血管内光学相干层析成像技术在冠状动脉粥样硬化斑块检测方面的应用

血管内光学相干层析成像(IVOCT)技术近年来在冠状动脉粥样硬化斑块检测方面发展非常迅速,可实现血管内病变组织高分辨率、无辐射、实时在体成像,在临床诊断方面发挥了重要的作用.本文简要介绍了IVOCT的成像原理、生物组织光学特征参数以及色散系数的计算方法,并对动脉粥样硬化斑块的机器学习算法进行了概述,为构建斑块的智能识别...     

Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles

The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P<0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P<0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques.     

Intravascular atherosclerotic imaging with combined fluorescence and optical coherence tomography probe based on a double-clad fiber combiner

We developed a multimodality fluorescence and optical coherence tomography probe based on a double-clad fiber (DCF) combiner. The probe is composed of a DCF combiner, grin lens, and micromotor in the distal end. An integrated swept-source optical coherence tomography and fluorescence intensity imaging system was developed based on the combined probe for the early diagnoses of atherosclerosis. This system is capable of real-time data acquisition and processing as well as image display. For fluorescence imaging, the inflammation of atherosclerosis and necrotic core formed with the annexin V-conjugated Cy5.5 were imaged. Ex vivo imaging of New Zealand white rabbit arteries demonstrated the capability of the combined system.     

Dental optical coherence tomography: new potential diagnostic system for cracked-tooth syndrome

Purpose

The aim of the present study was to determine the reliability of optical coherence tomography (OCT) in detecting cracked teeth and its relative clinical effectiveness by comparing it with other diagnostic methods including conventional visual inspection, trans-illumination, and micro-computed tomography (micro-CT).

Methods

The reliability of swept source OCT (SS-OCT) was verified by comparing the number of detected crack lines on 109 surfaces of 61 teeth with those detected with other conventional methods.

Results

One to one comparison revealed that crack lines that were invisible with naked eyes could be found in SS-OCT images. The detection ability of SS-OCT was superior or similar to those of micro-CT (100.0 %) and trans-illumination.

Conclusions

Crack lines shown in the SS-OCT images had distinct characteristics, and structural crack lines and craze lines could be distinguished in SS-OCT images. Thus, the detection ability of SS-OCT renders it an acceptable diagnostic device for cracked-tooth syndrome.

     

Ultrahigh resolution all-reflective optical coherence tomography system with a compact fiber-based supercontinuum source

We report the construction and characterization of an all-reflective optical coherence tomography (OCT) system using a newly developed compact fiber-based broadband supercontinuum source. The use of only reflective optical components has enabled us to avoid chromatic dispersion effects and to obtain ultrahigh resolution OCT images of biological samples. We achieved an axial resolution of 2 μm in air with 87 dB dynamic range at a center wavelength around 1300 nm.     

Combining optical coherence tomography with magnetic resonance angiography and Doppler ultrasonography for clinical detection of scleroderma

Scleroderma (SD) is a rare and agnogenic autoimmune disease whose progression can be modified by medical or surgical intervention if detected early. Multimodality imaging makes early detection of SD possible based on the structural and functional findings from different imaging methods. Combining optical coherence tomography (OCT) with magnetic resonance angiography (MRA) and Doppler ultrasonography (DUS) to identify the typical structural and functional features that can exhibit significant differences between SD patients and healthy controls. In this study, six participants (three healthy volunteers and three SD patients) were recruited and clinically examined by a rheumatologist. Participants’ fingers were scanned by MRA, DUS, and OCT, respectively. MRA and DSU imaging results showed that SD patients exhibited thicker finger skin, a loss of blood vessels, and lower blood flow, whereas OCT captured the high-resolution morphology changes of the skin, epidermal, dermis, and subcutaneous layers, demonstrating a distinct loss of the dermo-epidermal junction in SD patients. Multimodal imaging techniques offer a more comprehensive characterization of the morphological and functional information of biological tissues, which can assist physicians to achieve a more accurate SD diagnosis.     

