Anterior & Posterior Segment OCT: Current Technology & Future Applications Ashok Garg
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Optical Coherence Tomography: Current Technology and Future ApplicationsCHAPTER 1

Ashok Garg
(India)
Optical coherence tomography (OCT) was first introduced in 1991 by Huang et al. since then OCT has revolutionized the clinical practice of ophthalmology. It is a noninvasive imaging technique that provides high resolution cross-sectional images of the tissue. Advances in OCT technology provide for better understanding of pathogenesis, improved monitoring of progression and assistance in quantifying response to treatment modalities in diseases of the anterior and posterior segments of the eye.
Optical coherence tomography (OCT) is an optical signal acquisition and processing method. It captures micrometer-resolution, three-dimensional images from within optical scattering media. Optical coherence tomography is an interferometric technique, typically employing near-infrared light. The use of relatively long wavelength light allows it to penetrate into the scattering medium.
Depending on the properties of the light source (superluminescent diodes, ultrashort pulsed lasers and supercontinuum lasers have been employed), optical coherence tomography has achieved sub-micrometer resolution (with very wide-spectrum sources emitting over a ~100 nm wavelength range).
Optical coherence tomography is one of a class of optical tomographic techniques. A relatively recent implementation of optical coherence tomography, frequency domain optical coherence tomography, provides advantages in signal-to-noise ratio, permitting faster signal acquisition. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in ophthalmology where it can be used to obtain detailed images from anterior and posterior segments.
 
CLASSIFICATION OF OPTICAL COHERENCE TOMOGRAPHY (OCT)
  • Theory
    • Time domain OCT
    • Frequency domain OCT (FD-OCT)
      • Spatially encoded frequency domain OCT (spectral domain or Fourier domain OCT)
      • Time encoded frequency domain OCT (also swept source OCT)
  • Scanning schemes
    • Single point (confocal) OCT
    • Parallel (or full field) OCT
    • Smart detector array for parallel TD-OCT
  • Three selected applications.
 
INTRODUCTION
Starting from white-light interferometry for in vivo ocular eye measurements2,3 imaging of biological tissue, especially of the human eye, was investigated by multiple groups worldwide. A first two-dimensional in vivo depiction of a human 2eye fundus along a horizontal meridian based on white light interferometric depth scans was presented at the ICO-15 SAT conference in 1990.4 Further developed in 1990 by Naohiro Tanno,5,6 then a professor at Yamagata University, and in particular since 1991 by Huang et al.7 optical coherence tomography (OCT) with micrometer resolution and cross-sectional imaging capabilities has become a prominent biomedical tissue-imaging technique; it is particularly suited to ophthalmic applications and other tissue imaging requiring micrometer resolution and millimeter penetration depth.8 First in vivo OCT images – displaying retinal structures—were published in 1993.9,10 OCT has also been used for various art conservation projects, where it is used to analyze different layers in a painting. OCT has critical advantages over other medical imaging systems. Medical ultrasonography, magnetic resonance imaging (MRI) and confocal microscopy are not suited to morphological tissue imaging: the first two have poor resolution; the last lacks millimeter penetration depth.11,12
Optical coherence tomography (OCT) bases itself upon low coherence interferometry.1315 In conventional interferometry with long coherence length (laser interferometry), interference of light occurs over a distance of meters. In OCT, this interference is shortened to a distance of micrometers, thanks to the use of broadband light sources (sources that can emit light over a broad range of frequencies). Light with broad bandwidths can be generated by using superluminescent diodes (superbright LEDs) or lasers with extremely short pulses (femtosecond lasers). White light is also a broadband source with lower power.
The key benefits of OCT are:
  • Live subsurface images at near-microscopic resolution
  • Instant, direct imaging of tissue morphology
  • No preparation of the sample or subject
  • No ionizing radiation.
Optical coherence tomography (OCT) delivers high resolution because it is based on light, rather than sound or radiofrequency. An optical beam is directed at the tissue, and a small portion of this light that reflects from sub-surface features is collected. Note that most light is not reflected but, rather, scatters off at large angles. In conventional imaging, this diffusely scattered light contributes background that obscures an image. However, in OCT, a technique called interferometry is used to record the optical path length of received photons allowing rejection of most photons that scatter multiple times before detection. Thus OCT can build up clear 3D images of thick samples by rejecting background signal while collecting light directly reflected from surfaces of interest.
Within the range of noninvasive three-dimensional imaging techniques that have been introduced to the medical research community, OCT as an echo technique is similar to ultrasound imaging. Other medical imaging techniques such as computerized axial tomography, magnetic resonance imaging, or positron emission tomography do not utilize the echo-location principle.
The technique is limited to imaging 1–2 mm below the surface in biological tissue, because at greater depths the proportion of light that escapes without scattering is too small to be detected. No special preparation of a biological specimen is required, and images can be obtained ‘noncontact’ or through a transparent window or membrane. It is also important to note that the laser output from the instruments is low—eye-safe near-infrared light is used—and no damage to the sample is therefore likely.
 
