Tawimas Shaipanich

A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography

We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 µm diameter catheter ‒ consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube ‒ was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways.

Absolute Leukocyte Telomere Length in HIV-Infected and Uninfected Individuals: Evidence of Accelerated Cell Senescence in HIV-Associated Chronic Obstructive Pulmonary Disease

Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

In vivo lung microvasculature visualized in three dimensions using fiber-optic color Doppler optical coherence tomography

Abstract. For the first time, the use of fiber-optic color Doppler optical coherence tomography (CDOCT) to map in vivo the three-dimensional (3-D) vascular network of airway segments in human lungs is demonstrated. Visualizing the 3-D vascular network in the lungs may provide new opportunities for detecting and monitoring lung diseases such as asthma, chronic obstructive pulmonary disease, and lung cancer. Our CDOCT instrument employs a rotary fiber-optic probe that provides simultaneous two-dimensional (2-D) real-time structural optical coherence tomography (OCT) and CDOCT imaging at frame rates up to 12.5 frames per second. Controlled pullback of the probe allows 3-D vascular mapping in airway segments up to 50 mm in length in a single acquisition. We demonstrate the ability of CDOCT to map both small and large vessels. In one example, CDOCT imaging allows assignment of a feature in the structural OCT image as a large (∼1  mm diameter) blood vessel. In a second example, a smaller vessel (∼80  μm diameter) that is indistinguishable in the structural OCT image is fully visualized in 3-D using CDOCT.

Endoscopic Doppler optical coherence tomography and autofluorescence imaging of peripheral pulmonary nodules and vasculature

We present the first endoscopic Doppler optical coherence tomography and co-registered autofluorescence imaging (DOCT-AFI) of peripheral pulmonary nodules and vascular networks in vivo using a small 0.9 mm diameter catheter. Using exemplary images from volumetric data sets collected from 31 patients during flexible bronchoscopy, we demonstrate how DOCT and AFI offer complementary information that may increase the ability to locate and characterize pulmonary nodules. AFI offers a sensitive visual presentation for the rapid identification of suspicious airway sites, while co-registered OCT provides detailed structural information to assess the airway morphology. We demonstrate the ability of AFI to visualize vascular networks in vivo and validate this finding using Doppler and structural OCT. Given the advantages of higher resolution, smaller probe size, and ability to visualize vasculature, DOCT-AFI has the potential to increase diagnostic accuracy and minimize bleeding to guide biopsy of pulmonary nodules compared to radial endobronchial ultrasound, the current standard of care.

Early detection and chemoprevention of lung cancer

Abstract:  Lung cancer is the most common cause of cancer death worldwide with more than 1.3 million people dying of the disease annually. While antitobacco initiatives in young people are important in preventing lung cancer in the long term, additional measures such as early detection and chemoprevention are needed for individuals already at risk due to past exposure to tobacco smoke. This review highlights the potential use of sputum, exhaled breath and blood biomarkers as well as thoracic CT and autofluorescence bronchoscopy for early detection. The current status of chemoprevention is summarized. The case for using a two‐step screening strategy is also discussed.

Fluorescence and Navigational Bronchoscopy

Bronchoscopy is a minimally invasive method for lung cancer diagnosis. Smaller and more maneuverable bronchoscopes with higher image resolution and an adequate biopsy channel are being developed. High-resolution multiplanar computed tomography (CT) is used to produce 3-dimensional virtual images of the bronchial tree. The target lesion can be confirmed by a mini-radial ultrasound probe and potentially other technologies such as optical coherence tomography. These tools may provide a safer alternative method to CT-guided transthoracic lung biopsy for peripheral lung lesions that are not pleural based.

Endoscopic high-resolution autofluorescence imaging and OCT of pulmonary vascular networks.

High-resolution imaging from within airways may allow new methods for studying lung disease. In this work, we report an endoscopic imaging system capable of high-resolution autofluorescence imaging (AFI) and optical coherence tomography (OCT) in peripheral airways using a 0.9 mm diameter double-clad fiber (DCF) catheter. In this system, AFI excitation light is coupled into the core of the DCF, enabling tightly focused excitation light while maintaining efficient collection of autofluorescence emission through the large diameter inner cladding of the DCF. We demonstrate the ability of this imaging system to visualize pulmonary vasculature as small as 12 μm in vivo.

Reproducibility of optical coherence tomography airway imaging.

Optical coherence tomography (OCT) is a promising imaging technique to evaluate small airway remodeling. However, the short-term insertion-reinsertion reproducibility of OCT for evaluating the same bronchial pathway has yet to be established. We evaluated 74 OCT data sets from 38 current or former smokers twice within a single imaging session. Although the overall insertion-reinsertion airway wall thickness (WT) measurement coefficient of variation (CV) was moderate at 12%, much of the variability between repeat imaging was attributed to the observer; CV for repeated measurements of the same airway (intra-observer CV) was 9%. Therefore, reproducibility may be improved by introduction of automated analysis approaches suggesting that OCT has potential to be an in-vivo method for evaluating airway remodeling in future longitudinal and intervention studies.

A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia

Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906–14. ©2016 AACR.

Lung vasculature imaging using speckle variance optical coherence tomography

Architectural changes in and remodeling of the bronchial and pulmonary vasculature are important pathways in diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. However, there is a lack of methods that can find and examine small bronchial vasculature in vivo. Structural lung airway imaging using optical coherence tomography (OCT) has previously been shown to be of great utility in examining bronchial lesions during lung cancer screening under the guidance of autofluorescence bronchoscopy. Using a fiber optic endoscopic OCT probe, we acquire OCT images from in vivo human subjects. The side-looking, circumferentially-scanning probe is inserted down the instrument channel of a standard bronchoscope and manually guided to the imaging location. Multiple images are collected with the probe spinning proximally at 100Hz. Due to friction, the distal end of the probe does not spin perfectly synchronous with the proximal end, resulting in non-uniform rotational distortion (NURD) of the images. First, we apply a correction algorithm to remove NURD. We then use a speckle variance algorithm to identify vasculature. The initial data show a vascaulture density in small human airways similar to what would be expected.