Metasurfaces possess vast potential for flexible beam shaping with reduced physical footprint compared to traditional refractive bulk optics. Such devices have the potential to revolutionize catheter-based biomedical imaging modalities such as optical coherence tomography (OCT) by enabling smaller catheter designs with enhanced performance and functionality compared to traditional ball lens or GRIN based designs. Previously our group demonstrated the first-ever integration of a metalens into a fully functioning OCT catheter. Here we present the continuation of that work, discussing refinements in both design and fabrication, and our overall efforts to develop metalens catheters as a complete replacement for traditional design.
Metasurfaces possess vast potential for flexible beam shaping with reduced physical footprint compared to traditional refractive bulk optics. In our group we have recently investigated two applications for metasurfaces in optical coherence tomography (OCT): a compact metalens possessing wavefront shaping properties significantly improved over lens designs typically employed in endoscopic OCT; and a metasurface design in which the separation of the illumination and collection channels allows a narrow point spread function to be maintained over a large depth range. In this work we show OCT results obtained using these metasurfaces and discuss the future role of metasurfaces in endoscopic OCT.
Polarization sensitive imaging can reveal the arrangement of tissue constituents without the need for resolving power necessary to directly visualize them. Several clinical applications for diseases in the pulmonary tract and the coronary artery can benefit from such capability. Unfortunately, robust and reliable endoscopic polarimetry is plagued by the unpredictability of the polarization state of light delivered to and collected from tissue through fiber optic catheters. We propose a nano-optic endoscope that uses polarization-sensitive metalenses to deliver and collection light of known polarization states to and from tissue, enabling measurement of tissue retardation and optic axis unambiguously.
Diagnosis of peripheral lung nodules through transbronchial biopsy is highly prone to sampling errors due to the inability of current techniques to accurately locate and/or sample lesions. Volumetric optical imaging techniques such as optical coherence tomography (OCT) have the potential to address this issue, however, current imaging catheter designs cannot achieve sufficiently high-resolution, or diffraction-limited imaging; focusing elements bear spherical aberrations and multilayered structures with asymmetric curvatures in the optical path cause astigmatism. In this work, we propose a new class of optical imaging catheters – termed nano-optic endoscope – that use metalenses to achieve diffraction-limited endoscopic imaging at greatly extended depth-of-focus through negating non-chromatic aberrations and chromatic dispersion engineering. A metalens consists of a 2-dimentional array of subwavelength-spaced scatterers with specific geometric parameters and distribution that locally shift the phase of the incident light and modify its wavefront. The metalens ability to arbitrarily and accurately modify the phase allows the nano-optic endoscope to overcome spherical aberrations and astigmatism. 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, overcoming the compromise between transverse resolution and depth-of-focus. Endoscopic imaging is demonstrated ex vivo in resected human airway specimens and in vivo in sheep airways. Fine pathology such as irregular glandular pattern, the hallmark of adenocarcinoma, is readily visualized in high-resolution images captured by the nano-optic endoscope. The versatility and design flexibility of the nano-optic endoscope significantly elevate endoscopic imaging capabilities that will likely impact clinical applications.
Acquisition of high-resolution images from within internal organs using endoscopic optical imaging has several clinical applications. In particular, endoscopic optical coherence tomography (OCT) capable of visualizing tissue microstructures is emerging as a promising tool for detection, diagnosis, and monitoring of disease in luminal organs. However, difficulties associated with optical aberrations and the trade-off between transverse resolution and depth-of-focus significantly limits the scope of applications. This work presents a new class of optical imaging catheters termed nano-optic endoscopes that address the difficulties associated with current endoscopic imaging catheters. We incorporate a metalens with the ability to modify the phase of incident light at sub-wavelength level into the design of an OCT catheter to achieve near diffraction-limited imaging through negating non-chromatic aberrations. A metalens consists of a 2-dimentional array of subwavelength-spaced scatterers with specific geometric parameters and distribution that locally shift the phase of the incident light and modify its wavefront. The metalens ability to arbitrarily and accurately modify the phase allows the nano-optic endoscope to overcome spherical aberrations and astigmatism, the essential barriers to diffraction-limited imaging. 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, overcoming the compromise between transverse resolution and depth-of-focus. Endoscopic imaging is demonstrated in resected human and swine airway specimens and in sheep airways in vivo. The versatility and design flexibility of the nano-optic endoscope significantly elevate endoscopic imaging capabilities that will likely impact clinical applications.
