Dual modality intravascular optical coherence tomography (OCT) and near-infrared fluorescence (NIRF) imaging: a fully automated algorithm for the distance-calibration of NIRF signal intensity for quantitative molecular imaging

Intravascular optical coherence tomography (IVOCT) is a well-established method for the high-resolution investigation of atherosclerosis in vivo. Intravascular near-infrared fluorescence (NIRF) imaging is a novel technique for the assessment of molecular processes associated with coronary artery disease. Integration of NIRF and IVOCT technology in a single catheter provides the capability to simultaneously obtain co-localized anatomical and molecular information from the artery wall. Since NIRF signal intensity attenuates as a function of imaging catheter distance to the vessel wall, the generation of quantitative NIRF data requires an accurate measurement of the vessel wall in IVOCT images. Given that dual modality, intravascular OCT–NIRF systems acquire data at a very high frame-rate (>100 frames/s), a high number of images per pullback need to be analyzed, making manual processing of OCT–NIRF data extremely time consuming. To overcome this limitation, we developed an algorithm for the automatic distance-correction of dual-modality OCT–NIRF images. We validated this method by comparing automatic to manual segmentation results in 180 in vivo images from six New Zealand White rabbit atherosclerotic after indocyanine-green injection. A high Dice similarity coefficient was found (0.97 ± 0.03) together with an average individual A-line error of 22 µm (i.e., approximately twice the axial resolution of IVOCT) and a processing time of 44 ms per image. In a similar manner, the algorithm was validated using 120 IVOCT clinical images from eight different in vivo pullbacks in human coronary arteries. The results suggest that the proposed algorithm enables fully automatic visualization of dual modality OCT–NIRF pullbacks, and provides an accurate and efficient calibration of NIRF data for quantification of the molecular agent in the atherosclerotic vessel wall.National Institutes of Health (U.S.) (NIH R01HL093717)Merck & Co., Inc

Volumetric quantification of fibrous caps using intravascular optical coherence tomography

The rupture of thin-cap fibroatheroma accounts for most acute coronary events. Optical Coherence Tomography (OCT) allows quantification of fibrous cap (FC) thickness in vivo. Conventional manual analysis, by visually determining the thinnest part of the FC is subject to inter-observer variability and does not capture the 3-D morphology of the FC. We propose and validate a computer-aided method that allows volumetric analysis of FC. The radial FC boundary is semi-automatically segmented using a dynamic programming algorithm. The thickness at every point of the FC boundary, along with 3-D morphology of the FC, can be quantified. The method was validated against three experienced OCT image analysts in 14 lipid-rich lesions. The proposed method may advance our understanding of the mechanisms behind plaque rupture and improve disease management

Azimuthal registration of image sequences affected by nonuniform rotation distortion

Imaging modalities that use a mechanically rotated endoscopic probe to scan a tubular volume, such as an artery, often suffer from image degradation due to nonuniform rotation distortion (NURD). In this paper, we present a new method to align individual lines in a sequence of images. It is based on dynamic time warping, finding a continuous path through a cost matrix that measures the similarity between regions of two frames being aligned. The path represents the angular mismatch corresponding to the NURD. The prime advantage of this novel approach compared to earlier work is the line-to-line continuity, which accurately captures slow intraframe variations in rotational velocity of the probe. The algorithm is optimized using data from a clinically available intravascular optical coherence tomography (OCT) instrument in a realistic vessel phantom. Its efficacy is demonstrated on an in vivo recording, and compared with conventional global rotation block matching. Intravascular OCT is a particularly challenging modality for motion correction because, in clinical situations, the image is generally undersampled, and correlation between the speckle in different lines or frames is absent. The algorithm can be adapted to ingest data frame-by-frame, and can be implemented to work in real time.</p

Azimuthal registration of image sequences affected by nonuniform rotation distortion

Imaging modalities that use a mechanically rotated endoscopic probe to scan a tubular volume, such as an artery, often suffer from image degradation due to nonuniform rotation distortion (NURD). In this paper, we present a new method to align individual lines in a sequence of images. It is based on dynamic time warping, finding a continuous path through a cost matrix that measures the similarity between regions of two frames being aligned. The path represents the angular mismatch corresponding to the NURD. The prime advantage of this novel approach compared to earlier work is the line-to-line continuity, which accurately captures slow intraframe variations in rotational velocity of the probe. The algorithm is optimized using data from a clinically available intravascular optical coherence tomography (OCT) instrument in a realistic vessel phantom. Its efficacy is demonstrated on an in vivo recording, and compared with conventional global rotation block matching. Intravascular OCT is a particularly challenging modality for motion correction because, in clinical situations, the image is generally undersampled, and correlation between the speckle in different lines or frames is absent. The algorithm can be adapted to ingest data frame-by-frame, and can be implemented to work in real time.</p

Design and Validation of the Ball Lens-Based Intravascular Catheter for Optical Coherence Tomography and Fluorescence Lifetime Imaging Microscopy

