Improvement in dynamic range limitation of swept source optical coherence tomography by true logarithmic amplification.

We previously demonstrated, with both theoretical and experimental studies, the dynamic range limitation with spectral domain optical coherence tomography (OCT) relative to time domain OCT. A significant portion of this limitation was due to the difference of analog/digital conversion. In this paper, a new method of true logarithmic amplification is discussed theoretically and tested experimentally to increase the dynamic range of a swept source OCT. With the current experimental setup, an increase of the dynamic range by about 6 dB was obtained.

Experimental confirmation of potential swept source optical coherence tomography performance limitations.

Optical coherence tomography (OCT) has demonstrated considerable potential for a wide range of medical applications. Initial work was done in the time domain OCT (TD-OCT) approach, but recent interest has been generated with spectral domain OCT (SD-OCT) approaches. While SD-OCT offers higher data acquisition rates and no movable parts, we recently pointed out theoretical inferior aspects to its performance relative to TD-OCT. In this paper we focus on specific limitations of swept source OCT (SS-OCT), as this is the more versatile of the two SD-OCT embodiments. We present experimental evidence of reduced imaging penetration, increased low frequency noise, higher multiple scattering (which can be worsened still via aliasing), increased need to control the distance from the sample, and saturation of central bandwidth frequencies. We conclude that for scenarios where the dynamic range is relatively low (e.g., retina), the distance from the sample is relatively constant, or high acquisition rates are needed, SS-OCT has a role. However, when penetration remains important in the setting of a relatively high dynamic range, acquisition rates above video rate are not needed, or the distance to the tissue is not constant, TD-OCT may be the superior approach.

Applications of optical coherence tomography to cardiac and musculoskeletal diseases: bench to bedside?

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.

Theoretical and practical considerations on detection performance of time domain, Fourier domain, and swept source optical coherence tomography.

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.

High-resolution imaging of progressive articular cartilage degeneration.

The objective of this study was to develop and verify a new technique for monitoring the progression of osteoarthritis (OA) by combining a rat model with the imaging modality optical coherence tomography (OCT). Time-sequential, in vivo, OCT imaging was performed on the left femoral condyles of 12 Wistar rats following sodium-iodoacetic acid-induced OA progression. The right femoral condyles (untreated) were also imaged and served as controls. Imaging was performed on days 0, 10, 20, 30, and 60 with an OCT system capable of acquiring images at four frames per second and an axial resolution of 5 microm. Progressive changes were analyzed using an OA scoring system. OCT successfully identified progressive cartilage degeneration as well as alteration of the cartilage/bone interface. Significant changes to both of these structures were observed in the sodium-iodoacetic acid-injected condyles. Structural changes detected with OCT were confirmed histologically. OCT in combination with a well-known model used in arthritis research represents a powerful tool for following degenerative joint disease progression in a given animal by detecting changes to the cartilage/bone interface and articular cartilage.

Optical coherence tomography for identifying unstable coronary plaque.

This manuscript examines intravascular imaging with optical coherence tomography (OCT). OCT is a potentially attractive intravascular imaging technology due to its high resolution, small catheters/guidewires, and ability to be combined with spectroscopic techniques. Its potential disadvantages remain its limited penetration and signal attenuation by blood. The manuscript reviews unstable plaque, OCT principles, historical development, current challenges, and comparison with IVUS.

Assessment of coronary plaque collagen with polarization sensitive optical coherence tomography (PS-OCT).

INTRODUCTION: Current evidence indicates that most plaques classified as vulnerable or ruptured plaque 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. METHODS AND RESULTS: 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). 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. CONCLUSION: 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.

Monitoring osteoarthritis in the rat model using optical coherence tomography.

OBJECTIVE: A need exists for an animal model to assess therapeutics for osteoarthritis (OA) without sacrificing the animal. Our goal is to assess the progression of experimentally induced osteoarthritis in the rat knee joint by monitoring articular cartilage thickness, surface abnormalities, and collagen organization using a new technology known as optical coherence tomography (OCT). DESIGN: OA was generated in Wistar Hanover rats via injection of sodium iodoacetate into the left articular joint of the knee while normal saline was injected as a control in the contralateral right knee. Rats were sacrificed at 1-, 2-, 3-, 4-, and 8-week intervals and the knee joints were subsequently harvested and imaged using normal and polarization sensitive OCT (PS-OCT). Treated knees were compared to normal counterparts in the contralateral leg. Following imaging, knees underwent both routine histological processing and picrosirus staining for organized collagen. RESULTS: OCT images indicate that injection of sodium iodoacetate resulted in a progressive decrease in cartilage thickness and loss of the bone-cartilage interface which correlated with histology. In addition, PS-OCT was able to detect collagen disorganization, an early indicator of OA. CONCLUSIONS: The use of OCT in combination with the induction of OA in rats is a promising new animal model for assessing articular changes with the goal of monitoring therapeutics longitudinally. Future work will extend the model to in vivo assessments.

