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Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics

| EXPLORING THE INTERFACE OF LIGHT AND BIOMEDICINE

  • Editor: Gregory W. Faris
  • Vol. 4, Iss. 5 — May. 5, 2009
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Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina

Erich Götzinger, Michael Pircher, Bernhard Baumann, Christian Ahlers, Wolfgang Geitzenauer, Ursula Schmidt-Erfurth, and Christoph K. Hitzenberger  »View Author Affiliations


Optics Express, Vol. 17, Issue 5, pp. 4151-4165 (2009)
http://dx.doi.org/10.1364/OE.17.004151


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Abstract

Polarization sensitive OCT has recently been shown to provide tissue specific contrast, enabling direct identification of retinal layers based on the intrinsic properties of their interaction with light. However, the capabilities of displaying and analyzing 3D datasets in scientific publications were rather limited. Within the framework of the Interactive Science Publishing project, we present new ways of displaying and analyzing 3D sets of various polarization parameters recorded in healthy and diseased human retinas. These datasets can be interactively explored by the reader. Furthermore, we provide data of the 3D distribution of backscattered Stokes vectors to allow the reader to develop and test their own data processing algorithms.

© 2009 Optical Society of America

Data sets associated with this article are available at http://hdl.handle.net/10376/1178. Links such as View 1 that appear in figure captions and elsewhere will launch custom data views if ISP software is present.

1. Introduction

Optical coherence tomography (OCT) [1–3

1. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991). [CrossRef] [PubMed]

] is now a well-established tool for high-resolution cross sectional imaging of the human retina. While the original OCT technique was based on mechanically scanning a reference mirror to perform A-scans in time domain, spectral domain (SD) OCT [4–6

4. A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun. 117, 43–48 (1995). [CrossRef]

] has caused a paradigm change in the OCT community after the discovery of its huge sensitivity advantage [7–9

7. R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, “Performance of Fourier domain vs. time domain optical coherence tomography,” Opt. Express 11, 889–894 (2003). [CrossRef] [PubMed]

]. Various applications of SD-OCT to image the human retina with high speed and high resolution in 2 and 3 dimensions have been successfully demonstrated [10–12

10. T. C. Chen, B. Cense, M. C. Pierce, N. Nassif, B. H. Park, S. H. Yun, B. R. White, B. E. Bouma, G. J. Tearney, and J. F. de Boer, “Spectral domain optical coherence tomography - Ultra-high speed, ultra-high resolution ophthalmic imaging,” Arch. Ophthalmol. 123, 1715–1720 (2005). [CrossRef] [PubMed]

].

Conventional, intensity based OCT achieves a high depth resolution of a few µm and can resolve several retinal layers, however, it cannot directly differentiate different tissues. Polarization sensitive (PS) OCT takes advantage of the additional polarization information carried by the reflected light [13

13. M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992). [CrossRef]

, 14

14. J. F. deBoer, T. E. Milner, M. J. C. vanGemert, and J. S. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22, 934–936 (1997). [CrossRef]

] and can thereby reveal important information on the tissue that is unavailable in conventional OCT. Thereby, PS-OCT can generate tissue-specific contrast and also provide quantitative information.

Different methods of PS-OCT have been reported in literature. While early work measured only reflectivity and retardation [13

13. M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992). [CrossRef]

, 14

14. J. F. deBoer, T. E. Milner, M. J. C. vanGemert, and J. S. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22, 934–936 (1997). [CrossRef]

], newer work extended the measurements to various other parameters like Stokes vectors [15

15. J. F. de Boer, T. E. Milner, and J. S. Nelson, “Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography,” Opt. Lett. 24, 300–302 (1999). [CrossRef]

, 16

16. B. H. Park, C. Saxer, S. M. Srinivas, J. S. Nelson, and J. F. de Boer, “In vivo burn depth determination by high-speed fiber-based polarization sensitive optical coherence tomography,” J. Biomed. Opt. 6, 474–479 (2001). [CrossRef] [PubMed]

], Müller [17

17. G. Yao and L. V. Wang, “Two-dimensional depth-resolved Mueller matrix characterization of biological tissue by optical coherence tomography,” Opt. Lett. 24, 537–539 (1999). [CrossRef]

] and Jones matrix [18

18. S. L. Jiao and L. H. V. Wang, “Jones-matrix imaging of biological tissues with quadruple-channel optical coherence tomography,” J. Biomed. Opt. 7, 350–358 (2002). [CrossRef] [PubMed]

], birefringent axis orientation [19

19. C. K. Hitzenberger, E. Götzinger, M. Sticker, M. Pircher, and A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9, 780–790 (2001). [CrossRef] [PubMed]

] and diattenuation [20–22

20. B. H. Park, M. C. Pierce, B. Cense, and J. F. de Boer, “Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components,” Opt. Lett. 29, 2512–2514 (2004). [CrossRef] [PubMed]

]. We developed a method that combines the PS low coherence interferometry setup first devised by Hee et al. [13

13. M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992). [CrossRef]

] with a phase sensitive recording of the interferometric signals in the two orthogonal polarization channels [19

19. C. K. Hitzenberger, E. Götzinger, M. Sticker, M. Pircher, and A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9, 780–790 (2001). [CrossRef] [PubMed]

], thus allowing to measure three parameters, reflectivity, retardation, and birefringent axis orientation simultaneously, requiring only a single measurement per sample location. Originally developed for time domain OCT, the technique was later adapted to SD-OCT, enabling the acquisition of 20000 A-lines/s with a sensitivity of 98 dB [23

23. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13, 10217–10229 (2005). [CrossRef] [PubMed]

].

