White Paper

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Signal Processing Overview of Optical Coherence Tomography Systems for Medical Imaging
Murtaza Ali and Renuka Parlapalli

......................................................................................................

Optical Coherence Tomography (OCT) is a new medical imaging modality with resolution in the m range and depth of imaging in the mm range. OCT is based on the principle of low coherence interferometry. This modality has been applied to imaging in various biological applications including ophthalmology, gastroenterology, dentistry, cardiology, tumor margining, etc. OCT systems are signal processing intensive and well suited for embedded implementations using digital signal processors (DSP) and system-on-chip (SoC) application processors. Low-power DSP and SoC are key to making low cost, low power and portable OCT systems. The different types of OCT systems are described in this white paper with focus being on signal processing algorithms used in such systems.
Contents Introduction .................................................................................................................. 2 OCT Systems ................................................................................................................ 3 Basic Signal Processing Chain in OCT Systems ....................................................................... 9 Advanced Signal Processing in OCT Systems ........................................................................ 12 DSP for OCT Signal Processing ........................................................................................ 18 Conclusion .................................................................................................................. 18 References ................................................................................................................. 19 Acknowledgement ......................................................................................................... 21 List of Figures 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Schematic of OCT System Based on Michelson Interferometer...................................................... 3 Schematic of Time Domain OCT System................................................................................ 4 Example of Received Signals With Two Reflecting Surface .......................................................... 5 Schematic of Spectral Domain OCT System ............................................................................ 6 Example of Received Interference Signal Captured on an Array Detector.......................................... 7 Schematic of Swept Source OCT System ............................................................................... 8 Image Formation Path .................................................................................................... 10

1 2 3 4 5 6 7 8

........................................................................ Dispersion Compensation per Wojtkowski et al. ..................................................................... Dispersion Compensation per Marks et al. ............................................................................ Doppler Imaging Signal Chain Using Kasai Algorithm for OCT Systems .......................................... Example of a Polarization Sensitive OCT System Using Two Line Scan Camera ............................... Signal Processing Chain in Polarization Sensitive Spectral Domain OCT......................................... Spectroscopic Data Generation in Frequency Domain OCT ........................................................ Spectroscopic Data Generation in Frequency Domain OCT With Frequency Domain Windowing ............
Representation of Signals in the Signal Chain List of Tables

10 12 12 13 15 16 17 17

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Introduction

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Introduction
OCT is a new medical imaging modality with resolution in the m range and depth of imaging in the mm range [3], [8], [10], [28]. OCT uses the principle of low coherence interferometry to perform a depth resolved axial scan. By stacking the axial scans in X and/or Y directions, two or three dimensional imaging is feasible. OCT can be used to image various aspects of biological tissues. Some of these include: Structural information: This is the most typical OCT imaging. It measures the local reflectivity of the tissue. Blood flow: Using Doppler technique, the blood flow in tissues and vessels can be estimated. Polarization sensitive: The change of polarization states through tissues can be estimated. Elastography: The elastic parameters of the tissue can be estimated. Spectroscopy: The variation of absorption, reflectivity and scattering with wavelength can be measured providing clues to molecular content of the tissue. Any combination of the above imaging modes can be used to bring out specific features of biological tissues as desired. Applications of OCT in various biomedical imaging applications include: Ophthalmology: Very fine imaging of the retina with capability to identify several eye diseases is possible with OCT. Most of the commercial products available today are for ophthalmologic usage. Dermatology: To image subsurface structural and blood flow information. Dentistry: To image structure of teeth and gum line at the same time to visualize bacteria in concert with the tooth and roots. Gastroenterology: To image the gastrointestinal (GI) tract through endoscopic probes. Intra-vascular: To image plaques inside blood vessels. Cancer diagnosis: Several modes in OCT imaging can discriminate between malignant and normal tissues allowing cancer diagnosis through either non-invasive or minimally invasive procedures. Intra surgery for tumor margining: Enables discrimination between malignant and non-malignant tissue to decide the regions of tissue to be removed during surgery. OCT systems are signal processing intensive. The need for acquiring real-time data, processing the acquired data to extract meaningful information and then displaying the information in a clinically relevant way is well suited for embedded implementations using DSP and SoC application processors. The advent of low-power DSP and SoC is an added benefit for OEMs to develop low cost, low power and even portable systems based on OCT technologies without compromising the image quality needed for clinical applications. In addition, the programmability and scalability of these devices allow optimizing the signal chains for different applications on the same platform. This white paper concentrates on various signal processing algorithms used in OCT systems. Section 2 introduces three types of commonly used OCT techniques: time domain, spectral domain and swept source-based OCT. The latter two techniques are more popular due to their fast acquisition time, therefore, focus is on these systems in the rest of the paper. Section 3 describes the signal processing steps needed to form the image from the raw data. Section 4 describes the additional signal processing algorithms needed for different variations of OCT systems, e.g., in Doppler or polarization-based systems.

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OCT Systems

OCT Systems
OCT uses a standard Michelson Interferometer with a low-coherence light source as shown in Figure 1. In the interferometer, the incoming broadband beam of light is split into the reference path and the sample path which are recombined after back-reflection from the reference mirror and the multiple layers of the sample, respectively, to form an interference signal. The broadband nature of light causes interference of the optical fields to occur only when the path lengths of the reference and the sample arm are matched to within the coherence length of the light. This interference signal carries information about the sample at a depth determined by the reference path length.
Reference Mirror

Source Beam Splitter Photo Detector Sample

Figure 1. Schematic of OCT System Based on Michelson Interferometer These systems can be broadly classified into: Time domain (TD) OCT systems Spectral domain (SD) OCT systems Swept source (SS) OCT systems

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2.1

Time Domain Systems (TD-OCT)

TD-OCT systems are the conventional, first generation OCT systems. In TD-OCT, an interference pattern is obtained by moving the reference mirror in a linear fashion to change the reference path length and match multiple optical paths due to reflections within the sample (see Figure 2).
PhotoDetector ADC DSP B board Display

