Objective:Efforts to develop chondroprotective approaches to halt osteoarthritis (OA) progression have recently increased. Current imaging techniques are critical in managing advanced OA, but greater resolution is needed to identify reversible stages (pre-OA). Optical coherence tomography (OCT) is a micron scale imaging technology widely used in ophthalmology, cardiology, and neurology. We previously demonstrated that polarization sensitive OCT (PS-OCT) can identify pre-OA in vitro, in animals, and in open surgical fields. This feasibility study examines performing intraarticular PS-OCT using a flexible endocatheter introduced through a stiff 18-gauge spinal needle. Results are critical for designing larger clinical trials examining minimally invasive PS-OCT's ability to identify pre-OA. Design:Fifteen patients undergoing arthroscopic partial medial meniscectomy were selected to confirm their risk for rapid progression to OA. Magnetic resonance imaging (MRI) was obtained at time 0 and at 2.5 years to determine if significant OA developed over this short period and for correlation with time zero PS-OCT results. Results:Over half of the patients developed frank OA by 2.65 ± 0.28 years. All cartilage surfaces were successfully imaged by PS-OCT, but endocatheter redesign is needed. Normal to severely abnormal areas by PS-OCT (all normal by MRI) were successfully identified. PS-OCT assessments were promising for predicting OA progression (p < 0.008). However, the study's low power prevented definite conclusions regarding predictive value. Conclusions:This pilot study produced at least two outcomes critical for future larger trial designs: medial meniscectomy patients are well-suited for studying PS-OCT's ability to predict future OA and substantial endocatheter redesign is needed.