A very interesting application field for PS-OCT is retinal imaging. Using PS-OCT, the structures of the ocular fundus could be classified into polarization preserving (e.g., photoreceptor layer), birefringent (e.g., retinal nerve fiber layer (RNFL), Henle’s fiber layer, sclera, scar tissue) [23–28

23. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13, 10217–10229 (2005). [CrossRef] [PubMed]

], and polarization scrambling or depolarizing (e.g., retinal pigment epithelium (RPE)) [23

23. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13, 10217–10229 (2005). [CrossRef] [PubMed]

, 26–29

26. M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12, 5940–5951 (2004). [CrossRef] [PubMed]

]. Moreover, PS-OCT offers quantitative data on the birefringence of the RNFL [24

24. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography,” Opt. Lett. 27, 1610–1612 (2002). [CrossRef]

, 25

25. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45, 2606–2612 (2004). [CrossRef] [PubMed]

, 30–32

30. M. Mujat, B. H. Park, B. Cense, T. C. Chen, and J. F. de Boer, “Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination,” J. Biomed. Opt. 12, 041205 (2007). [CrossRef] [PubMed]

].

2. Methods

The principles and technical details of the SD PS-OCT setup used in this work are published elsewhere [23

23. E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13, 10217–10229 (2005). [CrossRef] [PubMed]

]. Here is a brief summary: Light emitted from a super luminescent diode (Superlum, Moscow; center wavelength 839 nm, FWHM bandwidth 53 nm) illuminates, after being vertically polarized, a bulk optics Michelson interferometer, where it is split by a non polarizing beam splitter (NPBS) into a sample and a reference beam. The reference light transmits a quarter wave plate (QWP) oriented at 22.5°, and is reflected by a mirror. After double passage of the QWP, the orientation of the polarization plane is at 45° to the horizontal, providing equal reference power in both channels of the polarization sensitive detection unit. The sample beam passes a QWP oriented at 45°, which provides right-handed circularly polarized light to the sample. An x-y galvanometer scanner scans the beam over the retina (fast scan direction: x=horizontal; 1/e2 diameter at cornea ~2 mm; diffraction limited focal spot size at retina ~12 µm).

Our system was operated at an A-scan rate of 20k A-lines/sec. 3D data of the human retina, covering a scan field of 15°×15° and consisting of 60 B-scans (1000(x)×1024(z) pixels) are acquired within ~3 seconds. Imaging depth (in air) is ~3 mm. The theoretic depth resolution within the retina (assuming a refractive index of 1.38) is 4.5 µm. Pixel spacing of original datasets is ~4.5 µm (x)×75 µm (y)×3 µm (z, measured in air). Because of a trigger delay between x-scanner and B-scan data acquisition, images were truncated by 50 pixels in x-direction at one side of the image, leaving 950 transverse pixels (or ~14.25°). To improve 3D data processing and interactive image manipulation speed with OSA ISP software, the data were further reduced (after all the image processing steps described below) before generating the final OSA ISP data files: in x-direction, data were downsampled by a factor of 2; in z-direction, data were downsampled by a factor of 2, then the images were cropped in z-direction to remove areas that contain no information (vitreous, noisy areas below the choroid). The final z-extension of the images was 1.5–1.8 mm (in air, details are given in figure captions). Table 1 summarizes pixel spacings, pixel counts, and approximate physical extensions of the OSA ISP datasets.

Table 1. Dimensions of OSA ISP Datasets.

table-icon
View This Table

After data collection the following data pre-processing steps were performed: At first fixed pattern noise, originating from the camera readout, was eliminated. This procedure consists of subtracting a mean spectrum (averaged over 1000 A-scans) from each spectral dataset, inverse Fourier transforming the dataset, removing two remaining sharp frequencies generated by the camera, and Fourier transforming the data back to obtain a spectrum free of fixed pattern noise. Afterwards, zero padding to 2048 pixels was performed, the data were rescaled into k-space (including residual dispersion compensation), and the inverse FFT of both signals was calculated, finally providing the pre-processed A-scan data of the horizontal and vertical polarization channels. Prior to calculation of the polarization data, the influence of anterior segment birefringence was compensated by a numerical method [33

33. M. Pircher, E. Götzinger, B. Baumann, and C. K. Hitzenberger, “Corneal birefringence compensation for polarization sensitive optical coherence tomography of the human retina,” J. Biomed. Opt. 12, 041210 (2007). [CrossRef] [PubMed]

].

RAH2+AV2,
(1)
δ=arctan[AVAH],
(2)
θ=180°ΔΦ2,
(3)

with A being the amplitude and Φ the phase of the respective channel, and the indices H and V denoting the horizontal and the vertical polarization channel, respectively. ΔΦ=ΦVH is the phase difference between the two channels. The unambiguous measurement ranges are 90° for δ and 180° for θ.

