Can We Improve Vaginal Tissue Healing Using Customized Devices: 3D Printing and Biomechanical Changes in Vaginal Tissue.

BACKGROUND: Determining biomechanical changes in vaginal tissue with tissue stretch is critical for understanding the role of mechanotransduction on vaginal tissue healing. Noncontact dynamic optical coherence elastography (OCE) can quantify biomechanical changes in vaginal tissues noninvasively. Improved vaginal tissue healing will reduce postoperative complications from vaginal surgery. AIMS: (1) To complete dimensional assessments (DAs) of the vaginal tract. (2) To elucidate biomechanical properties (BMP) of porcine vaginal tissues (PVT). (3) Compare BMPs of piglet and adult PVTs after placement of customized vaginal dilators (VD) by OCE and uniaxial mechanical testing (MT). METHODS: Pilot study using adult nulliparous pig and piglet PVTs (n = 20 each). DA of PVTs was performed using silicone molding. 3D-printed VDs were used to achieve different Relative Diameter Change (RDC) of the PVTs (no dilatation, and -50%, 0%, 50% RDC). Elastographic testing using OCE and MT. RESULTS: Using OCE, no significant differences (SD) were noted between adult and piglet PVT (p = 0.74) or by stretch direction (p = 0.300). SD was noted with increasing RDC (p = 0.023). Using MT, there were SD in tissue stiffness between adult and piglet PVT (p = 0.048), but no SD as a function of RDC (p = 0.750) or stretch direction (p = 0.592). CONCLUSIONS: This study quantified biomechanical changes in PVT with customized stretching by 3D printed VD using both OCE and MT. This work has implications for the mechanotransduction of vaginal wound healing and noninvasive assessment of vaginal diseases.

Direct four-dimensional structural and functional imaging of cardiovascular dynamics in mouse embryos with 1.5 MHz optical coherence tomography.

High-resolution three-dimensional (3D) imaging of cardiovascular dynamics in mouse embryos is greatly desired to study mammalian congenital cardiac defects. Here, we demonstrate direct four-dimensional (4D) imaging of the cardiovascular structure and function in live mouse embryos at a ∼43 Hz volume rate using an optical coherence tomography (OCT) system with a ∼1.5 MHz Fourier domain mode-locking swept laser source. Combining ultrafast OCT imaging with live mouse embryo culture protocols, 3D volumes of the embryo are directly and continuously acquired over time for a cardiodynamics analysis without the application of any synchronization algorithms. We present the time-resolved measurements of the heart wall motion based on the 4D structural data, report 4D speckle variance and Doppler imaging of the vascular system, and quantify spatially resolved blood flow velocity over time. These results indicate that the ultra-high-speed 4D imaging approach could be a useful tool for efficient cardiovascular phenotyping of mouse embryos.

Label-free optical imaging for brain cancer assessment.

Advances in label-free optical imaging offer a promising avenue for brain cancer assessment, providing high-resolution, real-time insights without the need for radiation or exogeneous agents. These cost-effective and intricately detailed techniques overcome the limitations inherent in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scans by offering superior resolution and more readily accessible imaging options. This comprehensive review explores a variety of such methods, including photoacoustic imaging (PAI), optical coherence tomography (OCT), Raman imaging, and IR microscopy. It focuses on their roles in the detection, diagnosis, and management of brain tumors. By highlighting recent advances in these imaging techniques, the review aims to underscore the importance of label-free optical imaging in enhancing early detection and refining therapeutic strategies for brain cancer.

Assessing the effects of prenatal poly-drug exposure on fetal brain vasculature using optical coherence angiography.

