Doppler optical coherence imaging of converging flow

The experimental methods of Doppler optical coherence tomography are applied for two-dimensional flow mapping of highly scattering fluid in flow with complex geometry. Converging flow (die entry) is used to demonstrate non-invasive methods to map varying velocity profiles before and after the entry. Complex geometry flow is scanned with approximately 10 x 10 x 10 microm3 spatial resolution. Structural images of the phantom and specific velocity images are demonstrated. A variety of velocity profiles have been obtained before and after the entry. Concave, blunted, parabolic and triangular profiles are obtained at different distances after the entry. Application of the technique to the study of blood circulation is discussed.     

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.     

Measuring red blood cell flow dynamics in a glass capillary using Doppler optical coherence tomography and Doppler amplitude optical coherence tomography

Blood, being a suspension of deformable red cells suspended in plasma, displays flow dynamics considerably more complicated than those of an ideal Newtonian fluid. Flow dynamics in blood capillaries of a few hundred micrometers in diameter are investigated using Doppler optical coherence tomography (DOCT) and Doppler amplitude optical coherence tomography (DAOCT), a novel extension of DOCT. Velocity profiles and concentration distributions of normal and rigidified in vitro red blood cell suspensions are shown to vary as functions of mean flow velocity, cell concentration, and cell rigidity. Deviation from the parabolic velocity profile expected for Pouseille flow is observed for both rigid and normal cells at low flow rates. Axial red cell migration both toward and away from the tube axis is observed for both rigid and normal cells as a function of flow velocity. Good agreement is found between our measurements, and theoretical expectations.     

光相干层析成像中的散斑

由于光相干层析成像中测量的干涉信号空间频带有限 ,因此会产生散斑。在高散射的生物组织图像中 ,散斑具有双重身份 ,即作为噪声源和作为组织微结构的信号载体。本文的前半部分对于光相干层析成像中散斑的产生原因、统计特性以及分类作了综述。通过采样束的相位和振幅扰动可以定义信号载体散斑和信号降低散斑。本文的后半部分讨论了减少散斑的 4种方法 :偏振合成法、空间合成法、频率合成法和数字信号处理方法 ,并且通过举例对每一种方法的有效性作了简单的分析。最后 ,文章提出了需进一步研究的问题     

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.     

Ultrahigh-resolution optical coherence tomography

In the past two decades, optical coherence tomography (OCT) has been established as an adjunct diagnostic technique for noninvasive, high-resolution, cross-sectional imaging in a variety of medical fields. The rapid development of ultrabroad bandwidth light sources has recently enabled a significant improvement in OCT imaging resolution, demonstrating the potential of OCT to accomplish its original goal of performing noninvasive optical biopsies, i.e., the in vivo visualization of microstructural morphology in situ, which had previously only been possible with histopathology. In addition, these novel light sources might also enable the use of spectroscopic OCT, an extension of ultrahigh-resolution OCT, for enhancing image contrast as well as detecting spatially resolved functional, biochemical tissue information. State-of-the-art-light sources that now permit ultrahigh-resolution OCT covering the whole wavelength region from 500 to 1600 nm are reviewed and fundamental limitations of OCT image resolution are discussed. Ex vivo ultrahigh-resolution OCT tomograms are compared with histological results; first clinical in vivo ultrahigh-resolution OCT and preliminary spectroscopic OCT results are presented and their impact for future clinical and research applications is discussed.     

Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography

The ability of ultra-high-resolution optical coherence tomography (UHR OCT) to discriminate between healthy and pathological human brain tissue is examined by imaging ex vivo tissue morphology of various brain biopsies. Micrometer-scale OCT resolution (0.9x2 microm, axialxlateral) is achieved in biological tissue by interfacing a state-of-the-art Ti:Al2O3 laser (lambda(c)=800 nm, delta lambda=260 nm, and P(out)=120 mW exfiber) to a free-space OCT system utilizing dynamic focusing. UHR OCT images are acquired from both healthy brain tissue and various types of brain tumors including fibrous, athypical, and transitional meningioma and ganglioglioma. A comparison of the tomograms with standard hematoxylin and eosin (H&E) stained histological sections of the imaged biopsies demonstrates the ability of UHR OCT to visualize and identify morphological features such as microcalcifications (>20 microm), enlarged nuclei of tumor cells (approximately 8 to 15 microm), small cysts, and blood vessels, which are characteristic of neuropathologies and normally absent in healthy brain tissue.     