Source

Coupler

Reference Mirror

Nonpolarized Beam Splitter

Sample

Lens System

GalvoControlled Mirror

Figure 2. Schematic of Time Domain OCT System The photo-detector detects the average intensity over the range of frequencies. The detected signal consists of a DC term and an interference term that contains the sample information. The use of a dual balanced approach where a portion of the source signal is subtracted through the use of a second photo-detector before digitizing the signal, can be used to remove the DC term at least partially [10]. The sample information is contained in the cross interference that can be written as a function of path difference, z, between the sample and reference as following the notations in [31].
2h Dz K g (t )h air - t dt c

Here, hair is the refractive index in air, c is the velocity of light, and g(t) is the complex temporal coherence function of the laser source, which is related to the source intensity spectrum, S(w) through the Fourier transform, i.e.,
g (t ) = S (w )e -iwt dw

Similarly, h(t) is the equivalent temporal response of the sample related to the sample frequency response by:
h (t ) = H (w )e -iwt dw

This response describes the reflections from all the structures within the sample in the z direction and can be written as:
+ i 2h (w, z )w z / c H (w ) = r (w, z )e dz -

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OCT Systems

where, r(w,z) represent the back-scattering coefficients from the sample structures and h(w,z) is the refractive index. Both these terms are depth and frequency dependent. Physically, the sample temporal response is related to sample structure in the z direction through the relation between the time of flight and the distance traveled by the light source. A low-coherence source is characterized by small width of the temporal coherence function, g(t). The equation above shows that the detected interference signal only consists of sample information in the neighborhood of z as determined by the corresponding time of flight difference. The axial resolution is then related to the width of the temporal coherence function of the source. For a single reflecting surface at the sample with path difference of z between the sample and reference, h(t) is a Dirac delta function at
h Dz t = air c

leading to the received interference signal as:

h Dz h Dz K g air cos w air c 0 c

Clearly for single reflecting sample, the detected interference is a cosine modulated signal modulated with the shape of the envelope of the temporal coherence function. As the path difference z is changed by moving the reference mirror, the received signal picks up information about the sample structure with varying depth (within the limit of light remaining collimated in the sample). This allows scanning of the sample in the axial or depth direction. Such a scan is often referred to as an A-scan. Figure 3 shows an example of received intensities with a sample having two reflecting surfaces. Two and three dimensional OCT images can be constructed by stacking several A-scans that are obtained by orthogonal displacements of the beam/sample using an x-y galvanometer.

Sample With Two Reflecting Surfaces

Received Intensity Signal

Envelope of Received Signal

Figure 3. Example of Received Signals With Two Reflecting Surface

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2.2

Spectral Domain Systems (SD-OCT)

Figure 4 represents a schematic diagram of the SD-OCT system. A broadband-source of light with short temporal coherence length is again used as an input to the interferometer. The depth information is obtained by measuring the spectral density in the detection arm of the interferometer using a spectrometer, where the interference beam is dispersed by a diffraction grating and the individual wavelength components are detected by an array detector. In SD-OCT systems the path difference z remains fixed and can be assumed to be zero without loss of generality. The received spectrum can then be written as [31].
I (w ) K S (w ) + K Re{ (w )H (w )} S 1 2

The first term represents a DC value. It is common to perform background subtraction by shutting off the sample arm that allows collection of the DC term and then subtracting this from the measured value with the sample present. The following equation shows what is left once the DC term is subtracted:
I ' (w ) = K Re{ (w )H (w )} S 2

The depth resolved sample structure is then obtained through the Fourier transform of the above, i.e.:
i (t ) = FT { ' (w )} I
Diffraction Grating

Lens Source Coupler Reference Mirror

Nonpolarized Beam Splitter

Line Scan Camera

DSP Board

Display Sample Lens System GalvoControlled Mirror

Figure 4. Schematic of Spectral Domain OCT System The CCD samples the spectrum from wmin and wmax with w0 being the center frequency assuming that the minimum and maximum frequency is chosen so that aliasing is not an issue. The fast Fourier transform is then used on this discrete data. Hence, effectively, the sampled spectrum can be considered as a demodulated version of I'(w}. This shows that the axial resolution, in the case of SD-OCT, continues to be determined by the width of the temporal coherence function, g(t), of the source, demodulated to DC. Due to the capture of only the real part of the interference and due to symmetry in the FFT, only half of the samples at the output of the FFT carry independent information. Techniques known as phase shifting can be used to capture the phase information as well [18]. This technique captures the interference with varying phase of the light and then reconstructs the complex interference. This technique is able to double the axial depth of measurement compared to conventional SD-OCT systems.

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OCT Systems

In practice, the array detector serves to digitize the received spectrum in frequency. However, there are a couple of important things to note about this digitization: The diffraction grating and array detector combination results in sampling the spectrum linearly in wavelength. The FFT operation normally used to perform the Fourier transform requires spectrum samples to be linear in frequency or k-space. Therefore, a re-sampling is usually needed before taking the FFT. The array detector has finite width, which means it integrates the spectrum over a finite wavelength. Therefore, the sampling cannot be described by usual Dirac delta function but with a box function with width equal to the pixel width. This finite width causes loss of sensitivity with the depth measurement [39]. Figure 5 shows an example of the interference signal with Gaussian source with a single reflecting surface for sample for SD-OCT system.
Received Interference Signal

Array Detector Wavelength

Figure 5. Example of Received Interference Signal Captured on an Array Detector The main advantage of the SD-OCT system is that the entire depth profile (A-Scan) is measured from a single spectrum with no mechanical scanning of the reference path. This permits faster acquisition of A-scans using a line scan CCD array. The use of a fast spectrometer has made video-rate imaging possible with this technique. High-speed acquisition without any moving parts minimizes any distortion in the OCT images due to motion in the sample. SD-OCT systems offer a fundamental sensitivity advantage over TD-OCT systems [6], [7], [19]. Further, in shot noise limit, the theoretical signal-to-noise (SNR) ratio of the SD-OCT system is independent of the spectral bandwidth of the light source. Therefore, the axial resolution of the system, which is dependent on the bandwidth of the source, could be increased without any deterioration of the SNR.

