Mechanical Analysis of Atherosclerotic Plaques Based on Optical Coherence Tomography

Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction.     

Quantitative upper airway endoscopy with swept-source anatomical optical coherence tomography

Minimally invasive imaging of upper airway obstructions in children and adults is needed to improve clinical decision-making. Toward this goal, we demonstrate an anatomical optical coherence tomography (aOCT) system delivered via a small-bore, flexible endoscope to quantify the upper airway lumen geometry. Helical scans were obtained from a proximally-scanned fiber-optic catheter of 820 μm outer diameter and >2 mm focal length. Coupled with a long coherence length wavelength-swept light source, the system exhibited an SNR roll-off of < 10 dB over a 10 mm range. Operating at 10 rotations/s, the average accuracy of segmented cross-sectional areas was found to be −1.4 ± 1.0%. To demonstrate the capability of this system, aOCT was performed on a pediatric airway phantom and on ex vivo swine trachea. The ability for quantitative endoscopy afforded by this system can aid in diagnosis, medical and surgical decision making, and predictive modeling of upper airway obstructive disorders.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.3890) Medical optics instrumentation, (170.2150) Endoscopic imaging     

Line-scanning laser ophthalmoscope

Scanning laser ophthalmoscopy (SLO) is a powerful imaging tool with specialized applications limited to research and ophthalmology clinics due in part to instrument size, cost, and complexity. Conversely, low-cost retinal imaging devices have limited capabilities in screening, detection, and diagnosis of diseases. To fill the niche between these two, a hand-held, nonmydriatic line-scanning laser ophthalmoscope (LSLO) is designed, constructed, and tested on normal human subjects. The LSLO has only one moving part and uses a novel optical approach to produce wide-field confocal fundus images. Imaging modes include multiwavelength illumination and live stereoscopic imaging with a split aperture. Image processing and display functions are controlled with two stacked prototype compact printed circuit boards. With near shot-noise limited performance, the digital LSLO camera requires low illumination power (<500 microW) at near-infrared wavelengths. The line-scanning principle of operation is examined in comparison to SLO and other imaging modes. The line-scanning approach produces high-contrast confocal images with nearly the same performance as a flying-spot SLO. The LSLO may significantly enhance SLO utility for routine use by ophthalmologists, optometrists, general practitioners, and also emergency medical personnel and technicians in the field for retinal disease detection and other diverse applications.     

Accurate Prediction of Collapse Temperature using Optical Coherence Tomography-Based Freeze-Drying Microscopy

The objective of this study was to assess the feasibility of developing and applying a laboratory tool that can provide three-dimensional product structural information during freeze-drying and which can accurately characterize the collapse temperature (T_c) of pharmaceutical formulations designed for freeze-drying. A single-vial freeze dryer coupled with optical coherence tomography freeze-drying microscopy (OCT–FDM) was developed to investigate the structure and T_c of formulations in pharmaceutically relevant products containers (i.e., freeze-drying in vials). OCT–FDM was used to measure the T_c and eutectic melt of three formulations in freeze-drying vials. The T_c as measured by OCT–FDM was found to be predictive of freeze-drying with a batch of vials in a conventional laboratory freeze dryer. The freeze-drying cycles developed using OCT–FDM data, as compared with traditional light transmission freeze-drying microscopy (LT-FDM), resulted in a significant reduction in primary drying time, which could result in a substantial reduction of manufacturing costs while maintaining product quality. OCT–FDM provides quantitative data to justify freeze-drying at temperatures higher than the T_c measured by LT-FDM and provides a reliable upper limit to setting a product temperature in primary drying.     

Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance

Fine needle aspiration biopsy (FNAB) is a rapid and cost-effective method for obtaining a first-line diagnosis of a palpable mass of the breast. However, because it can be difficult to manually discriminate between adipose tissue and the fibroglandular tissue more likely to harbor disease, this technique is plagued by a high number of nondiagnostic tissue draws. We have developed a portable, low coherence interferometry (LCI) instrument for FNAB guidance to combat this problem. The device contains an optical fiber probe inserted within the bore of the fine gauge needle and is capable of obtaining tissue structural information with a spatial resolution of 10 mum over a depth of approximately 1.0 mm. For such a device to be effective clinically, algorithms that use the LCI data must be developed for classifying different tissue types. We present an automated algorithm for differentiating adipose tissue from fibroglandular human breast tissue based on three parameters computed from the LCI signal (slope, standard deviation, spatial frequency content). A total of 260 breast tissue samples from 58 patients were collected from excised surgical specimens. A training set (N=72) was used to extract parameters for each tissue type and the parameters were fit to a multivariate normal density. The model was applied to a validation set (N=86) using likelihood ratios to classify groups. The overall accuracy of the model was 91.9% (84.0 to 96.7) with 98.1% (89.7 to 99.9) sensitivity and 82.4% (65.5 to 93.2) specificity where the numbers in parentheses represent the 95% confidence intervals. These results suggest that LCI can be used to determine tissue type and guide FNAB of the breast.     

Optical coherence tomography-based freeze-drying microscopy

A new type of freeze-drying microscope based upon time-domain optical coherence tomography is presented here (OCT-FDM). The microscope allows for real-time, in situ 3D imaging of pharmaceutical formulations in vials relevant for manufacturing processes with a lateral resolution of <7 μm and an axial resolution of <5 μm. Correlation of volumetric structural imaging with product temperature measured during the freeze-drying cycle allowed investigation of structural changes in the product and determination of the temperature at which the freeze-dried cake collapses. This critical temperature is the most important parameter in designing freeze-drying processes of pharmaceutical products.