Optical coherence tomography in gastroenterology: a review and future outlook.

Optical coherence tomography (OCT) is an imaging technique optically analogous to ultrasound that can generate depth-resolved images with micrometer-scale resolution. Advances in fiber optics and miniaturized actuation technologies allow OCT imaging of the human body and further expand OCT utilization in applications including but not limited to cardiology and gastroenterology. This review article provides an overview of current OCT development and its clinical utility in the gastrointestinal tract, including disease detection/differentiation and endoscopic therapy guidance, as well as a discussion of its future applications.

Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs.

Mucociliary transport (MCT) is an innate defense mechanism that removes particulates, noxious material, and microorganisms from the lung. Several airway diseases exhibit abnormal MCT, including asthma, chronic bronchitis, and cystic fibrosis. However, it remains uncertain whether MCT abnormalities contribute to the genesis of disease or whether they are secondary manifestations that may fuel disease progression.

Four-dimensional visualization of subpleural alveolar dynamics in vivo during uninterrupted mechanical ventilation of living swine.

Pulmonary alveoli have been studied for many years, yet no unifying hypothesis exists for their dynamic mechanics during respiration due to their miniature size (100-300 μm dimater in humans) and constant motion, which prevent standard imaging techniques from visualizing four-dimensional dynamics of individual alveoli in vivo. Here we report a new platform to image the first layer of air-filled subpleural alveoli through the use of a lightweight optical frequency domain imaging (OFDI) probe that can be placed upon the pleura to move with the lung over the complete range of respiratory motion. This device enables in-vivo acquisition of four-dimensional microscopic images of alveolar airspaces (alveoli and ducts), within the same field of view, during continuous ventilation without restricting the motion or modifying the structure of the alveoli.

Optical coherence tomography imaging during thyroid and parathyroid surgery: a novel system of tissue identification and differentiation to obviate tissue resection and frozen section.

Background: Optical coherence tomography (OCT) allows tissue histologic-like evaluation, but without tissue fixation or staining. We investigated OCT images from tissues obtained at thyroid and parathyroid surgeries to provide a preliminary assessment as to whether these images contain sufficient information for recognition and differentiation of normal neck tissues.

Methods: Normal tissues were obtained from patients undergoing surgical treatment.

Validation of two-dimensional and three-dimensional measurements of subpleural alveolar size parameters by optical coherence tomography.

Optical coherence tomography (OCT) has been increasingly used for imaging pulmonary alveoli. Only a few studies, however, have quantified individual alveolar areas, and the validity of alveolar volumes represented within OCT images has not been shown. To validate quantitative measurements of alveoli from OCT images, we compared the cross-sectional area, perimeter, volume, and surface area of matched subpleural alveoli from microcomputed tomography (micro-CT) and OCT images of fixed air-filled swine samples.

Evaluation of optical reflectance techniques for imaging of alveolar structure.

Three-dimensional (3-D) visualization of the fine structures within the lung parenchyma could advance our understanding of alveolar physiology and pathophysiology. Current knowledge has been primarily based on histology, but it is a destructive two-dimensional (2-D) technique that is limited by tissue processing artifacts. Micro-CT provides high-resolution three-dimensional (3-D) imaging within a limited sample size, but is not applicable to intact lungs from larger animals or humans.

Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo.

Advancing understanding of human coronary artery disease requires new methods that can be used in patients for studying atherosclerotic plaque microstructure in relation to the molecular mechanisms that underlie its initiation, progression and clinical complications, including myocardial infarction and sudden cardiac death. Here we report a dual-modality intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo using a combination of optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging. By providing simultaneous molecular information in the context of the surrounding tissue microstructure, this new catheter could provide new opportunities for investigating coronary atherosclerosis and stent healing and for identifying high-risk biological and structural coronary arterial plaques in vivo.

Longitudinal assessment of lung cancer progression in the mouse using in vivo micro-CT imaging.

Purpose: Small animal micro-CT imaging is being used increasingly in preclinical biomedical research to provide phenotypic descriptions of genomic models. Most of this imaging is coincident with animal death and is used to show the extent of disease as an end point. Longitudinal imaging overcomes the limitation of single time-point imaging because it enables tracking of the natural history of disease and provides qualitative and, where possible, quantitative assessments of the effects of an intervention.

Lung structure phenotype variation in inbred mouse strains revealed through in vivo micro-CT imaging.

Within pulmonary research, the development of mouse models has provided insight into disease development, progression, and treatment. Structural phenotypes of the lung in healthy inbred mouse strains are necessary for comparison to disease models. To date, progress in the assessment of lung function in these small animals using whole lung function tests has been made.

Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children.

Rationale: Although airway abnormalities are common in patients with cystic fibrosis (CF), it is unknown whether they are all secondary to postnatal infection and inflammation, which characterize the disease.

Objectives: To learn whether loss of the cystic fibrosis transmembrane conductance regulator (CFTR) might affect major airways early in life, before the onset of inflammation and infection.

Methods: We studied newborn CFTR⁻(/)⁻ pig trachea, using computed tomography (CT) scans, pathology, and morphometry.

A process model for direct correlation between computed tomography and histopathology application in lung cancer.

Rationale And Objectives: Multimodal imaging techniques for capturing normal and diseased human anatomy and physiology are being developed to benefit patient clinical care, research, and education. In the past, the incorporation of histopathology into these multimodal datasets has been complicated by the large differences in image quality, content, and spatial association.

Materials And Methods: We have developed a novel system, the large-scale image microtome array (LIMA), to bridge the gap between nonstructurally destructive and destructive imaging such that reliable registration between radiological data and histopathology can be achieved.

The porcine lung as a potential model for cystic fibrosis.

Airway disease currently causes most of the morbidity and mortality in patients with cystic fibrosis (CF). However, understanding the pathogenesis of CF lung disease and developing novel therapeutic strategies have been hampered by the limitations of current models. Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like that in humans.

Alveolar dynamics during respiration: are the pores of Kohn a pathway to recruitment?

The change in alveolar size and number during the full breathing cycle in mammals remains unanswered, yet these descriptors are fundamental for understanding alveolar-based diseases and for improving ventilator management. Genetic and environmental mouse models are used increasingly to evaluate the evolution of disease in the peripheral lung; however, little is known regarding alveolar structure and function in the fresh, intact lung. Therefore, we have developed an optical confocal process to evaluate alveolar dynamics in the fresh intact mouse lung and as an initial experiment, have evaluated mouse alveolar dynamics during a single respiratory cycle immediately after passive lung deflation.

Stress distribution in a three dimensional, geometric alveolar sac under normal and emphysematous conditions.

Pulmonary emphysema is usually the result of chronic exposure to cigarette smoke in at risk individuals. To investigate the hypothesis that lung damage in emphysema results from coincident weakening in the structural properties of the tissue and increased mechanical forces--as one explanation of the continued development of pulmonary emphysema after smoking cessation--we developed a three dimensional, geometric dodecahedron-based acinar model. Using the model numerical analysis of the stress distribution in normal conditions could be compared with those resulting in emphysematous conditions.

Large image microscope array for the compilation of multimodality whole organ image databases.

Three-dimensional, structural and functional digital image databases have many applications in education, research, and clinical medicine. However, to date, apart from cryosectioning, there have been no reliable means to obtain whole-organ, spatially conserving histology. Our aim was to generate a system capable of acquiring high-resolution images, featuring microscopic detail that could still be spatially correlated to the whole organ.