S=(IQUV)=(AH2+AV2AH2AV22AHAVcosΔϕ2AHAVsinΔϕ),
(4)

where I, Q, U, V denote the four Stokes vector elements. Then we average Stokes vectors over adjacent pixels by calculating the mean value of each Stokes vector element within a floating rectangular window (size 15(x)×6(z) pixels, or ~70(x)×18(y) µm) and derive DOPU within this window by the following equation:

DOPU=Qm2+Um2+Vm2,
(5)

In case of a polarization preserving or birefringent tissue, the value of DOPU is approximately 1, in case of a depolarizing layer, DOPU is lower than 1. To avoid erroneous data points caused by noise (which also gives rise to random Stokes vector elements), we first apply a thresholding procedure based on the intensity data to gate out areas with low signal intensity (threshold value: 3 times local intensity noise). To reduce computation time, software compensation of corneal retardation can be omitted for the calculation of DOPU (since randomness of polarization states can be judged also from uncorrected data).

Prior to generation of OSA ISP ready data, motion artifacts were corrected by correlation of B-scans (using ImageJ module “StackReg” [38

38. P. Thevenaz, U. E. Ruttimann, and M. Unser, “A pyramid approach to subpixel registration based on intensity,” IEEE Trans. Image Process. 7, 27–41 (1998). [CrossRef]

]). Reflectivity data are displayed on a logarithmic gray scale. Polarization data Δ, θ, and DOPU are displayed on a false color scale. For display of polarization data in 3D volume renderings and in cross sectional images through the 3D datasets by OSA ISP software, intensity and polarization datasets are fused to a combined dataset where the polarization values are encoded by color while the intensity data form the alpha channel (i.e., the opacity of a data point corresponds to the intensity) [39

39. M. Pircher, E. Goetzinger, R. Leitgeb, and C. K. Hitzenberger, “Three dimensional polarization sensitive OCT of human skin in vivo,” Opt. Express 12, 3236–3244 (2004). [CrossRef] [PubMed]

]. This method of display ensures that areas of low reflectivity appear transparent in a volume rendering, allowing an unobstructed view of the polarization data in high-reflectivity areas. Furthermore, erroneous polarization data caused by noise in low-intensity areas are gated out of 2D cross sections by this novel display method.

3. Results

3.1 Healthy subject

Figure 1 shows a 3D dataset obtained in the optic nerve head (ONH) region of the left eye of a male healthy volunteer (age 35). The figure is a tableau of snapshots from OSA ISP analysis sessions. Four different data are shown in the different snapshots: intensity (Fig. 1(a)), retardation (Fig. 1(b)), axis orientation (Fig. 1(c)), and degree of polarization uniformity DOPU (Fig. 1(d)). Each snapshot contains four images: volume rendering (top left), en face section (x-y; top right), horizontal cross section (x-z; bottom left), and vertical cross section (y-z; bottom right). (Because of the strongly anisotropic sampling ratio, the resolution is lower in the y-direction).

Fig. 1. 3D PS-OCT datasets of healthy human retina in the nerve head area. (a) Intensity (logarithmic gray scale) (View 1); (b) retardation (color bar: 0=0°, 255=90°) (View 2); (c) optic axis orientation (color bar: 0=-90°, 255=90°) (View 3); (d) degree of polarization uniformity DOPU (color bar: 0=0, 255=1) (View 4). Each of the figures (a) to (d) shows a snapshot of an OSA ISP session, each snapshot consists of a tableau of 4 images arranged as follows: top left, volume rendering; top right, x-y cross section; bottom left, x-z cross section; bottom right, y-z cross section (in (c), the x-y cross section is replaced by a slightly inclined section ~parallel to the retinal surface to better demonstrate the orientation of nerve fibers around the nerve head). The polarization images (b)-(d) are fused images of intensity (encodes opacity) and polarization value (encodes the color). Image size: ~14.25°(x)×15°(y)×1.8 mm(z, in air). See Appendix for supplementary data.

The intensity images (Fig. 1(a)) show the usual features like optic disk cupping with the lamina cribrosa at the bottom of the cup, vessel shadows (x-y image), and various retinal layers and vessel cross sections (x-z and y-z images).

The retardation images (Fig. 1(b)) show several interesting features that are not discernible in the intensity images. For clearer demonstration of some of the details, the volume rendering was cropped, the boundaries of the volume in Fig. 1(b) (top left) are indicated in the three cross sectional views. The following features can be observed (marked by arrows): the increase in retardation caused by the birefringent inferior RNFL bundle (color change from blue to green), the strongly birefringent scleral ring (rim of the scleral canal), and the thin polarization scrambling RPE layer (appearing in green color). Furthermore, the strongly birefringent sclera can be seen in some areas. (In this subject, the penetration of the probing light into deeper layers is stronger than usual, so the sclera can partly be observed. This gives rise to so-called “atypical scanning laser polarimetry (SLP) patterns” in some subjects imaged with SLP, a well known artifact of SLP imaging technology [40

40. H. Bagga, D. S. Greenfield, and W. J. Feuer, “Quantitative assessment of atypical birefringence images using scanning laser polarimetry with variable corneal compensation,” Am. J. Ophthalmol. 139, 437–446 (2005). [CrossRef] [PubMed]

, 41

41. E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, “Analysis of the origin of atypical scanning laser polarimetry patterns by polarization sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49, 5366–5372 (2008). [CrossRef] [PubMed]

]).

