For high-speed swept-source optical coherence tomography (SS-OCT), the real-time calibration process to convert the OCT signal to wave number space is highly essential. A novel calibration process/algorithm using a genetic algorithm and precise interpolation is developed. This algorithm is embedded and validated in a SS-OCT system with 16-kHz A-scan rate. The performance of the new algorithm is evaluated by measuring point spread functions at two distinct locations in the entire imaging range. The data is compared to the same system but embedded with a regular calibration algorithm, which demonstrates about 20% improvement in the axial resolution. The steady improvement at different locations of the range suggests the strong robustness of the algorithm, which will ultimately optimize the operation performance of this SS-OCT system in terms of resolution and dynamic range and improves details in biological tissues.
KEYWORDS: Optical coherence tomography, Cartilage, Polarization, Collagen, Tissues, Birefringence, In vivo imaging, Magnetic resonance imaging, Imaging systems, Standards development
Selected historical aspects of the transition of optical coherence tomography (OCT) research from the bench to bedside are focused on. The primary function of the National Institutes of Health (NIH) is to improve the diagnosis and treatment of human pathologies. Therefore, research funded by the NIH should have a direct envisioned pathway for transitioning bench work to the bedside. Ultimately, to be successful, this work must be accepted by physicians and by the general science community. This typically requires robustly validated hypothesis-driven research. Work that is not appropriately compared to the current gold standard or does not address a specific pathology is unlikely to achieve widespread acceptance. I outline OCT research in the musculoskeletal and cardiovascular systems, examining the rapid transition from bench to bedside and look at initial validated hypothesis-driven research data that suggested clinical utility, which drove technology development toward specific clinical scenarios. I also consider the time of initial funding compared to when it was applied in patients with clinical pathologies. Finally, ongoing bench work being performed in parallel with clinical studies is examined. The specific applications examined here are identifying unstable coronary plaque and the early detection of osteoarthritis, the former was brought to the bedside primarily through a commercial route while the latter through NIH-funded research.
KEYWORDS: Signal to noise ratio, Optical coherence tomography, Charge-coupled devices, Signal detection, Sensors, Interference (communication), Signal processing, Photodiodes, Signal attenuation, Tissues
Optical coherence tomography (OCT) based on spectral interferometry has recently been examined, with authors often suggesting superior performance compared with time domain approaches. The technologies have similar resolutions and the spectral techniques may currently claim faster acquisition rates. Contrary to many current opinions, their detection parameters may be inferior. The dynamic range and signal-to-noise ratio (SNR) correlate with image penetration, the contrast as a function of depth. This work examines the theoretical sensitivity, dynamic range, and SNR of the techniques, within the practical limits of optoelectronics, taking into account often ignored or misunderstood classical factors that affect performance, such as low frequency noise, analog to digital (AD) conversion losses, and methods for potentially improving sensitivity, including fast laser sweeping. The technologies are compared relative to these parameters. While Fourier domain OCT has some advantages such as signal integration, it appears unlikely that its disadvantages can ultimately be overcome for nontransparent tissue. Ultimately, time-domain (TD)-OCT appears to have the superior performance with respect to SNR and dynamic range. This may not be the case for transparent tissue of the eye. Certain positive aspects of swept source OCT leave the possibility open that its performance may approach that of (TD)-OCT in nontransparent tissue.
Collagen, the most abundant protein in the body, may provide invaluable clinical information of many major disorders
due to its birefringence. Assessing collagen birefringence with polarization sensitive optical coherence tomography (PSOCT)
could improve characterization of in vivo tissue pathology. Beyond detecting collagen organization, the
information potentially gained from PSOCT include collagen type, form vs. intrinsic birefringence, the local
environment, collagen angle, and the presence of multiple birefringence materials. In this work, we applied fast Fourier
transform (FFT) analysis to both the mathematical model and in vitro bovine meniscus for improved PS-OCT data
analysis. The FFT analysis yielded information on tissue composition in addition to identify the presence of organized
collagen. PS-OCT images of Helistat(R) phantoms (collagen type I) were also analyzed with the ultimate goal of
improved tissue characterization. This study could advance the insights gained from PS-OCT images beyond simply
determining the presence or absence of birefringence.