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.     

Monitoring of drug and stimulation induced cerebral blood flow velocity changes in rat sensory cortex using spectral domain Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) provides a novel method to measure blood flow velocity in vessels with diameter at micrometer scale. In this study, a developed spectral domain DOCT system is applied to monitor cerebral blood flow velocity changes in a rat. An animal model with a cranial window is used, and by application of a drug, light, and electric stimulations, changes in blood flow velocity of the pial artery in sensory cortex are measured in real time. The results show significant differences in blood flow velocity before and after drug administration or light and electric stimulations, demonstrating the feasibility of DOCT in cerebral microcirculation study. Given its noninvasive nature, high spatial resolution, high velocity sensitivity, and high imaging speed, DOCT shows great promise in brain research by imaging blood flow changes at micrometer scale vessels, which helps to understand the pathogenesis of cerebral diseases and neurodegenerative diseases.     

Subcellular imaging of epithelium with time-lapse optical coherence tomography

We present the first experimental result of direct delineation of the nuclei of living rat bladder epithelium with ultrahigh-resolution optical coherence tomography (uOCT). We demonstrate that the cellular details embedded in the speckle noise in a uOCT image can be uncovered by time-lapse frame averaging that takes advantage of the micromotion in living biological tissue. The uOCT measurement of the nuclear size (7.9+/-1.4 microm) closely matches the histological evaluation (7.2+/-0.8 microm). Unlike optical coherence microscopy (OCM), which requires a sophisticated high-NA microscopic objective, this approach uses a commercial-grade single achromatic lens (f/10 mm, NA/0.25) and provides a cross-sectional image over 0.6 mm of depth without focus tracking, thus holding great promise of endoscopic optical biopsy for diagnosis and grading of flat epithelial cancer such as carcinoma in situ in vivo.     

Assessment of blood vessel mimics with optical coherence tomography

Optical coherence tomography (OCT) is an imaging modality that enables assessment of tissue structural characteristics. Studies have indicated that OCT is a useful method to assess both blood vessel morphology and the response of a vessel to a deployed stent. We evaluated the ability of OCT to visualize the cellular lining of a tissue-engineered blood vessel mimic (BVM) and the response of this lining to a bare metal stent. We develop a side-firing endoscope that obtains intraluminal, longitudinal scans within the sterile bioreactor environment, enabling time-serial assessment. Seventeen BVMs are imaged with the endoscopic OCT system. The BVMs are then evaluated via fluorescence microscopy and/or standard histologic techniques. We determine that (1) the OCT endoscope can be repeatedly inserted without visible damage to the BVM cellular lining, (2) OCT provides a precise measure of cellular lining thickness with good correlation to measurements obtained from histological sections, and (3) OCT is capable of monitoring the accumulation of cellular material in response to a metallic stent. Our studies indicate that OCT is a useful technique for monitoring the BVM cellular lining, and that OCT may facilitate the use of BVMs for early stage device assessment.     