Figure 1(c) shows axis orientation data. The anatomically varying axis orientation of the nerve fiber bundles around the ONH can clearly be observed (for a better view of this feature, the x-y cross section (top right) is replaced by a slightly oblique section that is approximately parallel to the retinal surface). Figure 1(d) shows the degree of polarization uniformity DOPU. In most retinal layers, a high value of DOPU is observed (orange to red color). DOPU remains rather constant within the birefringent RNFL, and is only slightly decreased in layers below the RPE. The pronounced decrease of DOPU within the RPE (green color) is clearly observed. It should be noted that reduced DOPU values are also observed in parts of the lamina cribrosa and in the scleral ring. This is probably an artifact caused by the strong and locally varying birefringence that changes Stokes vectors significantly within the evaluation window in these areas.

Fig. 2. PS-OCT retardation image of healthy nerve head. Movie of animated volume rendering (same dataset as Fig. 1(b)) (Media 1).

Figure 2 shows a movie of the animated, volume rendered retardation dataset of Fig. 1(b), showing all the above mentioned features from various aspect angles. In addition, all four full 3D datasets can be interactively explored by using the OSA ISP viewer.

3.2 AMD patients

Fig. 3. 3D PS-OCT dataset of the retina and RPE layer of an AMD patient with choroidal neovascularization and extensive RPE atrophy (macular area). (a) Intensity (View 5); (b) DOPU (color bar: 0=0, 255=1) (View 6). Figure arrangement: see Fig. 1. (c) Fluorescein angiography. Image size of OCT images: ~14.25°(x)×15°(y)×1.5 mm(z, in air). See Appendix for supplementary data.

Figure 4 shows a 3D dataset of the macula of the right eye of a female AMD patient (age 77 years) with cystoidic macular edema and scarring. Visual acuity was 0.05. Large cysts and multiple smaller cysts are observed in the neurosensory retina (intensity images, Fig. 4(a)). The regularly stacked structure of the photoreceptor layer at the posterior side of the retina is missing, instead, a strong hyper reflective band is observed at the posterior boundary of the retina. From the intensity images, the type of tissue corresponding to this hyper reflective band is unclear, it cannot be told whether the RPE is still present or not. The DOPU images (Fig. 4(b)) clearly show that only small islands of depolarizing tissue (RPE; green and blue patches) are left, major parts of hyper reflective tissue show high DOPU values (orange-red), indicating that they likely consist of fibrotic scar tissue, conforming to an end stage of AMD. This can be seen in more detail in the movie of the animated 3D DOPU dataset (Fig. 5) and by interactive exploration of the 3D dataset by the OSA ISP viewer.

Fig. 4. 3D PS-OCT dataset of the retina of a patient with advanced AMD demonstrating multiple cysts overlying subretinal scarring (macular area). (a) Intensity (View 7); (b) DOPU (color bar: 0=0, 255=1) (View 8). Figure arrangement: see Fig. 1. (c) Fluorescein angiography. Image size of OCT images: ~14.25°(x)×15°(y)×1.5 mm(z, in air). See Appendix for supplementary data.
Fig. 5. PS-OCT DOPU image of the retina of an AMD patient. Movie of animated volume rendering (same dataset as Fig. 4(b)) (Media 2).

3.3 Patient with choroidal nevus

Figure 6 shows a 3D dataset of the retina of a 72 years old female patient with a flat choroidal nevus superior to the nerve head (12 o’clock position; a benign tumor; no change in size for the last years). The intensity dataset (Fig. 6(a)) shows a normally layered retina in most parts of the field of view. However, a small focal pigment epithelium detachment overlying a solid extrusion of the choroid can be seen (arrow) surrounded by an area of slightly increased backscattering below the retina. The retardation images (Fig. 6(b)) show an increased level of retardation in this area, however, it is unclear from this figure if the observed green color is caused by true retardation or by polarization scrambling. The DOPU images (Fig. 6(c)) clearly show strong depolarization in this area in addition to the thin depolarizing band of the RPE. Figures 6(d) and (e) show additional views of the bottom (inclined upwards and straight upwards) of the 3D rendered DOPU dataset that show the large extension of the depolarizing nevus. Figure 6(f) shows a conventional color fundus photo for comparison. More details can be found by interactively exploring the 3D datasets by the OSA ISP viewer.

Fig. 6. 3D PS-OCT dataset of the retina of a patient with a choroidal nevus. (a) Intensity (View 9); (b) retardation (color bar: 0=0°, 255=90°) (View 10); (c) DOPU (color bar: 0=0, 255=1) (View 11). Figure arrangement: see Fig. 1. (d) and (e) additional views of the volume rendered DOPU dataset: (d) inclined upwards and (e) upwards. For better comparison with the fundus photo (f), these reverse-direction images are mirrored. Image size of OCT images: ~14.25°(x)×15°(y)×1.5 mm(z, in air). See Appendix for supplementary data.

4. Discussion

We have shown that the polarization state of backscattered light can be used as an intrinsic, tissue specific contrast means for retinal imaging. While retardation images exploit the birefringence of the RNFL and the sclera for tissue identification and quantification (with axis orientation providing additional information on the orientation of RNFL bundles), the polarization scrambling properties of pigmented tissue like RPE and nevus can be used to clearly identify these tissues and locate areas of RPE lesions in AMD.

