Optical Frequency Domain Imaging System Research Articles

Presence of Plaque Neovascularization on Optical Frequency Domain Imaging Predicts Progression of Carotid Artery Stenosis

Neovascularization (NV) is regarded to be one of the important features of vulnerable plaque. The purpose of this study was to evaluate associations between the presence of NV, detected using optical frequency domain imaging (OFDI), and ischemic events and the progress of carotid artery stenosis. Carotid artery plaques were evaluated using an OFDI system before angioplasty. NV was defined as no-signal tubuloluminal structures recognized on at least 3 consecutive images. The total number of NVs was compared between symptomatic and asymptomatic plaques and between progressive and nonprogressive plaques. Carotid plaque was diagnosed as "progressive" when peak systolic velocity increased between serial carotid duplex scans. A total of 36 patients (17 symptomatic, 16 progressive) were included. The percentage of patients with smoking habits was significantly higher with progressive carotid plaque than with nonprogressive carotid plaque (P= 0.003). NV was detected in 34 patients (94%), and the total number of NVs was significantly higher with progressive carotid plaque (10.2 ± 4.8 vs. 3.7 ± 2.8; P<0.0001). There was no relationship between the number of NVs and ischemic events (symptomatic 6.0 ± 5.1 vs. asymptomatic 7.1 ± 5.0; P= 0.47). In multivariate logistic regression analysis, the number of NVs was an independent predictor of progressive carotid plaque (odds ratio 1.64 per 1 increase [95% confidence interval 1.19-2.64]; P= 0.0005). NV was more frequently observed in progressive carotid plaques. Evaluation of NV using OFDI may be useful in predicting progressive carotid plaques.

Coronary Plaque Microstructure and Composition Modify Optical Polarization: A New Endogenous Contrast Mechanism for Optical Frequency Domain Imaging

ObjectivesThis study aimed to evaluate whether polarimetry, performed using a modified optical frequency domain imaging (OFDI) system, can improve the assessment of histological features relevant to characterizing human coronary atherosclerosis. BackgroundThe microscopic structure and organization of the arterial wall influence the polarization of the infrared light used by OFDI. Modification of the OFDI apparatus, along with recently developed image reconstruction methods, permits polarimetric measurements simultaneously with conventional OFDI cross-sectional imaging through standard intravascular imaging catheters. MethodsThe main coronary arteries of 5 cadaveric human hearts were imaged with an OFDI system capable of providing polarimetric assessment. Cross-sectional views of tissue birefringence, measured in refractive index units, and depolarization, expressed as the ratio of depolarized signal to total intensity, were reconstructed, together with conventional OFDI images. Following imaging, the vessels underwent histological evaluation to enable interpretation of the observed polarization features of individual tissue components. ResultsBirefringence in fibrous tissue was significantly higher than in intimal tissue with minimal abnormality (0.44 × 10−3 vs. 0.33 × 10−3; p < 0.0001). Birefringence was highest in the tunica media (p < 0.0001), consistent with its high smooth muscle cell content, cells known to associate with birefringence. In fibrous areas, birefringence showed fine spatial features and close correspondence with the histological appearance of collagen. In contrast, necrotic cores and regions rich in lipid elicited significant depolarization (p < 0.0001). Depolarization was also evident in locations of cholesterol crystals and macrophages. ConclusionsIntravascular measurements of birefringence and depolarization can be obtained using conventional OFDI catheters in conjunction with a modified console and signal processing algorithms. Polarimetric measurements enhance conventional OFDI by providing additional information related to the tissue composition and offer quantitative metrics enabling characterization of plaque features.

Abstract WP145: Presence of Vasa Vasorum Neovascularization on Optical Frequency Domain Imaging Predicts Progression of Carotid Artery Stenosis

Background: Vasa vasorum neovascularization (VVN) is one of the characteristics of vulnerable plaque. The purpose of this study was to assess VVN using optical frequency domain imaging (OFDI) between symptomatic and asymptomatic carotid artery plaques, and to know its association with progression of stenosis. Methods: The carotid artery plaques were examined before angioplasty using OFDI system (LUNAWAVE TM , Terumo). VVN was defined as a no-signal tubuloluminal structures recognized on at least 3 consecutive images. A total number of VVN was compared between symptomatic and asymptomatic plaques. The stenosis was evaluated by carotid duplex scan within one year. The lesion was diagnosed as ‘progressive’ when the stenotic degree and peak systolic velocity were increased. Results: A total of 60 patients (29 symptomatic, 11 progression) were included. VVN was detected in 54 patients (90%), the total number of VVN was significantly higher in progressive stenosis (8.9 ± 5.7 vs. 4.5 ± 3.8, p = 0.02). However, there was no relationship between the number of VVN and ischemic symptom. Conclusions: VVN was more frequently observed in progressive stenosis. Evaluation of VVN using OFDI might be useful to predict progression of carotid artery stenosis.

