Origins of subdiffractional contrast in optical coherence tomography.

We demonstrate that OCT images quantify subdiffractional tissue structure. Optical coherence tomography (OCT) measures stratified tissue morphology with spatial resolution limited by the temporal coherence length. Spectroscopic OCT processing, on the other hand, has enabled nanoscale sensitive analysis, presenting an unexplored question: how does subdiffractional information get folded into the OCT image and how does one best analyze to allow for unambiguous quantification of ultrastructure? We first develop an FDTD simulation to model spectral domain OCT with nanometer resolution. Using this, we validate an analytical relationship between the sample statistics through the power spectral density (PSD) of refractive index fluctuations and three measurable quantities (image mean, image variance, and spectral slope), and have found that each probes different aspects of the PSD (amplitude, integral and slope, respectively). Finally, we found that only the spectral slope, quantifying mass scaling, is monotonic with the sample autocorrelation shape.

Spectral contrast optical coherence tomography angiography enables single-scan vessel imaging.

Optical coherence tomography angiography relies on motion for contrast and requires at least two data acquisitions per pointwise scanning location. We present a method termed spectral contrast optical coherence tomography angiography using visible light that relies on the spectral signatures of blood for angiography from a single scan using endogenous contrast. We demonstrate the molecular sensitivity of this method, which enables lymphatic vessel, blood, and tissue discrimination.

In vivo broadband visible light optical coherence tomography probe enables inverse spectroscopic analysis.

We report the design and characterization of a 6 mm outer diameter pull-back circumferential scanning visible optical coherence tomography probe. The probe's large visible bandwidth (500-695 nm) allowed for inverse spectroscopic analysis and an axial resolution of ∼1.1 µm in tissue. We verify spectral imaging capabilities by measuring microsphere backscattering spectra and demonstrate in vivo spatial nanoscale characterization of tissue.

Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography.

Measuring capillary oxygenation and the surrounding ultrastructure can allow one to monitor a microvascular niche and better understand crucial biological mechanisms. However, capillary oximetry and pericapillary ultrastructure are challenging to measure in vivo. Here we demonstrate a novel optical imaging system, dual-band dual-scan inverse spectroscopic optical coherence tomography (D2-ISOCT), that, for the first time, can simultaneously obtain the following metrics in vivo using endogenous contrast: (1) capillary-level oxygen saturation and arteriolar-level blood flow rates, oxygen delivery rates, and oxygen metabolic rates; (2) spatial characteristics of tissue structures at length scales down to 30 nm; and (3) morphological images up to 2 mm in depth. To illustrate the capabilities of D2-ISOCT, we monitored alterations to capillaries and the surrounding pericapillary tissue (tissue between the capillaries) in the healing response of a mouse ear wound model. The obtained microvascular and ultrastructural metrics corroborated well with each other, showing the promise of D2-ISOCT for becoming a powerful new non-invasive imaging tool.