Recent Advances in Optical Coherence Tomography for the Diagnoses of Lung Disorders

Randy Hou; Tho Le; Septimiu D Murgu; Zhongping Chen; Matt Brenner

Disclosures

Expert Rev Resp Med. 2011;5(5):711-724. 

In This Article

Basic Principles of Optical Coherence Tomography

Optical coherence tomography obtains imaging of subsurface mucosa with a resolution on the order of a low power microscope with a depth of penetration of 2–4 mm. It accomplishes this by directing a beam of near-infrared light from a broadband coherent light source, (e.g., a superluminescent diode) at target tissue, and capturing light that is back-scattered from that tissue. This phenomenon is similar to ultrasound imaging, only using light rather than sound (the time delay difference from light reflected from different tissue onto a detector cannot be quantified by directly measuring these time delays, but this problem is overcome by the use of interferometry as further discussed in the text). Different tissues have different qualities that influence the back-reflectance (the degree of intensity which that tissue reflects light). These qualities then allow the OCT image to differentiate layers of tissue based on the relative differences in the back-reflectance of the tissue composites. The longer the distance traveled, the longer the delay in returning to a detector. The delay in the returning light from deeper structures compared with shallow structures is used to reconstruct images in a 'time domain' OCT system (Figure 2A) (for light in the near-infrared region, the maximal resolution is around 2–10 µm currently, which would mean 10–50-fold greater resolution than ultrasound). The delay time of the reflected signal is equal to the distance the beam travels divided by the velocity. Since the echo delay time is proportional to the distance traveled, the detector has to be capable of resolving time delays equal to the time it takes light to travel a distance of approximately 1 µm, with an approximate time scale of femtoseconds. This problem has been overcome by the use of interferometry techniques to detect such small delays in a reflected signal.

Interferometry

The technique to resolve the back-scattered light signals using interferometry employs the use of a reference arm, which utilizes a laser light beam split from source with a beam splitter (a partially reflecting mirror), sending some to the target tissue (target arm), and the remaining portion sent to a reference mirror (reference arm) (Figure 2). Both beams are then reflected back to the beam splitter (from the sample and reference mirror, respectively) and directed back together to a detector. Only that reflected within the coherence pathlength of the laser light provide interference that is detected (i.e., when the distance to the reference mirror in the reference arm is equal to the distance to the reflecting target within the tissue). Therefore, by moving the reference mirror closer and farther from the beam splitter in a time domain system, a depth scan of reflecting targets within the tissue can be obtained. The area of interest is scanned to create cross-sectional images and stacked to create a 3D composite image.

Figure 2.

Optical coherence tomography system designs. (A) Time domain OCT system: the reference arm mirror moves closer and further from the beam splitter in order to obtain the axial (depth) scan. A broadband laser light source is directed to the beam splitter, where one beam goes to the reference mirror, and the other to the sample. Reflected signals return from both arms where they are recombined at the beam splitter and directed toward the detector. An axial scan is made by the sweep distance of the reference arm mirror. The sample beam is then moved in a linear pattern to obtain a 2D scan and moved to cover a surface array to develop a 3D scan. (B) Spectrally encoded Fourier domain OCT system: the broadband laser source is directed to the beam splitter with a fixed distance reference arm. When reflected signals from the sample and reference are recombined at the beam splitter and directed toward a spectrophotometer, the spectrally encoded information in the interference signal provides the axial depth scan reflectance information. (C) Swept source OCT system: the source laser rapidly sweeps across the spectral frequency band. As the reflected signals from the sample and fixed reference arm are combined at the beam splitter and directed towards the detector, an axial scan is constructed from the depth resolved spectral interference signals. OCT: Optical coherence tomography Composite figure adapted with permission from: (A) [70], (B) [101] and (C) [28].

There have been two main probe designs for OCT. One is a direct forward scanning, or translational probe, while the other utilizes a rotating motor and a 45° angled mirror to produce a radial probe that scans 360° at a 90° angle to the probe.[5] There are several different systems that utilizes a different process and have different advantages and applications.

