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Register a new userLarge Field, High Resolution Full Field Optical Coherence Tomography: A Pre-clinical study of human breast tissue and cancer assessment
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Osnath Assayag
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We present a benchmark pilot study in which high-resolution Full-Field Optical Coherence Tomography (FF-OCT) is used to image human breast tissue and is evaluated to assess its ability to aid the pathologists management of intra-operative diagnoses. Our aim included evaluating the safety of FF-OCT on human tissue and determining the concordance between the images obtained with routinely prepared histopathological material. The compact device used for this study provides a 2 {mu}m-lateral and a 1 {mu}m-axial resolution, and is able to scan a 1.5cm^2 specimen in about 7 minutes. 75 breast specimens obtained from 22 patients have been imaged. Because the contrast in the images is generated by endogenous tissue components, no biological, contrast agents or specimen preparation is required. We characterized the major architectural features and tissue structures of benign breast tissue, including adipocytes, fibrous stroma, lobules and ducts. We subsequently characterized features resulting from their pathological modification and developed a decision tree for diagnosis. Two breast pathologists applied these criteria, resulting in a demonstrable ability to distinguish between normal or benign tissue, in situ and invasive carcinomas using FF-OCT images, with a sensitivity of 97% and 90%, respectively, and specificity of 74% and 77% respectfully. FF-OCT shows great potential for the evaluation of human tissue and its characterization as normal/benign vs. lesional, for numerous ex-vivo clinical use-cases. Its high imaging accuracy for in-situ and invasive carcinoma paves the way for applications where a fast architectural assessment could improve the core needle biopsy workflow, tumor margin assessments, and provides quality assurance for tissue acquired for clinical care and research.
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The potential for improving the penetration depth of optical coherence tomography systems by using increasingly longer wavelength light sources has been known since the inception of the technique in the early 1990s. Nevertheless, the development of mid-infrared optical coherence tomography has long been challenged by the maturity and fidelity of optical components in this spectral region, resulting in slow acquisition, low sensitivity, and poor axial resolution. In this work, a mid-infrared spectral-domain optical coherence tomography system operating at 4 micron central wavelength with an axial resolution of 8.6 microns is demonstrated. The system produces 2D cross-sectional images in real-time enabled by a high-brightness 0.9-4.7 micron mid-infrared supercontinuum source with 1 MHz pulse repetition rate for illumination and broadband upconversion of more than 1 micron bandwidth from 3.58-4.63 microns to 820-865 nm, where a standard 800 nm spectrometer can be used for fast detection. Images produced by the mid-infrared system are compared with those delivered by a state-of-the-art ultra-high-resolution near-infrared optical coherence tomography system operating at 1.3 {mu}m, and the potential applications and samples suited for this technology are discussed. In doing so, the first practical mid-infrared optical coherence tomography system is demonstrated, with immediate applications in real-time non-destructive testing for the inspection of defects and thickness measurements in samples that are too highly scattering at shorter wavelengths.
We report on Mid-infrared (MIR) OCT at 4 $mu$m based on collinear sum-frequency upconversion and promote the A-scan scan rate to 3 kHz. We demonstrate the increased imaging speed for two spectral realizations, one providing an axial resolution of 8.6 $mu$m, and one providing a record axial resolution of 5.8 $mu$m. Image performance is evaluated by sub-surface micro-mapping of a plastic glove and real-time monitoring of CO$_2$ in parallel with OCT imaging.
Optical coherence tomography angiography (OCTA) has been established as a powerful tool for investigating vascular diseases and is expected to become a standard of care technology. However, its widespread clinical usage is hindered by technical gaps such as limited field of view (FOV), lack of quantitative flow information, and suboptimal motion correction. Here we report a new imaging platform, termed spectrally extended line field (SELF) OCTA that provides advanced solutions to the above-mentioned challenges. SELF-OCTA breaks the speed limitations and achieves two-fold gain in FOV without sacrificing signal strength through parallel image acquisition. Towards quantitative angiography, the frequency flow imaging mechanism overcomes the imaging speed bottleneck by obviating the requirement for superfluous B-scans. In addition, the frequency flow imaging mechanism facilitates OCTA-data based motion tracking with overlap between adjacent line fields. Since it can be implemented in any existing OCT device without significant hardware modification or affecting existing functions, we expect that SELF-OCTA will make non-invasive, wide field, quantitative, and low-cost angiographic imaging available to larger patient populations.
Optical coherence tomography (OCT) is a high-resolution three-dimensional imaging technique that enables non-destructive measurements of surface and subsurface microstructures. Recent developments of OCT operating in the mid-infrared (MIR) range (around 4 {mu}m) lifted fundamental scattering limitations and initiated applied material research in formerly inaccessible fields. The MIR spectral region, however, is also of great interest for spectroscopy and hyperspectral imaging, which allow highly selective and sensitive chemical studies of materials. In this contribution, we introduce an OCT system (dual-band, central wavelengths of 2 {mu}m m and 4 {mu}m) combined with MIR spectroscopy that is implemented as a raster scanning chemical imaging modality. The fully-integrated and cost-effective optical instrument is based on a single supercontinuum laser source (emission spectrum spanning from 1.1 {mu}m to 4.4 {mu}m). Capabilities of the in-situ correlative measurements are experimentally demonstrated by obtaining complex multidimensional material data, comprising morphological and chemical information, from a multi-layered composite ceramic-polymer specimen.
In X-ray imaging, photons are transmitted through and absorbed by the subject, but are also scattered in significant quantities. Previous attempts to use scattered photons for biological imaging used pencil or fan beam illumination. Here we present 3D X-ray Scatter Tomography using full-field illumination. Synchrotron imaging experiments were performed of a phantom and the chest of a juvenile rat. Transmitted and scattered photons were simultaneously imaged with separate cameras; a scientific camera directly downstream of the sample stage, and a pixelated detector with a pinhole imaging system placed at 45${}^circ$ to the beam axis. We obtained scatter tomogram feature fidelity sufficient for segmentation of the lung and major airways in the rat. The image contrast in scatter tomogram slices approached that of transmission imaging, indicating robustness to the amount of multiple scattering present in our case. This opens the possibility of augmenting full-field 2D imaging systems with additional scatter detectors to obtain complementary modes or to improve the fidelity of existing images without additional dose, potentially leading to single-shot or reduced-angle tomography or overall dose reduction for live animal studies.
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