Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study

Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in three swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23 % (p < 0.0001). This error was eliminated with careful refractive index calibration. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful refractive index compensation should be performed, taking into account the specific contrast agent used, in order to obtain accurate intravascular OFDI measurements.Merck & Co., Inc.National Institutes of Health (U.S.) (Grant Numbers R00CA134920, R01HL076398, R01HL093717

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies

Objectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background: Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods: The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results: Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions: This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data

Optical measurement of arterial mechanical properties: from atherosclerotic plaque initiation to rupture

Abstract. During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future

Schematic of the LSR optical setup

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Hajjarian1" target="_blank">[12]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Nadkarni2" target="_blank">[14]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Hajjarian2" target="_blank">[16]</a>. Light from a randomly polarized He-Ne laser (632 nm, 30 mW) is coupled into a single mode fiber (SMF600). The beam is polarized, collimated, and focused (focal length 25 cm, 50 µm spot size) at the sample surface. A beam-splitter is used to ensure speckle patterns are acquired at 180° back-scattering geometry. The cross-polarized component of back-scattered light is focused at the CMOS sensor of a high-speed camera (PL-761, Pixelink, Ontario, Canada), equipped with a focusing lens system (MLH-10×, Computar, Commack, NY). The acquired speckle frame series are transferred to a high-speed computer for further processing.</p

LSR of 90% glycerol-10% water mixtures with varying scattering concentrations.

<p>Speckle intensity temporal autocorrelation curves, <i>g₂^exp(t)</i>, for aqueous glycerol mixtures of 90%G-10%W and various concentrations of TiO₂ scattering particles (0.04%–2%, corresponding to <i>μ′_s : 1.3–84.8 mm⁻¹</i>, N = 18), along with theoretical DLS and DWS curves (dotted lines). By changing the scattering concentration <i>g₂^exp(t)</i> curves sweep the transition area between the two theoretical limits. This data demonstrates the dependence of <i>g₂^exp(t)</i> on optical scattering in samples with identical mechanical properties.</p

Detailed flow chart of the compensation algorithm.

<p><i>Block 1: Speckle acquisition and g₂(t) calculation:</i> Speckle frame series are acquired with sufficient frame rate, ROI, and pixel to speckle size ratio. Speckle intensity temporal autocorrelation curves, <i>g₂(t)</i>, are evaluated for phantom and tissue samples using sufficient temporal and spatial averaging. <i>Block 2: Measurement of optical properties</i>: The radial remittance profile is evaluated from temporally averaged speckle intensities and is converted to the photon flux, <i>ψ(ρ)</i>. Optical properties of the sample (<i>μ_a</i> and <i>μ′_s</i> ) are derived experimentally by fitting the photon flux profile to the model obtained from steady-state diffusion theory. <i>Block 3: PSCT-MCRT for simulating g₂(t)-MSD expression:</i> Experimentally evaluated optical properties, LSR configuration, and sample geometry are used in the PSCT-MCRT simulation to derive an expression for <i>g₂(t)</i> as a function of MSD. <i>Block 4: Evaluating MSD and</i> |<i>G*(ω)</i>|: Following the measurement of MSD using the modified expression, logarithmic slope of MSD, <i>α(t) = ∂ log <Δr²(t)>/∂ log t</i>, is calculated and replaced in the simplified GSER to evaluate the viscoelastic modulus <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Mason1" target="_blank">[18]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Mason3" target="_blank">[20]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Dasgupta1" target="_blank">[22]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Dasgupta2" target="_blank">[23]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Wu1" target="_blank">[25]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Moschakis1" target="_blank">[26]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Balucani1" target="_blank">[36]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014-Levine1" target="_blank">[41]</a>. Here <i>K_B</i> is the Boltzman constant (1.38×10⁻²³), <i>T</i> is temperature (degrees kelvin), <i>a</i> is the scattering particle size, <i><Δr²(1/ω)></i> corresponds to <i><Δr²(t)></i>, evaluated at t = 1/ω, ω = 1/t is the frequency, and <i>Γ</i> represents the gamma function.</p

MSD of scattering particles, derived using DWS expression, and the corresponding magnitude viscoelastic modulus |<i>G*(ω)</i>| curves for 90% glycerol-10% water mixtures.

<p>In panel (a), MSD is extracted from <i>g₂^exp(t)</i> assuming the validity of Diffusion approximation. Considerable variability is observed between MSD curves associated with different scattering concentrations. In panel (b) Generalized Stokes'-Einstein Relation is used to calculate |<i>G*(ω)</i>| from MSD obtained from Diffusion approximation. The curves fail to match the results of conventional rheometry and are biased by the corresponding scattering concentrations. Moreover, significant variation is observed between the evaluated modulus of sample with different scattering concentrations.</p

LSR results of |<i>G*(ω)</i>| for synovial fluid and vitreous humor measured with and without optical scattering correction.

<p>The red diamonds are the average |<i>G*(ω)</i>| moduli, of synovial fluid (panel (a)) and vitreous humor (panel (b)) samples of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone-0065014-g008" target="_blank">Fig. 8</a>, obtained from LSR by using the DWS expression (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014.e003" target="_blank">eqn. (3)</a>). The red error bars correspond to standard error values. The purple squares represent the average |<i>G*(ω)</i>| moduli, obtained from the corrected MSD values using <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014.e006" target="_blank">eqn. (6)</a>, and the purple error bars correspond to the standard errors. Also depicted in this figure are the |<i>G*(ω)</i>| values for the samples measured using a conventional rheometer (black solid line, round markers). While LSR results compensated for optical scattering show close correspondence with rheology measurements, the DWS-based approach results in an offset of about one decade relative to conventional testing results.</p

Compensated MSD of scattering particles and the corresponding magnitude viscoelastic modulus, |<i>G*(ω)</i>|, of 90% glycerol-10% water-TiO₂ suspensions.

<p>Panel (a) depicts the corrected MSD curves, deduced from <i>g₂^exp(t)</i> curves of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone-0065014-g004" target="_blank">Fig. 4</a> using <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014.e006" target="_blank">eqn. (6)</a>. The modified expression of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone.0065014.e006" target="_blank">eqn. (6)</a> resulted from PSCT-MCRT simulation of photon propagation and correlation transfer in LSR experimental setup considering the exact sample geometry and optical properties. Compared to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone-0065014-g005" target="_blank">Fig. 5(a)</a>, variability of MSD curves is significantly reduced, especially at intermediate times. Residual small deviations, still observed at very early or long times, are most likely due to electronic noise and speckle blurring, respectively. In panel (b) Generalized Stokes'-Einstein Relation is used to calculate |<i>G*(ω)</i>| from corrected MSD. It is observed that the variability between measured |<i>G*(ω)</i>| for different concentrations is considerably reduced, compared to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065014#pone-0065014-g005" target="_blank">Fig. 5(b)</a>. Moreover, a high correspondence is observed between LSR results for |<i>G*(ω)</i>| and mechanical rheometry.</p