MECHANISM
The principle OCT is white light or low coherence interferometry. The optical set-up typically consists of an interferometer (Fig. 1, typically Michelson type) with a low coherence, broad bandwidth light source. Light is split into and recombined from reference and sample arm, respectively.
 
Time Domain OCT
In time domain OCT the pathlength of the reference arm is translated longitudinally in time. A property of low coherence interferometry is that interference, i.e. the series of dark and bright fringes, is only achieved when the path difference lies within the coherence length of the light source. This interference is called autocorrelation in a symmetric interferometer (both arms have the same reflectivity), or cross-correlation in the common case. The envelope of this modulation changes as pathlength difference is varied, where the peak of the envelope corresponds to pathlength matching.
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zoom view
Fig. 1:
Full-field OCT optical set-up. Components include: super-luminescent diode (SLD), convex lens (Ll), 50/50 beamsplitter (BS), camera objective (CO), CMOS-DSP camera (CAM), reference (REF) and sample (SMP). The camera functions as a two-dimensional detector array, and with the OCT technique facilitating scanning in depth, a noninvasive three-dimensional imaging device is achieved
The interference of two partially coherent light beams can be expressed in terms of the source intensity, IS, as
where k1 + k2< 1 represents the interferometer beam splitting ratio, and γ(τ) is called the complex degree of coherence, i.e. the interference envelope and carrier dependent on reference arm scan or time delay τ, and whose recovery of interest in OCT. Due to the coherence gating effect of OCT the complex degree of coherence is represented as a Gaussian function expressed as15
where Δν represents the spectral width of the source in the optical frequency domain, and ν0is the center optical frequency of the source. In equation (2), the Gaussian envelope is amplitude modulated by an optical carrier. The peak of this envelope represents the location of sample under test microstructure, with an amplitude dependent on the reflectivity of the surface. The optical carrier is due to the Doppler effect resulting from scanning one arm of the interferometer, and the frequency of this modulation is controlled by the speed of scanning. Therefore, translating one arm of the interferometer has two functions; depth scanning and a Doppler-shifted optical carrier are accomplished by pathlength variation. In OCT, the Doppler-shifted optical carrier has a frequency expressed as:
where ν0 is the central optical frequency of the source, vs is the scanning velocity of the pathlength variation, and c is the speed of light.
The axial and lateral resolutions of OCT are decoupled from one another; the former being an equivalent to the coherence length of the light source and the latter being a function of the optics. The coherence length of a source and hence the axial resolution of OCT is defined as:
 
Frequency Domain OCT (FD-OCT)
In frequency domain OCT the broadband interference is acquired with spectrally separated detectors (either by encoding the optical frequency in time with a spectrally scanning source or with a dispersive detector, like a grating and a linear detector array). Due to the Fourier relation (Wiener-Khintchine theorem between the auto correlation and the spectral power density) the depth scan can be immediately calculated by a Fourier-transform from the acquired spectra, without movement of the reference arm.16,17 This feature improves imaging speed dramatically, while the reduced losses during a single scan improve the signal to noise proportional to the number of detection elements. The parallel detection at multiple wavelength ranges limits the scanning range, while the full spectral bandwidth sets the axial resolution.
 