Different versions of PS-OCT have been reported, the main differences are the use of bulk optic versus fiber optic interferometers, and the number of input polarization states required to obtain the polarization information. We use a bulk optics interferometer and illuminate the sample with circularly polarized light which has the advantage that only a single input state is needed for acquiring the polarization data shown in this paper. The drawback of our method is that it is not straightforward to be implemented in fiber optics, and that it relies on the assumption of negligible diattenuation. This assumption, however, seems to be largely warranted because diattenuation measured in various tissues by other multi-input state PS-OCT systems is very small [20–22

22. N. J. Kemp, H. N. Zaatari, J. Park, H. G. Rylander, and T. E. Milner, “Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT),” Opt. Express 13, 4611–4628 (2005). [CrossRef] [PubMed]

]. The main advantage of using a single input state is, apart from reduced measurement time and system complexity, that the system is not sensitive to phase changes that can occur between adjacent A-scans. Furthermore, it is less influenced by noise originating from uncorrelated speckle fields: PS-OCT methods based on fiber optics usually need at least four data points: two from the tissue surface and two from within the tissue, to eliminate the unknown fiber birefringence, and to derive the true (depth integrated) tissue birefringence corresponding to one point in the tissue. Images computed from these four datasets are more sensitive to noise degradation than images just computed from a single dataset.

The comprehensive 3D acquisition of intensity and polarization data provides new diagnostic opportunities and simultaneously poses new challenges in terms of appropriate data display. On the one hand, display of conventional structural data in the form of reflectivity images and volume renderings is required; on the other hand, an unobstructed view of polarization data is desirable. Our solution to this challenge was to combine intensity and polarization data to a combined dataset that encodes the polarization quantity into color and the reflectivity into opacity. In this way, low-intensity areas that cause large polarization noise (e.g., data from areas in the vitreous, where no light is reflected and therefore the corresponding polarization data consist entirely of random noise) appear totally transparent and provide an unobstructed view on the polarization data originating from true tissue structures.

Appendix

To give the readers the opportunity to develop and test their own algorithms for processing polarization data, we provide the most general form of these data, the 3D distribution of Stokes vectors. Figure 7 shows an OSA ISP snapshot of the Stokes vector dataset corresponding to Fig. 1. The data were only preprocessed in the intensity regime (fixed pattern noise removal, zero padding, re-scaling into k-space, dispersion compensation, Fourier transform to real space, alignment of B-scans to reduce motion artifacts; to avoid mathematically inconsistent Stokes vector elements that can be caused by interpolation between pixels, a simpler motion correction algorithm that only corrects for axial motions by integer pixel numbers was used in this case). No corneal birefringence compensation and no averaging of Stokes vector elements were performed to allow the reader to develop all the polarization state manipulations themselves. The data are encoded in the following way: intensity is encoded in the alpha channel (opacity), the Stokes vector elements Q, U, V are encoded into red, green, and blue colors of RGB color space, respectively (8 bit scales).

Fig. 7. 3D PS-OCT dataset of healthy human retina in the nerve head area (same original data as in Fig. 1). The 3D distribution of the backscattered Stokes vector is shown (View 12). Opacity is encoded by intensity, Stokes vector elements Q, U, V are encoded in red, green, and blue colors of RGB color space (0 corresponds to -1, 255 to +1 for each of the variables that are encoded by color values). Image size: ~14.25°(x)×15°(y)×1.8 mm(z, in air).

Acknowledgments

We thank Félix Fanjul-Vélez for his help with fusing intensity and polarization data. Financial support from the Austrian Science Fund (FWF grant P19624-B02) and from the European Union project FUN OCT (FP7 HEALTH, contract no. 201880) is gratefully acknowledged.

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J. F. de Boer, B. Cense, B. H. Park, M. C. Pierce, G. J. Tearney, and B. E. Bouma, “Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography,” Opt. Lett. 28, 2067–2069 (2003). [CrossRef] [PubMed]

9.

M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11, 2183–2189 (2003). [CrossRef] [PubMed]

10.

T. C. Chen, B. Cense, M. C. Pierce, N. Nassif, B. H. Park, S. H. Yun, B. R. White, B. E. Bouma, G. J. Tearney, and J. F. de Boer, “Spectral domain optical coherence tomography - Ultra-high speed, ultra-high resolution ophthalmic imaging,” Arch. Ophthalmol. 123, 1715–1720 (2005). [CrossRef] [PubMed]

11.

U. Schmidt-Erfurth, R. A. Leitgeb, S. Michels, B. Povazay, S. Sacu, B. Hermann, C. Ahlers, H. Sattmann, C. Scholda, A. F. Fercher, and W. Drexler, “Three-dimensional ultrahigh-resolution optical coherence tomography of macular diseases,” Invest. Ophthalmol. Vis. Sci. 46, 3393–3402 (2005). [CrossRef] [PubMed]

12.

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112, 1734–1746 (2005). [CrossRef] [PubMed]

13.

M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992). [CrossRef]

14.

J. F. deBoer, T. E. Milner, M. J. C. vanGemert, and J. S. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22, 934–936 (1997). [CrossRef]

15.