2.3

Swept Source Systems (SS-OCT)

An alternative way to obtain the spectrogram is to use a frequency-swept laser or a tunable laser with just a single detector, which is referred to as SS-OCT [15]. In SS-OCT like in SD-OCT, no moving parts are required for axial scan (ignoring tuning mechanism of the laser source). Figure 6 represents a schematic of a SS-OCT system. These systems require rapid tunable, narrow line-width lasers, which use high-speed analog-to-digital (A/D) converters and single-point detectors rather than bulky spectrometers. Instead of sampling the received spectrum over a finite wavelength, the sample is simply probed with narrow band but frequency varying source. Another equivalent interpretation is that the sample is probed with chirp like signal source and the receive signal is a beating of reflections from the reference and from the samples. In any case, once the data is captured the operations are the same as in SD-OCT. In SS-OCT, however, a dual-balanced detection is also feasible as in TD-OCT to remove the DC before digitization. Therefore, in SS-OCT, the full dynamic range can be used to capture the interference signal.

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PhotoDetector DSP Board

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ADC

Display

Swept Source

Coupler

Reference Mirror

Nonpolarized Beam Splitter

Sample

Lens System

GalvoControlled Mirror

Figure 6. Schematic of Swept Source OCT System

2.4
2.4.1

Resolution
Axial Resolution Axial resolution is an important parameter in OCT systems. It is used to measure how fine the structures can be resolved in the depth direction. In all types of OCT systems, the achievable axial resolution depend on the temporal coherence length of the light source. Axial resolution can be improved by the use of broadband source of light. The bandwidth of the source spectrum is usually defined by the full width half maximum (FWHM) of the source intensity spectrum. This is the difference between the two points in the spectrum, which is at half the peak value of the spectrum. The corresponding measure in temporal coherence function is known as the coherence length, lc, of the source. The axial resolution of OCT systems is generally taken to be the same as this coherence length. For Gaussian sources, it is possible to derive a closed form expression for the coherence length given by [28],
l2 0.44 o l h Dl c

Here, h is the material refractive index. However, for this equation to hold good, the dispersion in the reference sample arm must be matched. The axial resolution of the system varies on the nature of the broadband source. In general, the source is never strictly Gaussian. Further, chromatic dispersion degrades the resolution of OCT since dispersion tends to increase the signal width. The effect of dispersion can be reduced by choosing a light source with an optimum central wavelength at which the group velocity dispersion is negligible and by the use of appropriate dispersion compensation schemes.

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Basic Signal Processing Chain in OCT Systems

2.4.2

Lateral Resolution Lateral resolution is determined by the numerical aperture of the sampling lens using Abbes law [9], [31].
Dx = 1.22 l 2NA

where NA is the numerical aperture of the microscope objective. Though, a higher numerical aperture enhances the lateral resolution, the depth of focus, Z, is narrowed as indicated in the following equation [9], [31].
Z=2 lh NA2

where, h is the sample refractive index. A typical Z for a small NA system is several hundred microns, which is about 10 orders smaller than the scanning depth range of an OCT system. Limited Z of high NA objectives restricts the axial scanning range. Dynamic focusing or en face images that are obtained by focusing high NA objective further into the sample providing a series of two-dimensional depth scans can compensate for this problem to a certain extent [31]. Several numerical techniques to improve the lateral resolution have been reported in literature [23], [38].

Basic Signal Processing Chain in OCT Systems

Though the first generation of OCT systems was based on time domain systems, the popularity of frequency domain systems (whether spectral or swept source) are increasing due to their speed of acquisition and due to improved sensitivity. This section concentrates on the signal processing chain for frequency domain systems only.

3.1

Background Subtraction
To eliminate the reference power term, the reference spectrum from only the reference arm is detected and subtracted from the interference spectrum. The reference spectrum is acquired at the beginning of every image acquisition to account for fluctuations in the source between measurements. It may also be feasible to derive the reference spectrum from the acquired data since the interference is usually high frequency fringes, whereas, the background term has low frequency components. In swept source systems, using dual-balanced photo-detectors allows this subtraction in analog domain.

3.2

Re-Sampling
The interference produces fringes, which are detected by a spectrometer using a CCD or photodiode array detector. In SD-OCT systems, spectrometers measure optical intensity as a function of wavelength. Dispersion results from the non-linear function of the phase dependency of wavelength l. In order to apply the fast Fourier transform (FFT) reconstructing the axial scan as a function of depth, the spectrum should be evenly sampled in k-space. Therefore, the spectrometer output must be transformed from the wavelength to the frequency space. Following the method used in [14], N linearly spaced k values are defined between the range covered by
l min

and

l max

(the maximum and minimum wavelength recorded).

i = 0,1,,2,, N - 1

1 i 1 2p 1 = 2p + k = , l l max N - 1 l min l max i i

Each of the as follows:

l i

corresponding to the linearly spaced kI can be related through a non-linearity parameter SI

l -l min l =l + s . max N -1 i min i

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Using the equations above, non-linearity SI can be written as a function of I.

