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Contains fulltext : 197937.pdf (Publisher’s version ) (Open Access)

OBJECTIVES The purpose of this study was to derive a biomechanical stress metric that was based on the multifactorial assessment of coronary plaque morphology, likely related to the propensity of plaque rupture in patients.BACKGROUND Plaque rupture, the most frequent cause of coronary thrombosis, occurs at locations of elevated tensile stress in necrotic core fibroatheromas (NCFAs). Finite element modeling (FEM), typically used to calculate tensile stress, is computationally intensive and impractical as a clinical tool for locating rupture-prone plaques. This study derived a multifactorial stress equation (MSE) that accurately computes peak stress in NCFAs by combining the influence of several morphological parameters.METHODS Intravascular ultrasound and optical frequency domain imaging were conducted in 30 patients, and plaque morphological parameters were defined in 61 NCFAs. Multivariate regression analysis was applied to derive the MSE and compute a peak stress metric (PSM) that was based on the analysis of plaque morphological parameters. The accuracy of the MSE was determined by comparing PSM with FEM-derived peak stress values. The ability of the PSM in locating plaque rupture sites was tested in 3 additional patients.RESULTS The following parameters were found to be independently associated with peak stress: fibrous cap thickness (p < 0.0001), necrotic core angle (p = 0.024), necrotic core thickness (p < 0.0001), lumen area (p < 0.0001), necrotic core including calcium areas (p = 0.017), and plaque area (p = 0.003). The PSM showed excellent correlation (R = 0.85; p < 0.0001) with FEM-derived peak stress, thus confirming the accuracy of the MSE. In only 56% (n = 34) of plaques, the thinnest fibrous cap thickness was a determining parameter in identifying the cross section with highest PSM. In coronary segments with plaque ruptures, the MSE precisely located the rupture site.CONCLUSIONS The MSE shows potential to calculate the PSM in coronary lesions rapidly. However, further studies are warranted to investigate the use of biomechanical stress profiling for the prognostic evaluation of patients with atherosclerosis. (C) 2020 by the American College of Cardiology Foundation.

Objectives: The aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation. Background: Polarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure. Methods: Thirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model. Results: The median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD. Conclusions: Intravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients. © 2020 The Authors

Intravascular polarimetry with polarization sensitive optical frequency domain imaging (PS-OFDI) measures polarization properties of the vessel wall and offers characterization of coronary atherosclerotic lesions beyond the cross-sectional image of arterial microstructure available to conventional OFDI. A previous study of intravascular polarimetry in cadaveric human coronary arteries found that tissue birefringence and depolarization provide valuable insight into key features of atherosclerotic plaques. In addition to various tissue components, catheter and sample motion can also influence the polarization of near infrared light as used by PS-OFDI. This paper aimed to evaluate the robustness and repeatability of imaging tissue birefringence and depolarization in a clinical setting. 30 patients scheduled for percutaneous coronary intervention at the Erasmus Medical Center underwent repeated PS-OFDI pullback imaging, using commercial imaging catheters in combination with a custom-built PS-OFDI console. We identified 274 matching cross sections among the repeat pullbacks to evaluate the reproducibility of the conventional backscatter intensity, the birefringence, and the depolarization signals at each spatial location across the vessel wall. Bland-Altman analysis revealed best agreement for the birefringence measurements, followed by backscatter intensity, and depolarization, when limiting the analysis to areas of meaningful birefringence. Pearson correlation analysis confirmed highest correlation for birefringence (0.86), preceding backscatter intensity (0.83), and depolarization (0.78). Our results demonstrate that intravascular polarimetry generates robust maps of tissue birefringence and depolarization in a clinical setting. This outcome motivates the use of intravascular polarimetry for future clinical studies that investigate polarization properties of arterial atherosclerosis. © 1982-2012 IEEE.

Resonant Doppler Fourier Domain Optical Coherence Tomography is a functional imaging modality for quantifying fast tissue flow. The method profits from the effect of interference fringe blurring in spectrometer-based FDOCT in the presence of sample motion. If the reference path length is changed in resonance with the Doppler frequency of the sample flow the signals of resting structures will be suppressed whereas the signals of blood flow are enhanced. This allows for an easy extraction of vascularization structure. 3D images of blood vessels at the human optic nerve head are obtained with high axial resolution of 8 mu m in air and an imaging speed of 17.400 depth profiles per second. An electrooptic modulator allows controlled reference phase shifting during camera integration. A differential approach is presented for the quantification of fast flows that are un-accessible via standard phase sensitive Doppler analysis. Flow velocity analysis extracts only the axial component which is dependent on the orientation of the vessel with respect to the optical axis. 3D information of the segmented vessel structure is readily used to obtain the flow velocity vectors along the individual vessels and to calculate the true angle-corrected flow speed.