Using optical coherence tomography to guide articular cartilage ablation.

Current clinical imaging technologies are not capable of accurately resolving the microscopic components of articular cartilage. Optical coherence tomography (OCT) is a recently developed imaging modality analogous to ultrasound--OCT measures backreflection of infrared light instead of sound. In the study reported here, we wanted to determine the efficacy of OCT for monitoring cartilage laser ablation. Real-time imaging was conducted on bovine cartilage ablated by an argon laser in vitro. Image sequences were generated illustrating the extent of tissue degradation postablation. The images accurately correlated with histology. These results indicate that current ablation procedures could benefit from OCT guidance.

Image processing techniques for noise removal, enhancement and segmentation of cartilage OCT images.

Osteoarthritis, whose hallmark is the progressive loss of joint cartilage, is a major cause of morbidity worldwide. Recently, optical coherence tomography (OCT) has demonstrated considerable promise for the assessment of articular cartilage. Among the most important parameters to be assessed is cartilage width. However, detection of the bone cartilage interface is critical for the assessment of cartilage width. At present, the quantitative evaluations of cartilage thickness are being done using manual tracing of cartilage-bone borders. Since data is being obtained near video rate with OCT, automated identification of the bone-cartilage interface is critical. In order to automate the process of boundary detection on OCT images, there is a need for developing new image processing techniques. In this paper we describe the image processing techniques for speckle removal, image enhancement and segmentation of cartilage OCT images. In particular, this paper focuses on rabbit cartilage since this is an important animal model for testing both chondroprotective agents and cartilage repair techniques. In this study, a variety of techniques were examined. Ultimately, by combining an adaptive filtering technique with edge detection (vertical gradient, Sobel edge detection), cartilage edges can be detected. The procedure requires several steps and can be automated. Once the cartilage edges are outlined, the cartilage thickness can be measured.

Group velocity dispersion effects with water and lipid in 1.3 microm optical coherence tomography system.

Optical coherence tomography (OCT) has been introduced for the diagnosis of vulnerable plaques in the coronary arteries. When an OCT system images through tissue and biological liquids, group velocity dispersion (GVD) will occur, which may be useful in tissue characterization. This study compares the water and lipid induced GVD effects, important constituents in plaque, on the axial resolution. The point-spread function (PSF) was measured when a target mirror was immersed in either water or lipid. A Fourier transform was performed on the PSF data. No significant GVD was observed in oil up to 15 mm thickness. Water depths greater than 6 mm significantly broadened the PSF. This indicates that the distortion of the spectrum can be attributed to the GVD in water. These results suggest that when imaging through tissue (such as when performing intravascular imaging in vivo) one may be able to distinguish different tissue types for diagnostic purposes.

Practical Challenges of Current Video Rate OCT Elastography: Accounting for Dynamic and Static Tissue Properties.

Optical coherence tomography (OCT) elastography (OCTE) has the potential to be an important diagnostic tool for pathologies including coronary artery disease, osteoarthritis, malignancies, and even dental caries. Many groups have performed OCTE, including our own, using a wide range of approaches. However, we will demonstrate current OCTE approaches are not scalable to real-time, in vivo imaging. As will be discussed, among the most important reasons is current designs focus on the system and not the target. Specifically, tissue dynamic responses are not accounted, with examples being the tissue strain response time, preload variability, and conditioning variability. Tissue dynamic responses, and to a lesser degree static tissue properties, prevent accurate video rate modulus assessments for current embodiments. Accounting for them is the focus of this paper. A top-down approach will be presented to overcome these challenges to real time in vivo tissue characterization. Discussed first is an example clinical scenario where OTCE would be of substantial relevance, the prevention of acute myocardial infarction or heart attacks. Then the principles behind OCTE are examined. Next, constrains on in vivo application of current OCTE are evaluated, focusing on dynamic tissue responses. An example is the tissue strain response, where it takes about 20 msec after a stress is applied to reach plateau. This response delay is not an issue at slow acquisition rates, as most current OCTE approaches are preformed, but it is for video rate OCTE. Since at video rate each frame is only 30 msec, for essentially all current approaches this means the strain for a given stress is changing constantly during the B-scan. Therefore the modulus can't be accurately assessed. This serious issue is an even greater problem for pulsed techniques as it means the strain/modulus for a given stress (at a location) is unpredictably changing over a B-scan. The paper concludes by introducing a novel video rate approach to overcome these challenges.

Longitudinal necrotic shafts near TCFAs--a potential novel mechanism for plaque rupture to trigger ACS?

It has been questioned for over 15 years why only less than 20% of TCFAs trigger ACS. We illustrate TCFA rupture into adjacent longitudinal necrotic shafts of massive amounts of thrombogenic material into the blood, leading to catastrophic clot formation. This is the potential mechanism for TCFAs triggering ACS. One case presented also illustrates the dangers of stent edges rupturing TCFAs.