Significance: Maternal exposure to drugs during pregnancy is known to have detrimental effects on the fetus. Alcohol (ethanol) and nicotine are two of the most commonly co-abused substances during pregnancy, and prenatal poly-drug exposure is common due, in part, to the prevalence of unplanned pregnancies. The second trimester is a critical period for fetal neurogenesis and angiogenesis. When drug exposure occurs during this time, fetal brain development is affected. Several behavioral, morphological, and functional studies have evaluated the changes in fetal brain development due to exposure to these drugs individually. However, research on the combined effects of ethanol and nicotine is far more limited, specifically on fetal vasculature changes and development. Aim: We use correlation mapping optical coherence angiography (cm-OCA) to evaluate acute changes in fetal brain vasculature caused by maternal exposure to a combination of ethanol and nicotine. Approach: Ethanol (16.6% v/v, at a dose of 0.75g/kg) and nicotine (at a dose of 0.1 mg/kg) were administered to pregnant mice after initial cm-OCA measurements in utero. Subsequent measurements were taken at 5-min intervals for a total period of 45 min. Results from these experiments were compared to results from our previous studies in which the mother was exposed to only ethanol (dose: 0.75 g/kg) or nicotine (dose: 0.1 mg/kg). Results: While results from exposure to ethanol or nicotine independently showed vasoconstriction, no significant change in vasculature was observed with combined exposure. Conclusion: Results suggested antagonistic effects of ethanol and nicotine on fetal brain vasculature.

The Progress of Label-Free Optical Imaging in Alzheimer's Disease Screening and Diagnosis.

As the major neurodegenerative disease of dementia, Alzheimer's disease (AD) has caused an enormous social and economic burden on society. Currently, AD has neither clear pathogenesis nor effective treatments. Positron emission tomography (PET) and magnetic resonance imaging (MRI) have been verified as potential tools for diagnosing and monitoring Alzheimer's disease. However, the high costs, low spatial resolution, and long acquisition time limit their broad clinical utilization. The gold standard of AD diagnosis routinely used in research is imaging AD biomarkers with dyes or other reagents, which are unsuitable for in vivo studies owing to their potential toxicity and prolonged and costly process of the U.S. Food and Drug Administration (FDA) approval for human use. Furthermore, these exogenous reagents might bring unwarranted interference to mechanistic studies, causing unreliable results. Several label-free optical imaging techniques, such as infrared spectroscopic imaging (IRSI), Raman spectroscopic imaging (RSI), optical coherence tomography (OCT), autofluorescence imaging (AFI), optical harmonic generation imaging (OHGI), etc., have been developed to circumvent this issue and made it possible to offer an accurate and detailed analysis of AD biomarkers. In this review, we present the emerging label-free optical imaging techniques and their applications in AD, along with their potential and challenges in AD diagnosis.

Artificial intelligence-augmented, label-free molecular imaging method for tissue identification, cancer diagnosis, and cancer margin detection.

Label-free high-resolution molecular and cellular imaging strategies for intraoperative use are much needed, but not yet available. To fill this void, we developed an artificial intelligence-augmented molecular vibrational imaging method that integrates label-free and subcellular-resolution coherent anti-stokes Raman scattering (CARS) imaging with real-time quantitative image analysis via deep learning (artificial intelligence-augmented CARS or iCARS). The aim of this study was to evaluate the capability of the iCARS system to identify and differentiate the parathyroid gland and recurrent laryngeal nerve (RLN) from surrounding tissues and detect cancer margins. This goal was successfully met.

Optical coherence tomography angiography to evaluate murine fetal brain vasculature changes caused by prenatal exposure to nicotine.

Maternal smoking causes several defects ranging from intrauterine growth restriction to sudden infant death syndrome and spontaneous abortion. While several studies have documented the effects of prenatal nicotine exposure in development and behavior, acute vasculature changes in the fetal brain due to prenatal nicotine exposure have not been evaluated yet. This study uses correlation mapping optical coherence angiography to evaluate changes in fetal brain vasculature flow caused by maternal exposure to nicotine during the second trimester-equivalent of gestation in a mouse model. The effects of two different doses of nicotine were evaluated. Results showed a decrease in the vasculature for both doses of nicotine, which was not seen in the case of the sham group.

Dose-response analysis of microvasculature changes in the murine fetal brain and the maternal extremities due to prenatal ethanol exposure.

