In recent years, endoscopic optical coherence tomography (OCT) has garnered widespread attention for non-invasive advantages in achieving three-dimensional visualization of internal organ cavities. In early-stage lesions, microvascular alterations occur before morphological tissue changes. Therefore, utilizing endoscopic OCTA for the detection of superficial capillaries serves as an adjunctive method for early disease screening. About ten years ago, the advantages of high-speed and stable operation of distal motorized catheters enabled the realization of endoscopic OCTA. However, the internal micro-motors lead to a larger outer diameter of distal imaging catheters, which restricts their clinical applicability for monitoring diseases in narrow luminal structures. Consequently, proximal imaging catheters, with their smaller size, have found its wide application in the commercial arena. However, due to limitations in external motor speed and susceptibility to external vibrations, there were no reports of proximal imaging catheters achieving endoscopic OCTA for a long time. Recently, we proposed the MB-scan scheme to mitigate the impact of external motion artifacts and achieve endoscopic OCTA based on a proximal catheter. The Singular Value Decomposition (SVD) algorithm was employed to eliminate static tissue information and obtain en face OCTA images of the murine rectum. In this study, we proposed a fast endoscopic OCTA using proximal scanning catheter based on B-scan scheme and a customed image registration algorithm. Image registration based on the similarity between adjacent B-scan frames was utilized to reduce the impact of external motor vibrations and improve image quality. Based on the registered images at the same scanning position, the speckle variance (SVAR) algorithm was employed to calculate variation of OCT intensity signals. Finally, en face OCTA images were generated. Collecting data from the mouse rectum, endoscopic OCTA images were obtained from the registered data using the SVAR algorithm.
Electromechanical reshaping (EMR) has the potential to change corneal shape to correct refractive errors without altering the mechanical properties of the cornea. Using acoustic radiation force (ARF) to stimulate the cornea of ex vivo New Zealand white rabbit globes and optical coherence elastography (OCE) to detect corneal response, the cornea’s elasticity was quantitatively determined pre- and post-EMR treatment. In addition, an optical coherence tomography (OCT) system was used to determine changes in corneal curvature. Ultimately, EMR treatment induced a shape change in the cornea and the elasticity of the cornea was similar before and after EMR treatment, indicating minimal damage.
We present an early release of our study utilizing a fiber-based Optical Coherence Tomography (OCT) probe to acquire 3D images of the airway in sleep apnea patients. The probe, with a 1.3mm diameter, navigates from the nasal cavity to the vocal cords while rotating within a transparent protective sheath. Long-range OCT imaging (2-30mm) enables comprehensive airway visualization. Our approach facilitates airflow dynamic analysis, aiding in the identification of critical regions prone to collapse during sleep. This non-invasive technique promises to revolutionize sleep apnea diagnostics and personalized treatment planning, offering substantial benefits to patient care.
Proper ciliary dynamics is vital for effective mucociliary transport, the primary defense mechanism for the upper respiratory tract. Abnormal cilia behavior could lead to chronic respiratory disease, making it essential to conduct more detailed studies. In this study we present a multimodality system, specifically using optical coherence tomography (OCT) and phase-resolved spectrally encoded interferometric microscopy (PR-SEIM). We have already shown that PR-SEIM is capable of measuring cilia beat frequency ex vivo. Although we were able to visually identify the ciliary motion in the nasal cavity of rabbits in vivo, due to its sensitivity to motion artifacts, it has been difficult to quantitatively analyze ciliary dynamics. To overcome this obstacle, we incorporated OCT along with a high-speed laser source to compensate for bulk motion. Ultimately, this system will provide a way to study ciliary dynamics in its natural environment, thus allowing more in-depth understanding of ciliary functions.
In this study, Optical Coherence Tomography (OCT) was used to image the large upper airway in a rabbit model. U-net convolutional neural network (CNN) was used to automate the segmentation of large airway edema and tissue changes. Peak edema volume was reached at 30-minutes post-chlorine gas exposure, then down trended until the 6-hour timepoint. Herein, we show the streamlining of OCT imaging analysis status-post chlorine inhalation injury using CNNs.
