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Optical Coherence Tomography (OCT) for Cardiac Imaging is an invasive imaging technique that produces high resolution intra-coronary images. Like intravascular ultrasound (IVUS), OCT for cardiac imaging uses the difference in the backscattering of waves to resolve the image. However, unlike IVUS, this method uses infrared light rather than ultrasound to image the vessels.

OCT provides in vivo information on atherosclerotic plaque morphology with near light microscopy resolution. The high resolution of this imaging technique enables detailed evaluation not only of coronary atherosclerotic plaques but also regarding the vascular response to coronary interventional devices, such as new generation coronary stents, providing important information on neointima formation and strut coverage over time in patients, with potentially significant clinical implications. Moreover, compared to conventional intravascular ultrasound coronary imaging, OCT can be used as a guide for coronary intervention with improved resolution.

Theory
As light speeds are around 200,000x faster than sound, it is difficult to sample data at a rate that high when dealing with light sources. As a result, a technique called interferometry is used.

Wave Interference
Interferometry is based on the theory of interference between waves. If two coherent waves travel a different distance before coming together, there is likely to be a phase difference between them. A 180° phase difference results in the crest of wave 1 matching with the troughs of wave 2, resulting in destructive interference (i.e. no signal). If there is no phase shift between the two waves, then the amplitudes add to produce a signal with twice the amplitude, as the phases match.

Michelson Interferometer
In interferometry, one can measure distances directly in terms of wavelength of light used, by counting the interference fringes that move when one or the other of two mirrors are moved. In the Michelson interferometer, coherent beams are obtained by splitting a beam of light that originates from a single source with a partially reflecting mirror called a beam splitter. The resulting reflected and transmitted waves are then redirected by ordinary mirrors to a screen where they superimpose to create fringes. This is known as interference by division of amplitude. The Michelson interferometer can be seen in Figure 1.

The coherence length ($$l_c$$) is determined by multiplying the coherence time ($$\tau_c$$) by the speed of light (c) as seen in Equation 1 below. As the phase difference reaches closer to 180°, the coherence length decreases. The frequency spectrum seen in the interference of the two waves is Gaussian and is described by Equation (2) below. Therefore the coherence length can be expressed as seen in Equation (3). Therefore, as the light source becomes more coherent, the bandwidth of the source decreases, increasing the coherence length. As an increase in coherence length decreases resolution, a low coherence light source (wide bandwidth) is used for OCT.

$$l_c=\tau_c*c$$ 	 (1)

$$S(\omega)=\frac{1}{\sqrt{2\pi}\sigma_{\omega}}exp(\frac{-(\omega-\omega_{0})^2}{\sigma_{\omega}^2})$$ 	 (2)

$$l_c=\frac{4ln(2)}{\pi}\frac{\lambda_{0}^2}{\Delta\lambda}$$ 	 (3)

Time Domain vs Frequency Domain
The time-domain OCT (TD-OCT) is based on the Michelson interferometer setup. In this case the reference mirror moves to change the difference in the length between the reference mirror and the sample, producing known echo delays. The reflected signal returning from the tissue and reference arms are recombined in the fiber-coupler, and their interference fringes are detected by a photodetector. The difference produces a different phase difference between the reference and sample waves, resulting in a change in the AC component that is measured.

In frequency-domain OCT (FD-OCT), an optical frequency sweep is done with a fast tunable laser to change the center frequency (and center wavelength) of the spectrum. In using a frequency sweep, the center wavelength changes; thereby changing the depth that is in focus (constructive interference) over a range of frequencies. All backscatters on the A-line (intensity measurement) are measured simultaneously, while in TD-OCT, only some of the backscatters are measured at a given time.

As a result, current FD-OCT systems have higher frame rates and scanning speeds, enabling the acquisition of long coronary segments very rapidly. With FD-OCT, 100 frames\sec can be obtained, with an automatic pullback of 20 mm/sec and a resolution of 500.000 pixel/frame during a single injection of contrast bolus. TD-OCT used a broadband light whereas FD-OCT employs a laser that emits near monochromatic light which allows higher frame rate and speed of data acquisition.

