective treatment protocol cannot be established without a quantitative measuring tool that is able to establish significant improvement in skin texture. We utilized an out-of-plane polarimeter for the characterization of skin surface profile non-invasively. The system consists of an imaging Stokes vector polarimeter where the light source and imaging apparatus are arranged at an angle equal to forty degrees with respect to the tissue normal. The light source is rotated at various azimuth angles about the tissue normal. For each position of the incident beam the principal angle of polarization is calculated. This parameter relates indirectly to surface profile and architecture. The system was used to image the forehead and hands of healthy volunteers between eighteen and sixty years of age. A clear separation appeared among different age groups, establishing out-of-plane polarimetry as a promising technique for skin topography quantification.