Laser thermal therapy monitoring using complex differential variance in optical coherence tomography.

Conventional thermal therapy monitoring techniques based on temperature are often invasive, limited by point sampling, and are indirect measures of tissue injury, while techniques such as magnetic resonance and ultrasound thermometry are limited by their spatial resolution. The visualization of the thermal coagulation zone at high spatial resolution is particularly critical to the precise delivery of thermal energy to epithelial lesions. In this work, an integrated thulium laser thermal therapy monitoring system was developed based on complex differential variance (CDV), which enables the 2D visualization of the dynamics of the thermal coagulation process at high spatial and temporal resolution with an optical frequency domain imaging system. With proper calibration to correct for noise, the CDV-based technique was shown to accurately delineate the thermal coagulation zone, which is marked by the transition from high CDV upon heating to a significantly reduced CDV once the tissue is coagulated, in 3 different tissue types ex vivo: skin, retina, and esophagus. The ability to delineate thermal lesions in multiple tissue types at high resolution opens up the possibility of performing microscopicimage-guided procedures in a vast array of epithelial applications ranging from dermatology, ophthalmology, to gastroenterology and beyond.

Polarization sensitive optical frequency domain imaging system for endobronchial imaging

A polarization sensitive endoscopic optical frequency domain imaging (PS-OFDI) system with a motorized distal scanning catheter is demonstrated. It employs a passive polarization delay unit to multiplex two orthogonal probing polarization states in depth, and a polarization diverse detection unit to detect interference signal in two orthogonal polarization channels. Per depth location four electro-magnetic field components are measured that can be represented in a complex 2x2 field matrix. A Jones matrix of the sample is derived and the sample birefringence is extracted by eigenvalue decomposition. The condition of balanced detection and the polarization mode dispersion are quantified. A complex field averaging method based on the alignment of randomly pointing field phasors is developed to reduce speckle noise. The variation of the polarization states incident on the tissue due to the circular scanning and catheter sheath birefringence is investigated. With this system we demonstrated imaging of ex vivo chicken muscle, in vivo pig lung and ex vivo human lung specimens.

Polarization-sensitive OFDI using polarization-multiplexed wavelength-swept laser.

We demonstrate a novel polarization-sensitive optical frequency domain imaging system employing passive polarization multiplexing. Simple modification of a fiber delay line in the wavelength-swept light source enables illumination with two perpendicular polarizations that are required for determination of the Stokes vector components of the light reflected from each depth of the tissue. This simple all-passive approach provides a robust and low-cost solution for PS imaging replacing relatively complex conventional schemes such as polarization modulation or frequency-encoded polarization multiplexing.

Serial optical frequency domain imaging in STEMI patients: the follow-up report of TROFI study

To investigate the incidence of incomplete stent apposition and to explore the impact of the presence of thrombus and protruding plaque after stent implantation on neointima formation at follow-up in ST-segment elevation myocardial infarction (STEMI) patients with serial optical frequency domain imaging (OFDI) investigations. In a multi-centre study, 141 patients with ST elevation myocardial infarction <12 h from onset were randomized to either PPCI with thrombectomy (TB) using an Eliminate catheter (TB: n = 71) or without TB (non-TB: n = 70). OFDI after drug-eluting stenting was performed using TERUMO OFDI system. Per protocol, at follow-up 49 patients segments were reimaged. At post-procedure and follow-up, there were no differences in stent and lumen areas between the two groups. At follow-up, per strut-level analysis, percentage of incompletely apposed struts was 0.42 ± 0.94 vs. 0.38 ± 0.77% (P = 0.76), and percentage of covered struts was 92.7 ± 7.2 vs. 94.4 ± 9.2% (P = 0.47) in the TB and non-TB groups, respectively. There was a positive correlation between intra-stent structure (ISS) volume at post-procedure and the neointima volume at 6-month follow-up (Pearson's r = 0.409, P = 0.04). Up to 12 months, there have been two and four patients having target vessel failure in the TB and in the non-TB groups, respectively. In patients with STEMI, there were no significant differences in OFDI parameters between TB and non-TB groups at both post-procedure and 6-month follow-up. However, ISS volume at post-procedure was positively associated with neointimal volume at 6-month follow-up.

