Comparative "virtual biopsies" of normal skin and skin lesions using vibrational optical coherence tomography.

BACKGROUND: Increased tissue stiffness (also termed modulus) has been shown to be a characteristic of potential tumor metastasis. Measured values of the stiffness of tumors and cancer cells are reported in the literature to increase compared to neighboring normal tissues. Yet the relationship between the mechanical properties of cells and the extracellular matrix has yet to be correlated with the histopathology of cancerous lesions. MATERIALS AND METHODS: We have developed a technique to do virtual biopsies of skin lesions by combining images made using optical coherence tomography with stiffness measurements made simultaneously using vibrational analysis. The technique is termed vibrational optical coherence tomography (VOCT). RESULTS: In this paper, we report that precancerous and cancerous lesions are characterized by changes in both the morphology and stiffness of the cellular components of the skin. The ratio of the peak heights that correspond to the epidermal (40-60Hz) and dermal (140-160 Hz) resonant frequencies appear to be different for benign and cancerous or precancerous lesions compared with normal skin and scar. CONCLUSIONS: Cell-to-cell and epidermal-to-dermal interactions may be very important in evaluating the potential of skin lesions to become malignant. These interactions can be evaluated using VOCT, a new technique for performing "virtual biopsies" of skin lesions.

Maternal affective symptoms and sleep quality have sex-specific associations with placental topography.

BACKGROUND: The impacts of prenatal maternal affective symptoms on the placental structure are not well-established. Employing Geographic Information System (GIS) spatial autocorrelation, Moran's I, can help characterize placental thickness uniformity/variability and evaluate the impacts of maternal distress on placental topography. METHODS: This study (N = 126) utilized cohort data on prenatal maternal affective symptoms and placental 2D and 3D morphology. Prenatal maternal depression, stress, anxiety and sleep quality were scored for each trimester using the Edinburgh Postnatal Depression Scale (EPDS), Stressful Life Event Scale (SLE), Penn State Worry Questionnaire (PSWQ), and Pittsburgh Sleep Quality Index (PSQI), respectively. Placental shape was divided into Voronoi cells and thickness variability among these cells was computed using Moran's I for 4-nearest neighbors and neighbors within a 10 cm radius. Sex-stratified Spearman correlations and linear regression were used to study associations between mean placental thickness, placental GIS variables, placental weight and the average score of each maternal variable. RESULTS: For mothers carrying boys, poor sleep was associated with higher mean thickness (r = 0.308,p = 0.035) and lower placental thickness uniformity (r = -0.36,p = 0.012). Lower placental weight (r = 0.395,p = 0.003), higher maternal depression (r = -0.318,p = 0.019) and worry/anxiety (r = -0.362,p = 0.007) were associated with lower placental thickness uniformity for mothers carrying girls. LIMITATIONS: The study is exploratory and not all GIS models were developed. Excluding high-risk pregnancies prevented investigating pregnancy complications related hypotheses. A larger sample size is needed for greater confidence for clinical application. CONCLUSIONS: Placental topography can be studied using GIS theory and has shown that prenatal maternal affective symptoms and sleep have sex-specific associations with placental thickness.

Biomechanical analysis of decellularized dermis and skin: Initial in vivo observations using optical cohesion tomography and vibrational analysis.

Measurement of the mechanical properties of skin in vivo has been complicated by the lack of methods that can accurately measure the viscoelastic properties without assuming values of Poisson's ratio and tissue density. In this paper, we present the results of preliminary studies comparing the mechanical properties of skin and scar tissue measured using a technique involving optical cohesion tomography (OCT) and vibrational analysis. This technique has been reported to give values of the modulus that correlate with those obtained from tensile measurements made on decellularized dermis (Shah et al., Skin Res Technol 2016;23:399-406; Shah et al., J Biomed Mater Res Part 2017;105:15-22). The high correlation between moduli measured using vibrational studies and uniaxial tensile tests suggest that the modulus can be determined by measuring the natural frequency that occurs when a tissue is vibrated in tension. The results of studies on glutaric anhydride treated decellularized dermis suggest that vibrational analysis is a useful technique to look at changes in the properties of skin that occur after cosmetic and surgical treatments are used. Preliminary results suggest that the resonant frequency of scar tissue is much higher than that of adjacent normal skin reflecting the higher collagen content of scar. OCT in concert with vibrational analysis appears to be a useful tool to evaluate processes that alter skin properties in animals and humans as well to study the onset and pathogenesis of skin diseases such as cancer. This technique may be useful to evaluate the extent of wound healing in skin diabetic ulcers and other chronic skin conditions, scar tissue formation in response to implants, and other therapeutic treatments that alter skin properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1421-1427, 2018.

