Optical Coherence Tomography Contrast Research Articles

Ergodic speckle contrast optical coherence tomography velocimetry of rapid blood flow.

Visualizing a 3D blood flow velocity field through noninvasive imaging is crucial for analyzing hemodynamic mechanisms in areas prone to disorders. However, traditional correlation-based optical coherence tomography (OCT) velocimetry techniques have a maximum measurable flow velocity depending on the A-line rate. We presented the ergodic speckle contrast OCT (ESCOCT) to break the bottleneck in measuring the rapid blood flow velocity. It achieved a measurement of blood flow velocity ranging from 9.5 to 280 mm/s using a 100 kHz swept-source (SS) OCT based on 100 A-repeats scanning mode. Addressing the non-ergodic problem of temporal OCT signals by integrating more consecutive A-scans, ESCOCT can enable the estimation for lower velocity flows by increasing A-repeats. ESCOCT provided a wide dynamic range with no upper limit on measuring blood flow velocity with an adequate signal-to-noise ratio and improved the sensitivity and accuracy of the hemodynamic assessment.

Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology.

The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.

High-sensitivity synchronous angio-lymphography based on a speckle spectrum contrast OCT.

To achieve accurate selection and synchronous imaging of blood vessels and lymph, a speckle spectrum contrast method (SSC) based on spectral-domain optical coherence tomography (SD-OCT) is proposed in this Letter. In this method, the time-lapse optical coherence tomography (OCT) intensity signal is transformed to the Fourier frequency domain. By analyzing the frequency spectrum of the time-lapse OCT intensity signal, a parameter called SSC signal, which represents the ratio of different intervals of the high frequency to the low frequency, is utilized to extract and contrast different types of the vessels in the biological tissues. In the SSC spectrum, the SSC signals of the static tissue, lymphatic vessels, and vascular vessels can be separated in three different frequency intervals, enabling differentiation and synchronous imaging of the lymphatic-vascular vessels. A mouse ear was used to demonstrate the feasibility and efficiency of this method. By using the SSC signal as the imaging parameter, the lymphatic and blood vessels of the mouse ear are differentiated and visualized simultaneously. This study shows the feasibility of the three-dimensional (3D) synchronous angio-lymphography based on the SSC method, which provides a tool to improve the understanding for disease research and treatment.

Ag2 S Biocompatible Ensembles as Dual OCT Contrast Agents and NIR Ocular Imaging Probes.

Ag2 S nanoparticles (NPs) emerge as a unique system that simultaneously features in vivo near-infrared (NIR) imaging, remote heating, and low toxicity thermal sensing. In this work, their capabilities are extended into the fields of optical coherence tomography (OCT), as contrast agents, and NIR probes in both ex vivo and in vivo experiments in eyeballs. The new dual property for ocular imaging is obtained by the preparation of Ag2 S NPs ensembles with a biocompatible amphiphilic block copolymer. Rather than a classical ligand exchange, where surface traps may arise due to incomplete replacement of surface sites, the use of this polymer provides a protective extra layer that preserves the photoluminescence properties of the NPs, and the procedure allows for the controlled preparation of submicrometric scattering centers. The resulting NPs ensembles show extraordinary colloidal stability with time and biocompatibility, enhancing the contrast in OCT with simultaneous NIR imaging in the second biological window.

Three-dimensional Optical Coherence Thermometry Using Polymeric Nanogels.

In nanothermometry, the use of nanoparticles as thermal probes enables remote and minimally invasive sensing. In the biomedical context, nanothermometry has emerged as a powerful tool where traditional approaches, like infrared thermal sensing and contact thermometers, fall short. Despite the strides of this technology in preclinical settings, nanothermometry is not mature enough to be translated to the bedside. This is due to two major hurdles: the inability to perform three-dimensional thermal imaging and the requirement for tools that are readily available in the clinics. This work simultaneously overcomes both limitations proposing the technology of optical coherence thermometry (OCTh). This is achieved by combining thermoresponsive polymeric nanogels and optical coherence tomography (OCT) - a three-dimensional imaging technology routinely used in clinical practice. The volume phase transition of the thermoresponsive nanogels causes marked changes in their refractive index, making them temperature-sensitive OCT contrast agents. The ability of OCTh to provide three-dimensional thermal images was demonstrated in tissue phantoms subjected to photothermal processes, and its reliability was corroborated comparing experimental results with numerical simulations. The results included in this work set credible foundations for the implementation of nanothermometry in the form of OCTh in the clinical practice. This article is protected by copyright. All rights reserved.