Three-dimensional surface phase imaging based on integrated thermo-optic swept laser

We developed an optical frequency domain imaging (OFDI) system based on an integrated thermo-optic swept laser to achieve three-dimensional surface imaging. The wavelength was swept by applying a heating signal to a thermo-optic polymeric waveguide. The sub-micrometer surface profile was converted from the three-dimensional phase information of the OFDI system on various samples used as resolution targets with a step height of 120 nm.

Development of Dual Beam High Speed Doppler OFDI

This paper describes development of a high speed Doppler OFDI system for non-invasive vascular imaging. Doppler OFDI (optical frequency domain imaging) is one of the phase-resolved second generation OCT (optical coherence tomography) techniques for high resolution imaging of moving elements in biological tissues. To achieve a phase-resolved imaging, two temporally separated measurements are required. In a conventional Doppler OCT, a pair of massively oversampled successive A-lines is used to minimize de-correlation noise at the expense of significant imaging speed reduction. To minimize a de-correlation noise between targeted two measurements without suffering from significant imaging speed reduction, several methods have been developed such as an optimized scanning pattern and polarization multiplexed dual beam scanning. This research represent novel imaging technique using frequency multiplexed dual beam illumination to measure exactly same position with aimed time interval. Developed system has been verified using a tissue phantom and mouse vessel imaging.

Quantitative Optical Frequency Domain Imaging Assessment of In-Stent Structures in PatientsWith ST-Segment Elevation Myocardial Infarction

The impact of the sampling rate (SR) of optical frequency domain imaging (OFDI) on quantitative assessment of in-stent structures (ISS) such as plaque prolapse and thrombus remains unexplored. OFDI after stenting was performed in ST-segment elevation myocardial infarction (STEMI) patients using a TERUMO OFDI system (Terumo Europe, Leuven, Belgium) with 160 frames/s and pullback speed of 20 mm/s. A total of 126 stented segments were analyzed. ISS were classified as either attached or non-attached to stent area boundaries. The volume, mean area and largest area of ISS were assessed according to 4 frequencies of SR, corresponding to distances between the analyzed frames of 0.125, 0.25, 0.50 and 1.0 mm. ISS volume was calculated by integrating cross-sectional ISS areas multiplied by each sampling distance using the disk summation method. The volume and mean area of ISS became significantly larger, while the largest area became significantly smaller as sampling distance became larger (1.11 mm(2) for 0.125 mm vs. 1.00 mm(2) for 1.0 mm, P for trend=0.036). In addition, variance of difference was positively associated with increasing width of sampling distance. Quantification of ISS is significantly influenced by the applied frequency of SR. This should be taken into account when designing future OFDI studies in which quantitative assessment of ISS is critical for the evaluation of STEMI patients.

Optical frequency domain imaging system and catheters for volumetric imaging of the human esophagus.

Barrett's esophagus (BE) is a metaplastic disorder that can undergo dysplastic progression, leading to esophageal adenocarcinoma. Upper endoscopy is the standard of care for screening for BE, but this technique has a relatively low diagnostic accuracy and high cost due to the requirement of conscious sedation. Optical frequency domain imaging (OFDI) is a high-speed imaging modality that generates cross-sectional images of tissues with a resolution of approximately 10μm that is sufficient for detecting microscopic tissue architecture. In combination with a balloon-centering catheter, this method enables BE diagnosis over the entire distal esophagus.

Compensation of motion artifacts in intracoronary optical frequency domain imaging and optical coherence tomography

Intracoronary optical coherence tomography and optical frequency domain imaging (OFDI) have been utilized for two-dimensional and three-dimensional imaging of vascular microanatomy. Image quality and the spatial accuracy of multidimensional reconstructions, however, can be degraded due to artifacts resulting from relative motion between the intracoronary catheter and the vessel wall. To track the relative motion of a catheter with regard to the vessel, a motion tracking system was incorporated with a standard OFDI system by using wavelength division multiplexing techniques. Motion of the vessel was acquired by a frequency shift of the backscattered light caused by the Doppler effect. A single monochromatic beam was utilized for tracking the relative longitudinal displacements of a catheter-based fiber probe with regard to the vessel. Although two tracking beams are, in general, required to correct for longitudinal motion artifacts, the accurate reconstruction in a longitudinal view was achieved by the Doppler frequency information of a single beam. Our results demonstrate that the single beam based motion tracking scheme is a cost-effective, practical approach to compensating for longitudinal distortions due to cardiac dynamics, thus leading to accurate quantitative analysis of 3D intracoronary OFDI.