Can We Advance Macroscopic Quantum Systems Outside the Framework of Complex Decoherence Theory?

Macroscopic quantum systems (MQS) are macroscopic systems driven by quantum rather than classical mechanics, a long studied area with minimal success till recently. Harnessing the benefits of quantum mechanics on a macroscopic level would revolutionize fields ranging from telecommunication to biology, the latter focused on here for reasons discussed. Contrary to misconceptions, there are no known physical laws that prevent the development of MQS. Instead, they are generally believed universally lost in complex systems from environmental entanglements (decoherence). But we argue success is achievable MQS with decoherence compensation developed, naturally or artificially, from top-down rather current reductionist approaches. This paper advances the MQS field by a complex systems approach to decoherence. First, why complex system decoherence approaches (top-down) are needed is discussed. Specifically, complex adaptive systems (CAS) are not amenable to reductionist models (and their master equations) because of emergent behaviour, approximation failures, not accounting for quantum compensatory mechanisms, ignoring path integrals, and the subentity problem. In addition, since MQS must exist within the context of the classical world, where rapid decoherence and prolonged coherence are both needed. Nature has already demonstrated this for quantum subsystems such as photosynthesis and magnetoreception. Second, we perform a preliminary study that illustrates a top-down approach to potential MQS. In summary, reductionist arguments against MQS are not justifiable. It is more likely they are not easily detectable in large intact classical systems or have been destroyed by reductionist experimental set-ups. This complex systems decoherence approach, using top down investigations, is critical to paradigm shifts in MQS research both in biological and non-biological systems.

Current OCT Approaches Do Not Reliably Identify TCFAs.

It is now clearly established that Thin-Capped Fibroatheromas (TCFAs) lead to most Acute Coronary Syndromes (ACSs). The ability to selectively intervene on TCFAs predisposed to rupture and ACSs would dramatically alter the practice of cardiology. While the ability of OCT to identify thin walled plaques at micron scale resolutions has represented a major advance, it is a misconception that it can reliably identify TCFAs. One major reason is that the 'diffuse border' criteria currently used to determine 'lipid plaque' is almost undoubtedly from high scattering in the intima and not because of core composition (necrotic core). A second reason is that, rather than looking at lipid collections, studies need to be focused on identifying necrotic cores with OCT. Necrotic cores are characteristic of TCFAs and not lipid collections. Numerous other OCT approaches are available which can potentially accurately assess TCFAs, but these have not been aggressively pursed which we believe likely stems in part from the misconceptions over the efficacy of 'diffuse borders'.

Fossilized Teeth as a New Robust and Reproducible Standard for Polarization-Sensitive Optical Coherence Tomography.

A clinical need exists for a cheap and efficient standard for polarization sensitive optical coherence tomography (PS-OCT). We utilize prehistoric fossilized teeth from the Megalodon shark and European horse as an unconventional, yet robust standard. Given their easy accessibility and the microstructural consistency conferred by the process of fossilization, they provide a means of calibration to reduce error from sources such as catheter bending and temperature changes. We tested the maximum difference in birefringence values in each tooth and found the fossilized teeth to be fast and repeatable. The results were compared to measurements from bovine meniscus, tendon, and destroyed tendon, which were verified with histology.

The application of optical coherence tomography in musculoskeletal disease.

Many musculoskeletal disorders (MDs) are associated with irreversible bone and cartilage damage; this is particularly true for osteoarthritis (OA). Therefore, a clinical need exists for modalities which can detect OA and other MDs at early stages. Optical coherence tomography (OCT) is an infrared-based imaging, currently FDA approved in cardiology and ophthalmology, which has a resolution greater than 10 microns and acquisition rate of 120 frames/second. It has shown feasibility for imaging early OA, identifying changes prior to cartilage thinning both in vitro and in vivo in patients and in OA animal models. In addition, OCT has shown an ability to identify early rheumatoid arthritis (RA) and guide tendon repair, but has the potential for an even greater impact. Clinical trials in OA are currently underway, as well as in several other MDs.

The Advantages of Not Entangling Macroscopic Diamonds at Room Temperature.

The recent paper entitled by K. C. Lee et al. (2011) establishes nonlocal macroscopic quantum correlations, which they term "entanglement", under ambient conditions. Photon(s)-phonon entanglements are established within each interferometer arm. However, our analysis demonstrates, the phonon fields between arms become correlated as a result of single-photon wavepacket path indistinguishability, not true nonlocal entanglement. We also note that a coherence expansion (as opposed to decoherence) resulted from local entanglement which was not recognized. It occurred from nearly identical Raman scattering in each arm (importantly not meeting the Born and Markovian approximations). The ability to establish nonlocal macroscopic quantum correlations through path indistinguishability rather than entanglement offers the opportunity to greatly expand quantum macroscopic theory and application, even though it was not true nonlocal entanglement.