Spatially Encoded Frequency Domain OCT (Spectral Domain or Fourier Domain OCT)
Spatially encoded frequency domain (SEFD)-OCT extracts spectral information by distributing different optical frequencies onto a detector stripe (line-array CCD or CMOS) via a dispersive element (Fig. 2). Thereby the information of the full depth scan can be acquired within a single exposure.
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Fig. 2:
Spectral discrimination by Fourier-domain OCT. Components include: low coherence source (LCS), beamsplitter (BS), reference mirror (REF), sample (SMP), diffraction grating (DG) and full-field detector (CAM) act as a spectrometer, and digital signal processing (DSP)
However, the large signal to noise advantage of FD-OCT is reduced due the lower dynamic range of stripe detectors in respect to single photosensitive diodes, resulting in an SNR (signal to noise ratio) advantage of ~10 dB at much higher speeds. This is not much of a problem when working at 1300 nm, however, since dynamic range is not a serious problem at this wavelength range.
The drawbacks of this technology are found in a strong fall-off of the SNR, which is proportional to the distance from the zero delay and a sinc-type reduction of the depth dependent sensitivity because of limited detection linewidth. (One pixel detects a quasi-rectangular portion of an optical frequency range instead of a single frequency, the Fourier-transform leads to the sinc(z) behavior). Additionally the dispersive elements in the spectroscopic detector usually do not distribute the light equally spaced in frequency on the detector, but mostly have an inverse dependence. Therefore, the signal has to be resampled before processing, which cannot take care of the difference in local (pixelwise) bandwidth, which results in further reduction of the signal quality. However, the fall-off is not a serious problem with the development of new generation CCD or photodiode array with a larger number of pixels.
Synthetic array heterodyne detection offers another approach to this problem without the need for high dispersion.
 
Time Encoded Frequency Domain OCT (Also Swept Source OCT)
Time encoded frequency domain (TEFD)-OCT tries to combine some of the advantages of standard TD and SEFD-OCT. Here the spectral components are not encoded by spatial separation, but they are encoded in time. The spectrum either filtered or generated in single successive frequency steps and reconstructed before Fourier-transformation. By accommodation of a frequency scanning light source (i.e. frequency scanning laser) the optical set-up (Fig. 3) becomes simpler than SEFD, but the problem of scanning is essentially translated from the TD-OCT reference-arm into the TEFD-OCT light source. Here the advantage lies in the proven high SNR detection technology, while swept laser sources achieve very small instantaneous bandwidths (=linewidth) at very high frequencies (20–200 kHz).
zoom view
Fig. 3: Interference signals in TD-OCT vs FD-OCT
5
Drawbacks are the nonlinearities in the wavelength (especially at high scanning frequencies), the broadening of the linewidth at high frequencies and a high sensitivity to movements of the scanning geometry or the sample (below the range of nanometers within successive frequency steps).
 
SCANNING SCHEMES
Focusing the light beam to a point on the surface of the sample under test, and recombining the reflected light with the reference will yield an interferogram with sample information corresponding to a single A-scan (Z axis only). Scanning of the sample can be accomplished by either scanning the light on the sample, or by moving the sample under test. A linear scan will yield a two-dimensional data set corresponding to a cross-sectional image (X-Z axes scan), whereas an area scan achieves a three-dimensional data set corresponding to a volumetric image (X-Y-Z axes scan), also called full-field OCT.
 
Single Point (Confocal) OCT
Systems based on single point, or flying-spot time domain OCT, must scan the sample in two lateral dimensions and reconstruct a three-dimensional image using depth information obtained by coherence-gating through an axially scanning reference arm (Fig. 4). Two-dimensional lateral scanning has been electromechanically implemented by moving the sample17 using a translation stage, and using a novel microelectromechanical system scanner.18
 
Parallel (or Full-field) OCT
Parallel OCT using a charge-coupled device (CCD) camera has been used in which the sample is full-field illuminated and en face imaged with the CCD, hence eliminating the electromechanical lateral scan. By stepping the reference mirror and recording successive en face images a three-dimensional representation can be reconstructed. Three-dimensional OCT using a CCD camera was demonstrated in a phase-stepped technique,19 using geometric phase-shifting with a Linnik interferometer,20 utilizing a pair of CCDs and heterodyne detection,21 and in a Linnik interferometer with an oscillating reference mirror and axial translation stage.22
zoom view
Fig. 4:
Typical optical set-up of single point OCT. Scanning the light beam on the sample enables noninvasive cross-sectional imaging up to 3 mm in depth with micrometer resolution
Central to the CCD approach is the necessity for either very fast CCDs or carrier generation separate to the stepping reference mirror to track the high frequency OCT carrier.
 