-1 N -1 1 + i 1 - 1 - l min s = l max N - 1 l min l max l max - l min i

The equation above defines an array of real numbers i , which defines the new interpolation sampling points to resample the recorded discrete spectrum in order to obtain linearly sampled spectrum in k space. A couple of generic techniques for re-sampling are as follows: Linear interpolation: The spectrum is linearly interpolated between two recorded consecutive samples. This is simple and efficient but numerically less accurate resulting in errors at greater depths. Cubic B-spline interpolation: This is computationally more expensive but is more accurate. The accuracy of any interpolation like linear or spline as mentioned above can be improved by first up-sampling the data. It is usually performed by using an FFT, zero padding and then performing IFFT. Usually two to four times up-sampling is sufficient for this application. The above analysis assumes that the data is recorded linearly in wavelength domain. However, due to construction effects, the grating/array detector combination may not result in exact linearly spaced wavelength recording of the received spectrum. It is common to use a third order polynomial to capture the non-linear mapping between the k-space and wavelength. The non-linearity can then be expressed as:
s = i + b i2 + b i3 i 1 2

s , 0 i N - 1

The coefficients b1 and b2 can be computed either through a calibration mechanism or through auto focus algorithms. Some systems for swept source-based OCT uses a non-linear clocking scheme where the clocks are derived from a second interferometer so that the data acquisition becomes linear in k-space. Such a system can avoid the re-sampling step [29].

3.3

Image Formation (FFT)

The basic operation to get the depth resolved A-scan from the interference fringes is the FFT. The structural image is obtained by taking the magnitude of the complex FFT output; each FFT creates a particular A-scan. By moving the galvanometer in x direction, the successive A-scan line is created, which is stacked together to create a B mode image. By moving the galvanometer in both x-y direction, a full 3D volume can be generated. Figure 7 and Figure 8 illustrate the steps needed to create the depth resolved information of a single A-scan from the interferogram.
Detected Spectrum Noise Reduction (i.e., Fixed Pattern Noise) Resampling Dispersion Compensation Magnitude Computation Structural Image

FFT

Compression

Figure 7. Image Formation Path

Zero-padding and Interpolation

Remove Background

FT

Acquired Interferogram

l-Space

k-Space

Depth Profile

Figure 8. Representation of Signals in the Signal Chain

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Basic Signal Processing Chain in OCT Systems

3.4

Display
Two dimensional OCT images are typically represented using a density plot. The horizontal axis typically corresponds to the direction of transverse scanning and the vertical axis corresponds to the scanning depth. A gray level is plotted at a particular pixel on an image corresponding to the magnitude of the depth profile at a particular depth and transverse scanning position. Due to the high dynamic range, pixel intensity range is compressed before displaying it. It is common to use the logarithmic non-linearity to perform such compression. Alternately, a look-up tables-based compression can be used. Sometimes, color look-up tables are used instead of simple gray levels for the final display to bring out clinically relevant information better in the displayed image. It is also necessary to match the actual data collected to the display size. Bilinear interpolation is employed for this type of conversion of data collection co-ordinate system to the display co-ordinate system, which is commonly known as scan conversion. As 2D images may be insufficient to recognize features of interest, e.g., a blood vessel or a tissue boundary, 3D volume is created by collecting the A-scan line over x-y direction. This requires very fast data acquisition and processing systems. In such case, various 3D rendering techniques like ray tracing or maximum intensity projection (MIP) is used to display the data.

3.5

Image Enhancement
Speckle noise that arises from the interference between coherent waves backscattered from nearby scatters in a sample is the dominating source of noise in OCT images. Usually, non-linear direction preserving digital filters are used to improve the image quality [25]. Simple examples of such filters include mean and median filters. More advanced directional filters such as wavelet, anisotropic or bi-lateral filters are also used in reducing the noise while preserving the edges. Simple signal averaging over the same line can also be used to improve the signal-to-noise ratio of the data collected at the cost of reduced frame rate [26]. Involuntary movements of the sample during image scans can limit the performance of the OCT systems. A secondary camera is sometimes used to track such involuntary movements and control the data acquisition in a closed loop manner [11].

3.6

Dispersion Compensation
The refractive index of the biological tissues is, in general, frequency dependent slowing down certain optical frequencies to a greater extent than others, therefore, dispersing the light. Dispersion correction can take place both in the hardware and the software. A considerable amount of dispersion can be corrected, if the dispersions in both the reference and sample arms of the interferometer are equal and matched properly. One can balance dispersion in an OCT system by inserting variable-thickness, BK7, and fused silica prisms in the reference arm. These hardware-based methods can compensate material induced dispersion but the sample being imaged itself could also be dispersive. In that case, an automated numerical method of dispersion compensation is desirable. In spectral OCT, dispersion compensation can be performed by cancelling the frequency dependent nonlinear phase, which arises from the dispersion mismatch between the two arms of the interferometer. Dispersion compensation can be applied to this signal via a phase correction. The applied phase correction is computed as:
2 3 f (w ) = - a w - w - a w - w 2 0 3 0

where a2 is adjusted to compensate for the group velocity dispersion imbalance and a3 is adjusted to compensate for the third-order dispersion imbalance. Usually, dispersion up to the third order is sufficient assuming that the interferometer arms were approximately dispersion matched initially.

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3.6.1

Auto-Focusing Auto-focus algorithms are designed to automatically estimate the coefficients, a2, and a3. Several techniques have been proposed in literature. Figure 9 shows a schematic representation of the process Wojtkowski et al. [32]. The dispersion compensation is performed after background subtraction and re-sampling. The real-fringe data is converted to its analytic equivalent by the Hilbert transform. Phase correction is applied to this complex data before taking the FFT to generate the structural information of the sample. The metric used for optimizing the coefficients, a2, and, a3, is defined to be one divided by the total number of points in the axial scan intensity, which are above a predetermined threshold. The actual optimization is done via brute force search of over the parameter space.
Section of Computation for Searching Over a2, a3 if(w) Compute Metric

Hilbert Transform Q Background Subtraction Resampling I

Create Complex Signal

FFT

Magnitude Computation

Logarithmic Compression

Figure 9. Dispersion Compensation per Wojtkowski et al. [32] In [21], Marks et al. have used a metric that is the power sum of the magnitude of the calculated sample reflectance function around a dominant reflection point. They have jointly optimized the re-sampling as well as phase non-linearity. The overall scheme is shown in Figure 10. They perform an intelligent search over the parameter space using the bracketing and Golden section technique. The proposed signal chain includes Wiener filtering for optimum noise performance, followed by phase rotation for dispersion compensation and re-sampling and finally FFT.
Fn Hilbert Transform Background Subtraction

Wn Gn

e i f n
Gn

Resampling Array

Compute Metric

Fn

Gn
Resampling FFT

gn

Magnitude Computation

Logarithmic Compression

Wiener Filtering

Section of Computation for Searching Over a2, a3, b2, b3

Figure 10. Dispersion Compensation per Marks et al. [21]

Advanced Signal Processing in OCT Systems

This section provides a brief overview of some of the advancements and new imaging modes based on optical coherence tomography techniques. These include Doppler imaging, elastography, polarization sensitive, and spectroscopic OCT imaging. Of these, elastography and Doppler imaging have their counterpart in ultrasound medical imaging. Polarization related and spectroscopic imaging are unique to the specific nature of light used in OCT systems.