PyMieSim: an open-source library for fast and flexible far-field Mie scattering simulations

Mie scattering simulations are essential to designing sensing and imaging devices for atmospheric and biomedical sciences applications. Current simulators based on Lorenz-Mie theory allow obtaining scattering phase functions for several scatterer geometries. Still, they are not optimized for simulating ranging parameters and do not compute coupling powers into coherent or incoherent detectors. Here, we present PyMieSim: a Python interface wrapping a C++ parallelized core for a fast, flexible, and highly visual simulation package, allowing for the study of ranges of parameters for different source, scatterer, and detector configurations. We demonstrate two applications: flow-cytometry geometry optimization and few-mode optical coherence tomography contrast analysis.

Drug-eluting, balloon-expandable, bioresorbable vascular scaffolds reduce neointimal thickness and stenosis in an animal model of percutaneous peripheral intervention

ObjectiveRecanalization with balloon angioplasty and/or self-expanding stents (SES) has become the endovascular treatment of choice for symptomatic femoropopliteal occlusive disease. These strategies generate suboptimal clinical results, however, because they fail to expand the artery fully and ineffectively prevent recoil, neointimal hyperplasia, and restenosis. Balloon-expandable stents, given their greater radial force and rigid structure, represent a more effective treatment strategy, but only short lengths can be implanted safely in arteries that deform and bend with skeletal motion. The purpose of this preclinical experiment was to test the hypothesis that simultaneous implantation of a series of short, resorbable, balloon-expandable, paclitaxel-eluting scaffolds would prevent neointimal hyperplasia and stenosis compared with SES in an animal model of percutaneous femoropopliteal intervention. MethodsWe extruded 6 × 60 mm Efemoral Vascular Scaffold Systems (EVSS) from copolymers of poly-L-lactic acid, coated with paclitaxel 3 μg/mm2, crimped onto a single delivery balloon, and implanted percutaneously into the iliofemoral arteries of eight Yucatan mini-swine. We implanted 7- to 8-mm × 60 mm SES into the contralateral experimental arteries. The animals were serially imaged with contrast angiography and optical coherence tomography after 30, 90, 180, 365, and 730 days. The primary end point of this study was neointimal morphometry over time. Secondary end points included acute deformation and angiographic and optical coherence tomography-derived measurements of chronic vascular response. ResultsOver the 2-year study period, one SES was found to be completely occluded at 90 days; all EVSS were widely patent at all time points. Arteries treated with SES exhibited profound neointimal hyperplasia with in-stent stenosis. In contrast, arteries treated with EVSS exhibited only modest vascular responses and minimal stenosis. After 2 years, the mean neointimal thickness (0.45 ± 0.12 vs 1.31 ± 0.91 mm; P < .05) and area (8.41 ± 3.35 vs 21.86 ± 7.37 mm2; P < .05) were significantly decreased after EVSS implantation. By 2 years, all scaffolds in all EVSS-treated arteries had resorbed fully. ConclusionsIn this preclinical animal model of peripheral endovascular intervention, the EVSS decreased neointimal hyperplasia and stenosis significantly compared with SES, then dissolved completely between the first and second years after implantation.

In vivo tracking of individual stem cells labeled with nanowire lasers using multimodality imaging.

Emerging cell-based regenerative medicine and stem cell therapies have drawn wide attention in medical research and clinical practice to treat tissue damage and numerous incurable diseases. In vivo observation of the distribution, migration, and development of the transplanted cells is important for both understanding the mechanism and evaluating the treatment efficacy and safety. However, tracking the 3D migration trajectories for individual therapeutic cells in clinically relevant pathological environments remains technically challenging. Using a laser photocoagulation model in living rabbit eyes, this study demonstrates a multimodality imaging technology integrating optical coherence tomography (OCT), fluorescence microscopy (FM), and lasing emission for in vivo longitudinal tracking of the 3D migration trajectories of individual human retinal pigment epithelium cells (ARPE-19) labeled with CdS nanowires. With unique lasing spectra generated from the subtle microcavity differences, the surface-modified nanowires perform as distinct spectral identifiers for labeling individual ARPE-19 cells. Meanwhile, with strong optical scattering and natural fluorescence emission, CdS nanowires also served as OCT and FM contrast agents to indicate the spatial locations of the transplanted ARPE-19 cells. A longitudinal study of tracking individual ARPE-19 cells in rabbit eyes over a duration of 28 days was accomplished. This method could potentially promote an understanding of the pharmacodynamics and pharmacokinetics of implanted cells in the development of cell-based therapies.