Mucociliary clearance is an important physiological mechanism for clearing the upper airways. Previously, it has been shown that different disease processes and drugs affect ciliary beat frequency (CBF). Namely, epinephrine has been shown to accelerate CBF in various animal models. Additionally, phase contrast microscopy (PCM) and spectrally encoded interferometric microscopy (SEIM) have been used to image dynamic tissue of the upper airway. Herein, we explore the effects of epinephrine on human sinonasal mucosa through PCM and SEIM. Sinonasal mucosa was harvested from patients undergoing endoscopic sinus surgery (ESS). Tissue was imaged using PCM and SEIM, maintaining physiological temperature through the use of warmed HBSS and a heating plate. Videos were taken before addition of any drugs as baseline. Epinephrine was diluted to 1 mg/mL (1:1000) and 1mL of solution was introduced to the sinonasal mucosa. PCM and SEIM was performed after to determine effects of epinephrine on CBF. Data analysis was performed using MATLAB (Mathworks, Natick, Massachusetts). Human sinonasal mucosa, taken from various anatomic locations, showed CBF values on PCM and SEIM consistent with what has been shown in previous literature. Upon addition of epinephrine to sinonasal mucosa, a marked increase in CBF was observed in both PCM and SEIM. In conclusion, the addition of epinephrine to sinonasal mucosa increased ciliary beat frequency. This validates the use of SEIM for determining CBF in sinonasal tissues. Further studies include adding to our sample size to determine a more accurate magnitude of increase of CBF.
Mucociliary clearance is vital for preventing any foreign substances from entering the upper airway that can later develop into acute and/or chronic respiratory diseases. Therefore, it is essential to further advance our understanding of the mucociliary functions. Our lab has been able to make key developments in imaging cilia, specifically measuring cilia beat frequency, with phase-resolved Doppler optical coherence tomography. In this system, we have further developed the system by incorporating phase-resolved spectrally encoded interferometric microscopy (SIEM) system with an FDML laser with MHz sweep rate to image cilia with higher accuracy and to minimize motion artifacts. In addition, we have designed a compact handheld probe system with a GRIN lens for easier in vivo imaging. The development of this system will allow us to further investigate cilia dynamics and ultimately utilize the system for clinical applications.
Mucociliary clearance facilitated by healthy cilia beating is crucial to normal upper airway function. Phase-contrast microscopy (PCM) is the current golden standard for measuring ciliary beat frequency (CBF) and has limitations. With PCM, one cannot appreciate how CBF varies across the complex landscape of the nasal vault and sinus tissues. With Spectrally encoded interferometric microscopy (SEIM), en face imaging of cilia can be achieved, providing insight into the changes in CBF across tissue surfaces. This study aims to validate the use of SEIM to quantify ciliary beat frequency across ex vivo upper airway tissue.
In human airway, the ciliated cells and mucus are the first line of defense against inhaled pathogens and particulates, preventing them from invading the rest of the respiratory system. Ciliary dysfunction can quickly develop into a vulnerability for patients with acute and/or chronic diseases, including cystic fibrosis, asthma, chronic obstructive pulmonary disease, and primary cilia dyskinesia. Ciliary beating frequency (CBF) can provide a good standard for determining cilia functionality. In this study, we developed a homemade prototype front-facing endoscope based on a spectrally encoded interferometric microscopy (SEIM) system using a phase-resolved Doppler (PRD) algorithm to measure and map the ciliary beating frequency within an en face region. We evaluated the capability of assessing the CBF ex vivo. This study is the steppingstone to in-vivo studies and the translation of mapping spatial CBF in clinics.
In this work, we demonstrate the ability to image and quantify airway changes, we were able to quantify a decrease in airway compliance. The proposed approach will enable further investigations of using OCT assessing pulmonary injury to prevent/treat ARDS using a chlorine inhalation injury model, as well as diagnosing of large airway injury and compliance change due to airway toxic chemical exposure. With enhanced portability over conventional bronchoscopy, we believe our system is capable of field hospital deployment and investigating airway conditions in warfighters. Combining OCT and pressure transducer with bronchoscopy would enhance assessment and treatment of large airway chemical injury.