Current evidence indicates that most plaques classified as vulnerable or ruptured plaques do not lead to
unstable angina or myocardial infarction. Improved methods are needed to risk stratify plaques to identify
those which lead to most acute coronary syndromes. Collagen depletion in the intima overlying lipid
collections appears to be a critical component of unstable plaques. In this study, we use polarization
sensitive optical coherence tomography (PS-OCT) for the assessment of coronary plaque collagen.
Collagen is birefringent, meaning that different polarization states travel through it at different velocities.
Changes in PS-OCT images are a measure of tissue birefringence. Twenty-two coronary artery segments
were imaged with PS-OCT and analyzed by picrosirius staining (a measure of collagen intensity and fiber
size) and trichrome blue. The regression plot between PS-OCT changes and measured collagen yielded a
correlation coefficient value of 0.475 (p<0.002). Good correlation was noted between two blinded
investigators both with respect to PS-OCT measurements as well as luminosity as assessed by picrosirius.
The predictive value of a PS-OCT measurement of negligible birefringence (less than 33% change) for
minimal collagen was 93% while the predictive value of high birefringence (greater than 66% change) for
high collagen concentrations was 89%. The effect of fiber type (chemical composition) was minimal
relative to the effect due to fiber concentration. The capability of PS-OCT to assess plaque collagen
content, in addition to its ability to generate high resolution structural assessments, make it a potentially
powerful technology for identifying high risk plaques.
Structural and compositional analysis of normal and pathological tissues by OCT often is performed ex vivo and subsequently compared to the histology. Many of the tissues of interest require immediate fixation to prevent degradation of the sample. Frequently, samples are obtained up to a week prior to procuring images by OCT. We investigated whether fixation affects OCT image analysis by acquiring images of freshly isolated bovine ligament samples and repeating OCT imaging of the same area after fixation at 24 hours and at one week. Samples were divided into two groups: group one was fixed in 10% neutral buffered formalin for 24 hours and placed in normal saline while group two remained in formalin for one week. Tissue samples were processed for paraffin embedment and stained with Masson's trichrome or with picrosirius red. The banding pattern contrast ratio of the OCT images before and after fixation for both groups was measured and compared for possible differences. Histology was evaluated for tissue integrity and compared to the OCT images. The mean contrast ratio at time 0 was 5.41 ± 1.1 and 5.31 ± 0.6 for groups 1 and 2, respectively. Results at 1 week were slightly lower with 5.11 ± 0.3 and 5.20 ± 0.7, respectively. Statistical analysis of the data by ANOVA showed no difference in the contrast ratios with time or with treatment. This data indicates that 24 hours in formalin is sufficient to fix these small ligament samples with little effect on imaging up to one week after fixation.
Techniques based on spectral interferometry (SD-OCT) have recently been examined, with authors often suggesting
superior performance compared to time domain optical coherence tomography (TD-OCT) techniques. While these
technologies have similar resolutions and the spectral techniques may currently claim faster acquisition rates, their
detection parameters may be inferior. This work examines the theoretical signal to noise ratio and dynamic range of
these techniques including time domain. Considering the practical limits of optoelectronics, the often ignored or
misunderstood factors which affect performance, such as vacuum fluctuations, the actual source of thermal noise,
excess noise and A/D conversion losses, were taken into account. Methods for potentially improving signal to noise
ratio (SNR), such as fast laser sweeping with high laser intensities and CCD integration, were evaluated as well. This is
critical because dynamic range translates directly into imaging depth. The technologies are compared relative to the
differences in these parameters. While Fourier domain OCT (FD-OCT) has some advantages such as signal integration,
it appears unlikely that its disadvantages can ultimately be overcome. Ultimately, time TD-OCT appears to have the
superior performance with respect to SNR and dynamic range. However certain positive aspects of swept source OCT
(SS-OCT) leave open the possibility that its performance may approach that of TD-OCT.
Ultrahigh resolution OCT is used to visualize experimentally induced osteoarthritis in a rat knee model. Using a Cr4+:Forsterite laser, ultrahigh image resolutions of 5um are achieved. Progression of osteoarthritic remodeling and cartilage degeneration are quantified. The utility of OCT for the assessment of cartilage integrity is demonstrated.
