Computational approach for correcting defocus and suppressing speckle noise in line-field optical coherence tomography images.

The trade-off between transverse resolution and depth-of-focus (DOF) typical for optical coherence tomography (OCT) systems based on conventional optics, prevents "single-shot" acquisition of volumetric OCT images with sustained high transverse resolution over the entire imaging depth. Computational approaches for correcting defocus and higher order aberrations in OCT images developed in the past require highly stable phase data, which poses a significant technological challenge. Here, we present an alternative computational approach to sharpening OCT images and reducing speckle noise, based on intensity OCT data. The novel algorithm uses non-local priors to model correlated speckle noise within a maximum a posteriori framework to generate sharp and noise-free images. The performance of the algorithm was tested on images of plant tissue (cucumber) and in-vivo healthy human cornea, acquired with line-field spectral domain OCT (LF-SD-OCT) systems. The novel algorithm effectively suppressed speckle noise and sharpened or recovered morphological features in the OCT images for depths up to 13×DOF (depth-of-focus) relative to the focal plane.

In vivo, contactless, cellular resolution imaging of the human cornea with Powell lens based line field OCT.

Potentially blinding corneal diseases alter the morphology of the human cornea. At the early stages of disease development, these changes occur at the cellular level. The ability to visualize and quantify such changes can lead to early diagnostics of corneal pathologies, which is pivotal for the long-term preservation of vision. Here we present a Powell Lens-based Line-Field Optical Coherence Tomography system that combines high spatial resolution (2.4 µm × 2.2 µm × 1.7 µm (x × y × z)) in biological tissue, sufficient to resolve individual cells, high sensitivity (90.5 dB), sufficient to image the semi-transparent human cornea, and fast image acquisition rate (~ 2,400 fps), sufficient to suppress most involuntary eye motion artifacts and allow for contactless, in-vivo imaging of the cellular structure of the human cornea. Volumetric images acquired in-vivo from corneas of healthy subjects show epithelial, endothelial and keratocytes cells, as well as sub-basal and stromal nerves. The system's high axial resolution also allows for volumetric morphometry of the corneal endothelium, Descemet's membrane and the pre-Descemet's (Dua) layer.

In-vivo functional and structural retinal imaging using multiwavelength photoacoustic remote sensing microscopy.

Many important eye diseases as well as systemic disorders manifest themselves in the retina. Retinal imaging technologies are rapidly growing and can provide ever-increasing amounts of information about the structure, function, and molecular composition of retinal tissue in-vivo. Photoacoustic remote sensing (PARS) is a novel imaging modality based on all-optical detection of photoacoustic signals, which makes it suitable for a wide range of medical applications. In this study, PARS is applied for in-vivo imaging of the retina and estimating oxygen saturation in the retinal vasculature. To our knowledge, this is the first time that a non-contact photoacoustic imaging technique is applied for in-vivo imaging of the retina. Here, optical coherence tomography is also used as a well-established retinal imaging technique to navigate the PARS imaging beams and demonstrate the capabilities of the optical imaging setup. The system is applied for in-vivo imaging of both microanatomy and the microvasculature of the retina. The developed system has the potential to advance the understanding of the ocular environment and to help in monitoring of ophthalmic diseases.

Three-dimensional virtual histology in unprocessed resected tissues with photoacoustic remote sensing (PARS) microscopy and optical coherence tomography (OCT).

Histological images are critical in the diagnosis and treatment of cancers. Unfortunately, current methods for capturing these microscopy images require resource intensive tissue preparation that may delay diagnosis for days or weeks. To streamline this process, clinicians are limited to assessing small macroscopically representative subsets of tissues. Here, a combined photoacoustic remote sensing (PARS) microscope and swept source optical coherence tomography system designed to circumvent these diagnostic limitations is presented. The proposed multimodal microscope provides label-free three-dimensional depth resolved virtual histology visualizations, capturing nuclear and extranuclear tissue morphology directly on thick unprocessed specimens. The capabilities of the proposed method are demonstrated directly in unprocessed formalin fixed resected tissues. The first images of nuclear contrast in resected human tissues, and the first three-dimensional visualization of subsurface nuclear morphology in resected Rattus tissues, captured with a non-contact photoacoustic system are presented here. Moreover, the proposed system captures the first co-registered OCT and PARS images enabling direct histological assessment of unprocessed tissues. This work represents a vital step towards the development of a rapid histological imaging modality to circumvent the limitations of current histopathology techniques.