SIGNIFICANCE: Prenatal exposure to ethanol causes several morphological and neurobehavioral deficits. While there are some studies on the effects of ethanol exposure on blood flow, research focusing on acute changes in the microvasculature is limited. AIM: The first aim of this study was to assess the dose-dependent changes in murine fetal brain microvasculature of developing fetuses in response to maternal alcohol consumption. The second aim was to quantify changes in vasculature occurring concurrently in the mother's hindlimb and the fetus's brain after maternal exposure to alcohol. APPROACH: Correlation mapping optical coherence angiography was used to evaluate the effects of prenatal exposure to different doses of ethanol (3, 1.5, and 0.75 g / kg) on murine fetal brain vasculature in utero. Additionally, simultaneous imaging of maternal peripheral vessels and the fetal brain vasculature was performed to assess changes of the vasculature occurring concurrently in response to ethanol consumption. RESULTS: The fetal brain vessel diameters (VDs) decreased by ∼47 % , 30%, and 14% in response to ethanol doses of 3, 1.5, and 0.75 g / kg, respectively. However, the mother's hindlimb VD increased by 63% in response to ethanol at a dose of 3 g / kg. CONCLUSIONS: Results showed a dose-dependent reduction in vascular blood flow in fetal brain vessels when the mother was exposed to ethanol, whereas vessels in the maternal hindlimb exhibited concurrent vasodilation.

Tissue biomechanics during cranial neural tube closure measured by Brillouin microscopy and optical coherence tomography.

BACKGROUND: Embryonic development involves the interplay of driving forces that shape the tissue and the mechanical resistance that the tissue offers in response. While increasing evidence has suggested the crucial role of physical mechanisms underlying embryo development, tissue biomechanics is not well understood because of the lack of techniques that can quantify the stiffness of tissue in situ with 3D high-resolution and in a noncontact manner. METHODS: We used two all-optical techniques, optical coherence tomography (OCT) and Brillouin microscopy, to map the longitudinal modulus of the tissue from mouse embryos in situ. RESULTS: We acquired 2D mechanical maps of the neural tube region of embryos at embryonic day (E) 8.5 (n = 2) and E9.5 (n = 2) with submicron spatial resolution. We found the modulus of tissue varied distinctly within the neural tube region of the same embryo and between embryos at different development stages, suggesting our technique has enough sensitivity and spatial resolution to monitor the tissue mechanics during embryonic development in a noncontact and noninvasive manner. CONCLUSIONS: We demonstrated the capability of OCT-guided Brillouin microscopy to quantify tissue longitudinal modulus of mouse embryos in situ, and observed distinct change in the modulus during the closure of cranial neural tube. Although this preliminary work cannot provide definitive conclusions on biomechanics of neural tube closure yet as a result of the limited number of samples, it provides an approach of quantifying the tissue mechanics during embryo development in situ, thus could be helpful in investigating the role of tissue biomechanics in the regulation of embryonic development. Our next study involving more embryo samples will investigate systematic changes in tissue mechanics during embryonic development.

Assessing the acute effects of prenatal synthetic cannabinoid exposure on murine fetal brain vasculature using optical coherence tomography.

Marijuana is one of the most commonly abused substances during pregnancy. Synthetic cannabinoids (SCBs) are a group of heterogeneous compounds that are 40- to 600-fold more potent than Δ9 -tetrahydrocannabinol, the major psychoactive component of marijuana. With SCBs being legally available for purchase and the prevalence of unplanned pregnancies, the possibility of prenatal exposure to SCBs is high. However, the effects of prenatal SCB exposure on embryonic brain development are not well understood. In this study, we use complex correlation mapping optical coherence angiography to evaluate changes in murine fetal brain vasculature in utero, minutes after maternal exposure to an SCB, CP-55940. Results showed a significant decrease (P < 0.05) in fetal brain vessel diameter, length fraction and area density when compared to the sham group. This preliminary study shows that acute prenatal exposure to an SCB resulted in significant fetal brain vasoconstriction during the peak period for brain development.

Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography.