KEYWORDS: Motion models, Modeling and simulation, Nonuniformity corrections, Optical coherence tomography, In vivo imaging, Endoscopy, 3D image processing, Image registration, Imaging systems, Data acquisition
A model for motion artifacts for 3D/2D rotational catheter data and a motion correction method called azimuthal en face image registration is presented. Qualitative and quantitative evaluations of the method are analysed on optical coherence tomography (OCT) and AFI images.
We present a method for the correction of motion artifacts present in two- and three-dimensional in vivo endoscopic images produced by rotary-pullback catheters. This method can correct for cardiac/breathing-based motion artifacts and catheter-based motion artifacts such as nonuniform rotational distortion (NURD). This method assumes that en face tissue imaging contains slowly varying structures that are roughly parallel to the pullback axis. The method reduces motion artifacts using a dynamic time warping solution through a cost matrix that measures similarities between adjacent frames in en face images. We optimize and demonstrate the suitability of this method using a real and simulated NURD phantom and in vivo endoscopic pulmonary optical coherence tomography and autofluorescence images. Qualitative and quantitative evaluations of the method show an enhancement of the image quality.
Abstract: Optical coherence tomography (OCT) provides in vivo imaging with near-histologic resolution of tissue morphology. OCT has been successfully employed in clinical practice in non-pulmonary fields of medicine such as ophthalmology and cardiology. Studies suggest that OCT has the potential to be a powerful tool for the detection and localization of malignant and non-malignant pulmonary diseases. The combination of OCT with autofluorescence imaging (AFI) provides valuable information about the structural and metabolic state of tissues. Successful application of OCT or OCT-AFI to the field of pulmonary medicine requires overcoming several challenges. This work address those associated with motion: cardiac cycle, breathing and non-uniform rotation distortion (NURD) artifacts. Mechanically rotated endoscopic probes often suffer from image degradation due to NURD. In addition cardiac and breathing motion artifacts may be present in-vivo that are not seen ex-vivo. These motion artifacts can be problematic in OCT-AFI systems with slower acquisition rates and have been observed to generate identifiable prominent artifacts which make confident interpretation of observed structures (blood vessels, etc) difficult. Understanding and correcting motion artifact could improve the image quality and interpretation. In this work, the motion artifacts in pulmonary OCT-AFI data sets are estimated in both AFI and OCT images using a locally adaptive registration algorithm that can be used to correct/reduce such artifacts. Performance of the algorithm is evaluated on images of a NURD phantom and on in-vivo OCT-AFI datasets of peripheral lung airways.
Peripheral lung nodules found by CT-scans are difficult to localize and biopsy bronchoscopically particularly for those ≤ 2 cm in diameter. In this work, we present the results of endoscopic co-registered optical coherence tomography and autofluorescence imaging (OCT-AFI) of normal and abnormal peripheral airways from 40 patients using 0.9 mm diameter fiber optic rotary pullback catheter. Optical coherence tomography (OCT) can visualize detailed airway morphology endoscopically in the lung periphery. Autofluorescence imaging (AFI) can visualize fluorescing tissue components such as collagen and elastin, enabling the detection of airway lesions with high sensitivity. Results indicate that AFI of abnormal airways is different from that of normal airways, suggesting that AFI can provide a sensitive visual presentation for rapidly identifying possible sites of pulmonary nodules. AFI can also rapidly visualize in vivo vascular networks using fast scanning parameters resulting in vascular-sensitive imaging with less breathing/cardiac motion artifacts compared to Doppler OCT imaging. It is known that tumor vasculature is structurally and functionally different from normal vessels. Thus, AFI can be potentially used for differentiating normal and abnormal lung vasculature for studying vascular remodeling.
