Huang PC, Pande P, Ahmad A
… +4 more, Marjanovic M, Spillman DR, Odintsov B, Boppart SA
IEEE J Sel Top Quantum Electron
· 2016 · PMID 28163565
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Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Op...Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 28070154
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Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellula...Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27795663
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Three-dimensional high-resolution optical imaging systems are generally restricted by the trade-off between resolution and depth-of-field as well as imperfections in the imaging system or sample. Computed optical interfe...Three-dimensional high-resolution optical imaging systems are generally restricted by the trade-off between resolution and depth-of-field as well as imperfections in the imaging system or sample. Computed optical interferometric imaging is able to overcome these longstanding limitations using methods such as interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO) which manipulate the complex interferometric data. These techniques correct for limited depth-of-field and optical aberrations without the need for additional hardware. This paper aims to outline these computational methods, making them readily available to the research community. Achievements of the techniques will be highlighted, along with past and present challenges in implementing the techniques. Challenges such as phase instability and determination of the appropriate aberration correction have been largely overcome so that imaging of living tissues using ISAM and CAO is now possible. Computed imaging in optics is becoming a mature technology poised to make a significant impact in medicine and biology.
Men J, Huang Y, Solanki J
… +7 more, Zeng X, Alex A, Jerwick J, Zhang Z, Tanzi RE, Li A, Zhou C
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27721647
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Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissue...Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissues and embryonic structures with micrometer resolution and video rate imaging speed. Functional OCT enables label-free monitoring of hemodynamic and metabolic changes in the brain and in animal models. Due to its non-invasiveness nature, OCT enables longitudinal imaging of developing specimens without potential damage from surgical operation, tissue fixation and processing, and staining with exogenous contrast agents. In this paper, various OCT applications in brain imaging and developmental biology are reviewed, with a particular focus on imaging heart development. In addition, we report findings on the effects of a circadian gene () and high-fat-diet on heart development in . These findings contribute to our understanding of the fundamental mechanisms connecting circadian genes and obesity to heart development and cardiac diseases.
Liu C, Liu YL, Perillo EP
… +2 more, Dunn AK, Yeh HC
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27660404
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In the past two decades significant advances have been made in single-molecule detection, which enables the direct observation of single biomolecules at work in real time and under physiological conditions. In particular...In the past two decades significant advances have been made in single-molecule detection, which enables the direct observation of single biomolecules at work in real time and under physiological conditions. In particular, the development of single-molecule tracking (SMT) microscopy allows us to monitor the motion paths of individual biomolecules in living systems, unveiling the localization dynamics and transport modalities of the biomolecules that support the development of life. Beyond the capabilities of traditional camera-based tracking techniques, state-of-the-art SMT microscopies developed in recent years can record fluorescence lifetime while tracking a single molecule in the 3D space. This multiparameter detection capability can open the door to a wide range of investigations at the cellular or tissue level, including identification of molecular interaction hotspots and characterization of association/dissociation kinetics between molecules. In this review, we discuss various SMT techniques developed to date, with an emphasis on our recent development of the next generation 3D tracking system that not only achieves ultrahigh spatiotemporal resolution but also provides sufficient working depth suitable for live animal imaging. We also discuss the challenges that current SMT techniques are facing and the potential strategies to tackle those challenges.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27642246
