The demand for widefield OCTA is growing as many retinal diseases exhibit alterations in the peripheral microvascular network at the early stage. In this work, we demonstrate ultrawide-field retinal OCTA over the area spanning 20 mm in diameter in 5 seconds using a 4.74 MHz A-line rate stretched-pulse mode locking (SPML)-OCT system. A concentric-circular scanning with an automatic reference arm length adjustment enabled a wide-field and large-curvature retina imaging within a 2 GHz signal bandwidth. The automatic focal plane adjustment and the deep learning-based denoising were also utilized to enhance vessel visualization in ultrawide-field OCTA images.
Imaging speed of OCT is a crucial factor for various applications. In swept source OCT, the imaging speed is directly determined by the sweep repetition speed of the wavelength-swept laser. Recently, a stretched-pulse mode-locked (SPML) wavelength-swept laser has been developed, utilizing chromatic dispersion to generate the wavelength-swept output with repetition rates from a few MHz to over 10 MHz without using any mechanical filter. In this work, we investigated SPML lasers with various repetition rates of 10 MHz, 20 MHz, and 80 MHz utilizing 10 m (930 ps/nm), 5 m (465 ps/nm), and 1 m (93 ps/nm) long CFBGs, respectively. We present coherence length and relative intensity noise (RIN) performances of the SPML lasers with various speeds and show the comparison of images acquired using the SPML lasers of 10 MHz and 80 MHz repetition rates.
Blood flow dynamics in microvascular networks are intimately related to the health of tissues and organs. While numerous imaging modalities and techniques have been developed to assess blood flow dynamics for various applications, their utilization has been hampered by limited imaging speed and indirect quantification of blood flow dynamics. Here, we demonstrate direct blood cell flow imaging (DBFI) that provides visualization of individual motions of blood cells over a field of 0.71 mm x 1.42 mm with a time resolution of 0.69 ms (1450 frames per second) without using any exogenous agents. DBFI enables precise dynamic analysis of blood cell flow velocities and fluxes in various vessels over a large field, from capillaries to arteries and veins, with unprecedented time resolution. Several exemplary applications of DBFI illustrate the potential of this new imaging technology.
Three-dimensional (3D) cellular-resolution imaging of the living human retina over a large field of view would bring a great impact in clinical ophthalmology, potentially finding new biomarkers for early diagnosis and improving the pathophysiological understanding of ocular diseases. While hardware-based and computational Adaptive Optics (AO) Optical Coherence Tomography (OCT) have been developed to achieve cellular-resolution retinal imaging, these approaches support limited 3D imaging fields and their high cost, and their intrinsic hardware complexity limit their practical utility. Here, we demonstrate 3D depth-invariant cellular-resolution imaging of the living human retina over a 3-mm × 3-mm field of view using the intrinsically phase-stable multi-MHz retinal swept-source OCT and tailored computational defocus and aberration correction methods. Single-acquisition imaging of photoreceptor cells, retinal nerve fiber layer, and retinal capillaries is presented across unprecedented imaging fields. By providing wide-field 3D cellular-resolution imaging in the human retina using a standard point-scan architecture routinely used in the clinic, this platform proposes a strategy for expanded utilization of high-resolution retinal imaging in both research and clinical settings.
Optical coherence tomography (OCT) is a high-resolution imaging technique that provides wide field and high-speed imaging of three-dimensional volume. Stretched-pulse mode-locked (SPML) wavelength-swept laser has recently emerged as a promising ultrahigh-speed wavelength-swept laser that provides an A-line rate up to tens of MHz. The SPML laser utilizes chromatic dispersion to generate the wavelength-swept output with repetition rates from a few megahertz to over 10 MHz without using any mechanical wavelength scanning filter. For a simple and compact SPML laser design, utilization of a few meter-long chirped fiber Bragg grating (CFBG) as the intra-cavity dispersion element is recently demonstrated. In this work, we present SPML wavelength-swept laser using intra- and extra-cavity CFBG for the ultrahigh-speed OCT. We investigated the performance of the SPML laser as a light source for the ultrahigh-speed OCT by utilizing a combination of intra and extra-cavity stretching. We present that the noise performance and the coherence length performance of the laser can be adjusted and optimized through a proper combination of the intra and the extra cavity stretching in the SPML laser.
In vivo computational adaptive optics optical coherence tomography (CAO-OCT) has been challenging due to insufficient volume scan rate. We present video-rate volume-scanning CAO-OCT with a multi-MHz stretched-pulse mode-locked laser.
We demonstrate an all PMF-based CFBG-SPML laser at 1300 nm and OCT imaging using it. The laser performance of the PMF-based CFBG-SPML laser was as good as the SMF-based CFBG-SPML laser, while providing excellent stability, robustness, and ease of operation.