In this presentation, the application of optical coherence tomography (OCT) to the prevention of myocardial infarction and early identification of osteoarthritis is discussed. Myocardial infarction or a heart attack is the leading cause of death worldwide. It results from an acute loss of blood flow to a region of the heart resulting in death to that heart tissue. Most heart attacks are caused by small, thin walled lipid filled plaques which can not be detected by currently available imaging technologies. This paper outlines some of the advances demonstrating the potential of OCT for the identification of high risk plaque. Osteoarthritis is a major cause of mobility in the industrialized world. The hallmark of the disease is a degradation of articular cartilage. As new therapeutics have been shown to be effective in animal models, there effectiveness in humans remains unclear as there is no effective method for accurate monitoring changes in cartilage. In the second part of this manuscript, the effectiveness of OCT for monitoring articular cartilage is described.
During the last few years, OCT has demonstrated considerable promise as a method of high-resolution intravascular imaging. The goal of this study was to apply and to test the applicability of the rotating kernel transformation (RKT) technique to the speckle reduction and enhancement of OCT images. The technique is locally adaptive. It is based on sequential application of directional masks and selection of the maximum of all outputs. This method enhances the image features by emphasizing thin edges while suppressing a noisy background. Qualitatively, the RKT algorithm provides noticeable improvement over the original image. All processed images are smoother and have better-defined borders of media, intima, and plaque. The quantitative evaluation of RKT performance showed that in terms of average contrast-to-noise ratio, there is a significant improvement in image quality between original and enhanced images. The RKT image enhancement technique shows great promise in improving OCT images for superior boundary identification.
Technologies capable of imaging subsurface tissue structures offer improved visualization for surgical diagnostics and guidance. Endoscopic ultrasound catheters have been used for imaging the upper and lower gastrointestinal tract with 50 - 100 micrometers resolution. However, these resolutions are insufficient to resolve epithelial layers or early epithelial changes which occur in neoplasias and Barrett's esophagus. Optical coherence tomography (OCT) is a fiber- optic based imaging technology capable of acquiring in vivo image data of biological tissue at real-time rates and at resolutions 10 times higher than clinical endoscopic ultrasound. Using a compact amplifier super-luminescent diode light source, a portable OCT system has been constructed for use with minimally invasive endoscopic and surgical instruments including catheters, laparoscopes, microscopes, and hand-held surgical probes. The in vivo rabbit gastrointestinal tract is used as a model system. Beam delivery is accomplished with a radial-imaging OCT catheter that can be inserted into the working channel of an endoscope. This in vivo demonstration suggests that resolutions and acquisition rates are sufficient for imaging the human gastrointestinal tract. OCT shows promise for high-resolution image-guidance during diagnostic and surgical procedures.
High resolution imaging of intraarterial structure is necessary for the identification of high risk coronary plaque. Optical coherence tomography (OCT), a recently developed technology, is a compact, fiber optic based imaging modality with resolutions between 2-20 μm and real time image acquisition rate. Previous in vitro studies have demonstrated the capability of OCT to identify plaque morphology and distinguish plaques with high lipid content. This work demonstrates the feasibility for OCT imaging of in-vivo intraarterial structures. We demonstrate the detection of microstructural detail and the effects of blood on imaging. Saline injections were required during imaging to reduce the signal attenuation of blood. An axial resolution of 10 μm was achieved. Microstructure within the arterial wall was sharply defined and correlated with histology. OCT shows potential to assist in the risk stratification of plaques and the guidance of interventional procedures, such as stent deployment.
The longitudinal resolution of optical coherence tomography (OCT) is currently limited by the optical bandwidth of the light source, typically a superluminescent diodes, to approximately 10-15 micrometers . This resolution is insufficient to identify individual cells or to assess subcellular structures such as nuclei or mitotic figures. The ability to perform subcellular imaging with OCT could greatly enhance the detection of early neoplastic changes and improve early cancer diagnosis or the imaging of developing biological morphology. Higher resolution OCT would also improve specificity of diagnosis for several ocular diseases, such as glaucoma, which require precise, detailed imaging and measurement of retinal nerve fiber layer thickness. State of the art Kerr-lens mode-locked Ti:Al2O3 lasers using double chirped dispersion compensating mirrors can generate pulse durations of < 7 fs and bandwidths of 200 nm or more at 800 nm center wavelength. These pulse durations and bandwidths can be used for OCT, resulting in longitudinal resolutions of less than 2 micrometers . The use of such broad bandwidths also enables the extraction of localized, wavelength dependent absorption and scattering tissue characteristic by detecting the full interferometric fringe signa and using Fourier signal processing. In this paper we demonstrate an ultra-high-subcellular level resolution, spectroscopic OCT system based on a mode-locked Ti:Al2O3 laser. In vivo imaging of development biology specimens as well as preliminary in vivo spectroscopic OCT result are demonstrated.