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New diagnostic methods are needed for the accurate assessment of caries lesion activity to establish the need for surgical treatment. Detection of the highly mineralized surface layer that forms near the surface of the l...New diagnostic methods are needed for the accurate assessment of caries lesion activity to establish the need for surgical treatment. Detection of the highly mineralized surface layer that forms near the surface of the lesions as a result of remineralization is important for diagnosis of the lesion activity. Previous studies have demonstrated that novel imaging methods can be used to detect remineralization of artificial enamel caries lesions. In this paper, the activity of natural enamel caries lesions was assessed in-vitro via detection of the surface layer with PS-OCT and dehydration rate measurements with NIR reflectance and thermal imaging modalities. An automated approach for detecting the surface layer with PS-OCT yielded high sensitivity (= 0.79) and high specificity (= 0.93) with moderate correlation (R = 0.5920) with histology. Significant differences in dehydration rate measurements were found between the active and the arrested lesions using both the NIR reflectance and thermal imaging modalities. These results demonstrate that these novel imaging methods are ideally suited for nondestructive, noninvasive and quantitative measurement of lesion activity during a single clinical examination in real-time.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27551166
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Simultaneous imaging of cerebral hemodynamic changes in response to functional activation during drug intoxication provides a valuable strategy to assess cocaine induced neurovascular dysfunction. However, this requires...Simultaneous imaging of cerebral hemodynamic changes in response to functional activation during drug intoxication provides a valuable strategy to assess cocaine induced neurovascular dysfunction. However, this requires tools with sufficient spatiotemporal resolution and adequate signal to noise ratio (SNR). Though several technologies have been developed to address this demand during functional brain activation, their spatiotemporal resolution has been compromised to preserve SNR. In this study, we combine spatiotemporal-domain laser speckle contrast analysis and image correlation techniques to integrate multi-wavelength spectroimaging and laser speckle contrast imaging (MW-LSCI). Experimental results show that optimized spatiotemporal resolution with enhanced SNR were achieved that enabled simultaneous measurement of multiple hemodynamic responses (i.e., ΔHbO, ΔHbR, ΔHbT and ΔCBF) during cocaine administration. Specifically, cocaine-induced functional cerebral hemodynamic changes were accessed by measuring the activation responses to forepaw electrical stimulation at different times after cocaine administration. With improved spatiotemporal resolution and SNR, the system was able to differentiate the heterogeneity of cocaine's effects on the cerebral vasculature and on tissue metabolism, demonstrating the unique capability of MW-LSCI for various brain functional and pharmacological studies.
Parks JW, Wall TA, Cai H
… +2 more, Hawkins AR, Schmidt H
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27547024
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Silicon-based optofluidic devices are very attractive for applications in biophotonics and chemical sensing. Understanding and controlling the properties of their dielectric waveguides is critical for the performance of...Silicon-based optofluidic devices are very attractive for applications in biophotonics and chemical sensing. Understanding and controlling the properties of their dielectric waveguides is critical for the performance of these chips. We report that thermal annealing of PECVD-grown silicon dioxide (SiO) ridge waveguides results in considerable improvements to optical transmission and particle detection. There are two fundamental changes that yield higher optical transmission: (1) propagation loss in solid-core waveguides is reduced by over 70%, and (2) coupling efficiencies between solid- and liquid-core waveguides are optimized. The combined effects result in improved optical chip transmission by a factor of 100-1000 times. These improvements are shown to arise from the elimination of a high-index layer at the surface of the SiO caused by water absorption into the porous oxide. The effects of this layer on optical transmission and mode confinement are shown to be reversible by alternating subjection of waveguides to water and subsequent low temperature annealing. Finally, we show that annealing improves detection of fluorescent analytes in optofluidic chips with a signal-to-noise ratio improvement of 166x and a particle detection efficiency improvement of 94%.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27547023
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Mechanical flexibility and the advent of scalable, low-cost, and high-throughput fabrication techniques have enabled numerous potential applications for plasmonic sensors. Sensitive and sophisticated biochemical measurem...Mechanical flexibility and the advent of scalable, low-cost, and high-throughput fabrication techniques have enabled numerous potential applications for plasmonic sensors. Sensitive and sophisticated biochemical measurements can now be performed through the use of flexible plasmonic sensors integrated into existing medical and industrial devices or sample collection units. More robust sensing schemes and practical techniques must be further investigated to fully realize the potentials of flexible plasmonics as a framework for designing low-cost, embedded and integrated sensors for medical, environmental, and industrial applications.
