Rotational imaging optical coherence tomography for full-body mouse embryonic imaging.

Optical coherence tomography (OCT) has been widely used to study mammalian embryonic development with the advantages of high spatial and temporal resolutions and without the need for any contrast enhancement probes. However, the limited imaging depth of traditional OCT might prohibit visualization of the full embryonic body. To overcome this limitation, we have developed a new methodology to enhance the imaging range of OCT in embryonic day (E) 9.5 and 10.5 mouse embryos using rotational imaging. Rotational imaging OCT (RI-OCT) enables full-body imaging of mouse embryos by performing multiangle imaging. A series of postprocessing procedures was performed on each cross-section image, resulting in the final composited image. The results demonstrate that RI-OCT is able to improve the visualization of internal mouse embryo structures as compared to conventional OCT.

Quantitative methods for reconstructing tissue biomechanical properties in optical coherence elastography: a comparison study.

We present a systematic analysis of the accuracy of five different methods for extracting the biomechanical properties of soft samples using optical coherence elastography (OCE). OCE is an emerging noninvasive technique, which allows assessment of biomechanical properties of tissues with micrometer spatial resolution. However, in order to accurately extract biomechanical properties from OCE measurements, application of a proper mechanical model is required. In this study, we utilize tissue-mimicking phantoms with controlled elastic properties and investigate the feasibilities of four available methods for reconstructing elasticity (Young's modulus) based on OCE measurements of an air-pulse induced elastic wave. The approaches are based on the shear wave equation (SWE), the surface wave equation (SuWE), Rayleigh-Lamb frequency equation (RLFE), and finite element method (FEM), Elasticity values were compared with uniaxial mechanical testing. The results show that the RLFE and the FEM are more robust in quantitatively assessing elasticity than the other simplified models. This study provides a foundation and reference for reconstructing the biomechanical properties of tissues from OCE data, which is important for the further development of noninvasive elastography methods.

Algorithms for improved 3-D reconstruction of live mammalian embryo vasculature from optical coherence tomography data.

BACKGROUND: Robust reconstructions of the three-dimensional network of blood vessels in developing embryos imaged by optical coherence tomography (OCT) are needed for quantifying the longitudinal development of vascular networks in live mammalian embryos, in support of developmental cardiovascular research. Past computational methods [such as speckle variance (SV)] have demonstrated the feasibility of vascular reconstruction, but multiple challenges remain including: the presence of vessel structures at multiple spatial scales, thin blood vessels with weak flow, and artifacts resulting from bulk tissue motion (BTM). METHODS: In order to overcome these challenges, this paper introduces a robust and scalable reconstruction algorithm based on a combination of anomaly detection algorithms and a parametric dictionary based sparse representation of blood vessels from structural OCT data. RESULTS: Validation results using confocal data as the baseline demonstrate that the proposed method enables the detection of vessel segments that are either partially missed or weakly reconstructed using the SV method. Finally, quantitative measurements of vessel reconstruction quality indicate an overall higher quality of vessel reconstruction with the proposed method. CONCLUSIONS: Results suggest that sparsity-integrated speckle anomaly detection (SSAD) is potentially a valuable tool for performing accurate quantification of the progression of vascular development in the mammalian embryonic yolk sac as imaged using OCT.

Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging.

The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

Detection and Monitoring of Microparticles Under Skin by Optical Coherence Tomography as an Approach to Continuous Glucose Sensing Using Implanted Retroreflectors.

We demonstrate the feasibility of using optical coherence tomography (OCT) to image and detect 2.8 µm diameter microparticles (stationary and moving) on a highly-reflective gold surface both in clear media and under skin in vitro. The OCT intensity signal can clearly report the microparticle count, and the OCT response to the number of microparticles shows a good linearity. The detect ability of the intensity change (2.9% ± 0.5%) caused by an individual microparticle shows the high sensitivity of monitoring multiple particles using OCT. An optical sensing method based on this feasibility study is described for continuously measuring blood sugar levels in the subcutaneous tissue, and a molecular recognition unit is designed using competitive binding to modulate the number of bound microparticles as a function of glucose concentration. With further development, an ultra-small, implantable sensor might provide high specificity and sensitivity for long-term continuous monitoring of blood glucose concentration.