Femtosecond laser-assisted cataract surgery with integrated optical coherence tomography

About one-third of people in the developed world will undergo cataract surgery in their lifetime. Although marked improvements in surgical technique have occurred since the development of the current approach to lens replacement in the late 1960s and early 1970s, some critical steps of the procedure can still only be executed with limited precision. Current practice requires manual formation of an opening in the anterior lens capsule, fragmentation and evacuation of the lens tissue with an ultrasound probe, and implantation of a plastic intraocular lens into the remaining capsular bag. The size, shape, and position of the anterior capsular opening (one of the most critical steps in the procedure) are controlled by freehand pulling and tearing of the capsular tissue. Here, we report a technique that improves the precision and reproducibility of cataract surgery by performing anterior capsulotomy, lens segmentation, and corneal incisions with a femtosecond laser. The placement of the cuts was determined by imaging the anterior segment of the eye with integrated optical coherence tomography. Femtosecond laser produced continuous anterior capsular incisions, which were twice as strong and more than five times as precise in size and shape than manual capsulorhexis. Lens segmentation and softening simplified its emulsification and removal, decreasing the perceived cataract hardness by two grades. Three-dimensional cutting of the cornea guided by diagnostic imaging creates multiplanar self-sealing incisions and allows exact placement of the limbal relaxing incisions, potentially increasing the safety and performance of cataract surgery.     

Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography

We use Fourier domain optical coherence tomography (OCT) data to assess retinal blood oxygen saturation. Three-dimensional disk-centered retinal tissue volumes were assessed in 17 normal healthy subjects. After removing DC and low-frequency a-scan components, an OCT fundus image was created by integrating total reflectance into a single reflectance value. Thirty fringe patterns were sampled; 10 each from the edge of an artery, adjacent tissue, and the edge of a vein, respectively. A-scans were recalculated, zeroing the DC term in the power spectrum, and used for analysis. Optical density ratios (ODRs) were calculated as ODR(Art)=ln(Tissue(855)Art(855))ln(Tissue(805)Art(805)) and ODR(Vein)=ln(Tissue(855)Vein(855))ln(Tissue(805)Vein(805)) with Tissue, Art, and Vein representing total a-scan reflectance at the 805- or 855-nm centered bandwidth. Arterial and venous ODRs were compared by the Wilcoxon signed rank test. Arterial ODRs were significantly greater than venous ODRs (1.007+/-2.611 and -1.434+/-4.310, respectively; p=0.0217) (mean+/-standard deviation). A difference between arterial and venous blood saturation was detected. This suggests that retinal oximetry may possibly be added as a metabolic measurement in structural imaging devices.     

定量血管内光学相干层析成像的研究进展

血管内光学相干层析成像(IVOCT)是目前分辨率最高的血管内成像技术,可对冠状动脉血管腔及管壁内膜下病变进行快速、清晰的成像。仅根据组织结构的层析图像无法精确识别粥样硬化斑块成分(如钙化、纤维化、脂质和混合斑块),需要形态结构之外的生理信息的对比机制,获得具有临床诊断价值的组织参数,即定量IVOCT(qIVOCT)。本文针对根据IVOCT原始背向散射信号和灰阶图像定量测量血管壁组织的光学特性参数、弹性参数和血流动力学参数的研究现状进行归纳和总结,分析目前存在的问题,展望可能的发展方向。     

Advanced modelling of optical coherence tomography systems

Analytical and numerical models for describing and understanding the light propagation in samples imaged by optical coherence tomography (OCT) systems are presented. An analytical model for calculating the OCT signal based on the extended Huygens-Fresnel principle valid both for the single and multiple scattering regimes is reviewed. An advanced Monte Carlo model for calculating the OCT signal is also reviewed, and the validity of this model is shown through a mathematical proof based on the extended Huygens-Fresnel principle. Moreover, for the first time the model is verified experimentally. From the analytical model, an algorithm for enhancing OCT images is developed: the so-called true-reflection algorithm in which the OCT signal may be corrected for the attenuation caused by scattering. For the first time, the algorithm is demonstrated by using the Monte Carlo model as a numerical tissue phantom. Such algorithm holds promise for improving OCT imagery and to extend the possibility for functional imaging.     

Detection of tumorigenesis in rat bladders with optical coherence tomography.

Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross-sectional imaging of biological tissues. Because of its high resolution (approximately 10 microm), superior dynamic range (140 dB in our case) and up to 2-3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl-nitroso-urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher-state urothelial cancers, especially for papillary carcinomas.     