J. F. de Boer, T. E. Milner, and J. S. Nelson, “Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography,” Opt. Lett. 24, 300–302 (1999). [CrossRef]

16.

B. H. Park, C. Saxer, S. M. Srinivas, J. S. Nelson, and J. F. de Boer, “In vivo burn depth determination by high-speed fiber-based polarization sensitive optical coherence tomography,” J. Biomed. Opt. 6, 474–479 (2001). [CrossRef] [PubMed]

17.

G. Yao and L. V. Wang, “Two-dimensional depth-resolved Mueller matrix characterization of biological tissue by optical coherence tomography,” Opt. Lett. 24, 537–539 (1999). [CrossRef]

18.

S. L. Jiao and L. H. V. Wang, “Jones-matrix imaging of biological tissues with quadruple-channel optical coherence tomography,” J. Biomed. Opt. 7, 350–358 (2002). [CrossRef] [PubMed]

19.

C. K. Hitzenberger, E. Götzinger, M. Sticker, M. Pircher, and A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9, 780–790 (2001). [CrossRef] [PubMed]

20.

B. H. Park, M. C. Pierce, B. Cense, and J. F. de Boer, “Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components,” Opt. Lett. 29, 2512–2514 (2004). [CrossRef] [PubMed]

21.

M. Todorovic, S. L. Jiao, and L. V. Wang, “Determination of local polarization properties of biological samples in the presence of diattenuation by use of Mueller optical coherence tomography,” Opt. Lett. 29, 2402–2404 (2004). [CrossRef] [PubMed]

22.

N. J. Kemp, H. N. Zaatari, J. Park, H. G. Rylander, and T. E. Milner, “Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT),” Opt. Express 13, 4611–4628 (2005). [CrossRef] [PubMed]

23.

E. Götzinger, M. Pircher, and C. K. Hitzenberger, “High speed spectral domain polarization sensitive optical coherence tomography of the human retina,” Opt. Express 13, 10217–10229 (2005). [CrossRef] [PubMed]

24.

B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography,” Opt. Lett. 27, 1610–1612 (2002). [CrossRef]

25.

B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45, 2606–2612 (2004). [CrossRef] [PubMed]

26.

M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, “Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT,” Opt. Express 12, 5940–5951 (2004). [CrossRef] [PubMed]

27.

M. Pircher, E. Götzinger, O. Findl, S. Michels, W. Geitzenauer, C. Leydolt, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Human macula investigated in vivo with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 47, 5487–5494 (2006). [CrossRef] [PubMed]

28.

S. Michels, M. Pircher, W. Geitzenauer, C. Simader, E. Gotzinger, O. Findl, U. Schmidt-Erfurth, and C. K. Hitzenberger, “Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium,” Br. J. Ophthalmol. 92, 204–209 (2008). [CrossRef] [PubMed]

29.

M. Miura, M. Yamanari, T. Iwasaki, A. E. Elsner, S. Makita, T. Yatagai, and Y. Yasuno, “Imaging polarimetry in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 49, 2661–2667 (2008). [CrossRef] [PubMed]

30.

M. Mujat, B. H. Park, B. Cense, T. C. Chen, and J. F. de Boer, “Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination,” J. Biomed. Opt. 12, 041205 (2007). [CrossRef] [PubMed]

31.

M. Yamanari, M. Miura, S. Makita, T. Yatagai, and Y. Yasuno, “Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry,” J. Biomed. Opt. 13, 014013 (2008). [CrossRef] [PubMed]

32.

E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, “Retinal nerve fiber layer birefringence evaluated with polarization sensitive spectral domain OCT and scanning laser polarimetry: A comparison,” J. Biophotonics 1, 129–139 (2008). [CrossRef]

33.

M. Pircher, E. Götzinger, B. Baumann, and C. K. Hitzenberger, “Corneal birefringence compensation for polarization sensitive optical coherence tomography of the human retina,” J. Biomed. Opt. 12, 041210 (2007). [CrossRef] [PubMed]

34.

E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurt, and C. K. Hitzenberger, “Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography,” Opt. Express 16, 16416–16428 (2008). [CrossRef]

35.

S. L. Jiao, G. Yao, and L. H. V. Wang, “Depth-resolved two-dimensional Stokes vectors of backscattered light and Mueller matrices of biological tissue measured with optical coherence tomography,” Appl. Opt. 39, 6318–6324 (2000). [CrossRef]

36.

S. G. Adie, T. R. Hillman, and D. D. Sampson, “Detection of multiple scattering in optical coherence tomography using the spatial distribution of Stokes vectors,” Opt. Express 15, 18033–18049 (2007). [CrossRef] [PubMed]

37.

S. W. Lee, J. Y. Yoo, J. H. Kang, M. S. Kang, S. H. Jung, Y. Chong, D. S. Cha, K. H. Han, and B. M. Kim, “Optical diagnosis of cervical intraepithelial neoplasm (CIN) using polarization-sensitive optical coherence tomography,” Opt. Express 16, 2709–2719 (2008). [CrossRef] [PubMed]

38.

P. Thevenaz, U. E. Ruttimann, and M. Unser, “A pyramid approach to subpixel registration based on intensity,” IEEE Trans. Image Process. 7, 27–41 (1998). [CrossRef]

39.

