We introduce a new method to measure Doppler shifts more accurately and extend the dynamic range of Doppler optical coherence tomography (OCT). The two-point estimate of the conventional Doppler method is replaced with a regression that is applied to high-density B-scans in polar coordinates. We built a high-speed OCT system using a 1.68-MHz Fourier domain mode locked laser to acquire high-density B-scans (16,000 A-lines) at high enough frame rates (∼100 fps) to accurately capture the dynamics of the beating embryonic heart. Flow phantom experiments confirm that the complex regression lowers the minimum detectable velocity from 12.25 mm / s to 374 μm / s, whereas the maximum velocity of 400 mm / s is measured without phase wrapping. Complex regression Doppler OCT also demonstrates higher accuracy and precision compared with the conventional method, particularly when signal-to-noise ratio is low. The extended dynamic range allows monitoring of blood flow over several stages of development in embryos without adjusting the imaging parameters. In addition, applying complex averaging recovers hidden features in structural images.
Altered hemodynamics in developing embryonic hearts lead to congenital heart diseases, motivating close monitoring of blood flow over several stages of development. Doppler OCT can assess blood flow in tubular hearts where blood velocity increases drastically during the period of cardiac cushion (valve precursors) formation. The blood-induced shear stress undergoes dramatic changes as well, which affects gene expression by the endothelial cells. Previously, we built a high-speed OCT system using an FDML laser (Optores GmbH, Germany) at a sweep rate of 1.68 MHz (axial resolution - 12 μm, sensitivity - 105 dB, phase stability - 96 mrad). The ultra-fast A-line rate of this laser may be used to collect real-time volumetric images of the heart, or can be traded off to obtain dense B-scans for more accurate Doppler measurements with a larger dynamic range using Doppler complex regression. Since we cannot achieve volumetric imaging with dense B-scans, an image-based retrospective gating technique was developed to register the asynchronously acquired dense B-scans to the 4D volumes. The direction of flow was determined by finding the centroid of the Doppler signal from the rearranged B-scans along the heart tube to compute absolute velocity. Subsequently, the cross-section from which the shear stress is calculated was realigned orthogonal to the direction of blood flow to approximate the velocity gradient normal to the wall. In conclusion, our high-speed OCT system will enable semi-automated measurement of the absolute blood velocity, as well as mapping the shear stress exerted on the inner walls of the embryonic hearts.
The limited dynamic range of optical coherence tomography (OCT) Doppler velocity measurements makes it difficult to conduct experiments on samples requiring a large dynamic range without phase wrapping at high velocities or loss of sensitivity at slow velocities. Hemodynamics and wall motion undergo significant increases in velocity as the embryonic heart develops. Experimental studies indicate that altered hemodynamics in early-stage embryonic hearts can lead to congenital heart diseases (CHDs), motivating close monitoring of blood flow over several stages of development. We have built a high-speed OCT system using an FDML laser (Optores GmbH, Germany) at a sweep rate of 1.68 MHz (axial resolution - 12 μm, sensitivity - 105 dB, phase stability - 17 mrad). The speed of this OCT system allows us to acquire high-density B-scans to obtain an extended velocity dynamic range without sacrificing the frame rate (100 Hz). The extended dynamic range within a frame is achieved by varying the A-scan interval at which the phase difference is found, enabling detection of velocities ranging from tens of microns per second to hundreds of millimeters per second. The extra lines in a frame can also be utilized to improve the structural and Doppler images via complex averaging. In structural images where the presence of blood causes additional scattering, complex averaging helps retrieve features located deeper in the tissue. Moreover, high-density frames can be registered to 4D volumes to determine the orthogonal direction of flow for calculating shear stress as well as estimating the cardiac output. In conclusion, high density B-scans acquired by our high-speed OCT system enable image enhancement and direct measurement of biological parameters in cohort studies.