Time Domain OCT

In time domain OCT, the reference arm is moved to different distances from the beam source, allowing sampling of the target at different depths. In time domain OCT, the speed at which the reference arm can be moved limits the axial (depth) scanning speed (Figure 2A). While axial resolution is governed by OCT interference patterns, the lateral resolution in endoscopic and fiber-based OCT imaging is limited by the numerical aperture of the optical lens system and tends to run in the 15–30-µm deliverable range with small fiber endoscopic systems currently being employed.[6]

Frequency Domain OCT

More recently, spectral domain OCT systems have been developed that have the potential for much more rapid axial (depth) scanning capabilities. In spatially-encoded frequency domain (SEFD)-OCT, also known as Fourier domain OCT, the depth scan is obtained by analyzing the interference signal based on the wavelength of light. This eliminates the need for moving reference mirrors, and the entire axial depth scan is obtained for each point essentially 'simultaneously'. This enables many orders of magnitude higher scanning rates. A number of approaches to spectral domain OCT have been developed. The most commonly used spectral domain OCT systems at this time involve either a dispersive detector, used to break up the optical beam into light beams of different wavelengths at the detector region (SEFD-OCT) (Figure 2B), or a 'swept source laser' (SS-OCT) that rapidly sweeps the source laser across wavelengths (Figure 2C). Advantages of SS-OCT over SEFD-OCT include simpler setup, higher resolutions and improved signal-to-noise ratio (signal-to-noise ratio is the ratio of signal power to noise power. It is used to quantify how much of the signal is being distorted by the noise).[3,7] Compared to SEFD-OCT, the detection system for SS-OCT is simpler and cheaper because, a high performance spectrometer and charged couple device camera are not required. Spectral domain OCT technology has been demonstrated to comprehensively image the entire distal esophagus in a time (<2 min, 50 µm pitch) that is acceptable for an endoscopic procedures, and could be applied to airway pathology detection.[8] The faster axial scanning capabilities allow for improved in vivo application, higher resolution images enabling 3D reconstruction (fourier domain OCT has been demonstrated to provide higher acquisition speed and better signal-to-noise ratio than OCT with time domain detection), and reducing motion artifact.

Long-range OCT

One significant limitation in conventional OCT is the axial (depth) scanning range. Typical scanning range is to the order of several millimeters. This does not pose a problem when scanning portions of mucosa in which the probe is placed near or on the surface, or when performing radial scans of a small lumen, such as the distal airways or small caliber blood vessels. However, when attempting to radially scan large hollow organs such as the upper airway, large central airways or GI tract, the short scanning range is often insufficient. Several methods have been implemented to overcome short scanning range limitations for specific pulmonary application needs (such as when seeking dynamic assessment of airway caliber changes during respiration). These approaches include manipulation of the optical delay line, known as rapid-scanning frequency domain optical delay line (FDODL), shown to increase the scanning range to as high as 26 mm.[9] More recently, through the use of recirculation loops in both sample and reference arms, scanning ranges of up to 40 mm have been produced with a fast-scanning SS-OCT system. Each arm incorporates a separate optical ring with an adjustable path length allowing for a longer axial image depth. Investigators have also reported incorporating an acousto–optic frequency shifter and a semiconductor optical amplifier, allowing for multiple depths to be scanned simultaneously.[10] Images can be obtained in two distinct ways: by maintaining the rotational probe at a certain location and scanning that area continuously over a period of time, or by advancing the probe beyond the area of interest, and retracting the probe as it is actively scanning, the so-called 'pullback' method. This can generate a 3D image of the region of interest. The pullback method is also useful for identifying specific anatomical areas of interest that can later be analyzed over time using the first method. The purpose of long-range OCT (anatomical [a]OCT) is to evaluate the gross anatomical features of the tissue surface, and thus subsurface high resolution images are not required and typically not available with this technique. This aOCT approach can also be used for studying the dynamics and changes in cross sectional area in various upper and central airway processes.

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