4.1

Doppler Imaging With OCT

Doppler frequency estimation is used to evaluate the blood flow through various tissues, e.g., in and out of the heart, through retinal veins, etc., in modalities such as ultrasound. It is also feasible to estimate the Doppler frequency shift for OCT systems [24], [36]. Once the Doppler frequency shift has been identified, the velocity of the fluid can be estimated using the following equation:
v= f l d 0 2cos (q )

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l

Advanced Signal Processing in OCT Systems

where fd is the Doppler frequency, 0 is the center wavelength of the source and q is the angle between the light propagation direction and the blood flow direction. Doppler imaging can be carried in any type of OCT systems: time domain, spectral radar or swept source. In the spectral domain, after typical processing including re-sampling, dispersion compensation, noise filtering, and FFT, the amplitude and phase of the axial scan is given as a function of distance. The difference of phases of successive axial scan lines along the same direction in the sample can be used to measure the Doppler frequency. An alternate technique to estimate the Doppler frequency is the Kasai algorithm that has been used successfully in ultrasound applications [16], [36]. 4.1.1 Doppler Frequency Estimation Using Kasai Algorithm The Kasai algorithm uses multiple axial scan lines along the same direction of the sample. This set of multiple scan lines is known as ensemble in ultrasound literature. Assume that the number of axial scan lines in an ensemble is N. Also assume that a window of length M is used in the axial direction in the estimation. The Kasai algorithm starts by estimating the auto-correlation at unity lag (in discrete domain). Therefore, assuming that the complex axial scan line values are Am,n (the value of the output of FFT for the mth depth point and nth scan line in an ensemble), the auto-correlation at unity lag is given by
M N -1 1 R = A* =R + jR A M (N - 1) m = 1 n = 1 m, n + 1 m, n 1 1, real 1, imag

Then the Doppler estimate is given by

R f 1, imag f = a arctan d 2p R 1, real

Here, fa represents the axial scan line repetition rate. It is also possible to estimate the turbulence, which is a measure of the quality of blood flow. This requires the additional calculation of the auto-correlation at zero lag,
N 1 M R = A* A MN m = 1 n = 1 m, n m, n 0

The turbulence can then be computed as

R 2 1 - 1 s R 0

Based on the above computations, the signal chain of Doppler imaging with OCT systems are shown in Figure 11.
Recorded Fringe Data Noise Reduction (i.e., Fixed Pattern Noise, Background Subtraction) Resampling Dispersion Compensation
Magnitude Computation

FFT

Compression

Structural Image

Auto-Correlation Computation

Phase Computation

Color Flow Image

Figure 11. Doppler Imaging Signal Chain Using Kasai Algorithm for OCT Systems

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4.2

Elasticity Imaging With OCT

Elasticity imaging is imaging of the elastic behavior of biological samples. Due to very high resolution in OCT systems, elastographic techniques allow the study of microscopic deformation of biological tissues [27]. The main measure of tissue stiffness is the elastic modulus that is known to vary widely for different tissue types. A number of tissue diseases alter the elastic modulus; therefore, imaging the elastic modulus provides crucial clues to tissue diseases including assessment of malignancy. Elasticity imaging is carried out under compression. Techniques include imaging under two or more compression setting and pulsating compressions. One typical technique is to measure the displacement of tissue under two different compressions. The technique commonly used for measuring such displacements is called speckle tracking [3], [27]. This technique can be used with any OCT systems including time domain, spectral radar or swept source systems. After determining the axial scan line values (through noise filtering, re-sampling, dispersion compensation, and FFT for frequency domain systems), a two dimensional local cross-correlation in a pre-defined window of size M1 M2 is computed. This cross-correlation is given by:
M M 1 2 X - X Y - Y i, j i, j i = 1 j = 1 2 M M 2 1 2 X - X Y - Y i, j i = 1 j = 1 i , j

R = l, k

Here, Xi,j represent the pixel values at one compression and Yi,j the pixel values at the second compression with X and Y being the corresponding average value over the chosen window. Note that the cross-correlation is close to one in the correlated region and to zero in uncorrelated regions. Therefore, by searching for the maximum of the cross-correlation over the chosen window, the local displacement can be estimated. The lateral and axial displacement can then be presented into separate images or be combined to form a single image for view. The above technique is a case of displacement imaging. In ideal elasticity imaging, the ultimate goal is to derive the elastic modulus. Quantitative derivation of elastic modulus requires solving the inverse problem. This is an active area of research in both ultrasound and OCT imaging modalities. In OCT, some advanced techniques that use optimization methods using variational framework with a priori knowledge about biological tissue deformation have been reported in literature [5], [17]. The medical value of elasticity imaging in OCT is still under investigation [3].

4.3
4.3.1

Polarization Sensitive OCT

Polarization Sensitivities of Biological Tissues Biochemical composition has a tendency to change polarization state as light goes through or are reflected back from them due to their highly organized molecules. Therefore, the polarization state of the recorded light in OCT provides information regarding the bio-chemical structure of the tissues and can be used to reveal the bio-chemical composition of the tissue. Therefore, polarization sensitive OCT allows more of molecular or spectroscopic imaging rather than pure structural imaging that is performed in normal OCT systems. Three separate mechanism of altering the polarization state through biological tissues are of importance to OCT imaging [3]: Birefringence: Here the light propagation velocities (refractive index) are dependent on the spatial orientation of a biological sample, thus, the change in polarization states varies with the direction of incident light. Dichroism: This refers to the case where one polarization state is filtered but its orthogonal states passes through. Optical rotation: This rotates the axis of polarization states. The use of these features in polarization state changes in biological tissues is an active area of research in medical imaging community.