Clarification and 3-D visualization of immunolabeled human placenta villi.

We report here the successful 3D visualization of human placenta villous structures on the order of ∼1 mm3 by a combination of immunolabeling, rapid tissue clarification and laser scanning confocal microscopy. The resultant image sets exhibit a complex arrangement of villi and their contained vasculature that mirrors their arrangement in situ.

Vibrational analysis of implants and tissues: Calibration and mechanical spectroscopy of multi-component materials.

Several new methods have been used to non-destructively evaluate the mechanical properties of materials and tissues including magnetic resonance elastography, ultrasound elastography, optical coherence elastography, and various forms of vibrational analysis. One of the limitations of using these methods is the need to establish a relationship between the modulus measured using each new technique and moduli measured using well-established techniques such as constant rate-of-strain and incremental stress-strain curves. In addition, there are no available methods for analyzing the mechanical properties of the individual components of multi-component materials. In this article, we present data showing that there is a strong correlation (correlation coefficient >0.9) between the modulus measured using classical uniaxial tensile incremental stress-strain tests and those made using a combination of optical coherence tomography and vibrational analysis. Beyond this, we demonstrate that the moduli of the major structural components of pig skin can be measured using this technique. These results suggest that optical coherence tomography in concert with vibrational analysis can be used to measure the moduli of biological and implant materials without having to determine Poisson's ratio. In addition, each of the moduli of the major fibrous components of pig skin can be measured concurrently using this technique. These results may be useful in the characterization of synthetic implants and tissue derived materials without requiring removal of one or more components that are to be characterized. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1666-1671, 2017.

Hemodynamic analysis of blood flow in umbilical artery using computational modeling.

The umbilical cord is the crucial pathway for blood flow between the fetus and the placenta. Umbilical coiling and length have been separately linked to adverse clinical outcomes; however, the effects of variations of these parameters on umbilical arterial blood flow are not well understood. Using 3D computational model, we studied the individual and combined effects of umbilical coiling index, cord length and arterial diameter on umbilical artery hemodynamics. We found that specific combinations of umbilical coiling index, cord length and arterial diameter yielded pressure and flow drops incompatible with fetal life. Such models are useful as hypothesis-developing tools.

Chorionic vascular "fit" in the human placenta: Relationship to fetoplacental outcomes.

BACKGROUND: Novel measures of the chorionic plate and vessels are used to test the hypothesis that variation in placental structure is correlated with reduced birth weight (BW) independent of placental weight (PW), suggesting functionally compromised placentas. METHODS: 916 mothers recruited to the Pregnancy, Infection and Nutrition Study delivering singleton live born infants at >30 gestational weeks had placentas collected, digitally photographed and weighed prior to formalin fixation. The fetal-placental weight ratio (FPR) was calculated as birthweight/placental weight. Beta (beta) was calculated as ln(PW)/ln(BW). Chorionic disk perimeter was traced and chorionic surface shape (CS) area was calculated. "Fit" was defined as the ratio of the area of the vascular to the full chorionic surface area. The sites at which chorionic vessels dived beneath the chorionic surface were marked to calculate the chorionic surface vessel (CV) area. The centroids of shapes, the distance between centroids and other measures of shape irregularities were calculated. Principal components analysis (PCA) created three independent factors. Factors were used in regression analyses to explore relations to birth weight, trimmed placental weight, FPR, and beta. Specific measures of shape irregularity were also examined in regression analyses for interrelationships and to predict birth weight, placental weight, FPR, and beta. RESULTS: Variables related to disk size (CS area, perimeter) were correlated with BW, GA, trimmed PW and beta. "Fit" (the ratio of CV area to CS area), measures of shape irregularities, and the distance between the cord insertion and the centroids of surface and vascular areas were also correlated with one or more of the clinical outcome variables. PCA yielded three factors that had independent effects on birth weight, placental weight, the fetal-placental weight ratio, and beta (each p < 0.0001). Addition of GA did not alter the factors' associations with outcomes. Chorionic "fit" (ratio of areas), also included within the factor analysis, was a positive predictor of birth weight (p = 0.005) and FPR (p = 0.002) and a negative predictor of beta (p = 0.01). Fit was statistically significantly associated with greater distances between the umbilical cord insertion site and the CS (p < 0.001) and CV centroids (p < 0.001), and to lesser displacement between CS and CV centroids (p < 0.001). CONCLUSIONS: Measures of CS and CV account for variation in placental efficiency defined by beta, independent of GA. Macroscopic placenta measurements can identify suboptimal placental development.