M. Pircher, E. Goetzinger, R. Leitgeb, and C. K. Hitzenberger, “Three dimensional polarization sensitive OCT of human skin in vivo,” Opt. Express 12, 3236–3244 (2004). [CrossRef] [PubMed]

40.

H. Bagga, D. S. Greenfield, and W. J. Feuer, “Quantitative assessment of atypical birefringence images using scanning laser polarimetry with variable corneal compensation,” Am. J. Ophthalmol. 139, 437–446 (2005). [CrossRef] [PubMed]

41.

E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, “Analysis of the origin of atypical scanning laser polarimetry patterns by polarization sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49, 5366–5372 (2008). [CrossRef] [PubMed]

OCIS Codes
(170.4470) Medical optics and biotechnology : Ophthalmology
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(230.5440) Optical devices : Polarization-selective devices

ToC Category:
Functional OCT

History
Original Manuscript: October 30, 2008
Revised Manuscript: January 15, 2009
Manuscript Accepted: January 22, 2009
Published: March 2, 2009

Virtual Issues
Vol. 4, Iss. 5 Virtual Journal for Biomedical Optics
Interactive Science Publishing Focus Issue: Optical Coherence Tomography (OCT) (2009) Optics Express

Citation
Erich Götzinger, Michael Pircher, Bernhard Baumann, Christian Ahlers, Wolfgang Geitzenauer, Ursula Schmidt-Erfurth, and Christoph K. Hitzenberger, "Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina," Opt. Express 17, 4151-4165 (2009)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-17-5-4151