Intravascular optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm) provides co-registered structural and biochemical information of atherosclerotic plaques in a label-free manner. For intuitive image interpretation of OCT-FLIm, herein, we present a machine learning classifier where key biochemical components (lipids, lipids+macrophages, macrophages, fibrotic, and normal) related to plaque destabilization are characterized based on the combination of multispectral FLIm parameters and convolutional OCT features. Using dataset from in vivo atheromatous swine models, the classification accuracy was >92% for each plaque component according the five-fold cross validation. This highly translatable imaging strategy will open a new avenue for clinical intracoronary assessment of high-risk plaques.
Significance: Evaluation of vessel patency and blood flow direction is important in various medical situations, including diagnosis and monitoring of ischemic diseases, and image-guided vascular surgeries. While optical coherence tomography angiography (OCTA) is the most widely used functional extension of optical coherence tomography that visualizes three-dimensional vasculature, inability to provide information of blood flow direction is one of its limitations.
Aim: We demonstrate two-dimensional (2D) transverse blood flow direction imaging in en face OCTA.
Approach: A series of triangular beam scans for the fast axis was implemented in the horizontal direction for the first volume scan and in the vertical direction for the following volume scan, and the inter A-line OCTA was performed for the blood flow direction imaging while the stepwise pattern was used for each slow axis scan. The decorrelation differences between the forward and the backward inter A-line OCTA were calculated for the horizontal and the vertical fast axis scans, and the ratio of the horizontal and the vertical decorrelation differences was utilized to show the 2D transverse flow direction information.
Results: OCTA flow direction imaging was verified using flow phantoms with various flow orientations and speeds, and we identified the flow speed range relative to the scan speed for reliable flow direction measurement. We demonstrated the visualization of 2D transverse blood flow orientations in mouse brain vascular networks in vivo.
Conclusions: The proposed OCTA imaging technique that provides information of 2D transverse flow direction can be utilized in various clinical applications and preclinical studies.
Significance: Having a clear understanding of functional hyperemia is crucial for functional brain imaging and neurological disease research. Vasodilation induced by sensory stimulus propagates from the arterioles to the upstream pial arteries in a retrograde fashion. As retrograde vasodilation occurs briefly in the early stage of functional hyperemia, an imaging technique with a high temporal resolution is required for its measurement.
Aim: We aimed to present an imaging method to measure stimulus-induced retrograde vasodilation in awake animals.
Approach: An imaging method based on optical coherence tomography angiography, which enables a high-speed and label-free vessel diameter measurement, was developed and applied for the investigation.
Results: The propagation speed of retrograde vasodilation of pial artery was measured in awake mice. Other characteristics of functional hyperemia such as temporal profile and amplitude of the vascular response were also investigated.
Conclusions: Our results provide detailed information of stimulus-induced hemodynamic response in the brain of awake mice and suggest the potential utility of our imaging method for the study of functional hyperemia in normal and diseased brain.
Kidney transplantation is currently the most favorable treatment for patients with end stage renal disease (ESRD).1,2 Although transplantation from living donors (LD) promises higher survival rate, transplantation from deceased donors (DD) accounts for more than half of all kidney transplantation in the United States.5 Minimizing the ischemic damage on donor kidneys is essential for successful DD kidney transplantation because manifestations of the reperfusion injury after transplantation depend on the extent of ischemic insult.6 In this study, we investigate the correlation between the extent of ischemia and the renal microvasculature damage in an animal model of kidney ischemia and reperfusion injury using Optical Coherence Tomography Angiography (OCTA).
Multimodal optical coherence tomography (OCT) techniques are promising diagnostic tools to accurately assess highrisk atherosclerotic plaques. For rapid translation into clinical practice, the techniques should be performed through an intravascular imaging catheter without exogenous contrast agents under the same procedures as conventional imaging. In this study, we developed a label-free, multispectral, and catheter-based imaging system to simultaneously visualize the morphological and compositional information of coronary plaques by combining fluorescence lifetime imaging (FLIm) and OCT. Using a broadband hybrid optical rotary joint and a dual-modal imaging catheter, intravascular combined FLIm-OCT imaging was safely performed in an in vivo atherosclerotic coronary artery of atherosclerotic swine models without any imaging agent. Along with detailed coronary microstructure by OCT, the multispectral FLIm could accurately visualize fluorescence lifetime signature of key biochemical components of plaque in vivo (lipid, macrophage, and fibrous tissue) when comparing the corresponding histopathological stained-sections and ex vivo FLIm microscopy images. Especially, significant differences in fluorescence lifetime distribution were noted between lipid and macrophage (p < 0.0001), which were mostly indistinguishable with standalone OCT. Also, fluorescence lifetime distributions were significantly different according to plaque types (normal, fibrous vs. lipid-rich inflamed plaque, (p < 0.0001). With these statistical differences in plaque types and components, lipid distribution characterization and inflammation level estimation were provided in a pixel-by-pixel manner for the further assessment of the high-risk atherosclerotic plaque. This highly translatable imaging strategy can offer new opportunity for clinical intracoronary detection of high-risk plaques and will be a promising next-generation multimodal OCT technique.