Singh M, Li J, Vantipalli S
… +6 more, Wang S, Han Z, Nair A, Aglyamov SR, Twa MD, Larin KV
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27547022
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The mechanical properties of tissues can provide valuable information about tissue integrity and health and can assist in detecting and monitoring the progression of diseases such as keratoconus. Optical coherence elasto...The mechanical properties of tissues can provide valuable information about tissue integrity and health and can assist in detecting and monitoring the progression of diseases such as keratoconus. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess localized mechanical contrast in tissues with micrometer spatial resolution. In this work we present a noncontact method of optical coherence elastography to evaluate the changes in the mechanical properties of the cornea after UV-induced collagen cross-linking. A focused air-pulse induced a low amplitude (μm scale) elastic wave, which then propagated radially and was imaged in three dimensions by a phase-stabilized swept source optical coherence tomography (PhS-SSOCT) system. The elastic wave velocity was translated to Young's modulus in agar phantoms of various concentrations. Additionally, the speed of the elastic wave significantly changed in porcine cornea before and after UV-induced corneal collagen cross-linking (CXL). Moreover, different layers of the cornea, such as the anterior stroma, posterior stroma, and inner region, could be discerned from the phase velocities of the elastic wave. Therefore, because of noncontact excitation and imaging, this method may be useful for detection of ocular diseases such as keratoconus and evaluation of therapeutic interventions such as CXL.
Ozcelik D, Stott MA, Parks JW
… +4 more, Black JA, Wall TA, Hawkins AR, Schmidt H
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27524876
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We present fluorescence detection of single H1N1 viruses with enhanced signal to noise ratio () achieved by multi-spot excitation in liquid-core anti-resonant reflecting optical waveguides (ARROWs). Solid-core Y-splittin...We present fluorescence detection of single H1N1 viruses with enhanced signal to noise ratio () achieved by multi-spot excitation in liquid-core anti-resonant reflecting optical waveguides (ARROWs). Solid-core Y-splitting ARROW waveguides are fabricated orthogonal to the liquid-core section of the chip, creating multiple excitation spots for the analyte. We derive expressions for the increase after signal processing, and analyze its dependence on signal levels and spot number. Very good agreement between theoretical calculations and experimental results is found. enhancements up to 5x10 are demonstrated.
Wang Y, Kang S, Doerksen JD
… +2 more, Glaser AK, Liu JT
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27524875
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The imaging of dysregulated cell-surface receptors (or biomarkers) is a potential means of identifying the presence of cancer with high sensitivity and specificity. However, due to heterogeneities in the expression of pr...The imaging of dysregulated cell-surface receptors (or biomarkers) is a potential means of identifying the presence of cancer with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Recently, surface-enhanced Raman-scattering (SERS) nanoparticles (NPs) have attracted wide interest due to their potential for sensitive and multiplexed biomarker detection. In this review, we focus on the most recent advances in tumor imaging using SERS-coded NPs. A brief introduction of the structure and optical properties of SERS NPs is provided, followed by a detailed discussion of key imaging issues such as the administration of NPs in tissue (topical versus systemic), the optical configuration and imaging approach of Raman imaging systems, spectral demultiplexing methods for quantifying NP concentrations, and the disambiguation of specific vs. nonspecific sources of contrast through ratiometric imaging of targeted and untargeted (control) NP pairs. Finally, future challenges and directions are briefly outlined.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27440991
