Preclinical longitudinal imaging of tumor microvascular radiobiological response with functional optical coherence tomography.

Radiation therapy (RT) is widely used for cancer treatment, alone or in combination with other therapies. Recent RT advances have revived interest in delivering higher dose in fewer fractions, which may invoke both cellular and microvascular damage mechanisms. Microvasculature may thus be a potentially sensitive functional biomarker of RT early response, especially for such emerging RT treatments. However it is difficult to measure directly and non-invasively, and its time course, dose dependencies, and overall importance in tumor control are unclear. We use functional optical coherence tomography for quantitative longitudinal in vivo imaging in preclinical models of human tumor xenografts subjected to 10, 20 and 30 Gy doses, furnishing a detailed assessment of vascular remodeling following RT. Immediate (minutes to tens of minutes) and early (days to weeks) RT responses of microvascular supply, as well as tumor volume and fluorescence intensity, were quantified and demonstrated robust and complex temporal dose-dependent behaviors. The findings were compared to theoretical models proposed in the literature.

K-distribution three-dimensional mapping of biological tissues in optical coherence tomography.

Probability density function (PDF) analysis with K-distribution model of optical coherence tomography (OCT) intensity signals has previously yielded a good representation of the average number of scatterers in a coherence volume for microspheres-in-water systems, and has shown initial promise for biological tissue characterization. In this work, we extend these previous findings, based on single point M-mode or two-dimenstional slice analysis, to full three-dimensional (3D) imaging maps of the shape parameter α of the K-distribution PDF. After selecting a suitably sized 3D evaluation window, and verifying methodology in phantoms, the resultant parametric α images obtained in different animal tissues (rat liver and brain) show new contrasting ability not seen in conventional OCT intensity images.

Analysis of scattering statistics and governing distribution functions in optical coherence tomography.

The probability density function (PDF) of light scattering intensity can be used to characterize the scattering medium. We have recently shown that in optical coherence tomography (OCT), a PDF formalism can be sensitive to the number of scatterers in the probed scattering volume and can be represented by the K-distribution, a functional descriptor for non-Gaussian scattering statistics. Expanding on this initial finding, here we examine polystyrene microsphere phantoms with different sphere sizes and concentrations, and also human skin and fingernail in vivo. It is demonstrated that the K-distribution offers an accurate representation for the measured OCT PDFs. The behavior of the shape parameter of K-distribution that best fits the OCT scattering results is investigated in detail, and the applicability of this methodology for biological tissue characterization is demonstrated and discussed.

Probability density function formalism for optical coherence tomography signal analysis: a controlled phantom study.

The distribution of backscattered intensities as described by the probability density function (PDF) of tissue-scattered light contains information that may be useful for tissue assessment and diagnosis, including characterization of its pathology. In this Letter, we examine the PDF description of the light scattering statistics in a well characterized tissue-like particulate medium using optical coherence tomography (OCT). It is shown that for low scatterer density, the governing statistics depart considerably from a Gaussian description and follow the K distribution for both OCT amplitude and intensity. The PDF formalism is shown to be independent of the scatterer flow conditions; this is expected from theory, and suggests robustness and motion independence of the OCT amplitude (and OCT intensity) PDF metrics in the context of potential biomedical applications.

Automated Identification and Quantification of Subretinal Fibrosis in Neovascular Age-Related Macular Degeneration Using Polarization-Sensitive OCT.

PURPOSE: To identify and quantify subretinal fibrosis in eyes with advanced neovascular age-related macular degeneration (nAMD) using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: Eyes of patients with subretinal fibrosis secondary to nAMD were included in this case series. All patients underwent a complete ophthalmic examination to clearly identify advanced nAMD lesions with fibrosis. Examinations of PS-OCT were performed using a novel system with an integrated eye tracker. Areas of fibrosis in PS-OCT, automatically segmented using a custom-built algorithm, were compared with conventional imaging modalities including spectral-domain OCT, fluorescein angiography, and color fundus photography in their potential to visualize fibrosis in nAMD. RESULTS: Fifteen eyes of 15 consecutive patients were included. In polarization-sensitive OCT B-scans, a distinct "column-like" pattern was observed in averaged axis orientation images. En face analysis provided a precise mapping of the fibrotic scar component. Fibrous tissue was selectively identified by PS-OCT based on birefringence in all lesions, whereas in SD-OCT, subretinal hyperreflective material (SHRM) could not be further classified into scar tissue, fibrovascular material, or other AMD-specific material. Based on simultaneous polarization analyses in PS-OCT, the level of RPE alteration could be evaluated as well, showing thinning and loss of RPE associated with subretinal fibrosis. CONCLUSIONS: Using PS-OCT, subretinal fibrosis can be identified as an intrinsically birefringent structure and can be segmented based solely on tissue-specific contrast. Polarization-sensitive OCT offers a unique method to identify clinically relevant components of SHRM (i.e., neovascular tissue versus fibrous tissue) and therefore allows for an optimized disease management and evaluation of therapeutic strategies.

Retinal nerve fiber bundle tracing and analysis in human eye by polarization sensitive OCT.

We present a new semi-automatic processing method for retinal nerve fiber bundle tracing based on polarization sensitive optical coherence tomography (PS-OCT) data sets. The method for tracing is based on a nerve fiber orientation map that covers the fovea and optic nerve head (ONH) regions. In order to generate the orientation map, two types of information are used: optic axis orientation based on polarization data, and complementary information obtained from nerve fiber layer (NFL) local thickness variation to reveal fiber bundle structures around the fovea. The corresponding two orientation maps are fused into a combined fiber orientation map. En face maps of NFL retardation, thickness, and unit-depth-retardation (UDR, equivalent to birefringence) are transformed into "along-trace" maps by using the obtained traces of the nerve fiber bundles. The method is demonstrated in the eyes of healthy volunteers, and as an example of further analyses utilizing this method, maps illustrating the gradients of NFL retardation, thickness, and UDR are demonstrated.

Analysis of optimum conditions of depolarization imaging by polarization-sensitive optical coherence tomography in the human retina.

Measurement and imaging of depolarization by polarization-sensitive optical coherence tomography (PS-OCT) requires averaging of Stokes vector elements within two- or three-dimensional (3-D) evaluation windows to obtain the degree of polarization uniformity (DOPU). By use of a PS-OCT system with an integrated retinal tracker, we analyze optimum conditions for depolarization imaging, data processing, and segmentation of depolarizing tissue in the human retina. The trade-offs between figures of merit like DOPU imaging sensitivity, efficiency, and susceptibility are evaluated in terms of 3-D resolution. The results are used for a new, detailed interpretation of PS-OCT high-resolution images of the human retinal pigment epithelium and Bruch's membrane.

Motion artifact and speckle noise reduction in polarization sensitive optical coherence tomography by retinal tracking.

We present a novel polarization sensitive optical coherence tomography (PS-OCT) system with an integrated retinal tracker. The tracking operates at up to 60 Hz, correcting PS-OCT scanning positions during the acquisition to avoid artifacts caused by eye motion. To demonstrate the practical performance of the system, we imaged several healthy volunteers and patients with AMD both with B-scan repetitions for frame averaging and with 3D raster scans. Under large retinal motions with up to 1 mm amplitude at 0.5 ~a few Hz frequency range, motion artifact suppression in the PS-OCT images as well as standard deviation noise reduction in the frame averaged retardation images are presented.