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4.3.2

Polarization Sensitive OCT Polarization sensitive OCT systems can be designed to be of both time domain and frequency domain types. Due to higher speed of acquisition and higher sensitivities, frequency domain polarization sensitive OCT systems are getting popular. Several such implementations reported in literature are described in this section. The common features of all polarization sensitive OCT is the addition of a polarizer to provide a known polarization state of the source as shown in Figure 12. Additional elements are also included in the optics path to optimize the system. These include: Quarter wave plate (QWP) or half wave plates (HWP): These provide proper rotations of the polarization states to match the optical elements preceding and following them. Polarization controllers (PC): These are used to fine tune the polarization states. Polarization modulators (PM): These elements are used to switch the polarization states of the source. Polarizing beam splitter (PBS): These devices split the beam into its orthogonal polarization states.
HalfWave Plate Coupler HalfWave Plate Coupler

Diffraction Grating

Polarized Beam Splitter

Diffraction Grating

Polarizer Source Coupler

Density Filter

Quarter Wave Reference Plate Mirror

Lens

Line Scan Camera

Nonpolarized Beam Splitter QuarterWave Plate

Line Scan Camera

DSP Board

Display Sample Lens System GalvoControlled Mirror

Figure 12. Example of a Polarization Sensitive OCT System Using Two Line Scan Camera There are differences in the way the receiver is designed for PS-OCT systems in spectral domain. Here is an example of some variations of receiver designs: One single line camera design for spectral radar systems: In this design, the spectrometer is designed in such a way that the orthogonal polarizations states of receive light is focused on different pixels of a single line CCD camera. In the design by Cense et al. [4], a 2048 single line CCD camera is used. The first 1024 pixels were used to capture one polarization state and the next 1024 pixels are used to capture the orthogonal polarization state. 2D single camera design for spectral radar systems: In this design, a 2D camera is used where the two different polarization states are focused on different lines of the CCD camera [37] Two single line camera design for spectral radar systems: In this design the polarization states are separated by polarizing beam splitters and then focused on two separate single line CCD cameras [12], [35]. Two detector design for swept source systems: In this design a swept source laser is used. The receiver is then simply two sets of detectors whose inputs are the two orthogonal polarizations states separated using a polarizing beam splitter [40].
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The basic operations for the spectra of the orthogonal polarization states of the received light captured through either line scan CCD camera (for broadband source) or through detectors (for swept source) are the same as normal spectral domain processing. These include re-sampling, dispersion compensation, noise filtering, and FFT. Once FFT is performed, the amplitudes and phases of the two orthogonal states (vertical and horizontal) as a function of depth are obtained. Note that the received complex vectors for the two polarization states as a function of depth, Z , by:
A ( z )exp i F ( z ) and A ( z )exp i F ( z ) H V H V

Then the polarization independent reflectivity, R, the retardation, d, and the optics axis orientation, q, can be defined as [12]:
R (z ) A (z ) H 2 + A (z ) V 2

A (z ) d = tan-1 V A (z ) H p - F - F H V q = 2

The retardation, d, is a measure of birefringence of the optical tissue and the optics axis orientation, q, is a measure of optical axis rotation in the tissue. By imaging these three parameters above, the structural, the birefringence and the optical axis rotation of the biological samples are actually being imaged. Figure 13 shows the signal processing chain for these types of polarization sensitive OCT imaging.
Horizontal Polarization State Noise Reduction (i.e., Fixed Pattern Noise, Background Subtraction) Dispersion Compensation Reflectivity Computation (Sum of Squares) Structural Iimage

Resampling

FFT

Compression

Vertical Polarization State

Noise Reduction (i.e., Fixed Pattern Noise, Background Subtraction)

Retardation Computation (arctan) Resampling Dispersion Compensation FFT Optical Axis Orientation Computation (arctan)

Birefringence Image

Optical Axis Rotation Image

Figure 13. Signal Processing Chain in Polarization Sensitive Spectral Domain OCT Light polarization is sometimes described via the 4-tuple known as Stokes Vectors and corresponding Muller and Jones matrix. The PS-OCT measurements can also be used to determine the Stokes Vectors as follows [12].
A2 + A2 H V 2 - A2 A H V 2 A A cos F - F H V H V 2 A A sin F - F H V H V

It is possible to provide the images of individual components of Stokes vectors (four images) [13].

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Advanced Signal Processing in OCT Systems

Techniques have also been explored to obtain the Jones and Mueller matrix of the biological sample. This technique involves the use of polarization modulator, [37]. This way the source light can be polarized into two orthogonal polarized states; for each of the source polarization states, two receive polarization can be determined. Therefore, you have the input and output vector for the Jones calculus from which the full Jones matrix can be determined, which can then be used to determine the Mueller matrix. In this case, the viewing represents the individual components of the Mueller matrix (total of 16 images) or the phase and amplitude of individual components of the Jones matrix (total of eight images).