Altered hemodynamics in developing embryonic hearts lead to congenital heart diseases, motivating close monitoring of blood flow over several stages of development. Doppler OCT can assess blood flow in tubular hearts, but the maximum velocity increases drastically during the period of cardiac cushion (valve precursors) formation. Therefore, the limited dynamic range of Doppler OCT velocity measurement makes it difficult to conduct longitudinal studies without phase wrapping at high velocities or loss of sensitivity to slow velocities. We have built a high-speed OCT system using an FDML laser (Optores GmbH, Germany) at a sweep rate of 1.68 MHz (axial resolution - 12 μm, sensitivity - 105 dB, phase stability - 17 mrad). The speed of this OCT system allows us to acquire high-density B-scans to obtain an extended velocity dynamic range without sacrificing the frame rate. The extended dynamic range within a frame is achieved by varying the A-scan interval at which the phase difference is found, enabling detection of velocities ranging from tens of microns per second to hundreds of mm per second. The extra lines in a frame can also be utilized to improve the structural and Doppler images via complex averaging. In structural images where presence of blood causes additional scattering, complex averaging helps retrieve features located deeper in the tissue. Moreover, high-density frames can be registered to 4D volumes to determine the orthogonal direction of flow and calculate shear stress. In conclusion, our high-speed OCT system will enable automated Doppler imaging of embryonic hearts in cohort studies.
We sought to elucidate the mechanisms underlying two common intravascular optical coherence tomography (IV-OCT) artifacts that occur when imaging metallic stents: “merry-go-rounding” (MGR), which is an increase in strut arc length (SAL), and “blooming,” which is an increase in the strut reflection thickness (blooming thickness). Due to uncontrollable variables that occur in vivo, we performed an in vitro assessment of MGR and blooming in stented vessel phantoms. Using Xience V and Driver stents, we examined the effects of catheter offset, intimal strut coverage, and residual blood on SAL and blooming thickness in IV-OCT images. Catheter offset and strut coverage both caused minor MGR, while the greatest MGR effect resulted from light scattering by residual blood in the vessel lumen, with 1% hematocrit (Hct) causing a more than fourfold increase in SAL compared with saline (p<0.001). Residual blood also resulted in blooming, with blooming thickness more than doubling when imaged in 0.5% Hct compared with saline (p<0.001). We demonstrate that a previously undescribed mechanism, light scattering by residual blood in the imaging field, is the predominant cause of MGR. Light scattering also results in blooming, and a newly described artifact, three-dimensional-MGR, which results in “ghost struts” in B-scans.
Effect of catheter eccentricity on the appearance of stent struts in IV-OCT images in presence of thick neointimas was examined by simulation of light-stent interaction. A phantom blood vessel was constructed from a mix of polydimethylsiloxane (PDMS) and titanium dioxide to simulate the elastic and optical scattering properties of the arterial wall. A Cordis CYPHER® sirolimus-eluting stent was deployed within the phantom vessel and high resolution Micro-CT images of the stent strut were recorded to create a three-dimensional representation. Simulation of IV-OCT catheter and reflection of light from the stent strut and neointima was implemented for different catheter eccentricities. An optical model of the IV-OCT catheter was constructed and IV-OCT images corresponding to rotation of the light beam over the stent strut were simulated. The measured parameters included intensity and optical path length of light reflecting from the stent strut and coupled into catheter. The results indicate that in presence of thick neointimas sunflower effect is not observed and neointimal thickness measurement using IV-OCT is consistent with true values irrespective of catheter eccentricity.
Effect of stent surface-scattering properties on the appearance of stent struts in IV-OCT images was examined by
simulation of light-stent interaction by an optical design software package. A phantom blood vessel was constructed
from a mix of polydimethylsiloxane (PDMS) and titanium dioxide to simulate the elastic and optical scattering
properties of the arterial wall. A Cordis CYPHER® sirolimus-eluting stent was deployed within the phantom vessel and
high resolution Micro-CT images of the stent strut were recorded to create a three-dimensional representation that was
imported into software. A Gaussian surface-scattering model (bi-directional scattering distribution function) was
assumed for the strut. Simulation of IV-OCT catheter and reflection of light from the stent strut was implemented for
different surface scattering properties. A model of IV-OCT catheter was defined in the optical model and the rotation of
the light beam over the stent strut was simulated. The measured parameters included: fraction of the reflected rays
returning to the catheter and coordinate locations on the stent struts of returned rays. The results indicate that when the
surface scattering of the strut increases, reflectivity is higher, while the angular spread of the light beam that is reflected
back to the catheter is wider.
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