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HomeCirculationVol. 140, No. 23Inadequate Intimal Angiogenesis as a Source of Coronary Plaque Instability Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBInadequate Intimal Angiogenesis as a Source of Coronary Plaque InstabilityImplications for Healing Mark Brezinski, MD, PhD, Frank Willard, PhD and Maria Rupnick, MD, PhD Mark BrezinskiMark Brezinski Mark E. Brezinski, MD, PhD, Massachusetts Institute of Technology, 77 Massachusetts Ave, Bldg 36-345, Cambridge, MA 01239. Email E-mail Address: [email protected] Brigham and Women's Hospital, Boston, MA (M.B.). Harvard Medical School, Boston, MA (M.B.). Massachusetts Institute of Technology, Cambridge (M.B.). University of New England, Biddeford, ME (M.B., F.W.). , Frank WillardFrank Willard University of New England, Biddeford, ME (M.B., F.W.). and Maria RupnickMaria Rupnick North Shore Medical Center, Salem, MA (M.R.). Originally published2 Dec 2019https://doi.org/10.1161/CIRCULATIONAHA.119.042192Circulation. 2019;140:1857–1859It is a widely believed paradigm that intimal angiogenesis in coronary atherosclerosis contributes to plaque instability through both hemorrhagic plaque expansion and cholesterol deposition.1 However, this article supports an alternative concept in which angiogenesis is actually essential for plaque stabilization and healing.2,3 The prevailing paradigm has its origins primarily in histopathology work from the 1980s by Barger's group reported by Kamat et al.4 We argue that misinterpretation of their results has skewed the understanding of vulnerable plaque for >35 years. This misconception still endures in recent plaque angiogenesis reviews, affecting understanding of acute coronary syndromes (ACS) pathophysiology.1Most coronary plaque ruptures/erosions do not lead to ACS. ACS research focuses primarily on vessel breakdown through mechanisms such as inflammation. We have instead proposed that vessel repair mechanisms that oppose instability fail, leading to ACS.3 ACS is then a double hit of rupture/erosion and failed vascular healing. Here, we assert that intimal angiogenesis, needed to maintain cellular reparative functions (ie, healing), if inadequate, leads to coronary plaque instability. Angiogenesis is the supply line to reparative cells in healing regions. In plaques with long necrotic cores, this supply line to compromised regions may not be reliably established.In their 1984 report, Barger's group injected silicone into human coronary arteries in vitro and filmed the flow into mural microvessels.4 They described a primarily short centripetal angiogenesis pattern from the vasa vasorum to the intima. Their discussion linked angiogenesis to plaque hemorrhage with rapid plaque expansion as a trigger for ACS. Our data and literature analysis, including re-examination of the results of Barger and colleagues, do not support primarily centripetal angiogenesis. Instead, we find axial angiogenesis extending many millimeters yet perhaps remaining insufficient to reach compromised intima.We acknowledge that leaky immature microvessels lead to small intimal hemorrhages that contribute red blood cell cholesterol.2 However, hemorrhage is not a significant source of coronary plaque rapid expansion.2 This is unlike human carotid arteries or most animal arteries, often used as models in intimal angiogenesis research, in which hemorrhagic plaque expansion is common.1 We instead propose that coronary angiogenesis is a critical stabilizing factor. Our conclusions are derived from an examination of human coronary plaque in the long axis rather than in conventional cross section, as well as re-evaluating published data, including the work by Barger and colleagues. These conclusions are also supported by data that angiogenesis inhibitors (eg, sunitinib and sorafenib) increase, not decrease, the risk of vascular occlusion in humans.Examining plaques axially rather than in conventional cross section was critical in our questioning of the current paradigms. The most common morphology found after ACS is thin-walled plaques with a large necrotic core by cross section.2 However, only a minority of these plaques (<20%) progress to ACS. Most heal. This brings into question whether these plaques should be called vulnerable plaques. Since 2014, our data have supported the novel concept that ACS risk is a function of necrotic core axial extent.3,5 Three recent in vivo optical coherence tomography studies, which we reviewed elsewhere, have supported this mechanism.3 Studying long axial necrotic cores, we observed that intimal microvessels tracked long distances predominately in the luminal intima above the core on a longitudinal rather than centripetal course. A representative long axial plaque is shown in the Figure. The data supports the model that, in the presence of long cores, these immature microvessels track many millimeters in the intima above the core parallel to the lumen. These findings are consistent with our re-examination of the 1980s data in the next paragraph. The cellularity needed for promoting healing requires maintaining this angiogenesis, which is challenging with long cores.Download figureDownload PowerPointFigure. Human coronary artery axial histopathology showing a long necrotic core (NC); microvessels become sparse in a thin intimal cap. A, Coronary artery axial section (Masson trichrome stain) with intima (I), media (M), and adventitia (A). The long NC extends beyond the image and approaches the right luminal surface (thin intimal cap). Microvessels course longitudinally over the core with decreasing density as the intima thins, seen in magnifications of boxes B and C. B(1) and C(1), Endothelium fluorescently stained for von Willebrand factor (red/orange). B(2) and C(2), Contrast-enhanced endothelium appears white within vessel lumens (yellow arrows) by converting the red channel to gray scale. Intima thickness diminishes from B(1,2) across C(1,2). Microvessel density is highest in the thicker cap of B(1,2) and tapers across C(1,2) until absent (no yellow arrows) where the intima is thinnest (<200 μm). We assert that angiogenesis occurs axially over long NCs and is essential for intimal cap healing. Inadequate microvessel extension over long axial NCs, as shown here, confers vulnerability. Thin-capped fibroatheroma NCs are defined only in cross-section (D). This may explain why <20% lead to acute coronary syndromes; most may have limited axial extent and therefore maintain adequate angiogenesis to heal. Concept illustrated in drawings of NC in cross-section (E) and long axis (F). Artist was Oran Suta.The angiogenesis patterns we observed are in conflict with currently held paradigms and initially seemed to be in conflict with the results of the Barger group, leading us to re-examine their data.4 In their second article, the authors quantified regional microvessel densities