Biomechanical Stress Profiling of Coronary Atherosclerosis: Identifying a Multifactorial Metric to Evaluate Plaque Rupture Risk.

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.

Intravascular Polarimetry in Patients With Coronary Artery Disease.

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.

Repeatability Assessment of Intravascular Polarimetry in Patients.

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.

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

OBJECTIVES: This 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. BACKGROUND: The 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. METHODS: The 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. RESULTS: Birefringence 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. CONCLUSIONS: Intravascular 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.

Terahertz endoscopic imaging for colorectal cancer detection: Current status and future perspectives.

Terahertz (THz) imaging is progressing as a robust platform for myriad applications in the field of security, health, and material science. The THz regime, which comprises wavelengths spanning from microns to millimeters, is non-ionizing and has very low photon energy: Making it inherently safe for biological imaging. Colorectal cancer is one of the most common causes of death in the world, while the conventional screening and standard of care yet relies exclusively on the physician's experience. Researchers have been working on the development of a flexible THz endoscope, as a potential tool to aid in colorectal cancer screening. This involves building a single-channel THz endoscope, and profiling the THz response from colorectal tissue, and demonstrating endogenous contrast levels between normal and diseased tissue when imaging in reflection modality. The current level of contrast provided by the prototype THz endoscopic system represents a significant step towards clinical endoscopic application of THz technology for in-vivo colorectal cancer screening. The aim of this paper is to provide a short review of the recent advances in THz endoscopic technology and cancer imaging. In particular, the potential of single-channel THz endoscopic imaging for colonic cancer screening will be highlighted.

Single-channel prototype terahertz endoscopic system.

We demonstrate the design and development of an innovative single-channel terahertz (THz) prototype endoscopic imaging system based on flexible metal-coated THz waveguides and a polarization specific detection technique. The continuous-wave (CW) THz imaging system utilizes a single channel to transmit and collect the reflected intrinsic THz signal from the sample. Since the prototype system relies on a flexible waveguide assembly that is small enough in diameter, it can be readily integrated with a conventional optical endoscope. This study aims to show the feasibility of waveguide enabled THz imaging. We image various objects in transmission and reflection modes. We also image normal and cancerous colonic tissues in reflectance mode using a polarization specific imaging technique. The resulting cross-polarized THz reflectance images showed contrast between normal and cancerous colonic tissues at 584 GHz. The level of contrast observed using endoscopic imaging correlates well with contrast levels observed in ex vivo THz reflectance studies of colon cancer. This indicates that the single-channel flexible waveguide-based THz endoscope presented here represents a significant step forward in clinical endoscopic application of THz technology to aid in in vivo cancer screening.

Characterization of bending loss in hollow flexible terahertz waveguides.

Attenuation characteristics of hollow, flexible, metal and metal/dielectric coated polycarbonate waveguides were investigated using an optically pumped far infrared (FIR) laser at 215 µm. The bending loss of silver coated polycarbonate waveguides were measured as a function of various bending angles, bending radii, and bore diameters. Minimal propagation losses of 1.77, 0.96 dB/m were achieved by coupling the lowest loss TE11 mode into the silver or gold coated waveguide, and HE11 mode into the silver/polystyrene coated waveguides respectively. The maximal bending loss was found to be less than 1 dB/m for waveguides of 2 to 4.1 mm bore diameters, with a 6.4 cm bend radius, and up to 150° bending angle. The investigation shows the preservation of single laser mode in smaller bore waveguides even at greater bending angles.