Molecular Contrast Optical Coherence Tomography and Its Applications in Medicine

The growing need to understand the molecular mechanisms of diseases has prompted the revolution in molecular imaging techniques along with nanomedicine development. Conventional optical coherence tomography (OCT) is a low-cost in vivo imaging modality that provides unique high spatial and temporal resolution anatomic images but little molecular information. However, given the widespread adoption of OCT in research and clinical practice, its robust molecular imaging extensions are strongly desired to combine with anatomical images. A range of relevant approaches has been reported already. In this article, we review the recent advances of molecular contrast OCT imaging techniques, the corresponding contrast agents, especially the nanoparticle-based ones, and their applications. We also summarize the properties, design criteria, merit, and demerit of those contrast agents. In the end, the prospects and challenges for further research and development in this field are outlined.

Bismuth Selenide Nanostructured Clusters as Optical Coherence Tomography Contrast Agents: Beyond Gold-Based Particles.

Optical coherence tomography (OCT) is an imaging technique currently used in clinical practice to obtain optical biopsies of different biological tissues in a minimally invasive way. Among the contrast agents proposed to increase the efficacy of this imaging method, gold nanoshells (GNSs) are the best performing ones. However, their preparation is generally time-consuming, and they are intrinsically costly to produce. Herein, we propose a more affordable alternative to these contrast agents: Bi2Se3 nanostructured clusters with a desert rose-like morphology prepared via a microwave-assisted method. The structures are prepared in a matter of minutes, feature strong near-infrared extinction properties, and are biocompatible. They also boast a photon-to-heat conversion efficiency of close to 50%, making them good candidates as photothermal therapy agents. In vitro studies evidence the prowess of Bi2Se3 clusters as OCT contrast agents and prove that their performance is comparable to that of GNSs.

Au/Si Bilayer Nanodisks with Tunable Localized Surface Plasmon Resonance for Optical Coherence Tomography in the Second Near‐Infrared Window

Bioimaging in the second near‐infrared (NIR‐II) window can help to obtain high‐resolution images and a high penetration depth. This study proposes an Au/Si bilayer plasmonic nanodisk (Au/Si ND) that has a resonance wavelength in the NIR‐II window caused by Si ND stacking on top of the Au ND with a resonance wavelength in the first near‐infrared window; the Si ND has a high refractive index. Au/Si NDs are physically synthesized using nanoimprint lithography and vacuum deposition. Optical coherence tomography (OCT) imaging is performed using synthesized Au/Si NDs as OCT contrast agents in the NIR‐II window. Due to the 2D circular shape and its remarkable response to random incident light, the Au/Si NDs exhibit approximately 250‐fold greater OCT signal intensity than do commercial 1D Au nanorods, as well as fourfold greater penetration depth and improved OCT image contrast.

Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography.

.Significance: After three decades, more than 75,000 publications, tens of companies being involved in its commercialization, and a global market perspective of about USD 1.5 billion in 2023, optical coherence tomography (OCT) has become one of the fastest successfully translated imaging techniques with substantial clinical and economic impacts and acceptance.Aim: Our perspective focuses on disruptive forward-looking innovations and key technologies to further boost OCT performance and therefore enable significantly enhanced medical diagnosis.Approach: A comprehensive review of state-of-the-art accomplishments in OCT has been performed.Results: The most disruptive future OCT innovations include imaging resolution and speed (single-beam raster scanning versus parallelization) improvement, new implementations for dual modality or even multimodality systems, and using endogenous or exogenous contrast in these hybrid OCT systems targeting molecular and metabolic imaging. Aside from OCT angiography, no other functional or contrast enhancing OCT extension has accomplished comparable clinical and commercial impacts. Some more recently developed extensions, e.g., optical coherence elastography, dynamic contrast OCT, optoretinography, and artificial intelligence enhanced OCT are also considered with high potential for the future. In addition, OCT miniaturization for portable, compact, handheld, and/or cost-effective capsule-based OCT applications, home-OCT, and self-OCT systems based on micro-optic assemblies or photonic integrated circuits will revolutionize new applications and availability in the near future. Finally, clinical translation of OCT including medical device regulatory challenges will continue to be absolutely essential.Conclusions: With its exquisite non-invasive, micrometer resolution depth sectioning capability, OCT has especially revolutionized ophthalmic diagnosis and hence is the fastest adopted imaging technology in the history of ophthalmology. Nonetheless, OCT has not been completely exploited and has substantial growth potential—in academics as well as in industry. This applies not only to the ophthalmic application field, but also especially to the original motivation of OCT to enable optical biopsy, i.e., the in situ imaging of tissue microstructure with a resolution approaching that of histology but without the need for tissue excision.