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Small molecule therapeutic drugs must reach their intended cellular targets (pharmacokinetics) and engage them to modulate therapeutic effects (pharmacodynamics). These processes are often difficult to measure in vivo du...Small molecule therapeutic drugs must reach their intended cellular targets (pharmacokinetics) and engage them to modulate therapeutic effects (pharmacodynamics). These processes are often difficult to measure in vivo due to their complexities and occurrence within single cells. It has been particularly difficult to directly measure cellular drug target binding. Fluorescence polarization is commonly used in pharmacological screening assays to measure drug-protein or protein-protein interactions. We hypothesized that fluorescence polarization imaging could be adapted and used with fluorescently labeled drugs to measure drug target engagement in vivo. Here we summarize recent results using two photon fluorescence anisotropy microscopy. Our imaging technique offers quantitative pharmacological binding information of diverse molecular interactions at the microscopic level, differentiating between bound and unbound states. Used in combination with other recent advances in the development of novel fluorescently labeled drugs, we expect that the described imaging modality will provide a window into the distribution and efficacy of drugs in real time and in vivo at the cellular and subcellular level.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27429543
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Optical coherence tomography (OCT) has gained widespread application for many biomedical applications, yet the traditional array of contrast agents used in incoherent imaging modalities do not provide contrast in OCT. Ow...Optical coherence tomography (OCT) has gained widespread application for many biomedical applications, yet the traditional array of contrast agents used in incoherent imaging modalities do not provide contrast in OCT. Owing to the high biocompatibility of iron oxides and noble metals, magnetic and plasmonic nanoparticles, respectively, have been developed as OCT contrast agents to enable a range of biological and pre-clinical studies. Here we provide a review of these developments within the past decade, including an overview of the physical contrast mechanisms and classes of OCT system hardware addons needed for magnetic and plasmonic nanoparticle contrast. A comparison of the wide variety of nanoparticle systems is also presented, where the figures of merit depend strongly upon the choice of biological application.
Qu Y, Ma T, He Y
… +8 more, Zhu J, Dai C, Yu M, Huang S, Lu F, Shung KK, Zhou Q, Chen Z
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27293369
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We report on a real-time acoustic radiation force optical coherence elastography (ARF-OCE) system to map the relative elasticity of corneal tissue. A modulated ARF is used as excitation to vibrate the cornea while OCE se...We report on a real-time acoustic radiation force optical coherence elastography (ARF-OCE) system to map the relative elasticity of corneal tissue. A modulated ARF is used as excitation to vibrate the cornea while OCE serves as detection of tissue response. To show feasibility of detecting mechanical contrast using this method, we performed tissue-equivalent agarose phantom studies with inclusions of a different stiffness. We obtained 3-D elastograms of a healthy cornea and a highly cross-linked cornea. Finally we induced a stiffness change on a small portion of a cornea and observed the differences in displacement.
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27013847
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Microbial contamination of cell culture is a major problem encountered both in academic labs and in the biotechnology/pharmaceutical industries. A broad spectrum of microbes including mycoplasma, bacteria, fungi, and vir...Microbial contamination of cell culture is a major problem encountered both in academic labs and in the biotechnology/pharmaceutical industries. A broad spectrum of microbes including mycoplasma, bacteria, fungi, and viruses are the causative agents of cell culture contamination. Unfortunately, the existing disinfection techniques lack selectivity and/or lead to the development of drug-resistance, and more importantly there is no universal method to address all microbes. Here, we report a novel, chemical-free visible ultrashort pulsed laser method for cell culture disinfection. The ultrashort pulsed laser technology inactivates pathogens with mechanical means, a paradigm shift from the traditional pharmaceutical and chemical approaches. We demonstrate that ultrashort pulsed laser treatment can efficiently inactivate mycoplasma, bacteria, yeast, and viruses with good preservation of mammalian cell viability. Our results indicate that this ultrashort pulsed laser technology has the potential to serve as a universal method for the disinfection of cell culture.
Choi B, Tan W, Jia W
… +7 more, White SM, Moy WJ, Yang BY, Zhu J, Chen Z, Kelly KM, Nelson JS
IEEE J Sel Top Quantum Electron
· 2016 · PMID 27013846
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Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable...Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with anti-angiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.