In this work, we present multimodal imaging of peripheral airways in vivo using an endoscopic imaging system capable of co-registered optical coherence tomography and autofluorescence imaging (OCT-AFI). This system employs a 0.9 mm diameter double-clad fiber optic-based catheter for endoscopic imaging of small peripheral airways. Optical coherence tomography (OCT) can visualize detailed airway morphology in the lung periphery and autofluorescence imaging (AFI) can visualize fluorescent tissue components such as collagen and elastin, improving the detection of airway lesions. Results from in vivo imaging of 40 patients indicate that OCT and AFI offer complementary information that may increase the ability to identify pulmonary nodules in the lung periphery and improve the safety of biopsy collection by identifying large blood vessels. AFI can rapidly visualize in vivo vascular networks using fast scanning parameters resulting in vascular-sensitive imaging with less breathing/cardiac motion artifacts compared to Doppler OCT imaging. By providing complementary information about structure and function of tissue, OCT-AFI may improve site selection during biopsy collection in the lung periphery.
Endoscopic catheter-based imaging systems that employ a 2-dimensional rotary or 3-dimensional rotary-pullback scanning mechanism require constant angular velocity at the distal tip to ensure correct angular registration of the collected signal. Non-uniform rotational distortion (NURD) – often present due to a variety of mechanical issues – can result in inconsistent position and velocity profiles at the tip, limiting the accuracy of any measurements. Since artifacts like NURD are difficult to identify and characterize during tissue imaging, phantoms with well-defined patterns have been used to quantify position and/or velocity error. In this work we present a fast, versatile, and cost-effective method for making fused deposition modeling 3D printed phantoms for identifying and quantifying NURD errors along an arbitrary user-defined pullback path. Eight evenly-spaced features are present at the same orientation at all points on the path such that deviations from expected geometry can be quantified for the imaging catheter. The features are printed vertically and then folded together around the path to avoid issues with printer head resolution. This method can be adapted for probes of various diameters and for complex imaging paths with multiple bends. We demonstrate imaging using the 3D printed phantoms with a 1mm diameter rotary-pullback OCT catheter and system as a means of objectively evaluating the mechanical performance of similarly constructed probes.
Diagnosis of peripheral lung nodules is challenging because they are rarely visualized endobronchially. Imaging
techniques such as endobronchial ultrasound (EBUS) are employed to improve tumor localization. The current EBUS
probe provides limited nodule characterization and has an outer diameter of 1.4 mm that restricts access to small
peripheral airways. We report a novel co-registered autofluoresence Doppler optical coherence tomography (AF/DOCT)
system with a 0.9 mm diameter probe to characterize peripheral lung nodules prior to biopsy in vivo.
Method: Patients referred for evaluation of peripheral lung nodules underwent bronchoscopy with examination of
standard EBUS and the novel AF/DOCT system. The lesion of interest was first identified with EBUS and then imaged
with the AF/DOCT system. The abnormal area was biopsied. AF/DOCT images of pathology proved lung malignancies
were reviewed by a panel of a pathologist, respirologists, and AF/DOCT experts.
Results: Eleven patients with biopsy proven lung cancer underwent examination with AF/DOCT. The majority of the
cancers were adenocarcinoma. AF/DOCT images were obtained in all patients. There were no complications to the
procedures. Lung abnormalities visualized in AF/ OCT images were observed in 11 cases. In one case large blood
vessels were identified and biopsy was avoided.
Conclusion: In this pilot study, AF/DOCT obtained high quality images of peripheral pulmonary nodules. The present
study supports the safety and feasibility of AF/DOCT for the evaluation of lung cancer. The addition of Doppler
information may improve biopsy site selection and reduce hemorrhage.