Optical coherence tomography for live phenotypic analysis of embryonic ocular structures in mouse models.

Mouse models of ocular diseases provide a powerful resource for exploration of molecular regulation of eye development and pre-clinical studies. Availability of a live high-resolution imaging method for mouse embryonic eyes would significantly enhance longitudinal analyses and high-throughput morphological screening. We demonstrate that optical coherence tomography (OCT) can be used for live embryonic ocular imaging throughout gestation. At all studied stages, the whole eye is within the imaging distance of the system and there is a good optical contrast between the structures. We also performed OCT eye imaging in the embryonic retinoblastoma mouse model Pax6-SV40 T-antigen, which spontaneously forms lens and retinal lesions, and demonstrate that OCT allows us to clearly differentiate between the mutant and wild type phenotypes. These results demonstrate that OCTin utero imaging is a potentially useful tool to study embryonic ocular diseases in mouse models.

ASSESSMENT OF TISSUE OPTICAL CLEARING AS A FUNCTION OF GLUCOSE CONCENTRATION USING OPTICAL COHERENCE TOMOGRAPHY.

One of the major challenges in imaging biological tissues using optical techniques, such as optical coherence tomography (OCT), is the lack of light penetration due to highly turbid structures within the tissue. Optical clearing techniques enable the biological samples to be more optically homogeneous, allowing for deeper penetration of light into the tissue. This study investigates the effect of optical clearing utilizing various concentrations of glucose solution (10%, 30%, and 50%) on porcine skin. A gold-plated mirror was imaged beneath the tissue and percentage clearing was determined by monitoring the change in reflected light intensity from the mirror over time. The ratio of percentage clearing per tissue thickness for 10%, 30% and 50% glucose was determined to be 4.7 ± 1.6% mm(-1) (n = 6), 10.6 ± 2.0% mm(-1) (n = 7) and 21.8 ± 2.2% mm(-1) (n = 5), respectively. It was concluded that while higher glucose concentration has the highest optical clearing effect, a suitable concentration should be chosen for the purpose of clearing, considering the osmotic stress on the tissue sample.

Monitoring of glucose permeability in monkey skin in vivo using Optical Coherence Tomography.

Topical trans-dermal delivery of drugs has proven to be a promising route for treatment of many dermatological diseases. The aim of this study is to monitor and quantify the permeability rate of glucose solutions in rhesus monkey skin noninvasively in vivo as a primate model for drug diffusion. A time-domain Optical Coherence Tomography (OCT) system was used to image the diffusion of glucose in the skin of anesthetized monkeys for which the permeability rate was calculated. From 5 experiments on 4 different monkeys, the permeability for glucose-20% was found to be (4.41 +/- 0.28) 10(-6) cm/sec. The results suggest that OCT might be utilized for the noninvasive study of molecular diffusion in the multilayered biological tissues in vivo.

Live imaging of blood flow in mammalian embryos using Doppler swept-source optical coherence tomography.

Studying hemodynamic changes during early mammalian embryonic development is critical for further advances in prevention, diagnostics, and treatment of congenital cardiovascular (CV) birth defects and diseases. Doppler optical coherence tomography (OCT) has been shown to provide sensitive measurements of blood flow in avian and amphibian embryos. We combined Doppler swept-source optical coherence tomography (DSS-OCT) and live mouse embryo culture to analyze blood flow dynamics in early embryos. SS-OCT structural imaging was used for the reconstruction of embryo morphology and the orientation of blood vessels, which is required for calculating flow velocity from the Doppler measurements. Spatially and temporally resolved blood flow profiles are presented for the dorsal aorta and a yolk sac vessel in a 9.5-day embryo. We demonstrate that DSS-OCT can be successfully used for structural analysis and spatially and temporally resolved hemodynamic measurements in developing early mammalian embryos.