In vivo optical coherence tomography detection of differences in regional large airway smoke inhalation induced injury in a rabbit model

Smoke inhalation injury causes acute airway injury that may result in airway compromise with significant morbidity and mortality. We investigate the ability of high resolution endobronchial optical coherence tomography (OCT) to obtain real-time images for quantitatively assessing regional differences between upper tracheal versus lower tracheal and bronchial airway injury responses to smoke inhalation in vivo using a prototype spectral domain (SLD)-OCT system we constructed, and flexible fiber optic probes. 33 New Zealand White rabbits are intubated and mechanically ventilated. The treatment groups are exposed to inhaled smoke. The OCT probe is introduced through the endotracheal tube and maintained in place for 5 to 6 h. Images of airway mucosa and submucosa are obtained at baseline and at specified intervals postexposure. Starting within less than 15 min after smoke inhalation, there is significant airway thickening in the smoke-exposed animals. This is maintained over 5 h of imaging studies. The lower tracheal airway changes, correlating closely with carboxyhemoglobin levels, are much greater than upper tracheal changes. Significant differences are seen in lower trachea and bronchi after acute smoke inhalation compared to upper trachea as measured in vivo by minimally invasive OCT. OCT is capable of quantitatively detecting regional changes in airway swelling following inhalation injury.     

Detecting cell death with optical coherence tomography and envelope statistics

Currently no standard clinical or preclinical noninvasive method exists to monitor cell death based on morphological changes at the cellular level. In our past work we have demonstrated that quantitative high frequency ultrasound imaging can detect cell death in vitro and in vivo. In this study we apply quantitative methods previously used with high frequency ultrasound to optical coherence tomography (OCT) to detect cell death. The ultimate goal of this work is to use these methods for optically-based clinical and preclinical cancer treatment monitoring. Optical coherence tomography data were acquired from acute myeloid leukemia cells undergoing three modes of cell death. Significant increases in integrated backscatter were observed for cells undergoing apoptosis and mitotic arrest, while necrotic cells induced a decrease. These changes appear to be linked to structural changes observed in histology obtained from the cell samples. Signal envelope statistics were analyzed from fittings of the generalized gamma distribution to histograms of envelope intensities. The parameters from this distribution demonstrated sensitivities to morphological changes in the cell samples. These results indicate that OCT integrated backscatter and first order envelope statistics can be used to detect and potentially differentiate between modes of cell death in vitro.     

Group velocity dispersion effects with water and lipid in 1.3 microm optical coherence tomography system

Optical coherence tomography (OCT) has been introduced for the diagnosis of vulnerable plaques in the coronary arteries. When an OCT system images through tissue and biological liquids, group velocity dispersion (GVD) will occur, which may be useful in tissue characterization. This study compares the water and lipid induced GVD effects, important constituents in plaque, on the axial resolution. The point-spread function (PSF) was measured when a target mirror was immersed in either water or lipid. A Fourier transform was performed on the PSF data. No significant GVD was observed in oil up to 15 mm thickness. Water depths greater than 6 mm significantly broadened the PSF. This indicates that the distortion of the spectrum can be attributed to the GVD in water. These results suggest that when imaging through tissue (such as when performing intravascular imaging in vivo) one may be able to distinguish different tissue types for diagnostic purposes.     

Imaging ex vivo and in vitro brain morphology in animal models with ultrahigh resolution optical coherence tomography

The feasibility of ultrahigh resolution optical coherence tomography (UHR OCT) to image ex vivo and in vitro brain tissue morphology on a scale from single neuron cells to a whole animal brain was investigated using a number of animal models. Sub-2-microm axial resolution OCT in biological tissue was achieved at different central wavelengths by separately interfacing two state-of-the-art broad bandwidth light sources (titanium:sapphire, Ti:Al2O3 laser, lambdac=800 nm, Deltalambda=260 nm, Pout=50 mW and a fiber laser light source, lambdac=1350 nm, Deltalambda=470 nm, Pout=4 mW) to free-space or fiber-based OCT systems, designed for optimal performance in the appropriate wavelength regions. The ability of sub-2-microm axial resolution OCT to visualize intracellular morphology was demonstrated by imaging living ganglion cells in cultures. The feasibility of UHR OCT to image the globular structure of an entire animal brain as well as to resolve fine morphological features at various depths in it was tested by imaging a fixed honeybee brain. Possible degradation of OCT axial resolution with depth in optically dense brain tissue was examined by depositing microspheres through the blood stream to various depths in the brain of a living rabbit. It was determined that in the 1100 to 1600-nm wavelength range, OCT axial resolution was well preserved, even at depths greater than 500 microm, and permitted distinct visualization of microspheres 15 microm in diameter. In addition, the OCT image penetration depth and the scattering properties of gray and white brain matter were evaluated in tissue samples from the visual cortex of a fixed monkey brain.     