from the coronary cinematography described in their first article. They published a table of microvessel densities for the adventitia, inner media, and intima from cross sections of diseased human coronaries. The average microvessel densities (not paired data) were 9.8±1.3 and 10.3±4.6 in the adventitia and intima, respectively. However, the inner media vessel density was only 2.2±0.7 and was not explained in the article. This is inconsistent with predominately centripetal penetration. Microvessel densities should correlate across artery wall layers if penetration is centripetal with microvessels growing directly from adventitia through media to intima. We found no significant paired correlation between the microvessel densities of the intima and inner media (paired t test, P<0.0009), nor was there a significant correlation between the adventitia and intima microvessel densities for each vessel (Pearson paired correlation r=0.25, P=0.24).In arteries with significant plaque, all data are consistent with intimal microvessel propagation in a predominately longitudinal course. Our efforts to obtain the original silicone injection films were unsuccessful. On close examination of their still images (see Figure 1 in Reference 4), silicone is rarely seen penetrating directly from the adventitia into the luminal intima.4 These uncommon centripetal penetrations connect to microvessels coursing above the core, parallel to and near the lumen. These were not the conclusions drawn from their article. Re-examination of their data is instead consistent with the longitudinal intimal angiogenesis shown in our analysis of plaques axially.Intact healing mechanisms, dependent on the microvasculature, are critical for preventing intimal thinning, plaque rupture/erosion, and ACS.3 This includes maintaining the presence and function of noncontractile, synthetic (-ACTA2) smooth muscle cells.2,3 We have shown that longitudinal angiogenesis occurs over long necrotic cores and fails to reach some areas in the intimal cap (Figure). We propose that these areas are at risk for thinning, rupture/erosion, and ACS as a result of impaired healing mechanisms. In this model, ACS requires a double hit of both rupture/erosion and impaired vascular healing from inadequate angiogenesis. Clinically, this model supports moving away from angiogenesis inhibition to a strategy of augmenting healing.AcknowledgmentsThe authors thank Peter Caradonna for his technical support in histopathology generation.Sources of FundingHistopathology was funded by National Institutes of Health R01 HL55686 (Dr Brezinski), National Institutes of Health R01 EB02638/HL63953 (Dr Brezinski), and a University of New England Office of Scholarship and Research grant (Drs Brezinski and Willard).DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circMark E. Brezinski, MD, PhD, Massachusetts Institute of Technology, 77 Massachusetts Ave, Bldg 36-345, Cambridge, MA 01239. Email [email protected]eduReferences1. Camaré C, Pucelle M, Nègre-Salvayre A, Salvayre R. Angiogenesis in the atherosclerotic plaque.Redox Biol. 2017; 12:18–34. doi: 10.1016/j.redox.2017.01.007CrossrefMedlineGoogle Scholar2. Kramer MC, Rittersma SZ, de Winter RJ, Ladich ER, Fowler DR, Liang YH, Kutys R, Carter-Monroe N, Kolodgie FD, van der Wal AC, et al. Relationship of thrombus healing to underlying plaque morphology in sudden coronary death.J Am Coll Cardiol. 2010; 55:122–132. doi: 10.1016/j.jacc.2009.09.007CrossrefMedlineGoogle Scholar3. Brezinski ME. Comparing the risk factors of plaque rupture and failed plaque healing in acute coronary syndrome.JAMA Cardiol. 2019; 4:329–331. doi: 10.1001/jamacardio.2019.0312CrossrefMedlineGoogle Scholar4. Kamat BR, Galli SJ, Barger AC, Lainey LL, Silverman KJ. Neovascularization and coronary atherosclerotic plaque: cinematographic localization and quantitative histologic analysis.Hum Pathol. 1987; 18:1036–1042. doi: 10.1016/s0046-8177(87)80220-4CrossrefMedlineGoogle Scholar5. Brezinski ME, Harjai KJ. Longitudinal necrotic shafts near TCFAs: a potential novel mechanism for plaque rupture to trigger ACS?Int J Cardiol. 2014; 177:738–741. doi: 10.1016/j.ijcard.2014.09.144CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Yao J, Chen Y and Xu M (2022) The critical role of short-chain fatty acids in health and disease: A subtle focus on cardiovascular disease-NLRP3 inflammasome-angiogenesis axis, Clinical Immunology, 10.1016/j.clim.2022.109013, 238, (109013), Online publication date: 1-May-2022. Zheng Y, Kou J, Wang P, Ye T, Wang Z, Gao Z, Cong L, Li M, Dong B, Yang W, Li Q, Li H, Wang R and Yang L (2021) Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages, Aging, 10.18632/aging.202566, 13:5, (7096-7119), Online publication date: 15-Mar-2021. Ameri P, Tini G, Spallarossa P, Mercurio V, Tocchetti C and Porto I (2021) Cardiovascular safety of the tyrosine kinase inhibitor nintedanib, British Journal of Clinical Pharmacology, 10.1111/bcp.14793, 87:10, (3690-3698), Online publication date: 1-Oct-2021. Lyu Q, Tian X, Ding Y, Yan Y, Huang Y, Zhou P and Hui P (2020) Evaluation of Carotid Plaque Rupture and Neovascularization by Contrast-Enhanced Ultrasound Imaging: an Exploratory Study Based on Histopathology, Translational Stroke Research, 10.1007/s12975-020-00825-w, 12:1, (49-56), Online publication date: 1-Feb-2021. Alkhalil M (2020) A promising tool to tackle the risk of cerebral vascular disease, the emergence of novel carotid wall imaging, Brain Circulation, 10.4103/bc.bc_65_19, 6:2, (81), . Otsuka K, Villiger M, Nadkarni S and Bouma B (2020) Intravascular Polarimetry: Clinical Translation and Future Applications of Catheter-Based Polarization Sensitive Optical Frequency Domain Imaging, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2020.00146, 7 Díaz-Flores L, Gutiérrez R, García M, Gayoso S, Carrasco J, Díaz-Flores L, González-Gómez M and Madrid J (2020) Intussusceptive Angiogenesis and Peg–Socket Junctions between Endothelial Cells and Smooth Muscle Cells in Early Arterial Intimal Thickening, International Journal of Molecular Sciences, 10.3390/ijms21218049, 21:21, (8049) Feng X, Liu Y, Yang J, Zhai G, Zhou Y and Guo Q (2021) Prevalence of Healed Plaque and Factors Influencing Its Characteristics Under Optical Coherence Tomography in Patients With Coronary Artery Disease: A Systematic Review, Meta-Analysis, and Meta-Regression, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2021.761208, 8 December 3, 2019Vol 140, Issue 23 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.042192PMID: 31790293 Originally publishedDecember 2, 2019 Keywordstomography, optical coherenceacute coronary syndromeneovascularization, physiologicplaque, atheroscleroticrupturePDF download Advertisement SubjectsAcute Coronary SyndromesAortic Valve Replacement/Transcatheter Aortic Valve ImplantationCoronary Artery DiseaseHypertensionOptical Coherence Tomography (OCT)