PURPOSE: To perform high speed and completely non-invasive 3D angiography at the optic nerve head region and to reconstruct vectorial 3D blood flow from optically segmented blood vessel structure as a pre-requisite for testing retinal function and physiology. METHODS: A novel Doppler Fourier domain OCT systems, so-called resonant Doppler OCT, allows circumventing the limitations of standard FDOCT to record fast blood flow signals. Standard Doppler FDOCT suffers from fringe blurring due to sample motion which leads to a small velocity detection range. The novel resonant scheme tunes a Doppler shift in the reference arm to the sample Doppler shift resulting in enhanced signal for moving structures whereas static structure signals are suppressed. As a result one obtains already optically a segmentation or optical vivisection of retinal blood flow in 3D. This data is used for extracting the true flow vectors along the retinal vessels (any single beam Doppler method yields only the axial projection of the flow velocity). The realized resonant FDOCT system works at 20.000 scans/sec with an axial resolution of 8µm in air. A full 3D volume of 2240(X) x 88(Y) x 1024(Z) pixels takes 10sec. RESULTS: 3D volumes of retinal structure at the optic nerve head region are recorded with different reference Doppler offsets. The images yield a clear segmentation of 3D vessel structure with suppressed static structure signals. Sets of 3D images with opposite reference Doppler shift are recorded. Differential analysis of the images yields the quantitative bidirectional axial velocity components in 3D. Axial flow components of up to +/-10mm/s with a velocity precision of 400µm/s were measured enhancing standard Doppler FDOCT velocity ranges by a factor of four. Advanced image processing algorithms allow in addition reconstruction of the true vectorial flow along the blood vessels assuming laminar flow. CONCLUSIONS: Resonant Doppler OCT yields completely non-invasive 3D angiography. It allows assessing depth resolved and quantitative blood flow at the optical nerve head with high precision and large velocity range providing directly the 3D vascularization structure. Any physiologic changes at the retina will result in changes of blood flow especially in large vessels close to the optic nerve head that provide the inner retinal blood supply. The method might therefore have high clinical value for the assessment of retinal function.

We demonstrate a simple and cheap method for phase shifting that does not need additional devices. A small beam offset at the fast scanning mirror introduces a causal phase shift which can be used for recently introduced B-scan based complex image reconstruction as well as for enhancing flow signals with resonant Doppler imaging. It can be directly implemented in any FDOCT setup without additional cost. The method is demonstrated on human skin in vivo for spectrometer based FDOCT operating at 1300nm employing a handheld scanner. The latter includes the reference arm and is equipped with a single point scanner.

Fourier domain Optical coherence microscopy (FDOCM) offers excellent sensitivity and high axial resolution to image the structure of biological tissue. The depth information is extracted in parallel and allows very high volume acquisition rates. An illumination scheme employing an axicon lens produces a Bessel-like interference pattern to obtain a laterally highly confined illumination needle, extending over a long axial range. High lateral resolution is provided over an extended depth of field (xf). For increased efficiency, the detection occurs decoupled from the illumination, avoiding a double pass through the axicon. The achieved xf-OCM signal reveals the spatial distribution of changes of the refractive index in the sample with high contrast and constant near isotropic resolution of about 2μm. First tomograms of mouse pancreas show a high contrast between the exocrine tissue and the endocrine islets without any labeling or staining. The tissue vascularization and the lobular exocrine architecture are also clearly imaged. Images acquired with classical microscopy techniques, involving stained and fluorescent samples, validate these structures and emphasize the high contrast of the tomograms. It is comparable to the contrast achieved with classical techniques, but employing neither staining, labeling nor slicing of the samples, stressing the high potential of xf- OCM for minimally invasive in vivo small animal imaging.

Rapid acquisition of volumetric data is a mandatory prerequisite for small animal in vivo imaging. Due to its high sensitivity and capacity to extract the sample depth profile in parallel Fourier Domain Optical Coherence Tomography (FDOCT) complies with this requirement. The absence of labeling further simplifies its use for in vivo application. In order to provide the high spatial resolution necessary to gain biologically relevant insights focusing optics from microscopy are usually employed. The resulting focal spot however has a limited depth of field and compromises with imaging speed and parallel depth extraction. Using a Bessel‐like illumination beam, obtained by use of a conical lens, and detection optics with a low numerical aperture, we achieve a compromise between high lateral resolution and extended depth of field and obtain near isotropic resolution. Together with a scanning system deflecting the beam rapidly in the lateral directions and a fast signal acquisition and processing routine this extended focus Optical Coherence Microscope (xfOCM) was used to measure murine islets of Langerhans. These endocrine islets are assemblies of insulin secreting beta cells contained within the exocrine tissue of the pancreas. Assessing the structure and function of individual islets is important to further the understanding of diabetes’ mechanisms. In this work we used xfOCM to measure islets, pancreatic lobules, ducts and blood vessels, first in excised tissue, and then we demonstrate the potential of this method with volumetric measurements of the pancreatic islets in vivo and in situ.

Fourier Domain Optical Coherence Tomography (FDOCT) is a high speed biomedical imaging modality which extracts the sample structure in depth. The axial resolution is given by the coherence length of the employed light source. The lateral resolution on the other hand is determined by the numerical aperture (NA) of the objective. The parallel detection of the depth information has the drawback of loosing transverse resolution along the optical axis, limiting the depth of field (DOF) and the use of FDOCT in the field of microscopy. The principle idea to overcome this problem is to illuminate the sample with a cylindrically symmetric interference pattern. Such Bessel beam illumination creates a laterally highly confined needle extending several 100μm along the optical axis in depth.

Fourier Domain OCT proved to be an outstanding tool for measuring 3D retinal structures with high sensitivity, resolution, and speed. We extended the FDOCT concept towards functional imaging by analyzing the spectroscopic tissue properties, polarization contrast and Doppler velocity imaging. Differential spectral contrast FDOCT allows optical staining of retinal tomograms and to contrast tissue of high pigmentation such as the retinal pigment epithelium (RPE). The latter shows strong correlation if compared to polarization sensitive OCT images. First implementations of Doppler FDOCT systems demonstrated the capability of measuring in-vivo retinal blood flow profiles and pulsatility. We developed a new concept of Doppler FDOCT that allows measuring also large flow velocities typically close to the optic nerve head. Studies of retinal perfusion based on Laser Doppler Flowmetry (LDF) demonstrated the high sensitivity of blood flow to external stimuli. We performed first experiments of studying retinal perfusion in response to flicker stimulation. An increase in vessel diameter by 11% and of flow velocity by 49% was measured. We believe that a multi- modal functional imaging concept is of high value for an accurate and early diagnosis and understanding of retinal pathologies and pathogenesis.