Optical coherence photoacoustic microscopy: accomplishing optical coherence tomography and photoacoustic microscopy with a single light source

We developed optical coherence photoacoustic microscopy (OC-PAM) to demonstrate that the functions of optical coherence tomography (OCT) and photoacoustic microscopy (PAM) can be achieved simultaneously by using a single illuminating light source. We used a pulsed broadband laser centered at 580 nm and detected the absorbed photons through photoacoustic detection and the back-scattered photons with an interferometer. In OC-PAM, each laser pulse generates both one OCT A-line and one PAM A-line simultaneously; as a result, the two imaging modalities are intrinsically co-registered in the lateral directions. In vivo images of the mouse ear were acquired to demonstrate the capabilities of OC-PAM.     

Automatic detection of stent struts with thick neointimal growth in intravascular optical coherence tomography image sequences

To assist cardiologists investigating neointimal tissue growth on stents during follow-up with optical coherence tomography (OCT), we developed an automatic algorithm to locate deeply buried stent struts and to quantify the restenosis burden. The technique is based on an improved steerable filter for computing the local ridge strength and orientation. It also uses an ellipsoid fitting algorithm and continuity criteria to obtain globally optimal stent localization. The restenosis burden calculations were compared to manual assessment of OCT coronary artery image data obtained from in vivo human clinical studies. Compared to manual assessment by expert readers, the algorithm operated with >?97% accuracy in the measurement of mean and maximum restenosis burden. The results indicated that the technique yielded comparable accuracy in measuring restenosis burden, and significantly reduced user interaction time.     

Comparison of diffuse optical tomography of human breast with whole-body and breast-only positron emission tomography

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.     

Methods and applications of full-field optical coherence tomography: a review

SignificanceFull-field optical coherence tomography (FF-OCT) enables en face views of scattering samples at a given depth with subcellular resolution, similar to biopsy without the need of sample slicing or other complex preparation. This noninvasive, high-resolution, three-dimensional (3D) imaging method has the potential to become a powerful tool in biomedical research, clinical applications, and other microscopic detection.AimOur review provides an overview of the disruptive innovations and key technologies to further improve FF-OCT performance, promoting FF-OCT technology in biomedical and other application scenarios.ApproachA comprehensive review of state-of-the-art accomplishments in OCT has been performed. Methods to improve performance of FF-OCT systems are reviewed, including advanced phase-shift approaches for imaging speed improvement, methods of denoising, artifact reduction, and aberration correction for imaging quality optimization, innovations for imaging flux expansion (field-of-view enlargement and imaging-depth-limit extension), new implementations for multimodality systems, and deep learning enhanced FF-OCT for information mining, etc. Finally, we summarize the application status and prospects of FF-OCT in the fields of biomedicine, materials science, security, and identification.ResultsThe most worth-expecting FF-OCT innovations include combining the technique of spatial modulation of optical field and computational optical imaging technology to obtain greater penetration depth, as well as exploiting endogenous contrast for functional imaging, e.g., dynamic FF-OCT, which enables noninvasive visualization of tissue dynamic properties or intracellular motility. Different dynamic imaging algorithms are compared using the same OCT data of the colorectal cancer organoid, which helps to understand the disadvantages and advantages of each. In addition, deep learning enhanced FF-OCT provides more valuable characteristic information, which is of great significance for auxiliary diagnosis and organoid detection.ConclusionsFF-OCT has not been completely exploited and has substantial growth potential. By elaborating the key technologies, performance optimization methods, and application status of FF-OCT, we expect to accelerate the development of FF-OCT in both academic and industry fields. This renewed perspective on FF-OCT may also serve as a road map for future development of invasive 3D super-resolution imaging techniques to solve the problems of microscopic visualization detection.     

Theoretical and practical considerations on detection performance of time domain, Fourier domain, and swept source optical coherence tomography

Optical coherence tomography (OCT) based on spectral interferometry has recently been examined, with authors often suggesting superior performance compared with time domain approaches. The technologies have similar resolutions and the spectral techniques may currently claim faster acquisition rates. Contrary to many current opinions, their detection parameters may be inferior. The dynamic range and signal-to-noise ratio (SNR) correlate with image penetration, the contrast as a function of depth. This work examines the theoretical sensitivity, dynamic range, and SNR of the techniques, within the practical limits of optoelectronics, taking into account often ignored or misunderstood classical factors that affect performance, such as low frequency noise, analog to digital (AD) conversion losses, and methods for potentially improving sensitivity, including fast laser sweeping. The technologies are compared relative to these parameters. While Fourier domain OCT has some advantages such as signal integration, it appears unlikely that its disadvantages can ultimately be overcome for nontransparent tissue. Ultimately, time-domain (TD)-OCT appears to have the superior performance with respect to SNR and dynamic range. This may not be the case for transparent tissue of the eye. Certain positive aspects of swept source OCT leave the possibility open that its performance may approach that of (TD)-OCT in nontransparent tissue.     

Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents and studied with optical coherence tomography

The depth of light penetration into highly scattering tissues can be improved by the application of biocompatible and osmotically active chemical agents. We compare the dynamics of optical clearing of tissue by the topical application of glycerol and dimethyl sulfoxide (DMSO) using optical coherence tomography (OCT). It is demonstrated experimentally that both agents can largely improve the OCT imaging depth for porcine stomach tissue. During a period of approximately 20 to 30 min after the application of glycerol image contrast is also enhanced. This enhancement disappears over time. Such enhancement of image contrast is not observed with DMSO. Glycerol causes a higher degree of dehydration of the tissue than DMSO does. We suggest that these phenomena are caused by a two-stage diffusion of the chemicals. The first stage of diffusion is from the top tissue to the intercellular space, and the second is into the cell matrix. During the first stage, the imaging contrast could be improved by dehydration.     

Ex vivo detection and characterization of early dental caries by optical coherence tomography and Raman spectroscopy

Early dental caries detection will facilitate implementation of nonsurgical methods for arresting caries progression and promoting tooth remineralization. We present a method that combines optical coherence tomography (OCT) and Raman spectroscopy to provide morphological information and biochemical specificity for detecting and characterizing incipient carious lesions found in extracted human teeth. OCT imaging of tooth samples demonstrated increased light backscattering intensity at sites of carious lesions as compared to the sound enamel. The observed lesion depth on an OCT image was approximately 290 microm matching those previously documented for incipient caries. Using Raman microspectroscopy and fiber-optic-based Raman spectroscopy to characterize the caries further, spectral changes were observed in PO4 (3-) vibrations arising from hydroxyapatite of mineralized tooth tissue. Examination of various ratios of PO4 (3-) nu2, nu3, nu4 vibrations against the nu1 vibration showed consistent increases in carious lesions compared to sound enamel. The changes were attributed to demineralization-induced alterations of enamel crystallite morphology and/or orientation. OCT imaging is useful for screening carious sites and determining lesion depth, with Raman spectroscopy providing biochemical confirmation of caries. The combination has potential for development into a new fiber-optic diagnostic tool enabling dentists to identify early caries lesions with greater sensitivity and specificity.     

Imaging caries lesions and lesion progression with polarization sensitive optical coherence tomography

New diagnostic tools are needed for the characterization of dental caries in the early stages of development. If carious lesions are detected early enough, they can be arrested without the need for surgical intervention. The objective of this study was to demonstrate that polarization sensitive optical coherence tomography (PS-OCT) can be used for the imaging of early caries lesions and for the monitoring of lesion progression over time. High-resolution polarization resolved images were acquired of natural caries lesions and simulated caries lesions of varying severity created over time periods of 1 to 14 days. Linearly polarized light was incident on the tooth samples and the reflected intensity in both orthogonal polarizations was measured. PS-OCT was invaluable for removing the confounding influence of surface reflections and native birefringence necessary for the enhanced resolution of the surface structure of caries lesions. This study demonstrated that PS-OCT is well suited for the imaging of interproximal and occlusal caries, early root caries, and for imaging decay under composite fillings. Longitudinal measurements of the reflected light intensity in the orthogonal polarization state from the area of simulated caries lesions linearly correlated with the square root of time of demineralization indicating that PS-OCT is well suited for monitoring changes in enamel mineralization over time.     

Myocardial tissue characterization based on a polarization-sensitive optical coherence tomography system with an ultrashort pulsed laser

A polarization-sensitive optical coherence tomography (PSOCT) system using a femtosecond-laser as the broadband light source is implemented with the axial resolution of 5 microm in free space. Through the design of path-length difference between the two polarization inputs and the modulation of one of the polarization inputs, the PSOCT images of various input and output polarization combinations can be distinguished and simultaneously collected. The PSOCT system is then used for in vitro scanning of the myocardium tissues of normal and infarcted rat hearts. The destruction of the birefringence nature of the fiber muscle in the infarcted heart can be clearly observed.