Polarization Sensitive Optical Coherence Tomography (PSOCT) is a functional extension of Optical Coherence
Tomography (OCT) that is sensitive to well-structured, birefringent tissue such as scars, smooth muscle and cartilage. In
this work, we present a novel completely fiber based swept source PSOCT system using a fiber-optic rotary pullback
catheter. This PSOCT implementation uses only passive optical components and requires no calibration while adding
minimal additional cost to a standard structural OCT imaging system. Due to its complete fiber construction, the system
can be made compact and robust, while the fiber-optic catheter allows access to most endoscopic imaging sites. The
1.5mm diameter endoscopic probe can capture 100 frames per second at pullback speeds up to 15 mm/s allowing rapid
traversal of large imaging fields. We validate the PSOCT system with known birefringent tissues and demonstrate in vivo
PSOCT imaging of human oral scar tissue.
Autofluorescence (AF) imaging can provide valuable information about the structural and metabolic state of tissue that can be useful for elucidating physiological and pathological processes. Optical coherence tomography (OCT) provides high resolution detailed information about tissue morphology. We present coregistered AF-OCT imaging of human lung sections. Adjacent hematoxylin and eosin stained histological sections are used to identify tissue structures observed in the OCT images. Segmentation of these structures in the OCT images allowed determination of relative AF intensities of human lung components. Since the AF imaging was performed on tissue sections perpendicular to the airway axis, the results show the AF signal originating from the airway wall components free from the effects of scattering and absorption by overlying layers as is the case during endoscopic imaging. Cartilage and dense connective tissue (DCT) are found to be the dominant fluorescing components with the average cartilage AF intensity about four times greater than that of DCT. The epithelium, lamina propria, and loose connective tissue near basement membrane generate an order of magnitude smaller AF signal than the cartilage fluorescence.
Autofluorescence (AF) imaging provides valuable information about the structural and chemical states of tissue that can be used for early cancer detection. Optical scattering and absorption of excitation and emission light by the epithelium can significantly affect observed tissue AF intensity. Determining the effect of epithelial attenuation on the AF intensity could lead to a more accurate interpretation of AF intensity. We propose to use optical coherence tomography coregistered with AF imaging to characterize the AF attenuation due to the epithelium. We present imaging results from three vital tissue models, each consisting of a three-dimensional tissue culture grown from one of three epithelial cell lines (HCT116, OVCAR8, and MCF7) and immobilized on a fluorescence substrate. The AF loss profiles in the tissue layer show two different regimes, each approximately linearly decreasing with thickness. For thin cell cultures (<300 μm ), the AF signal changes as AF(t)/AF(0)=1−1.3t (t is the thickness in millimeter). For thick cell cultures (>400 μm ), the AF loss profiles have different intercepts but similar slopes. The data presented here can be used to estimate AF loss due to a change in the epithelial layer thickness and potentially to reduce AF bronchoscopy false positives due to inflammation and non-neoplastic epithelial thickening.
In this paper, we conduct a phantom study for modeling the autofluorescence (AF) properties of tissue. A combined optical coherence tomography (OCT) and AF imaging system is proposed to measure the strength of the AF signal in terms of the scattering layer thickness and concentration. The combined AF-OCT system is capable of estimating the AF loss due to scattering in the epithelium using the thickness and scattering concentration calculated from the co-registered OCT images. We define a correction factor to account for scattering losses in the epithelium and calculate a scatteringcorrected AF signal. We believe the scattering-corrected AF will reduce the diagnostic false-positives rate in the early detection of airway lesions due to confounding factors such as increased epithelial thickness and inflammations.
In this paper, we review recent progress towards efficient and versatile waveguides and
transmission lines for terahertz applications. Terahertz waveguides are compared in terms of loss
and coupling efficiency. Different loss mechanisms and fundamental limits are treated. We also
propose a slot-line structure suitable for terahertz frequencies.
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