Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-μm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

Acquisition of high-resolution images from within internal organs using endoscopic optical imaging has numerous clinical applications. However, difficulties associated with optical aberrations and the trade-off between transverse resolution and depth-of-focus significantly limit the scope of applications. Here, we integrate a metalens, with the ability to modify the phase of incident light at sub-wavelength level, into the design of an endoscopic optical coherence tomography catheter (termed nano-optic endoscope) to achieve near diffraction-limited imaging through negating non-chromatic aberrations. Remarkably, the tailored chromatic dispersion of the metalens in the context of spectral interferometry is utilized to maintain high-resolution imaging beyond the input field Rayleigh range, easing the trade-off between transverse resolution and depth-of-focus. We demonstrate endoscopic imaging both in resected human lung specimens and in sheep airways in vivo. The combination of the superior resolution and higher imaging depth-of-focus of the nano-optic endoscope will likely increase the clinical utility of endoscopic optical imaging.

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Nano-optic endoscope for high-resolution optical coherence tomography in vivo

Optical coherence tomography (OCT), a fairly new non-invasive optical real-time imaging modality, is an emergent in vivo technique, based on the interference (Michelson interferometry) of infrared radiation and living tissues, that allows high-resolution, 2- or 3-dimensional, cross-sectional visualisation of microstructural morphology of tissues. OCT provides depth-resolved images of tissues with resolution up to a few micrometers and depth up to several millimetres depending on tissue type. The investigations using OCT to assess skin structure in clinical settings started in the past decade and consequently proved that this imaging method is useful in visualizing subsurface structures of normal skin, including the epidermis, dermoepidermal junction, dermis, hair follicles, blood vessels and sweat ducts. An increasing number of papers brought evidence of the utility and the precision of OCT technology, in its different technical variants, in diagnosing and monitoring skin disorders, including malignancies and inflammatory conditions, respectively. The present comprehensive review describes and illustrates technical aspects and clinical applications of OCT methods in dermatology.

http://www.biopsypen.eu/wp-content/uploads/2014/12/Optical-coherence-tomography-in-dermatology.pdf

Optical coherence tomography in dermatology: technical and clinical aspects

https://www.europeanurology.com/article/S0302-2838(12)01144-X/pdf/ICUD-EAU+International+Consultation+on+Bladder+Cancer+2012%3A+Screening%2C+Diagnosis%2C+and+Molecular+Markers

ICUD-EAU international consultation on bladder cancer 2012: Screening, diagnosis, and molecular markers

Ultra-high resolution optical coherence tomography (OCT) imaging is demonstrated simultaneously at 840 nm and 1230 nm central wavelength using an off-the-shelf turn-key supercontinuum light source. Spectral filtering of the light source emission results in a double peak spectrum with average powers exceeding 100 mW and bandwidths exceeding 200 nm for each wavelength band. A free-space OCT setup optimized to support both wavelengths in parallel is introduced. OCT imaging of biological tissue ex vivo and in vivo is demonstrated with axial resolutions measured to be <2 µm and <4 µm at 840 nm and 1230 nm, respectively. This measuring scheme is used to extract spectroscopic features with outstanding spatial resolution enabling enhanced image contrast.

Simultaneous dual-band ultra-high resolution optical coherence tomography

Visualization of the basement membrane zone of the bladder by optical coherence tomography: feasibility of noninvasive evaluation of tumor invasion.