Prenatal alcohol exposure (PAE) can result in a range of anomalies including brain and behavioral dysfunctions, collectively termed fetal alcohol spectrum disorder. PAE during the 1st and 2nd trimester is common, and research in animal models has documented significant neural developmental deficits associated with PAE during this period. However, little is known about the immediate effects of PAE on fetal brain vasculature. In this study, we used in utero speckle variance optical coherence tomography, a high spatial- and temporal-resolution imaging modality, to evaluate dynamic changes in microvasculature of the 2nd trimester equivalent murine fetal brain, minutes after binge-like maternal alcohol exposure. Acute binge-like PAE resulted in a rapid (<1 hour) and significant decrease (P < .001) in vessel diameter as compared to the sham group. The data show that a single binge-like maternal alcohol exposure resulted in swift vasoconstriction in fetal brain vessels during the critical period of neurogenesis.

Evaluating biomechanical properties of murine embryos using Brillouin microscopy and optical coherence tomography.

Embryogenesis is regulated by numerous changes in mechanical properties of the cellular microenvironment. Thus, studying embryonic mechanophysiology can provide a more thorough perspective of embryonic development, potentially improving early detection of congenital abnormalities as well as evaluating and developing therapeutic interventions. A number of methods and techniques have been used to study cellular biomechanical properties during embryogenesis. While some of these techniques are invasive or involve the use of external agents, others are compromised in terms of spatial and temporal resolutions. We propose the use of Brillouin microscopy in combination with optical coherence tomography (OCT) to measure stiffness as well as structural changes in a developing embryo. While Brillouin microscopy assesses the changes in stiffness among different organs of the embryo, OCT provides the necessary structural guidance.

Ultra-fast line-field low coherence holographic elastography using spatial phase shifting.

Optical coherence elastography (OCE) is an emerging technique for quantifying tissue biomechanical properties. Generally, OCE relies on point-by-point scanning. However, long acquisition times make point-by-point scanning unfeasible for clinical use. Here we demonstrate a noncontact single shot line-field low coherence holography system utilizing an automatic Hilbert transform analysis based on a spatial phase shifting technique. Spatio-temporal maps of elastic wave propagation were acquired with only one air-pulse excitation and used to quantify wave velocity and sample mechanical properties at a line rate of 200 kHz. Results obtained on phantoms were correlated with data from mechanical testing. Finally, the stiffness of porcine cornea at different intraocular pressures was also quantified in situ.

Optical coherence elastography assessment of corneal viscoelasticity with a modified Rayleigh-Lamb wave model.

The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.

Assessing the effects of riboflavin/UV-A crosslinking on porcine corneal mechanical anisotropy with optical coherence elastography.

In this work we utilize optical coherence elastography (OCE) to assess the effects of UV-A/riboflavin corneal collagen crosslinking (CXL) on the mechanical anisotropy of in situ porcine corneas at various intraocular pressures (IOP). There was a distinct meridian of increased Young's modulus in all samples, and the mechanical anisotropy increased as a function of IOP and also after CXL. The presented noncontact OCE technique was able to quantify the Young's modulus and elastic anisotropy of the cornea and their changes as a function of IOP and CXL, opening new avenues of research for evaluating the effects of CXL on corneal biomechanical properties.

Optical coherence tomography for embryonic imaging: a review.

Embryogenesis is a highly complex and dynamic process, and its visualization is crucial for understanding basic physiological processes during development and for identifying and assessing possible defects, malformations, and diseases. While traditional imaging modalities, such as ultrasound biomicroscopy, micro-magnetic resonance imaging, and micro-computed tomography, have long been adapted for embryonic imaging, these techniques generally have limitations in their speed, spatial resolution, and contrast to capture processes such as cardiodynamics during embryogenesis. Optical coherence tomography (OCT) is a noninvasive imaging modality with micrometer-scale spatial resolution and imaging depth up to a few millimeters in tissue. OCT has bridged the gap between ultrahigh resolution imaging techniques with limited imaging depth like confocal microscopy and modalities, such as ultrasound sonography, which have deeper penetration but poorer spatial resolution. Moreover, the noninvasive nature of OCT has enabled live imaging of embryos without any external contrast agents. We review how OCT has been utilized to study developing embryos and also discuss advances in techniques used in conjunction with OCT to understand embryonic development.

Evaluating the Effects of Riboflavin/UV-A and Rose-Bengal/Green Light Cross-Linking of the Rabbit Cornea by Noncontact Optical Coherence Elastography.