Spectral- and Polarization-Dependent Scattering of Gold Nanobipyramids for Exogenous Contrast in Optical Coherence Tomography.

Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT’s structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could well be extended to other anisotropic nanoparticle-based OCT contrast agents and presents significant progress toward enabling OCT molecular imaging.

Microscopic optical coherence tomography (mOCT) at 600 kHz for 4D volumetric imaging and dynamic contrast.

Volumetric imaging of dynamic processes with microscopic resolution holds a huge potential in biomedical research and clinical diagnosis. Using supercontinuum light sources and high numerical aperture (NA) objectives, optical coherence tomography (OCT) achieves microscopic resolution and is well suited for imaging cellular and subcellular structures of biological tissues. Currently, the imaging speed of microscopic OCT (mOCT) is limited by the line-scan rate of the spectrometer camera and ranges from 30 to 250 kHz. This is not fast enough for volumetric imaging of dynamic processes in vivo and limits endoscopic application. Using a novel CMOS camera, we demonstrate fast 3-dimensional OCT imaging with 600,000 A-scans/s at 1.8µm axial and 1.1 µm lateral resolution. The improved speed is used for imaging of ciliary motion and particle transport in ex vivo mouse trachea. Furthermore, we demonstrate dynamic contrast OCT by evaluating the recorded volumes rather than en face planes or B-scans. High-speed volumetric mOCT will enable the correction of global tissue motion and is a prerequisite for applying dynamic contrast mOCT in vivo. With further increase in imaging speed and integration in flexible endoscopes, volumetric mOCT may be used to complement or partly replace biopsies.

Contrast sensitivity and quality of life following intravitreal ranibizumab injection for central retinal vein occlusion

Synopsis/precisWe investigated the relationship between contrast sensitivity (CS) and vision-related quality of life (VR-QOL) in patients with central retinal vein occlusion following ranibizumab intravitreal injection; CS showed a stronger association...

Origins of subdiffractional contrast in optical coherence tomography.

We demonstrate that OCT images quantify subdiffractional tissue structure. Optical coherence tomography (OCT) measures stratified tissue morphology with spatial resolution limited by the temporal coherence length. Spectroscopic OCT processing, on the other hand, has enabled nanoscale sensitive analysis, presenting an unexplored question: how does subdiffractional information get folded into the OCT image and how does one best analyze to allow for unambiguous quantification of ultrastructure? We first develop an FDTD simulation to model spectral domain OCT with nanometer resolution. Using this, we validate an analytical relationship between the sample statistics through the power spectral density (PSD) of refractive index fluctuations and three measurable quantities (image mean, image variance, and spectral slope), and have found that each probes different aspects of the PSD (amplitude, integral and slope, respectively). Finally, we found that only the spectral slope, quantifying mass scaling, is monotonic with the sample autocorrelation shape.

Zero contrast optical coherence tomography-guided percutaneous coronary intervention in patients with non-ST segment elevation myocardial infarction and chronic kidney disease.