Resolution
Similar to its acoustic analog, OCT has two forms of resolution that need to be considered: axial and lateral.

Axial
Axial resolution (also known as depth, longitudinal, or azimuthal resolution) is related to the coherence length and lies parallel to the light beam from the OCT system. The wider the coherence length, the more particles a single wavelength will pass through, meaning that fewer particles will be resolved. As the coherence length decreases, smaller and smaller particles will be able to be resolved. It is consistent throughout the entire length of propagation and is thus not affected by depth of imaging.

OCT for coronary imaging utilizes light in the infrared spectrum--with a central wavelength around 1250-1350 nm--allowing for a much better resolution than ultrasound. The axial resolution is typically 10-20 micron. The consequence of a higher resolution is that there is lower depth penetration of the tissue (about 1.5 - 3 mm), which is acceptable when imaging coronary arteries since they are closer to the surface of the skin.

Lateral
Lateral resolution is the ability to resolve objects in a field of view that is perpendicular to the beam of propagation. This is more dependent on the physical system itself and how wide of a beam is being output as well as the depth of imaging. The lateral resolution is best at shallow depths since the beams typically diverge in the far field.

Normally, the spatial resolution would be measured by using the Modulation Transfer Function, but because of additional noise from electronic systems being implemented in OCT, we must add in additional considerations such as source power, interferometer parameters, and sample reflectivity.

OCT- Coronary Artery Imaging
Intravascular Time Domain Optical Coherence Tomography (IVTD-OCT) evolved from optical 1- dimensional low-coherence reflectometry, which uses a Michelson interferometer and a broadband light source. IVTD-OCT uses a single fiber optic wire that both emits light and records the reflection while simultaneously rotating and being pulled back along the artery, producing a continuous image from the point at which the interferometer records the light reflected from the surface.

An optical signal that is transmitted through or reflected from a biological tissue will contain information regarding the time that the photons of traveled, which yields spatial information about tissue microstructure. Time-resolved transmission spectroscopy has been used to measure absorption and scattering properties in tissues and has been demonstrated as a noninvasive diagnostic measure of hemoglobin oxygenation in the brain. In contrast to time domain techniques, low-coherence reflectometry is performed with continuous-wave light without using ultrashort pulse laser sources, which makes it useful for longer continuous intravascular imaging. Furthermore, low-coherence reflectometry can also be used for the construction of compact and modular systems that use diode light sources and fiber optics and have achieved micrometer spatial resolutions and high detection sensitivities.

The OCT system performs multiple longitudinal scans at a series of lateral locations to provide a two-dimensional map of reflection sites in the sample, which is similar to the ultrasound B-mode scan.

OCT catheters contain a single optical fiber that emits infrared light that is used to capture information from the surrounding blood vessels. OCTs measure the echo time delay and the signal intensity after its reflection or back-scattering from the coronary wall structures while simultaneously operating a pull-back along the coronary artery, and thus performing a scan of the segment of interest. The system then creates cross sections of the coronary artery allowing for real- and off-line analysis of each section. It uses light in the infrared spectrum with central wavelength between 1,250 and 1,350 nm. While longer wavelengths allow for deeper penetration, the infrared spectrum is used as the tissue absorption characteristics and the refractive index of the interface between the catheter and vessel wall are minimized in this region. As a result, the backscatter increases, resulting in a greater SNR. However, using this wavelength the tissue penetration is limited to 1 to 3 mm as compared with 4 to 8 mm achieved by intravascular ultrasound (IVUS), with the exception of calcified lesions in which sound has a limited penetration.

As the speed of light is greater than that of ultrasound, an interferometer is needed to measure the backscattered light, as computer systems are not fast enough to process data at the rate of light travel and reflection. As a result, resolution is improved, as the optical recordings allow for greater focus and precision in imaging. Axial resolution with OCT is 10-20 micron whereas it is typically only 100-200 micron with intravascular ultrasounds. OCT resolution is also superior to non-invasive coronary imaging techniques such as computer tomography coronary angiography (CTCA) and cardiac magnetic resonance (CMR).

The optical sectioning capability of OCT is similar to that of confocal microscopic systems. However, although the longitudinal resolution of confocal microscopy depends on the available numerical aperture, OCT’s resolution is limited only by the coherence length of the light source. Thus, OCT can maintain high depth resolution even when the available aperture is small.