Optical coherence tomography has become an important imaging technology in cardiology and ophthalmology, with other applications under investigations. Major advances in optical coherence tomography (OCT) imaging are likely to occur through a quantum field approach to the technology. In this paper, which is the first part in a series on the topic, the quantum basis of OCT first order correlations is expressed in terms of full field quantization. Specifically first order correlations are treated as the linear sum of single photon interferences along indistinguishable paths. Photons and the electromagnetic (EM) field are described in terms of quantum harmonic oscillators. While the author feels the study of quantum second order correlations will lead to greater paradigm shifts in the field, addressed in part II, advances from the study of quantum first order correlations are given. In particular, ranging errors are discussed (with remedies) from vacuum fluctuations through the detector port, photon counting errors, and position probability amplitude uncertainty. In addition, the principles of quantum field theory and first order correlations are needed for studying second order correlations in part II.

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.

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.

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.

Serious concerns exist about the Review by Otsuka et al. (Clinical classification of plaque morphology in coronary disease. Nat. Rev. Cardiol. 11, 379–389; 2014),1 some of which are discussed in this Correspondence. The concerns are predominately about the authors' understanding of the principles and application of optical coherence tomography (OCT),… Download references

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'.

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.

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.

Single channel PS-OCT has advantages for assessing birefringent tissue components in various clinical scenarios, with implications for assessing pathology, ranging from osteoarthritis to myocardial infarction. While the technique has been successfully used both in vitro and in vivo, there have been limited attempts to optimize single channel PS-OCT with respect to performance, particularly paddle rotation. In this study, we developed and tested a new approach for the real-time assessment of birefringence through tailoring of reference arm polarization. Different polarization rotation patterns, as depicted on a Poincare sphere, were assessed with polarization filters and retarders. When further tested in tissue, PS-OCT assessments of bovine cartilage and tendon demonstrated that contrast was sensitive to the pattern selected, indicating that rotation pattern influenced birefringence assessment and providing insights into optimal patterns. We also discuss the difference between diagnostic accuracy and precision with respect to both the construction and application of PS-OCT embodiments.

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.

The utilization and control of nonlocal quantum interactions is an area of active investigation. This is not limited to subatomic structures but extends to the macroscopic level. Nonlocal interactions can be from either entanglement or path indistinguishability (the path integral for larger systems), with the latter being further subdivided as discussed. These two distinct phenomenon have recently been treated often in the literature as essentially identical, which is problematic when utilizing them for practical applications. The confusion may lie in misunderstanding the physics of the type II spontaneous parameteric downconversion source (SPDS), which is used extensively with entanglement studies. This paper examines the distinction, and why it is important for practical applications, between quantum correlations from path indistinguishability versus entanglement. The path indistinguishability approaches discussed, under ambient conditions, are performed with a thermal source or, a coherent source (single photon wavepacket) when local entanglements in both arm have specific characteristics. The latter we will show has the property that it can surprisingly lead to coherence expansion rather than decoherence under the proper conditions. Nonlocal quantum correlations are a complex topic that extends beyond quantum entanglement.

Rotator cuff repair (RCR) is a crucial surgical procedure, but has unacceptable mechanical failure rates between 25–60%. Examining supplemental synergistic interventions, such as biological augmentations (ex: growth factors) to improve fibrocartilage formation rather than scar tissue formation, would make tears more amenable to surgical repair. Due to the large number of agents and application methods (and times), improved techniques are needed for assessing RCR in animals. In particular, high-resolution real-time imaging is needed to guide tissue engineering in animal models. Optical coherence tomography (OCT) is well suited for this role, with resolutions 25 × greater than any clinical imaging modality and an ability to identify organized collagen with polarization sensitive techniques. For example, it can determine severe collagen depletion in visually normal tendons. The images here show the first OCT and PS-OCT of the rotator cuff in male Wistar rats. The structure of the supraspinatus tendon, enthesis, and humerus are well defined. For histological comparison, this sample was stained with both Masson's Trichrome, to expose any structural abnormalities, and Picrosirius Red, to determine collagen content using a polarization filter. OCT studies offer the potential of understanding RCR failure mechanisms and potential tissue altering agents, substantially impacting outcomes.

The presented work demonstrates that using a true logarithmic amplifier to precondition the frequency clock signal in swept source OCT can obtain optimal calibration hence improve the imaging performance such as axial resolution and SNR.