To investigate a strategy for ultra-low volume contrast percutaneous coronary intervention (PCI) with the aims of preserving renal function and observing the 90-day clinical endpoint in patients with non-ST-elevated myocardial infarction (non-STEMI) and chronic kidney disease (CKD). The feasibility, safety, and clinical utility of PCI with ultra-low radio-contrast medium in patients with non-STEMI and CKD are unknown. A total of 29 patients with non-STEMI and CKD (estimated glomerular filtration rate [eGFR] of ≤60 ml/min/1.73 m2 ) were included. Ultra-low volume contrast PCI was performed after minimal contrast coronary angiography using zero contrast optical coherence tomography (OCT) guidance. Pre- and post-PCI angiographic measurements were performed using quantitative flow ratio (QFR) for pre-perfusion assessment and verifying improvement. The median creatinine level was 2.1 (inter-quartile range 1.8-3.3), and mean eGFR was 48 ± 8 ml/min/1.73 m2 pre-PCI. During the PCI procedure, OCT revealed 15 (52%) cases of abnormalities post-dilation. There was no significant change in the creatinine level and eGFR in the short- or long-term, and no major adverse events were observed. In non-STEMI patients with high-risk CKD who require revascularization, QFR and no contrast OCT-guided ultra-low contrast PCI may be performed safely without major adverse events.

High performance OCTA enabled by combining features of shape, intensity, and complex decorrelation

Motion contrast optical coherence tomography angiography (OCTA) entails a precise identification of dynamic flow signals from the static background, but an intermediate region with voxels exhibiting a mixed distribution of dynamic and static scatterers is almost inevitable in practice, which degrades the vascular contrast and connectivity. In this work, the static-dynamic intermediate region was pre-defined according to the asymptotic relation between inverse signal-to-noise ratio (iSNR) and decorrelation, which was theoretically derived for signals with different flow rates based on a multi-variate time series (MVTS) model. Then the ambiguous voxels in the intermediate region were further differentiated using a shape mask with adaptive threshold. Finally, an improved OCTA classifier was built by combining shape, iSNR, and decorrelation features, termed as SID-OCTA, and the performance of the proposed SID-OCTA was validated experimentally through mouse retinal imaging.

Comprehensive review of surgical microscopes: technology development and medical applications.

.Significance: Surgical microscopes provide adjustable magnification, bright illumination, and clear visualization of the surgical field and have been increasingly used in operating rooms. State-of-the-art surgical microscopes are integrated with various imaging modalities, such as optical coherence tomography (OCT), fluorescence imaging, and augmented reality (AR) for image-guided surgery.Aim: This comprehensive review is based on the literature of over 500 papers that cover the technology development and applications of surgical microscopy over the past century. The aim of this review is threefold: (i) providing a comprehensive technical overview of surgical microscopes, (ii) providing critical references for microscope selection and system development, and (iii) providing an overview of various medical applications.Approach: More than 500 references were collected and reviewed. A timeline of important milestones during the evolution of surgical microscope is provided in this study. An in-depth technical overview of the optical system, mechanical system, illumination, visualization, and integration with advanced imaging modalities is provided. Various medical applications of surgical microscopes in neurosurgery and spine surgery, ophthalmic surgery, ear-nose-throat (ENT) surgery, endodontics, and plastic and reconstructive surgery are described.Results: Surgical microscopy has been significantly advanced in the technical aspects of high-end optics, bright and shadow-free illumination, stable and flexible mechanical design, and versatile visualization. New imaging modalities, such as hyperspectral imaging, OCT, fluorescence imaging, photoacoustic microscopy, and laser speckle contrast imaging, are being integrated with surgical microscopes. Advanced visualization and AR are being added to surgical microscopes as new features that are changing clinical practices in the operating room.Conclusions: The combination of new imaging technologies and surgical microscopy will enable surgeons to perform challenging procedures and improve surgical outcomes. With advanced visualization and improved ergonomics, the surgical microscope has become a powerful tool in neurosurgery, spinal, ENT, ophthalmic, plastic and reconstructive surgeries.

Gold nanoparticles to enhance ophthalmic imaging.

The use of gold nanoparticles as diagnostic tools is burgeoning, especially in the cancer community with a focus on theranostic applications to both cancer diagnosis and treatment. Gold nanoparticles have also demonstrated great potential for use in diagnostic and therapeutic approaches in ophthalmology. Although many ophthalmic imaging modalities are available, there is still a considerable unmet need, in particular for ophthalmic molecular imaging for the early detection of eye disease before morphological changes are more grossly visible. An understanding of how gold nanoparticles are leveraged in other fields could inform new ways they could be utilized in ophthalmology. In this paper, we review current ophthalmic imaging techniques and then identify optical coherence tomography (OCT) and photoacoustic imaging (PAI) as the most promising technologies amenable to the use of gold nanoparticles for molecular imaging. Within this context, the development of gold nanoparticles as OCT and PAI contrast agents are reviewed, with the most recent developments described in detail.