The traditional phase-resolved Doppler method demonstrates great success for in-vivo imaging of blood flow and blood vessels. However, the phase-resolved method always requires high phase stability of the system. In phase instable situations, the performance of the phase-resolved methods will be degraded. We propose a modified Doppler variance algorithm that is based on the intensity or amplitude value. Performances of the proposed algorithm are compared with traditional phase-resolved Doppler variance and color Doppler methods for both phase stable and phase instable systems. For the phase instable situation, the proposed algorithm demonstrates images without phase instability induced artifacts. In-vivo imaging of window-chamber hamster skin is demonstrated for phase instable situation with a spectrometer-based Fourier domain OCT system. A microelectromechanical systems (MEMS) based swept source OCT (SSOCT) system is also used to demonstrate the performance of the proposed method in a phase instable situation. The phase stability of the SSOCT system is analyzed. In-vivo imaging of the blood vessel of human skin is demonstrated with the proposed method and the SSOCT system. For the phase stable situation, the proposed algorithm also demonstrates comparable performance with traditional phase-resolved methods. In-vivo imaging of the human choroidal blood vessel network is demonstrated with the proposed method under the phase stable situation. Depth-resolved fine choroidal blood vessel networks are shown.
Abstract. Many diseases involve changes in the biomechanical properties of tissue, and there is a close correlation between tissue elasticity and pathology. We report on the development of a phase-resolved acoustic radiation force optical coherence elastography method (ARF-OCE) to evaluate the elastic properties of tissue. This method utilizes chirped acoustic radiation force to produce excitation along the sample's axial direction, and it uses phase-resolved optical coherence tomography (OCT) to measure the vibration of the sample. Under 500-Hz square wave modulated ARF signal excitation, phase change maps of tissue mimicking phantoms are generated by the ARF-OCE method, and the resulting Young's modulus ratio is correlated with a standard compression test. The results verify that this technique could efficiently measure sample elastic properties accurately and quantitatively. Furthermore, a three-dimensional ARF-OCE image of the human atherosclerotic coronary artery is obtained. The result indicates that our dynamic phase-resolved ARF-OCE method can delineate tissues with different mechanical properties.
Ciliary motion plays a critical role in the overall respiratory health of the upper airway. These cilia beat at a native frequency and in a synchronized pattern to continuously transport foreign particulate trapped in a layer of mucous out of the upper airway. Disruption of ciliary motion can lead to severe respiratory diseases and compromised respiratory function. Currently, the study of cilia requires expensive high speed cameras and high powered microscopes which is unsuitable for in vivo imaging and diagnosis. Doppler based optical coherence tomography has the potential to visualize the microscopic motion of cilia during their beating cycle. We demonstrate the development of a high-speed Doppler optical coherence tomography system that not only can rapidly determine the cilia beat frequency, but also simultaneously visualize the temporal cilia beating pattern which plays critical roles in cilia function.
Rationale: Subglottic edema and acquired subglottic stenosis are potentially airway-compromising sequelae in neonates following endotracheal intubation. At present, no imaging modality is capable of in vivo diagnosis of subepithelial airway wall pathology as signs of intubation-related injury.Objectives: To use Fourier domain long-range optical coherence tomography (LR-OCT) to acquire micrometer-resolution images of the airway wall of intubated neonates in a neonatal intensive care unit setting and to analyze images for histopathology and airway wall thickness.Methods: LR-OCT of the neonatal laryngotracheal airway was performed a total of 94 times on 72 subjects (age, 1-175 d; total intubation, 1-104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records were reviewed retrospectively for extubation outcome. Measurements and Main Results:Backward stepwise regression analysis demonstrated a statistically significant association between log(duration of intubation) and both laryngeal (P , 0.001; multiple r 2 = 0.44) and subglottic (P , 0.001; multiple r 2 = 0.55) airway wall thickness. Subjects with positive histopathology on LR-OCT images had a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer intubation time was found to be significantly associated with extubation failure.Conclusions: LR-OCT allows for high-resolution evaluation and measurement of the airway wall in intubated neonates. Our data demonstrate a positive correlation between laryngeal and subglottic wall thickness and duration of intubation, suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the early diagnosis of postintubation subglottic injury and help reduce the incidences of failed extubation caused by subglottic edema or acquired subglottic stenosis in neonates.Clinical trial registered with www.clinicaltrials.gov (NCT 00544427).
Thermosynechococcus is a genus of thermophilic unicellular cyanobacteria that are dominant in microbial mats at about 50-65 • C in alkaline hot springs of eastern Asia. We used PacBio SMRT Sequencing to sequence the complete genome of a novel strain of thermophilic cyanobacterium, Thermosynechococcus sp. CL-1, isolated from the Chin-Lun hot spring (pH 9.3, 62 • C) in Taiwan. Genome-scale phylogenetic analysis and average nucleotide identity (ANI) results suggested that CL-1 is a new species in the genus Thermosynechococcus. Comparative genome analysis revealed divergent genome structures of Thermosynechococcus strains. In addition, the distinct genetic differences between CL-1 and the other Thermosynechococcus strains are related to photosynthesis, transporters, signal transduction, the chaperone/usher system, nitric oxide protection, antibiotic resistance, prokaryotic immunity systems, and other physiological processes. This study suggests that Thermosynechococcus strains have actively acquired many putative horizontally transferred genes from other bacteria that enabled them to adapt to different ecological niches and stressful conditions in hot springs.
Diagnosis and treatment of vocal fold lesions has been a long-evolving science for the otolaryngologist. Contemporary practice requires biopsy of a glottal lesion in the operating room under general anesthesia for diagnosis. Current in-office technology is limited to visualizing the surface of the vocal folds with fiber-optic or rigid endoscopy and using stroboscopic or high-speed video to infer information about submucosal processes. Previous efforts using optical coherence tomography (OCT) have been limited by small working distances and imaging ranges. Here we report the first full field, high-speed, and long-range OCT images of awake patients’ vocal folds as well as cross-sectional video and Doppler analysis of their vocal fold motions during phonation. These vertical-cavity surface-emitting laser source (VCSEL) OCT images offer depth resolved, high-resolution, high-speed, and panoramic images of both the true and false vocal folds. This technology has the potential to revolutionize in-office imaging of the larynx.
Optical coherence tomography (OCT) has gained wide adoption in biological research and medical imaging due to its exceptional tissue penetration, 3D imaging speed and rich contrast. However, OCT plays a relatively small role in molecular and cellular imaging due to the lack of suitable biomolecular contrast agents. In particular, while the green fluorescent protein has provided revolutionary capabilities to fluorescence microscopy by connecting it to cellular functions such as gene expression, no equivalent reporter gene is currently available for OCT. Here we introduce gas vesicles, a class of naturally evolved gas-filled protein nanostructures, as genetically encodable OCT contrast agents. The differential refractive index of their gas compartments relative to surrounding aqueous tissue and their nanoscale motion enables gas vesicles to be detected by static and dynamic OCT. Furthermore, the OCT contrast of gas vesicles can be selectively erased in situ with ultrasound, allowing unambiguous assignment of their location. In addition, gas vesicle clustering modulates their temporal signal, enabling the design of dynamic biosensors. We demonstrate the use of gas vesicles as reporter genes in bacterial colonies and as purified contrast agents In Vivo in the mouse retina. Our results expand the utility of OCT to image a wider variety of cellular and molecular processes.
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