Diagnosis of atherosclerosis requires morphological and biochemical information in vivo and one single imaging system cannot provide comprehensive details. Therefore, researchers have been interested in combining two different imaging systems to diagnose atherosclerosis simultaneously with fiber endoscope. This dissertation focuses on the development of dual-modality ball lens-based fiber endoscope for Optical Coherence Tomography (OCT) and Fluorescence Lifetime Imaging Microscopy (FLIM) for intravascular atherosclerosis diagnosis. We proposed a combined simulation, fabrication, and measurement method for ball lens-based endoscope based on double clad fiber (DCF) for OCT and FLIM. Simulation is important to minimize manufacturing time by establishing a preferred shape for the partial ellipsoid lens before optimizing the manufacturing process. It also allows us, in conjunction with optical performance characterization techniques, to predict the performance of any given endoscope in the intravascular environment. Different fiber endoscopes based on different fiber were designed, optimized and fabricated for OCT system, Time-Domain FLIM system, Frequency-Domain FLIM system, and dual-modality OCT/FLIM system. Each type endoscope optical performance, mechanical performance and application to atherosclerosis was confirmed with a series of experiments. The dual-modality OCT/FLIM system compatible with the endoscope was designed and developed. The operating wavelength for OCT and FLIM were 1310nm and 375nm, respectively. The combined system was used to image atherosclerosis through a dual-modality ball lens-based endoscope. The morphological and biochemical information of the atherosclerosis images were collected and studied. The whole system also was minimized inside the moveable cart for convenient usage

TOWARDS HIGH RESOLUTION ENDOSCOPIC OPTICAL COHERENCE TOMOGRAPHY FOR IMAGING INTERNAL ORGANS

Optical coherence tomography (OCT) is a light based interferometric imaging technique that can provide high resolution (5-20 µm at 1300 nm), depth resolved, images in real-time. With recent advances in portable low coherent light sources for OCT it is now possible to achieve ultrahigh axial resolutions (≤ 3 µm) by moving to shorter central wavelengths such as 800 nm while utilizing a broad spectral bandwidth. Our goal was to push ultrahigh resolution OCT technology to in vivo imaging of internal organs for endoscopic assessment of tissue microstructure. This dissertation is separated into technological developments and biomedical imaging studies. Technological developments in this dissertation included development of a high speed, ultrahigh resolution distal scanning catheter. This catheter was based upon a miniature DC micromotor capable of rotational velocities in excess of 100 rps, a diffractive compound lens design that minimized chromatic aberrations, and a mechanical assembly that limited field of view blockage to less than 7.5% and maintained an outer diameter of 1.78 mm (with plastic sheath). In conjunction with the algorithm described in chapter 4 to correct for non-uniform rotational distortion, the overall imaging system was capable of high quality endoscopic imaging of internal organs in vivo. Equipped with the ultrahigh resolution endoscopic OCT system, imaging was performed in small airways and colorectal cancer. Imaging results demonstrated the ability to directly visualization of microstructural details such as airway smooth muscle in the small airways representing a major step forward in pulmonary imaging. With the ability to visualize airway smooth muscle, morphological changes in COPD and related diseases can be further investigated. Additionally, longitudinal changes in an ETBF induced colon cancer model in APCMin mice were studied as well. Quantitative assessment of tissue microarchitecture was performed by measuring the attenuation coefficient to find a bimodal distribution separating normal healthy tissue from polyps. Finally, results from two additional projects were also demonstrated. Chapter 7 shows some results from vascular imaging in a tumor angiogenesis model and middle cerebral artery occlusion model. Chapter 8 describes an endoscopic multimodal OCT and fluorescence imaging platform with results in ex vivo rabbit esophagus

Endoscopic Optical Coherence Tomography imaging of the airway

A narrowing, either of the nasal airway or the large airways, causes impaired airflow and results in respiratory insufficiency. Imaging the airways is important for the diagnostic evaluation of airway disorders. Existing approaches, such as bronchoscopy/ endoscopy or Computed Tomography (CT), are either qualitative or are impractical to use for routine assessments. Endoscopic Optical coherence Tomography (OCT) can be used to obtain quantitative images of the dynamic airway in real-time and to reconstruct airway volumes.In order to image the large airways, an OCT system with a long imaging range and high sensitivity is necessary. The data acquisition scheme for an endoscopic OCT system with a wavelength swept laser source was developed and refined to enable imaging in the large airways. A pressure acquisition system was also integrated to allow synchronous, invasive, pressure measurements to be made in conjunction with OCT scans. Experiments were performed in mechanically ventilated pigs to demonstrate the airway imaging capabilities of the OCT system. The results obtained from OCT were validated against CT scans acquired during the same exam. The combined pressure and OCT-derived cross sectional area plots, measured in vivo over a respiratory cycle, exhibited hysteresis loops, indicating the viscoelastic nature of the airway deformation. Endoscopic OCT imaging was also performed in the nasal cavities of cadaver heads to assess the outcomes of functional rhinoplasty procedures. OCT-derived volumes of the nasal airway were compared against CT volumes and found to depict the nasal vault faithfully.A fiber-optic probe with a low numerical aperture lens at its tip is better suited for imaging large luminal organs, as the distance between the probe and the tissue surface is unknown and variable. A novel, multi-segment, all-fiber lens, that can produce nearly collimated beams with working distances larger than 14 mm, was designed, fabricated, and tested. Finally, the non-unform rotation distortion produced by a super-elastic Nitinol tube drive-shaft was compared against the performance of a torque coil drive-shaft. It is hoped that the results presented will help advance the adoption of endoscopic OCT in routine clinical practice for the assessment of airway disorders.Doctor of Philosoph