4.4

Spectroscopic OCT
Spectroscopic OCT (SOCT) analyzes the frequency dependencies of the absorption of signal in OCT systems. SOCT has been demonstrated in the context of both time domain systems [1], [22], [33] and frequency domain systems [20], [34]. In time domain SOCT systems, the system is very typical of TD-OCT systems. The time depth resolved data from the photo detector is sampled at very high rate. Several techniques have been proposed for analyzing the data wavelength dependencies. A short time Fourier transform (STFT) can be used in the depth direction to determine localized absorption as a function wavelength [1], [33]. For better wavelength selectivity, a chirped Z transform (CZT) is proposed in [1]. A wavelet transform (e.g., Morlet wavelet) providing varying wavelength-localization property has also been studied [22]. In spectral or frequency domain SOCT systems, the front end processing is similar to typical SD-OCT systems, i.e., it includes background subtraction, re-sampling of the fringe data into linear spaced data in k space domain. At this point an FFT can be taken to obtain the depth resolved reflectivity information. This can be followed by localized Fourier analysis with any of techniques used in time domain SOCT systems [34]. Figure 14 shows the processing steps of such a system.
Recorded Fringe Data Noise Reduction (i.e., Fixed Pattern Noise, Background Subtraction) Localized Frequency Analysis (e.g., STFT)

Resampling

Dispersion Compensation

FFT

Spectroscopic Data

Figure 14. Spectroscopic Data Generation in Frequency Domain OCT An alternate approach is to multiply the recorded fringe data (after re-sampling) by a frequency window centered at the wavelength of interest and then take the Fourier transform [20]. Specifically, this technique determines the following equation:
i (t ,w ) = FT I ' (w )W w - w , Dw n 0

Where W(w-w0,w) represents a window around the frequency of interest, w0 with a bandwidth of w and I'(w) is the recorded spectrum. The choice of the window bandwidth determines the resolution depth and wavelength for this spectroscopic analysis. The processing steps for this method are shown in Figure 15.
Recorded Fringe Data Noise Reduction (i.e., Fixed Pattern Noise, Background Subtraction)

Resampling

Dispersion Compensation

Frequency Localized Window

FFT

Spectroscopic Data

Figure 15. Spectroscopic Data Generation in Frequency Domain OCT With Frequency Domain Windowing

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DSP for OCT Signal Processing

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DSP for OCT Signal Processing

For details of benchmarking of the key signal processing algorithms needed to produce a B-mode image, see [2]. This benchmarking was done on Texas Instruments C64x+ DSP architecture. TIs DSP portfolio includes several devices based on TMS320C64x+ DSP. These devices vary in the number of C64x+ cores available, the speed of the core, the amount of memory, interfaces, etc. This benchmarking shows that TIs multi-core device, like the TMS320C6472, is capable of handling processing of scan-lines at a rate from 35 K lines per second to 100 K lines per second depending on the configuration. The processing rate variation is due to the amount of signal processing that is needed to be done, i.e., the addition of additional processing for dispersion compensation reduces the processing rate. These numbers show that such devices are quite capable performing the OCT signal processing needs. These devices also come with very high bandwidth data input/output capabilities. The TMS320C6472 device has two serial rapid I/O (SRIO) interface with the total capability of 5 Gbps bi-directional throughput. The DSP-based OCT systems have been reported in literature with the use of multiple DSPs [30]. The advent of multi-core DSPs with advanced features allows the use of single such device in OCT systems. DSPs provide several advantages for the implementation of OCT systems such as: TI has several variations of processors based on C64x+ architecture. The OCT system manufacturer has the ability to choose one of these devices to suit their need based on processing capability, I/O requirement, memory available, cost and power. Since these devices are based on the same core, the manufacturer can quickly move to a different device without major software change to address new market needs. These devices allow development of OCT systems at a fractional power compared to x86 or graphics processing unit (GPU) based units while maintaining the same programmability feature that is essential for field upgrades as well as for new applications. Within limits of processing capabilities, the same device can be used to perform various modes of operations like B-mode imaging, Doppler, polarization sensitive, etc. These modes of operations differ in post-processing after the post FFT complex image is formed. Due to programmability, the same processing unit used for main signal chain can be utilized for calibration and different estimation algorithms needed to identify system parameters (like background signal, re-sampling points, phase corrections for dispersion compensation, etc.). These parameters are either pre-computed during calibration or computed automatically before the image acquisition process. In an FPGA-based systems, separate data paths would be needed to perform these functions. Due to smaller footprint, DSP-based systems allow the development of smaller, low power, low cost as well as battery-operated portable systems. Based on the understanding and analysis of OCT systems as well as the capabilities of current and next generation DSPs, DSP will play a very similar role to OCT that it has played in other imaging modalities, like ultrasound, to develop low-power cost effective solution. Therefore, DSPs allow more ubiquitous use of OCT systems in medical imaging and diagnostics.

Conclusion
OCT is a new imaging modality somewhat comparable to ultrasound in that it provides structural information without ionizing radiation. Since it uses frequency ranges in visible or near infra red spectrum, the resulting resolution is in the order of m. The depth of penetration is low compared to ultrasound (in the range of few mm). Like ultrasound, Doppler and elasticity imaging is also possible. In addition, polarization sensitive and spectroscopic imaging modes allow additional information regarding the biological tissues to be imaged. OCT has been used both ex vivo and in vivo. It has also been used non-invasively as well as in minimally invasive in vivo imaging. Imaging via endoscopic and needle like instruments allow localized imaging of fine structures in tissues. Intra-operative use of OCT systems to allow better visualization during surgery has also been reported.

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References

The signal processing of the more popular spectral domain or swept source OCT system is dominated by FFT operations. Several application dependent pre and post processing is needed to perform noise reduction, dispersion compensation, image enhancement as well as estimation of additional parameters like flow velocity, elasticity, polarization parameters, etc. All of these processing are well suited for embedded implementation on TI DSPs. TI multi-core DSP family along with SoC-based on C64x+ architecture provides a scalable and programmable low power, low cost platform for implementing OCT systems for various applications.