Limitations
Current maximum tissue penetration with OCT is approximately 1.5 mm-3 mm. Consequently, deeper vessel structures such as external elastic lamina are difficult to visualize in cases of coexisting large atherosclerotic plaque.

In addition, red blood cells interfere with the propagation of infrared light. To resolve this issue, blood is displaced from the vessel’s lumen to avoid artifacts during reconstruction. Previously, the process was complex, which occuluded the coronary lumen with an inflated balloon and simultaneously flushing the vessel with saline through the balloon catheter. However, recently, contrast media has been to flush the coronary arteries to displace the blood pool to reduce occlusion.

Medical Applications
The main applications of the OCT coronary imaging are: atherosclerotic plaque assessment; stent struts coverage and apposition assessment, and in stent restenosis evaluation; and PCI guide and optimization.

Imaging of coronary atherosclerotic plaque morphology aids in identifying atherosclerotic plaque at risk of rupture and thrombosis, a frequent cause of acute coronary syndromes. Atherosclerotic plaque at risk of rupture is characterized by a thin fibrous cap (< 65 µm), a large lipid pool, and inflammation with activated macrophages near the fibrous cap. OCT imaging can detect locations of plaque vulnerability and distinguish differences in plaque composition to a high specificity, even when compared to histopathology. In addition, OCT imaging can identify intraluminal thrombi that appear as irregular structures protruding into the coronary lumen while also being able to differentiate red and white thrombi due to differences in signal attenuation.

OCT coronary imaging can also aid in post-implantation stent assessment regarding quantifying stent struts coverage over time. In many studies, incomplete neointimal coverage of stent struts has been shown to be an indicator of stent thrombosis and endothelialization. OCT can accurately detect and quantify in-stent coverage and strut healing with higher reproducibility than IVUS which provides lower resolution and more artifacts close to the metal struts. OCT analysis also enables identification of in-stent restenosis (exceeding neointimal proliferation).

OCT imaging can help in PCI (percutaneous coronary intervention) by providing accurate measurements of coronary lumen diameters and minimal lumen area at the level of plaque useful for assessment of intermediate angiographic stenosis. OCT can also characterize plaque lesion, length, calcification, and ulceration or rupture with intraluminal thrombus or if there is intimal dissection close to the plaque. For bifurcation lesions, OCT can provide information about the side branch and whether or not to stent it. Following PCI, OCT can provide information about luminal diameters and area of stented coronary segments which corresponds to risk of restenosis. In addition, OCT can identify incomplete coverage of an atherosclerotic lesion and thus assess the need for a second stent. IVUS imaging can demonstrate stent strut malapposition in only approximately 7% of cases while OCT imaging has been found to identify malapposition in 9.1+7.4% of cases due to greater resolution of imaging. OCT can also identify plaque protrusion into the stent or plaque shift after implantation and thus be used in recommending the need for post-dilatation if there is stent under-expansion or improper result of stent deployment. Additionally, OCT can visualize edge dissection after stent implantation better than IVUS thus reducing risk of acute or sub-acute stent thrombosis when using the former instead of the latter.

Safety
Because OCT for coronary imaging is an invasive procedure, there are many more safety considerations when compared to other imaging modalities. The energy that is applied during a scan is only on the order of 5-8 mW and is thus not large enough to cause tissue damage. In both occlusive and non-occlusive forms of measurement, blood flow is temporarily stopped, but not for a long enough time period to cause significant ischemia. In previous studies of the safety of the procedure of both occlusive and non-occlusive methods in a couple hundred patients, major complications were highly uncommon, occurring less than 2% of the time.

Research Applications
In clinical research, OCT analysis of stent placement aids in evaluating vascular response to newly developed coronary stents. In the ATLANTA trial (assessment of the latest non-thrombogenic angioplasty stent), OCT was used to determine 99.5% coverage of stent struts at a six month follow-up therefore providing data on the efficacy of the newly developed Polyzene-F® coated coronary stent as a potential alternative to both BMS and DES without increased risk of stent thrombosis.