KEYWORDS: Retina, Angiography, Optical coherence tomography, Visualization, Laser coagulation, Pathogens, 3D modeling, Animal model studies, Pathophysiology, Drug development
To understand the pathogenesis of ophthalmic disease, utilizing small animal models such as mouse is necessary because of their ease of maintenance and availability. For identifying pathophysiology and drug development of retinal diseases in mouse model, optical coherence tomography angiography (OCTA) is promising imaging modality visualizing not only microstructure but also microvasculature. In this study, we serially imaged 3D structure and angiography of laser-induced choroidal neovascularization (CNV) in the mouse retina with/without anti-VEGF treatment. Also, the volume changes of CNV and avascular region in choroid layer are measured for identifying effects of anti-VEGF.
A lab-built high-speed OCTA prototype using the wavelength-swept laser centered at 1040 nm with 230 kHz A-scan rate acquired 3-D volumetric data consisted of 1024 x 1024 x 3 A-scans. The OCTA scanned 1.7 mm x 1.7 mm area around ONH. For obtaining angiography, amplitude decorrelation from 3 consecutive B-scans at each position was generated. Seven days after the laser photocoagulation at mouse retina for generation of the laser-induced CNV, intravitreal administration of Fc and VEGF-Trap was given in the therapeutic arm. The OCTA were performed at 6, 14, 21 and 35 days after laser photocoagulation. Vasculatures of inner retina, outer retina and choroid layers were separately visualized after RPE flattening and layer segmentation. To investigate therapeutic effects of anti-VEGF treatment, the relative area and volume of CNV in outer retina layer is measured. Also, total volume of avascular zone surrounding the laser injury site in choroid layer is also analyzed.
Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the internal structures of walls of coronary arteries in vivo. However, accurate characterization of atherosclerotic plaques with gray-scale IV-OCT images is often limited by various intrinsic artifacts. In this study, we present an algorithm for characterizing lipid-rich plaques with a spectroscopic OCT technique based on a Gaussian center of mass (GCOM) metric. The GCOM metric, which reflects the absorbance properties of lipids, was validated using a lipid phantom. In addition, the proposed characterization method was successfully demonstrated in vivo using an atherosclerotic rabbit model and was found to have a sensitivity and specificity of 94.3% and 76.7% for lipid classification, respectively.
KEYWORDS: Optical coherence tomography, In vivo imaging, Heart, Visualization, Information visualization, Angiography, Tissue optics, Spatial resolution, Temporal resolution, Imaging systems
Optical coherence tomography (OCT) is a useful imaging method for in vivo tissue imaging with deep penetration and high spatial resolution. However, imaging of the beating mouse heart is still challenging due to limited temporal resolution or penetration depth. Here, we demonstrate a multifunctional OCT system for a beating mouse heart, providing various types of visual information about heart pathophysiology with high spatiotemporal resolution and deep tissue imaging. Angiographic imaging and polarization-sensitive (PS) imaging were implemented with the electrocardiogram (ECG)-triggered beam scanning scheme on the high-speed OCT platform (A-line rate: 240 kHz). Depth-resolved local birefringence and the local orientation of the mouse myocardial fiber were visualized from the PS-OCT. ECG-triggered angiographic OCT (AOCT) with the custom-built motion stabilization imaging window provided myocardial vasculature of a beating mouse heart. Mice underwent coronary artery ligation to derive myocardial infarction (MI) and were imaged with the multifunctional OCT system at multiple time points. AOCT and PS-OCT visualize change of functionality of coronary vessels and myocardium respectively at different phases (acute and chronic) of MI in an ischemic mouse heart. Taken together, the integrated imaging of PS-OCT and AOCT would play an important role in study of MI providing multi-dimensional information of the ischemic mouse heart in vivo.
Recently, Optical Coherence Tomography (OCT) has become one of the preferred clinical techniques for intracoronary
diagnostic imaging. Thanks to its high resolution imaging capability, the OCT technique allows to identify microscopic
features associated with various types of coronary plaque and to track of stent position, malaposition and neo-intimal
tissue growth after stent implantation. Accurate visualization of stent struts can help to examine the status of implanted stents potentially leading to proper treatment of the coronary artery disease. However, unfortunately, current stent identification involves time-consuming segmentation algorithms sometimes requiring labor-intensive manual analysis process. To resolve the problem, we propose a high-speed automatic segmentation algorithm of intravascular stent struts in OCT images. Unlike the other "automatic" stent segmentation algorithms, which are mainly based on time-consuming machine learning algorithms with manual addition and removal of stent struts for correction during the analysis process, our algorithm does not require any manual adjustments of stent struts. Our algorithm first analyzes 10 consecutive crosssectional OCT images to take boundary information into account to enhance the accuracy of guide-wire segmentation and lumen segmentation. Then, it performs stent segmentation by automatically eliminating guide-wire signals using the previous segmentation results. The implementation of our algorithm uses the Intel(R) IPP library on CPU and the CUDA technology on GPU, which achieves the average analysis time of 0.28 s/frame and the detection rate ranging from 84% to 88.6% for about 120 continuous images per patient. As such, the proposed algorithm is robust and fast enough to be integrated in clinical routine.
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