Smart Detector Array for Parallel TD-OCT
A two-dimensional smart detector array, fabricated using a 2 μm complementary metal-oxide-semiconductor (CMOS) process, was used to demonstrate full-field OCT.23 Featuring an uncomplicated optical set-up (Fig. 5), each pixel of the 58 × 58 pixel smart detector array acted as an individual photodiode and included its own hardware demodulation circuitry.
 
Clinical Applications
 
Retina
Optical coherence tomography (OCT) is useful in the diagnosis of many retinal conditions, especially when the media is clear. In general, lesions in the macula are eas ier to image than lesions in the mid and far periphery. OCT can be particularly helpful in diagnosing:
  • Macular hole
  • Macular pucker
    6
    zoom view
    Fig. 5:
    Spectral discrimination by swept-source OCT. Components include: swept source or tunable laser (SS), beamsplitter (BS), reference mirror (REF), sample (SMP), photodetector (PD), digital signal processing (DSP)
  • Vitreomacular traction
  • Macular edema
  • Detachments of the neurosensory retina and retinal pigment epithelium (e.g. central serious retinopathy or age-related macular degeneration)
  • Drusen
  • ARMD
  • Choroidal neovascular membrane (CNVM) lesions
  • Retinal nerve fiber layer (RNFL)
  • Internal limiting membrane (ILM)
  • Retinal pigment epithelium (RPE)
  • Pigment epithelial detachment (PED)
  • Anterior face of hemorrhage
  • Hard exudates
  • Epiretinal membrane
  • Cystoid macular edema (CME).
In some cases, OCT alone may yield the diagnosis (e.g. macular hole). Yet, in other disorders, especially retinal vascular disorders, it may be helpful to order additional tests (e.g. fluorescein angiogram).
 
Optic Neuropathies
Optical coherence tomography (OCT) is gaining increasing popularity when evaluating optic nerve disorders such as glaucoma. OCT can accurately and reproducibly evaluate the nerve fiber layer thickness.
 
Anterior Segment
Anterior segment OCT utilizes higher wavelength light than traditional posterior segment OCT. This higher wavelength light results in greater absorption and less penetration. In this fashion, images of the anterior segment (cornea, anterior chamber, iris and angle) can be visualized.
 
Future Perspectives of OCT
  • Future perspectives of intraoperative use of OCT in anterior segment surgery especially cataract surgery shall include continuous monitoring of the anterior chamber depth or volume to prevent surge phenomena and automated posterior capsule recognization module could be used to prevent phaco tip contact to posterior capsule and capsular breaks. This will increase significantly the safety of phaco surgery. OCT assisted grading of hardness of crysaline lens with automated selection of machine settings will optimize energy, fluidics and increase in safety of phaco surgery. Intraoperative control of intraocular lens position will help to prevent complications. The new development of OCT mounted to a operative microscope will be useful for intraoperative images. SL-OCT (Slit Lamp Adapted OCT) can improve all the clinical situations in which a precise cross-sectional image of anterior segment of eye is required.
  • SL-OCT shall be most useful for anterior segment surgery especially refractive surgery and glaucoma screening. SL-OCT shall provide precise cross-sectional image of the cornea and anterior chamber enabling it to corneal thickness measurement, flab visualization and determination of the residual, stromal thickness during LASIK surgery.
  • Imaging of corneal disorders such as corneal scarring with depth determination before PTK is possible with SL-OCT which will help him corneal transplant procedures. New OCT shall be helpful in performing deep anterior lamellar keratoplasty (DALK), Descemet's membrane endothelium keratoplasty (DMEK). OCT assisted adaptation of transplant to corneal bed could be controlled intraoperatively.
  • In the field of glaucoma SL-OCT can be used for objective screening of narrow angles or pre- and postoperative determination of anterior 7chamber angle such as after filtering surgery or iridotomies. OCT can also be useful to replace gonioscopy. Intraoperative OCT shall be helpful in canaloplasty specially deep sclerectomy.
  • Advances in OCT shall be useful in preoperative and postoperative measurements in oculoplastic surgery and their accurate documentation.
  • New technologies of OCT (swept) technology shall be useful pediatric imaging specially for retinopathy of prematurity (ROP) and intraocular tumors. SD-OCT shall be useful in pediatric patients with aniridia, cataract, glaucoma and foveal hypoplasia. The type of cataract, IOL position, posterior capsular opacity and corneal incision healing shall be visualized by SD-OCT.
 