Imaging and anatomical parameters of the lacrimal punctum and vertical canaliculus using optical coherence tomography

Purpose: The anatomical parameters of normal lacrimal puncta and vertical canaliculus using optical coherence tomography (OCT) and the OCT imaging features of punctal lesions were analyzed to provide a basis for clinical diagnosis and treatment.Methods: From June to September 2019, 40 volunteers (80 eyes) from Tongji Hospital were enrolled. The external punctal diameter (ELP) was measured using slit-lamp microscopy and OCT. The internal lacrimal punctal diameter (ILP) at 100 μm, vertical canalicular length (VCL), and tear meniscus depth were measured by OCT with open eyes. Twenty-eight volunteers (56 eyes) underwent the same examinations with their eyes closed. The OCT imaging features of 26 patients (27 eyes) with lacrimal lesions were examined.Results: The ELP of the right and left healthy eyes under slit-lamp microscopy were 564.40 and 555.40 µm respectively. Under OCT, the ELP, ILP, and VCL of the right and left eyes were 628.20 um and 616.85 µm, 343.40 µm and 346.95 µm, 731.95 um and 709.20 µm respectively. The ELP was larger when measured by OCT than slit-lamp microscopy (p<0.05). Twenty-eight volunteers (56 eyes) had measurements taken under different conditions. The ELP, ILP, and VCL of the open and closed right eyes were 667.54 and 567.21 µm, 369.18 and 303.18 µm, 715.00 and 417.14 µm, respectively. The ELP, ILP, and VCL of the open and closed left eyes were 655.86 um and 551.68 µm, 369.25 um and 313.54 µm, 719.96 um and 433.89 µm respectively. The anatomical parameters of the open eyes were greater than those of the closed eyes (p<0.05). Thus, we identified the imaging features of lacrimal stenosis, punctal obstruction, punctal tear, lacrimal atresia, and lacrimal mass using OCT.Conclusions: OCT can be used to measure the anatomical parameters of lacrimal puncta and vertical canaliculus in vivo. In addition, OCT can detect punctal lesions in vivo and provide an objective basis for the clinical diagnosis and treatment of punctal lesions.     

Real-time in vivo color Doppler optical coherence tomography

Color Doppler optical coherence tomography (CDOCT) is a functional extension of optical coherence tomography (OCT) that can image flow in turbid media. We have developed a CDOCT system capable of imaging flow in real time. Doppler processing of the analog signal is accomplished in hardware in the time domain using a novel autocorrelation technique. This Doppler processing method is compatible with a high speed OCT system capable of imaging in real time. Using this system, we demonstrate cross-sectional imaging of bidirectional flow with CDOCT at four frames per second in a tissue-simulating phantom consisting of intralipid solution flowing in glass capillaries. As a demonstration of real-time imaging of blood flow in vivo we imaged pulsatible blood flow in a rat femoral artery at eight frames per second. Issues of velocity sensitivity, imaging speed, and range of velocity measurement are discussed, as well as potential applications of real-time CDOCT.     

Jones-matrix imaging of biological tissues with quadruple-channel optical coherence tomography

Two-dimensional depth-resolved Jones-matrix images of scattering biological tissues were measured with novel double-source double-detector polarization-sensitive optical coherence tomography (OCT). The Jones matrix can be determined in a single scan with this OCT system. The experimental results show that this system can be effectively applied to the measurement of soft tissues, which are less stable than hard tissues. Polarization parameters such as diattenuation, birefringence, and orientation of the fast axis can be extracted through decomposition of the measured Jones matrix. The Jones matrix of thermally treated porcine tendon showed a reduction of birefringence from thermal damage. The Jones matrices of porcine skin and bovine cartilage also revealed that the density and orientation of the collagen fibers in porcine skin and bovine cartilage are not distributed as uniformly as in porcine tendon. Birefringence is sensitive to changes in tissue because it is based on phase contrast.