This work demonstrates the feasibility of OCT for identifying early osteoarthritic pathology. In addition to structural abnormalities, changes in collagen fiber organization, an indicator of very early osteoarthritis, were assessed with a polarization sensitive OCT system. A portable, real time, modular OCT system, suitable for both laboratory and clinical settings, has been developed. Preliminary in vivo imaging results obtained during partial knee replacement surgery are discussed.
A technology capable of imaging tissue, at or near the cellular level, could lead to the detection of neoplasias at earlier stages than currently possible. This could significantly improve patient outcomes, since once cancer becomes metastatic, cure is difficult. Optical coherence tomography (OCT), a recently developed imaging technology, has ben shown to achieve resolution in the cellular and subcellular range, and it could improve the diagnostic range of clinical imaging procedures. To assess the clinical applicability of OCT, neoplastic specimens from the urinary, gastrointestinal and female reproductive tract were imaged. Sharp differentiation of structures included the mucosa/submucosal/muscularis boundaries, epithelium, glands, supportive tissue, and intramural cysts. The ability of optical coherence tomography to image tissue microstructure at or near the cellular level make it a potentially powerful technology for minimally invasive assessment of tissue microstructure. The resolution of optical coherence tomography, which is greater than any current clinical imaging modality, make it particularly attractive for the assessment of early neoplastic changes.
Optical coherence tomography (OCT) is a recently developed optical imaging technique that uses low coherence interferometry to perform high resolution, cross-sectional imaging in biological systems. While in vitro studies have been performed to demonstrate the feasibility of performing optical biopsy in human tissues, key technologies must be developed to extend this technique to in vivo internal organ systems. These advances include improvements in image acquisition speed, and the development of an OCT compatible catheter-endoscope. A fast scanning OCT system has recently been constructed. This system employs a high power (200 mW) chromium doped forsterite laser as the low coherence source and a piezoelectric fiber stretcher to induce reference arm optical path length delay. The fast scanning system acquires OCT images with an acquisition rate of four images per second, an axial resolution of 15 micrometers, and a signal to noise ratio of 112 dB. When incorporated with the recently constructed OCT compatible catheter-endoscope, this system is capable of obtaining high resolution endoscopic diagnostic images of tissue microstructure in vivo.
A high speed technique for performing 'optical biopsies,' or optical diagnostic imaging of in vivo tissue architectural morphology, would greatly enhance the diagnosis and clinical management of many diseases. Optical coherence tomography (OCT) is a novel optical imaging technique that uses low coherence interferometry to obtain micron scale, cross- sectional images of biological systems. OCT was initially applied in ophthalmology to provide high resolution, cross sectional, tomographic images of the transparent structures in the eye and clinical studies show that OCT has considerable promise for the diagnosis of a wide range of retinal macular diseases. OCT imaging in other human tissues is more difficult due to optical scattering. However, recent in vitro studies have shown that OCT can image architectural morphology in highly optically scattering tissues. One of the key technological issues for OCT in optical biopsy is the development of low coherence laser sources. Essential attributes of a clinically viable light source for OCT include high single-transverse-mode power, short coherence length, and a central wavelength optimal for deep penetration within human tissue. Passively mode locked solid state lasers based on Ti:Al2O3 and Cr:Mg2SiO4 are capable of providing hundreds of milliwatts of single-transverse mode light with coherence lengths as short as 1.8 microns. We present recent developments in the optimization of mode locked solid state lasers for application to OCT and demonstrate the resulting capability to enable fast acquisition of high resolution tomographic images.
Optical Coherence Tomography (OCT) is a new technique that is used to obtain cross- sectional images of highly scattering tissue. OCT has been applied to image both architectural and cellular morphologic structures in clinically relevant in vitro human tissues, including the human epiglottis and full-thickness skin. The performance of OCT at 850 nm and 1300 nm is compared. In addition, high numerical aperture OCT enhanced confocal microscopy have potential for non-invasive in vivo diagnosis.
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