OBJECTIVES Imaging techniques with high resolution are evolving rapidly for medical applications and may substitute invasive diagnostic techniques. The use of ultrahigh resolution optical coherence tomography (UHR-OCT) to image healthy and morphologically altered bladder tissue with virtual histology is evaluated ex vivo to define parameters necessary for future, diagnostically relevant in vivo systems. Here, special focus is on the visualization of the basement membrane zone. METHODS Optical coherence tomography examinations were performed by using a modified commercial OCT system comprising a Ti:sapphire femtosecond laser to support an enhanced resolution of 3 m axial 10 m lateral. Tomograms of 142 fresh human bladder tissue samples from cystectomies, radical prostatectomies, and transurethral tumor resections were recorded and referenced to histologic sections using standard hematoxylin and eosin staining. RESULTS OCT of normal bladder mucosa allows for a clear differentiation of urothelium and lamina propria. The basement membrane zone is identified as a narrow, low-scattering band between these layers. This allows for reliable exclusion of invasion. Healthy urothelial tissue, carcinoma in situ, and transitional cell carcinoma can be differentiated using this imaging technique. Sensitivity of UHR-OCT for malignant bladder tissue could be determined to be 83.8%, and specificity to be 78.1%. CONCLUSIONS UHR-OCT is considered promising in the attempt to strive forfluorescence cystoscopy-guided virtual histology as a means of supporting therapeutic decisions for bladder neoplasia. UROLOGY 72: 677‐681, 2008. © 2008 Elsevier Inc.

Technology and Engineering Visualization of the Basement Membrane Zone of the Bladder by Optical Coherence Tomography: Feasibility of Noninvasive Evaluation of Tumor Invasion

An off-the-shelf turn-key supercontinuum light source based on a passively mode-locked fiber laser, a fiber amplifier and a highly nonlinear fiber is evaluated for its application in ultrahigh resolution optical coherence tomography (OCT). Two spectral bands - one red shifted and one blue shifted in reference to the wavelength of the fiber laser - are employed as low coherence sources in OCT. Usable spectral bandwidths exceed 300 nm centered either at 790 or 1340 nm, with corresponding coherence lengths of 1.2 and 2.6 μm, respectively. Optimization of the spectrum for simultaneous imaging at both spectral bands results in spectral bandwidths exceeding 200 nm for each band after filtering. A free-space OCT setup supporting the full spectral bandwidth is introduced which allows for ultrahigh resolution OCT imaging using both spectral bands simultaneously. Axial free space resolutions were measured to be less than 2 and 4 μm at 840 and 1230 nm, respectively. This approach combines ultrahigh resolution obtained at 840 nm with large penetration depths at 1230 nm. Frequency compounding of the OCT images can be used for speckle reduction while extracting spatially resolved spectroscopic features facilitates enhanced image contrast.

Ultrahigh resolution optical coherence tomography at two infrared wavelength regions using a single light source

An off-the-shelf turn-key supercontinuum light source based on a passively
 mode-locked fiber laser, a fiber amplifier and a highly nonlinear fiber is evaluated
 for its application in ultrahigh resolution optical coherence tomography (OCT). Two
 spectral bands — one red shifted and one blue shifted in reference to the
 wavelength of the fiber laser — are employed as low coherence sources in
 OCT. Usable spectral bandwidths exceed 300 nm centered either at 790 or 1340 nm,
 with corresponding coherence lengths of 1.2 and 2.6 —, respectively.
 Optimization of the spectrum for simultaneous imaging at both spectral bands results
 in spectral bandwidths exceeding 200 nm for each band after filtering. A free-space
 OCT setup supporting the full spectral bandwidth is introduced which allows for
 ultrahigh resolution OCT imaging using both spectral bands simultaneously. Axial
 free space resolutions were measured to be less than 2 and 4 μm at 840
 and 1230 nm, respectively. This approach combines ultrahigh resolution obtained at
 840 nm with large penetration depths at 1230 nm. Frequency compounding of the OCT
 images can be used for speckle reduction while extracting spatially resolved
 spectroscopic features facilitates enhanced image contrast.

Barbara Hermes

Papers

Simultaneous dual-band ultra-high resolution optical coherence tomography

Visualization of the basement membrane zone of the bladder by optical coherence tomography: feasibility of noninvasive evaluation of tumor invasion.

Technology and Engineering Visualization of the Basement Membrane Zone of the Bladder by Optical Coherence Tomography: Feasibility of Noninvasive Evaluation of Tumor Invasion

Ultrahigh resolution optical coherence tomography at two infrared wavelength regions using a single light source

Ultrahigh resolution optical coherence tomography at two infrared wavelength regions using a single light source