In this work, we demonstrate the ability to image and quantify airway changes, edema, and epithelial layer separation using OCT and automated tissue boundary identification in the rabbit large airways as early as 30-minutes post-chlorine gas exposure. We propose this novel approach will enable further investigations into using OCT for pre-hospital and point-of-care diagnostics of large airway injury due to airway toxic chemical exposure. With enhanced portability over conventional bronchoscopy, we believe our system is capable of field hospital deployment and investigating airway conditions in warfighters. Combining OCT with bronchoscopy would enhance the assessment and treatment of large airway chemical injury.
Spectrally encoded interferometric microscopy (SEIM) is capable of detecting nanometer displacement at a frame rate in the kilohertz regime. By employing a wavelength-sweeping laser and a spectral disperser, SEIM can achieve en face imaging via one-axis scanning. In this study, we compared different processing algorithms for visualizing cilia-induced motion. Our Doppler-based method, combined with phase stabilization and bulk motion correction, provides the highest sensitivity for measuring ciliary beating frequency amongst the tested methods. Traveling waves induced by coordinated cilia motion were visualized. These results demonstrate the potential clinical utility of SEIM for monitoring respiratory function and therapeutic effects.
Phase stability of an optical coherence elastography (OCE) system is the key determining factor for precision elasticity measurement. In this study, we developed an OCE system based on swept-source optical coherence tomography (SS-OCT) with a common-path configuration (SS-OCECP). Our system has a phase stability of 4.2 mrad without external stabilization or extensive post-processing, such as averaging. This phase stability allows us to detect a displacement as small as ~300 pm. We validated the SS-OCECP performance in a tissue-mimicking phantom and an in vivo rabbit model, and the results demonstrated significant improved phase stability compared to conventional SS-OCE. To the best of our knowledge, we demonstrated the first SS-OCECP system, which possess high phase stability and can be utilized to significantly improve the sensitivity of elastography.
Degenerative joint disease (DJD) is a disease that the articular cartilage changes from hyaline cartilage to fibrous cartilage. PS-OCT may provide a method to quantitatively analyze cartilage birefringence and diagnose DJD. Here, we proposed a novel PS-OCT system that uses spun fiber to construct the sample arm. In this work, phase retardation map, optical axis map, and conventional OCT images of hyaline cartilage and fibrous cartilage are presented, and the differences in the birefringence of these two types of cartilage are identified. The proposed PS-OCT system demonstrates great potential for accurate diagnosis of DJD in the clinic.
Endoscopic optical coherence tomography (OCT) and near-infrared (NIR) fluorescence imaging system was developed for characterization of colorectal cancer (CRC). NIR fluorescence is able to highlight the cancer-suspected area based on significant change of tumor vascular density and morphology. Co-registered OCT images has the capability of visualizing subsurface tissue layer architecture, so the suspected regions can be further investigated by the altered light scattering resulted from the morphological abnormality. The imaging result from in vivo rat experiment has demonstrated the enhanced capability of identification and classification of CRC compared to using any of these technologies alone, thus has the potential to provide a new clinical tool to advance gastroenterology practice.
Colorectal cancer, the third most common type of cancer globally, has ~1.4 million new cases and 694,000 deaths annually. Endoscopic photoacoustic (PA) imaging is a non-invasive imaging modality that provides structural, functional and molecular information while maintaining a deep depth. Several groups have reported different designs of endoscopic PA imaging systems that represent a significant step forward for the characterization of gastrointestinal (GI) cancer. However, these imaging systems are still not adequate for in-vivo clinical translation due to insufficient field-of-view, large probe diameters, and slow imaging speed. Endoscopic dual-modality photoacoustic and ultrasound imaging has the potential for early detection of cancer in the gastrointestinal tract. Currently, slow imaging speed is one of the limitations for clinical translation. In this study, we demonstrate an integrated endoscopic PA and US imaging system. Utilizing a high repetition rate pulsed laser, optimized rotary joint as well as proximal scanning method, this integrated imaging system is able to obtain morphological tissue information and vasculature of the GI tract simultaneously at a high imaging speed up to 50 frames/s (the fastest speed reported to date). We conducted in-vivo animal studies to demonstrate the performance of our imaging system for evaluating the GI tract. The results obtained from the in-vivo rat experiment showed that the typical layered architecture and vasculature can be identified by this integrated system with a high imaging speed.
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