Cheng B, Wei MY, Liu Y
… +5 more, Pitta H, Xie Z, Hong Y, Nguyen KT, Yuan B
IEEE J Sel Top Quantum Electron
· 2014 · PMID 26052192
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In this work we first introduced a recently developed high-resolution, deep-tissue imaging technique, ultrasound-switchable fluorescence (USF). The imaging principles based on two types of USF contrast agents were review...In this work we first introduced a recently developed high-resolution, deep-tissue imaging technique, ultrasound-switchable fluorescence (USF). The imaging principles based on two types of USF contrast agents were reviewed. To improve USF imaging techniques further, excellent USF contrast agents were developed based on high-performance thermoresponsive polymers and environment-sensitive fluorophores. Herein, such contrast agents were synthesized and characterized with five key parameters: (1) peak excitation and emission wavelengths (λ and λ), (2) the fluorescence intensity ratio between on and off states (I/I), (3) the fluorescence lifetime ratio between on and off states (τ/τ), (4) the temperature threshold to switch on fluorophores (T), and (5) the temperature transition bandwidth (T). We mainly investigated fluorescence intensity and lifetime changes of four environment-sensitive dyes [7-(2-Aminoethylamino)-N,N-dimethyl-4-benzofurazansulfonamide (DBD-ED), St633, Sq660, and St700] as a function of temperature, while the dye was attached to poly(N-isopropylacrylamide) linear polymers or encapsulated in nanoparticles. Six fluorescence resonance energy transfer systems were invented in which both the donor (DBD-ED or ST425) and the acceptor (Sq660) were adopted. Our results indicate that three Förster resonance energy transfer systems, where both I/I and τ/τ are larger than 2.5, are promising for application in future surface tissue bioimaging by USF technique.
IEEE J Sel Top Quantum Electron
· 2014 · PMID 25642129
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Lymphatic vessels are a part of circulatory system in vertebrates that maintain tissue fluid homeostasis and drain excess fluid and large cells that cannot easily find their way back into venous system. Due to the lack o...Lymphatic vessels are a part of circulatory system in vertebrates that maintain tissue fluid homeostasis and drain excess fluid and large cells that cannot easily find their way back into venous system. Due to the lack of non-invasive monitoring tools, lymphatic vessels are known as forgotten circulation. However, lymphatic system plays an important role in diseases such as cancer and inflammatory conditions. In this paper, we start to briefly review the current existing methods for imaging lymphatic vessels, mostly involving dye/targeting cell injection. We then show the capability of optical coherence tomography (OCT) for label-free non-invasive in vivo imaging of lymph vessels and nodes. One of the advantages of using OCT over other imaging modalities is its ability to assess label-free blood flow perfusion that can be simultaneously observed along with lymphatic vessels for imaging the microcirculatory system within tissue beds. Imaging the microcirculatory system including blood and lymphatic vessels can be utilized for imaging and better understanding pathologic mechanisms and treatment technique development in some critical diseases such as inflammation, malignant cancer angiogenesis and metastasis.
Zawadzki RJ, Capps AG, Kim DY
… +4 more, Panorgias A, Stevenson SB, Hamann B, Werner JS
IEEE J Sel Top Quantum Electron
· 2014 Mar · PMID 25544826
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Recent progress in retinal image acquisition techniques, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), combined with improved performance of adaptive optics (AO) instrumentation, h...Recent progress in retinal image acquisition techniques, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), combined with improved performance of adaptive optics (AO) instrumentation, has resulted in improvement in the quality of images of cellular structures in the human retina. Here, we present a short review of progress on developing AO-OCT instruments. Despite significant progress in imaging speed and resolution, eye movements present during acquisition of a retinal image with OCT introduce motion artifacts into the image, complicating analysis and registration. This effect is especially pronounced in high-resolution datasets acquired with AO-OCT instruments. Several retinal tracking systems have been introduced to correct retinal motion during data acquisition. We present a method for correcting motion artifacts in AO-OCT volume data after acquisition using simultaneously captured adaptive optics-scanning laser ophthalmoscope (AO-SLO) images. We extract transverse eye motion data from the AO-SLO images, assign a motion adjustment vector to each AO-OCT -scan, and re-sample from the scattered data back onto a regular grid. The corrected volume data improve the accuracy of quantitative analyses of microscopic structures.