Phase-stabilized optical frequency domain imaging at 1-µm for the measurement of blood flow in the human choroid

In optical frequency domain imaging (OFDI) the measurement of interference fringes is not exactly reproducible due to small instabilities in the swept-source laser, the interferometer and the data-acquisition hardware. The resulting variation in wavenumber sampling makes phase-resolved detection and the removal of fixed-pattern noise challenging in OFDI. In this paper this problem is solved by a new post-processing method in which interference fringes are resampled to the exact same wavenumber space using a simultaneously recorded calibration signal. This method is implemented in a high-speed (100 kHz) high-resolution (6.5 µm) OFDI system at 1-µm and is used for the removal of fixed-pattern noise artifacts and for phase-resolved blood flow measurements in the human choroid. The system performed close to the shot-noise limit (<1dB) with a sensitivity of 99.1 dB for a 1.7 mW sample arm power. Suppression of fixed-pattern noise artifacts is shown up to 39.0 dB which effectively removes all artifacts from the OFDI-images. The clinical potential of the system is shown by the detection of choroidal blood flow in a healthy volunteer and the detection of tissue reperfusion in a patient after a retinal pigment epithelium and choroid transplantation.

Co‐registered spectrally encoded confocal microscopy and optical frequency domain imaging system

Spectrally encoded confocal microscopy and optical frequency domain imaging are two non-contact optical imaging technologies that provide images of tissue cellular and architectural morphology, which are both used for histopathological diagnosis. Although spectrally encoded confocal microscopy has better transverse resolution than optical frequency domain imaging, optical frequency domain imaging can penetrate deeper into tissues, which potentially enables the visualization of different morphologic features. We have developed a co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system and have obtained preliminary images from human oesophageal biopsy samples to compare the capabilities of these imaging techniques for diagnosing oesophageal pathology.

Compensation of motion artifacts in catheter-based optical frequency domain imaging

A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated. To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques. Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe. Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter-based imaging.

Guided Esophageal Surveillance Biopsy with a Laser Marking Optical Frequency Domain Imaging System

Guided Esophageal Surveillance Biopsy with a Laser Marking Optical Frequency Domain Imaging System

Real-Time FPGA Processing for High-Speed Optical Frequency Domain Imaging

We present a novel algorithm for reconstructing interferograms acquired in optical frequency domain imaging (OFDI). The algorithm was developed specifically for processing in field programmable gate arrays (FPGAs) and featured the use of a finite-impulse-response (FIR) filter implementation of B-spline interpolation for efficiently re-sampling k-space. When implemented in FPGAs, the algorithm allowed for real-time processing of interferograms acquired with a high-speed OFDI system at 54 kHz and a sampling rate of 100 MS/s.

Miniature swept source for point of care Optical Frequency Domain Imaging

Point of care (POC) medical technologies require portable, small, robust instrumentation for practical implementation. In their current embodiment, optical frequency domain imaging (OFDI) systems employ large form-factor wavelength-swept lasers, making them impractical in the POC environment. Here, we describe a first step toward a POC OFDI system by demonstrating a miniaturized swept-wavelength source. The laser is based on a tunable optical filter using a reflection grating and a miniature resonant scanning mirror. The laser achieves 75 nm of bandwidth centered at 1340 nm, a 0.24 nm instantaneous line width, a 15.3 kHz repetition rate with 12 mW peak output power, and a 30.4 kHz A-line rate when utilizing forward and backward sweeps. The entire laser system is approximately the size of a deck of cards and can operate on battery power for at least one hour.

Comprehensive microscopy of the esophagus in human patients with optical frequency domain imaging

Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas. The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (approximately 6.0 cm) in patients. A pilot feasibility study. Massachusetts General Hospital. Twelve patients undergoing routine EGD. Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion. Inability to obtain direct correlation of OFDI data and histopathologic diagnoses. Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.

Single-detector polarization-sensitive optical frequency domain imaging using high-speed intra A-line polarization modulation

We demonstrate a novel high-speed polarization-sensitive optical frequency domain imaging system employing high-speed polarization modulation. Rapid and continuous polarization modulation of light prior to illumination of the sample is accomplished by shifting the frequency of one polarization eigenstate by an amount equal to one quarter of the digitization sampling frequency. This approach enables polarization-sensitive imaging with a single detection channel and overcomes artifacts that may arise from temporal variations of the birefringence in fiber-optic imaging probes and spatial variation of birefringence in the sample.