References
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19. R. A. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, Performance of Fourier Domain vs. Time Domain Optical Coherence Tomography, Optics Express, pp. 889-894, Vol. 11, No. 8, Apr. 2003. 20. R. A. Leitgeb, M. Wojtkowski, A. Kowalczyk, C. K. Hitzenberger, M. Sticker, and A. F. Fercher, Spectral Measurement of Absorption by Spectroscopic Frequency-Domain Optical Coherence Tomography, Optics Letters, pp. 820-822, Vol. 25, No. 11, Jun. 01, 2000. 21. D. L. Marks, A. L. Oldenburg, J. J. Reynolds and S. A. Boppart, Autofocus Algorithm for Dispersion Correction in Optical Coherence Tomography, Applied Optics, pp. 3038-3046, Vol. 42, No. 16, Jun. 2003. 22. U. Morgner, W. Drexler, F. X. Kartner, X. D. Li, C. Pitris, E. P. Ippen, and J. G. Fujimoto, Spectroscopic Optical Coherence Tomography, Optics Letters, pp. 111-113, Vol. 25, No. 2, Jan. 2000. 23. T S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, Real-Time Interferometric Synthetic Aperture Microscopy, Optics Express, pp. 2555-2569, Vol. 16, No. 4, Feb. 2008. 24. A. M. Rollins, S. Yazdanfar, J. K. Barton, and J. A. Izatt, Real-Time in Vivo Color Doppler Optical Coherence Tomography, Journal of Biomedical Optics, pp. 123-129, Vol. 7, No. 1, Jan. 2002. 25. J. Rowgowska, and M. E. Brezinski, Image Processing Techniques for Noise Removal, Enhancement and Segmentation of Cartilage OCT Images, Physics in Medicine and Biology, Vol. 47, pp. 641-655, 2002. 26. B. Sander, M. Larsen, L. Thrane, J L Hougaard, and T.M. Jorgensen, Enhanced Optical Coherence Tomography Imaging by Multiple Scan Averaging, British Journal of Ophthalmology, pp. 207-212, Vol. 89, 2005. 27. J. M. Schmitt, OCT Elastography: Imaging Microscopic Deformation and Strain of Tissue, Optics Express, pp. 199-211, Vol. 3, No. 6, Aug. 1998. 28. J. M. Schmitt, Optical Coherence Tomography (OCT): A Review, IEEE J. of Selected Topics in Quantum Electronics, pp. 1205-1215, Vol. 5, No. 4, Jul/Aug. 1999. 29. V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, Ultrahigh-Speed Optical Coherence Tomography for Three-Dimensional and En Face Imaging of the Retina and Optic Nerve Head, Investigative Ophthalmology and Visual Science, pp. 5103-5110, Vol. 49, No. 11, Nov. 2008. 30. J. Su et al., Real-Time Swept Source Optical Coherence Tomography Imaging of the Human Airway Using a Microelectromechanical System Endoscope and Digital Signal Processor, J. Biomed. Opt., Vol. 13(3), 2008. 31. P.H. Tomlins and R.K. Wang, Theory, Developments and Applications of Optical Coherence Tomography, Journal of Physics D: Applied Physics, pp. 2519 - 2535, Vol. 38, Jul. 2005. 32. M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, Ultrahigh-Resolution, High-Speed, Fourier Domain Optical Coherence Tomography and Methods for Dispersion Compensation, Optics Express, pp. 2404-2422, Vol. 12, No. 11, May 2004. 33. C. Xu, D. L. Marks, M. N. Do, and S. A. Boppart, Separation of Absorption and Scattering Profiles in Spectroscopic Optical Coherence Tomography Using Least-Squares Algorithm, Optics Express, pp. 4790-4802, Vol. 12, No. 20, Oct. 2004. 34. C. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, and S. A. Boppart, Spectroscopic Spectral-Domain Optical Coherence Microscopy, Optics Letters, pp. 1079-1081, Vol. 31, No. 8, Apr. 2006. 35. M. Yamanari, S. Makita, V. D. Madjarova, T. Yatagai, and Y. Yasuno, Fiber-Based Poloarization-Sensitive Fourier Domain Optical Coherence Tomography Using B-Scan-Oriented Polarization Modulation Method, Optics Express, pp. 6502-6515, Vol. 14, No. 14, July, 2006. 36. V. X. D. Yang, M. L. Gordon, B. Qi, J. Pekar, S. Lo, E. Seng-Yue, A. Mok, B. C. Wilson, and I. A. Vitkin, High-Speed, Wide Velocity Dynamic Range Doppler Optical Coherence Tomography (part I): System Design, Signal processing, and Performance, Optics Express, pp. 794-809, Vol. 11, No. 7, April. 2003. 37. Y. Yasuno, S. Makita, T. Endo, M. Itoh, T. Yatagai, M. Takahashi, C. Katada, and M. Mutoh, Polarization-Sensitive Complex Fourier Domain Optical Coherence Tomography for Jones matrix Imaging of Biological Samples, Applied Physics letters, pp. 3023-3025, Vol. 85, No. 15, Oct. 2004. 38. L. Yu, B. Rao, J. Zhang, J. Su, Q. Wang, S. Guo, and Z. Chen, Improved Lateral Resolution in Optical Coherence Tomography by Digital Focusing Using Two Dimensional Numerical Diffraction Method. Optics Express, pp. 7634-7641, Vol. 15, No. 12, June 2007.

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Acknowledgement

39. S. H. Yun, G. J. Tearney, B. E. Bouma, B. H. Park, and J. F. de Boer, High-Speed Spectral-Domain Optical Coherence Tomography at 1.3 m Wavelength, Optics Express, pp. 3598-3604, Vol. 11, No. 26, Dec. 2003. 40. J. Zhang, W. Jung, J. S. Nelson, and Z. Chen, Full Range Polarization-Sensitive Fourier Domain Optical Coherence Tomography, Optics Express, pp. 6033-6039, Vol. 12, No. 24, Nov. 2004.

Acknowledgement
The authors would like to express their thanks to Professor Stephen A. Boppart of the University of Illinois at Urbana-Champaign and Professor James G. Fujimoto of the Massachusetts Institute of Technology. They graciously shared their expertise in optical coherence tomography with us and helped us understand OCT system processing requirements. Professor Boppart hosted us at the Biophotonics Imaging Laboratory at Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. The system and application understanding we received from him and his team have been integral in defining our effort in this medical imaging modality.

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