PURPOSE: The purpose of this study was to use noncontact optical coherence elastography (OCE) to evaluate and compare changes in biomechanical properties that occurred in rabbit cornea in situ after corneal collagen cross-linking by either of two techniques: ultraviolet-A (UV-A)/riboflavin or rose-Bengal/green light. METHODS: Low-amplitude (≤10 µm) elastic waves were induced in mature rabbit corneas by a focused air pulse. Elastic wave propagation was imaged by a phase-stabilized swept source OCE (PhS-SSOCE) system. Corneas were then cross-linked by either of two methods: UV-A/riboflavin (UV-CXL) or rose-Bengal/green light (RGX). Phase velocities of the elastic waves were fitted to a previously developed modified Rayleigh-Lamb frequency equation to obtain the viscoelasticity of the corneas before and after the cross-linking treatments. Micro-scale depth-resolved phase velocity distribution revealed the depth-wise heterogeneity of both cross-linking techniques. RESULTS: Under standard treatment settings, UV-CXL significantly increased the stiffness of the corneas by ∼47% (P < 0.05), but RGX did not produce statistically significant increases. The shear viscosities were unaffected by either cross-linking technique. The depth-wise phase velocities showed that UV-CXL affected the anterior ∼34% of the corneas, whereas RGX affected only the anterior ∼16% of the corneas. CONCLUSIONS: UV-CXL significantly strengthens the cornea, whereas RGX does not, and the effects of cross-linking by UV-CXL reach deeper into the cornea than cross-linking effects of RGX under similar conditions.

Quantifying tissue viscoelasticity using optical coherence elastography and the Rayleigh wave model.

This study demonstrates the feasibility of using the Rayleigh wave model (RWM) in combination with optical coherence elastography (OCE) technique to assess the viscoelasticity of soft tissues. Dispersion curves calculated from the spectral decomposition of OCE-measured air-pulse induced elastic waves were used to quantify the viscoelasticity of samples using the RWM. Validation studies were first conducted on 10% gelatin phantoms with different concentrations of oil. The results showed that the oil increased the viscosity of the gelatin phantom samples. This method was then used to quantify the viscoelasticity of chicken liver. The Young's modulus of the chicken liver tissues was estimated as E=2.04±0.88??kPa with a shear viscosity ?=1.20±0.13??Pa?s. The analytical solution of the RWM correlated very well with the OCE-measured phased velocities (R2=0.96±0.04). The results show that the combination of the RWM and OCE is a promising method for noninvasively quantifying the biomechanical properties of soft tissues and may be a useful tool for detecting disease.

Lorentz force optical coherence elastography.

Quantifying tissue biomechanical properties can assist in detection of abnormalities and monitoring disease progression and/or response to a therapy. Optical coherence elastography (OCE) has emerged as a promising technique for noninvasively characterizing tissue biomechanical properties. Several mechanical loading techniques have been proposed to induce static or transient deformations in tissues, but each has its own areas of applications and limitations. This study demonstrates the combination of Lorentz force excitation and phase-sensitive OCE at ?1.5??million A-lines per second to quantify the elasticity of tissue by directly imaging Lorentz force-induced elastic waves. This method of tissue excitation opens the possibility of a wide range of investigations using tissue biocurrents and conductivity for biomechanical analysis.

Applicability, usability, and limitations of murine embryonic imaging with optical coherence tomography and optical projection tomography.

We present an analysis of imaging murine embryos at various embryonic developmental stages (embryonic day 9.5, 11.5, and 13.5) by optical coherence tomography (OCT) and optical projection tomography (OPT). We demonstrate that while OCT was capable of rapid high-resolution live 3D imaging, its limited penetration depth prevented visualization of deeper structures, particularly in later stage embryos. In contrast, OPT was able to image the whole embryos, but could not be used in vivo because the embryos must be fixed and cleared. Moreover, the fixation process significantly altered the embryo morphology, which was quantified by the volume of the eye-globes before and after fixation. All of these factors should be weighed when determining which imaging modality one should use to achieve particular goals of a study.