Non-invasive depth-resolved measurement of hemoglobin oxygen saturation (SaO2) levels in discrete blood vessels may have implications for diagnosis and treatment of various pathologies. We introduce a novel Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) for non-invasive depth-resolved measurement of SaO2 levels in a blood vessel phantom. DWP OCT SaO2 is linearly correlated with blood-gas SaO2 measurements. We demonstrate 6.3% precision in SaO2 levels measured a phantom blood vessel using DWP-OCT with 800 and 765 nm excitation wavelengths. Sources of uncertainty in SaO2 levels measured with DWP-OCT are identified and characterized.

PURPOSE. We identified candidate optical coherence tomography (OCT) markers for early glaucoma diagnosis. Time variation of retinal nerve fiber layer (RNFL) thickness, phase retardation, birefringence, and reflectance using polarization sensitive optical coherence tomography (PS-OCT) were measured in three non-human primates with induced glaucoma in one eye. We characterized time variation of RNFL thickness, phase retardation, birefringence, and reflectance with elevated intraocular pressure (IOP). METHODS.One eye of each of three non-human primates was laser treated to increase IOP. Each primate was followed for a 30-week period. PS-OCT measurements were recorded at weekly intervals. Reflectance index (RI) is introduced to characterize RNFL reflectance. Associations between elevated IOP and RNFL thickness, phase retardation, birefringence, and reflectance were characterized in seven regions (entire retina, inner and outer rings, and nasal, temporal, superior and inferior quadrants) by linear and non-linear mixed-effects models.RESULTS. Elevated IOP was achieved in three non-human primate eyes with an average increase of 13 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in the nasal region (P ¼ 0.0002), decreased RNFL phase retardation in the superior (P ¼ 0.046) and inferior (P ¼ 0.021) regions, decreased RNFL birefringence in the nasal (P ¼ 0.002) and inferior (P ¼ 0.029) regions, and loss of RNFL reflectance in the outer rings (P ¼ 0.018). When averaged over the entire retinal area, only RNFL reflectance showed a significant decrease (P ¼ 0.028).CONCLUSIONS. Of the measured parameters, decreased RNFL reflectance was the most robust correlate with glaucomatous damage. Candidate cellular mechanisms are considered for decreased RNFL reflectance, including mitochondrial dysfunction and retinal ganglion cell apoptosis. (Invest Ophthalmol Vis Sci. 2012;53:4380-4395) DOI:10.1167/iovs.11-9130 G laucoma is an optic neuropathy characterized by the progressive death of retinal ganglion cells and loss of associated axons in the retinal nerve fiber layer (RNFL). Without early diagnosis and therapeutic intervention, glaucoma eventually results in visual field abnormalities and vision loss. Studies indicate that as many as 40% of the axons may die before the visual field is affected, 1 suggesting an opportunity for the development of diagnostic tools that can prevent visual field loss in conjunction with application of neuroprotective strategies. As axons in the RNFL are lost, an associated RNFL thinning is observed. 2-4Optical coherence tomography (OCT) is an imaging modality that provides high-resolution (2-15 lm) cross-sectional images of the retina at video rate, and can quantify macroscopic changes in the optic nerve head (ONH) and RNFL. Inasmuch as previous studies have demonstrated a link between decreased RNFL thickness measured with OCT and glaucoma, 3 OCT measurements of RNFL thickness have become a routine component of glaucoma screening, diagnosis, and monitoring protocols...

Higher precision surgical devices are needed for tumor resections near critical brain structures. The goal of this study is to demonstrate feasibility of a system capable of precise and bloodless tumor ablation. An image-guided laser surgical system is presented for excision of brain tumors in vivo in a murine xenograft model. The system combines optical coherence tomography (OCT) guidance with surgical lasers for high-precision tumor ablation (Er:YAG) and microcirculation coagulation (Thulium (Tm) fiber laser). Methods: A fluorescent human glioblastoma cell line was injected into mice and allowed to grow four weeks. Craniotomies were performed and tumors were imaged with confocal fluorescence microscopy. The mice were subsequently OCT imaged prior, during and after laser coagulation and/or ablation. The prior OCT images were used to compute three-dimensional tumor margin and angiography images, which guided the coagulation and ablation steps. Histology of the treated regions was then compared to post-treatment OCT images. Results: Tumor sizing based on OCT margin detection matched histology to within experimental error. Although fluorescence microscopy imaging showed the tumors were collocated with OCT imaging, margin assessment using confocal microscopy failed to see the extent of the tumor beyond ~ 250 µm in depth, as verified by OCT and histology. The two-laser approach to surgery utilizing Tm wavelength for coagulation and Er:YAG for ablation yielded bloodless resection of tumor regions with minimal residual damage as seen in histology. Conclusion: Precise and bloodless tumor resection under OCT image guidance is demonstrated in the murine xenograft brain cancer model. Tumor margins and vasculature are accurately made visible without need for exogenous contrast agents.