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References

  1. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991). [CrossRef] [PubMed]
  2. B. Bouma, and G. Tearney, Handbook of optical coherence tomography (Marcel Dekker, New York, 2002).
  3. A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, "Optical coherence tomography - principles and applications," Rep. Prog. Phys. 66, 239-303 (2003). [CrossRef]
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  6. M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, "In vivo human retinal imaging by Fourier domain optical coherence tomography," J. Biomed. Opt. 7, 457-463 (2002). [CrossRef] [PubMed]
  7. R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, "Performance of fourier domain vs. time domain optical coherence tomography," Opt. Express 11, 889-894 (2003). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-8-889. [CrossRef] [PubMed]
  8. J. F. de Boer, B. Cense, B. H. Park, M. C. Pierce, G. J. Tearney, and B. E. Bouma, "Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography," Opt. Lett. 28, 2067-2069 (2003). [CrossRef] [PubMed]
  9. M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, "Sensitivity advantage of swept source and Fourier domain optical coherence tomography," Opt. Express 11, 2183-2189 (2003). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-18-2183. [CrossRef] [PubMed]
  10. T. C. Chen, B. Cense, M. C. Pierce, N. Nassif, B. H. Park, S. H. Yun, B. R. White, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "Spectral domain optical coherence tomography - Ultra-high speed, ultra-high resolution ophthalmic imaging," Arch. Ophthalmol. 123, 1715-1720 (2005). [CrossRef] [PubMed]
  11. U. Schmidt-Erfurth, R. A. Leitgeb, S. Michels, B. Povazay, S. Sacu, B. Hermann, C. Ahlers, H. Sattmann, C. Scholda, A. F. Fercher, and W. Drexler, "Three-dimensional ultrahigh-resolution optical coherence tomography of macular diseases," Invest. Ophthalmol. Vis. Sci. 46, 3393-3402 (2005). [CrossRef] [PubMed]
  12. M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, "Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography," Ophthalmology 112, 1734-1746 (2005). [CrossRef] [PubMed]
  13. M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, "Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging," J. Opt. Soc. Am. B-Opt.Phys. 9, 903-908 (1992). [CrossRef]
  14. J. F. deBoer, T. E. Milner, M. J. C. vanGemert, and J. S. Nelson, "Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography," Opt. Lett. 22, 934-936 (1997). [CrossRef]
  15. J. F. de Boer, T. E. Milner, and J. S. Nelson, "Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography," Opt. Lett. 24, 300-302 (1999). [CrossRef]
  16. B. H. Park, C. Saxer, S. M. Srinivas, J. S. Nelson, and J. F. de Boer, "In vivo burn depth determination by high-speed fiber-based polarization sensitive optical coherence tomography," J. Biomed. Opt. 6, 474-479 (2001). [CrossRef] [PubMed]
  17. G. Yao, and L. V. Wang, "Two-dimensional depth-resolved Mueller matrix characterization of biological tissue by optical coherence tomography," Opt. Lett. 24, 537-539 (1999). [CrossRef]
  18. S. L. Jiao, and L. H. V. Wang, "Jones-matrix imaging of biological tissues with quadruple-channel optical coherence tomography," J. Biomed. Opt. 7, 350-358 (2002). [CrossRef] [PubMed]
  19. C. K. Hitzenberger, E. Götzinger, M. Sticker, M. Pircher, and A. F. Fercher, "Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography," Opt. Express 9, 780-790 (2001). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-9-13-780. [CrossRef] [PubMed]
  20. B. H. Park, M. C. Pierce, B. Cense, and J. F. de Boer, "Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components," Opt. Lett. 29, 2512-2514 (2004). [CrossRef] [PubMed]
  21. M. Todorovic, S. L. Jiao, and L. V. Wang, "Determination of local polarization properties of biological samples in the presence of diattenuation by use of Mueller optical coherence tomography," Opt. Lett. 29, 2402-2404 (2004). [CrossRef] [PubMed]
  22. N. J. Kemp, H. N. Zaatari, J. Park, H. G. Rylander, and T. E. Milner, "Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT)," Opt. Express 13, 4611-4628 (2005). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-13-12-4611. [CrossRef] [PubMed]
  23. E. Götzinger, M. Pircher, and C. K. Hitzenberger, "High speed spectral domain polarization sensitive optical coherence tomography of the human retina," Opt. Express 13, 10217-10229 (2005). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-13-25-10217. [CrossRef] [PubMed]
  24. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, "In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography," Opt. Lett. 27, 1610-1612 (2002). [CrossRef]
  25. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, "Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography," Invest. Ophthalmol. Vis. Sci. 45, 2606-2612 (2004). [CrossRef] [PubMed]
  26. M. Pircher, E. Götzinger, R. Leitgeb, H. Sattmann, O. Findl, and C. K. Hitzenberger, "Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT," Opt. Express 12, 5940-5951 (2004). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-12-24-5940. [CrossRef] [PubMed]
  27. M. Pircher, E. Götzinger, O. Findl, S. Michels, W. Geitzenauer, C. Leydolt, U. Schmidt-Erfurth, and C. K. Hitzenberger, "Human macula investigated in vivo with polarization-sensitive optical coherence tomography," Invest. Ophthalmol. Vis. Sci. 47, 5487-5494 (2006). [CrossRef] [PubMed]
  28. S. Michels, M. Pircher, W. Geitzenauer, C. Simader, E. Gotzinger, O. Findl, U. Schmidt-Erfurth, and C. K. Hitzenberger, "Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium," Br. J. Ophthalmol. 92, 204-209 (2008). [CrossRef] [PubMed]
  29. M. Miura, M. Yamanari, T. Iwasaki, A. E. Elsner, S. Makita, T. Yatagai, and Y. Yasuno, "Imaging polarimetry in age-related macular degeneration," Invest. Ophthalmol. Vis. Sci. 49, 2661-2667 (2008). [CrossRef] [PubMed]
  30. M. Mujat, B. H. Park, B. Cense, T. C. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 6 (2007). [CrossRef] [PubMed]
  31. M. Yamanari, M. Miura, S. Makita, T. Yatagai, and Y. Yasuno, "Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry," J. Biomed. Opt. 13, 10 (2008). [CrossRef] [PubMed]
  32. E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, "Retinal nerve fiber layer birefringence evaluated with polarization sensitive spectral domain OCT and scanning laser polarimetry: A comparison," Journal of Biophotonics 1, 129-139 (2008). [CrossRef]
  33. M. Pircher, E. Götzinger, B. Baumann, and C. K. Hitzenberger, "Corneal birefringence compensation for polarization sensitive optical coherence tomography of the human retina," J. Biomed. Opt. 12, 10 (2007). [CrossRef] [PubMed]
  34. E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurt, and C. K. Hitzenberger, "Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography," Optics Express 16, 16416-16428 (2008). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-16-21-16416. [CrossRef]
  35. S. L. Jiao, G. Yao, and L. H. V. Wang, "Depth-resolved two-dimensional Stokes vectors of backscattered light and Mueller matrices of biological tissue measured with optical coherence tomography," Appl. Optics 39, 6318-6324 (2000). [CrossRef]
  36. S. G. Adie, T. R. Hillman, and D. D. Sampson, "Detection of multiple scattering in optical coherence tomography using the spatial distribution of Stokes vectors," Optics Express 15, 18033-18049 (2007). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-15-26-18033. [CrossRef] [PubMed]
  37. S. W. Lee, J. Y. Yoo, J. H. Kang, M. S. Kang, S. H. Jung, Y. Chong, D. S. Cha, K. H. Han, and B. M. Kim, "Optical diagnosis of cervical intraepithelial neoplasm (CIN) using polarization-sensitive optical coherence tomography," Opt. Express 16, 2709-2719 (2008). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-16-4-2709. [CrossRef] [PubMed]
  38. P. Thevenaz, U. E. Ruttimann, and M. Unser, "A pyramid approach to subpixel registration based on intensity," Ieee Transactions on Image Processing 7, 27-41 (1998). [CrossRef]
  39. M. Pircher, E. Goetzinger, R. Leitgeb, and C. K. Hitzenberger, "Three dimensional polarization sensitive OCT of human skin in vivo," Opt. Express 12, 3236-3244 (2004). http://www.opticsexpress.org/abstract.cfm?URI=OPEX-12-14-3236. [CrossRef] [PubMed]
  40. H. Bagga, D. S. Greenfield, and W. J. Feuer, "Quantitative assessment of atypical birefringence images using scanning laser polarimetry with variable corneal compensation," Am. J. Ophthalmol. 139, 437-446 (2005). [CrossRef] [PubMed]
  41. E. Götzinger, M. Pircher, B. Baumann, C. Hirn, C. Vass, and C. K. Hitzenberger, "Analysis of the origin of atypical scanning laser polarimetry patterns by polarization sensitive optical coherence tomography," Invest Ophthalmol Vis Sci 49, 5366-5372 (2008). [CrossRef] [PubMed]

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