Future Directions
 
Swept Source Technology
An accurate assessment of the choroid using OCT requires that the choroid be visualized up to the choroid-sclera interface. Studies using Cirrus OCT system report a clear visualization of the choroid-scleral interface. Studies using Cirrus OCT system report a clear visualization of the choroid-scleral interface in 70–75% of healthy and diseased eyes.
To our knowledge, the percentage of eyes that have a clearly delineated choroid-sclera interface has not been reported with spectralis and RTVue OCT systems. For adequate analysis of choroidal thickness and volume in healthy and diseased states, the clarity of the choroid-sclera interface is imperative. This can be achieved by increasing the depth of tissue penetration using a longer wavelength of incidents light centered near 1050 nm, so that attenuation from scattering can be reduced. Prototype OCT system using longer wavelength have demonstrated an enhanced visualization of the choroid. Because swept laser light sources can rapidly sweep the required frequencies, the acquisition of scans is must fast in SS-OCT, when compared with the SD-OCT system. The SS-OCT system have axial scan rates of up to resolutions in tissue. Because data can be acquired much faster, volumetric assessment of the choroid is also feasible.
As longer-wavelength OCT systems including SS-OCT become available, the visualization of choroid-sclera interface expected to improve. This is important in diseases such as central serous chorioretinopathy (CSCR), where the choroid is thicker than normal, and thus difficult to evaluate across its entire width. In addition, volumetric analysis of the choroid as well as that of the various pathological features such as choroidal neovascularization and subretinal/intraretinal fluid may be possible. Such a volumetric analysis is expected to help with monitoring the progression of the diseases such as wet age related macular degeneration (AMD), central serous chorioretinopathy and diabetic retinopathy as well as assessment of the treatments response such as antiVEGF agents laser photocoagulation and photodynamic therapy (PDT).
 
Doppler Optical Coherence Tomography
In contrast to ICG and fluorescein angiography, which are two-dimensional investigations for blood flow analysis, Doppler OCT is a promising technology in that it is depth resolved, such that precise location of vascular abnormalities can be localized using cross-sectional imaging Doppler OCT can evaluate blood flow and volume of retinal and choroidal vascular. Given the evidence of choroidal angiopathy in various retinal diseases, this technology promises to help with monitoring of chorioretinal diseases, in particular wet AMD. IT is also expected to aid in the differentiation among diseases such as wet AMD, CSCR and PCV.
Doppler OCT for retinal angiography and blood flow measurement is an emerging area, i.e. under investigation. It will allow us to measure retinal blood flow in diabetic retinopathy, retinal vein occlusion, neuro-ophthalmology and glaucoma. Cross-sectional studies can evaluate glaucoma suspects those with glaucoma and normals. Longitudinal studies can evaluate the effect of medical therapy and surgical pressure lowering on blood flow.
 
En-face Imaging
Software modifications, improvements and efficient processing of data are important for effective evaluation of change in retina and choroid in posterior segment diseases. One of the advancements, known as en-face imaging allows the clinician to visualize three-dimensional data in a fundus projection.
Using this technique, particular retinal and/or choroidal layers at a given depth are projected onto an en-face view.
8Although cross-sectional image (B-scans) have helped delineate pathological features in retinal disease, as such, microstructural changes and morphology of the retinal and choroidal vasculature are hard to evaluate using B-scan. This is expected to improve as en-face imaging provides further detail about the subtle pathological features in the retina and choroid in diseased states. In addition, the involvement of the specific vascular layers of the choroid in different diseases such as AMD, CSCR, diabetic retinopathy and inherited retinal dystrophies is expected to delineate in further detail using this technique.
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