We report on a fibre-based forward-imaging swept-source optical coherence tomography system using a high-reflectivity two-axis microelectromechanical scanning mirror for high-speed 3D in vivo visualization of cellular-scale architecture of biological specimens. The scanning micromirrors, based on electrostatic staggered vertical comb drive actuators, can provide ±9 • of optical deflection on both rotation axes and uniform reflectivity of greater than 90% over the range of imaging wavelengths (1260-1360 nm), allowing for imaging turbid samples with good signal-to-noise ratio. The wavelength-swept laser, scanning over 100 nm spectrum at 20 kHz rate, enables fast image acquisition at 10.2 million voxels s −1 (for 3D imaging) or 40 frames s −1 (for 2D imaging with 500 transverse pixels per image) with 8.6 μm axial resolution. Lateral resolution of 12.5 μm over 3 mm field of view in each lateral direction is obtained using ZEMAX optical simulations for the lateral beam scanning system across the scanning angle range of the 500 μm × 700 μm micromirror. We successfully acquired en face and tomographic images of rigid structures (scanning micromirror), in vitro biological samples (onion peels and pickle slices) and in vivo images of human epidermis over 2 × 1 × 4 mm 3 imaging volume in real time at faster-than-video 2D frame rates. The results indicate that our system framework may be suitable for image-guided minimally invasive examination of various diseased tissues.

A Swept Source Polarization-Sensitive Optical Coherence Tomography (SS-PS-OCT) instrument has been designed, constructed, and verified to provide high sensitivity depth-resolved birefringence and phase retardation measurements of the retinal nerve fiber layer. The swept-source laser had a center wavelength of 1059 nm, a full-width-half-max spectral bandwidth of 58 nm and an A-line scan rate of 34 KHz. Power incident on the cornea was 440 µW and measured axial resolution was 17 µm in air. A multiple polarization state nonlinear fitting algorithm was used to measure retinal birefringence with low uncertainty. Maps of RNFL phase retardation in a subject measured with SS-PS-OCT compare well with those generated using a commercial scanning laser polarimetry instrument. Peak-to-valley variation of RNFL birefringence given here is less than values previously reported at 840nm.

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Microvasculature hemoglobin oxygen saturation (SaO2) is important in the progression of various pathologies. Non-invasive depth-resolved measurement of SaO2 levels in tissue microvasculature has the potential to provide early biomarkers and a better understanding of the pathophysiological processes allowing improved diagnostics and prediction of disease progression. We report proof-of-concept in vivo depth-resolved measurement of SaO2 levels in selected 30 µm diameter arterioles in the murine brain using Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) with 800 nm and 770 nm photothermal excitation wavelengths. Depth location of back-reflected light from a target arteriole was confirmed using Doppler and speckle contrast OCT images. SaO2 measured in a murine arteriole with DWP-OCT is linearly correlated (R2=0.98) with systemic SaO2 values recorded by a pulse-oximeter. DWP-OCT are steadily lower (10.1%) than systemic SaO2 values except during pure oxygen breathing. DWP-OCT is insensitive to OCT intensity variations and is a candidate approach for in vivo depth-resolved quantitative imaging of microvascular SaO2 levels.

Selective laser sintering (SLS) is an efficient process in additive manufacturing that enables rapid part production from computer-based designs. However, SLS is limited by its notable lack of in-situ process monitoring when compared to other manufacturing processes. We report the incorporation of optical coherence tomography into an SLS system in detail and demonstrate access to surface and sub-surface features. Video frame rate cross-sectional imaging reveals areas of sintering uniformity and areas of excessive heat error with high temporal resolution. We propose a set of image processing techniques for SLS process monitoring with OCT and report the limitations and obstacles for further OCT integration with SLS systems.