proceedings of spie

PROCEEDINGS OF SPIE SPIEDigitalLibrary.org/conference-proceedings-of-spie

Optimization of modified scanning protocol based correlation mapping optical coherence tomography at 200 kHz VCSEL source for in vivo microcirculation imaging applications Cerine Lal, James McGrath, Hrebesh Subhash, Martin Leahy

Cerine Lal, James McGrath, Hrebesh Subhash, Martin Leahy, "Optimization of modified scanning protocol based correlation mapping optical coherence tomography at 200 kHz VCSEL source for in vivo microcirculation imaging applications," Proc. SPIE 9697, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XX, 96973C (21 March 2016); doi: 10.1117/12.2214797 Event: SPIE BiOS, 2016, San Francisco, California, United States Downloaded From: https://www.spiedigitallibrary.org/conference-proceedings-of-spie on 11/20/2017 Terms of Use: https://www.spiedigitallibrary.org/terms-of-use

Optimization of modified scanning protocol based correlation mapping optical coherence tomography at 200 kHz VCSEL source for in vivo microcirculation imaging applications Cerine Lal1, James McGrath1, Hrebesh Subhash1, Martin Leahy *1, 2 1

Tissue optics and microcirculation imaging Facility, National Biophotonics and Imaging Platform, National University of Ireland, Galway 2 Royal College of Surgeons (RCSI), Dublin, Ireland 1. INTRODUCTION

Optical Coherence Tomography (OCT) is a non-invasive 3 dimensional optical imaging modality that enables high resolution cross sectional imaging in biological tissues and materials. Unlike other 3 D medical imaging modalities, OCT provides high axial and lateral resolution combined with high sensitivity, imaging depth and wide field of view which makes it suitable for wide variety of medical imaging applications1. Apart from analysing the morphological characteristics of the biological organs with micron scale axial and lateral resolution, OCT also provides functional information from the biological sample. Among the various functional extensions of OCT, angiographic OCT that enables visualization of lumens of blood vessels from the acquired OCT B scan images has been of high research interest in the recent past. OCT angiography techniques are based on red blood cells (RBC) scattering that exhibits phase or amplitude fluctuations over time, while static tissue scattering remains relatively constant over time. The development of Fourier domain OCT techniques has enabled high-speed, high-resolution volumetric angiography. Several algorithms have been developed for OCT angiography. These techniques are either based on the changes in the adjacent B scan intensities or phase changes over time at the same location. Major amplitude based OCT angiographic techniques include correlation mapping (cmOCT)2, 3, speckle variance4, full spectrum amplitude decorrelation and split spectrum amplitude decorrelation5. Phase based angiographic techniques include optical Doppler tomography6, 7, phase variance8, 9 , and optical microangiography (OMAG)10,11. The disadvantage of phase based technique is that they are subjected to the bulk motion artifacts of the imaging sample and require complex phase correction methods to eliminate the artifacts. Correlation mapping-OCT (cmOCT) is a magnitude based flow mapping technique introduced in 2011, which is based on the decorrelation between 2 adjacent B frames. In areas of vascular region, the adjacent B frames are decorrelated to the extent determined by the flow through the region. The earliest reported cmOCT used a dense scan protocol to accomplish correlation between adjacent B-frames such that the inter frame separation was within the resolution limit of the OCT system to insure strong correlation between adjacent frames. However, it required relatively longer scan acquisition time because of the relatively low axial scan rate (16 kHz) of the swept source OCT system and requirement of high density Bframes2, 3. In a recent work, cmOCT was shown to be capable of high speed imaging of 92 kHz scan rate using a modified scanning protocol12, 13. This modified protocol acquired repeated B scans at the same location to generate high sensitive correlation map which provided better background suppression and larger field of view within a short scanning time. Increasing the imaging speed and improving the resolution of OCT has been the major aspects that have made OCT widely used in clinical studies. Compared to super luminescent diodes (SLD’s) which were used in spectral domain OCT systems, swept source lasers offer higher scanning speeds, extended depth range with reduced sensitivity roll-off, reduced fringe washout and improved light detection efficiency due to dual balanced detection14. *[email protected] Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XX, edited by Joseph A. Izatt, James G. Fujimoto, Valery V. Tuchin, Proc. of SPIE Vol. 9697, 96973C · © 2016 SPIE · CCC code: 1605-7422/16/$18 · doi: 10.1117/12.2214797 Proc. of SPIE Vol. 9697 96973C-1 Downloaded From: https://www.spiedigitallibrary.org/conference-proceedings-of-spie on 11/20/2017 Terms of Use: https://www.spiedigitallibrary.org/terms-of-use

Reduced scan time using a swept source OCT can provide better background suppression and wider field of view which can be used for real time clinical studies. In this study, we optimize the cmOCT angiographic algorithm using a 200 kHz VCSEL for in vivo microcirculation imaging applications by a modified scanning protocol. In order to demonstrate high speed cmOCT angiography, first we perform the experiments to detect the motion of intralipid particles in a translucent capillary tube. Further, it is extended to nail fold capillary imaging and to study corneal angiogenesis.

2. MATERIALS & METHODS 2.1 Experimental set up We used a commercial swept source OCT from Thorlabs for conducting our studies. The schematic of the system configuration is show in Fig.1. It uses a MEMS vertical-cavity surface-emitting laser (MEMS-VCSEL) swept sources operating at central wavelength of 1300 nm (coherence length of 100 nm) and an imaging depth range of imaging depth range of 12 mm. The system uses a 5X objective that provides a spatial resolution of 25µm. The swept source provides an axial scan rate of 200 kHz and axial resolution of 16 µm in air. For conducting angiographic studies, we acquired 8 B frames at each location with 1000 A lines in each B frame. In the Y scan direction, 200 sample positions were set to cover 5 mm distance. Thus, a 3D OCT scan produced 1600 B frames over the selected field of view for a 3mm depth range. For each sample locations, cmOCT was applied to the 8 frames acquired over time at the same location. The sensitivity plot for the system is shown in Fig 2.

TRIO D4

Figure.1 The schematic of Thorlabs VCSEL based SS-OCT system. swept laser source (SS), fiber coupler (FC), polarization controller (PC), circulator (CIR), collimator (C), adjustable pinhole variable attenuator (AP), and mirror (M).

Proc. of SPIE Vol. 9697 96973C-2 Downloaded From: https://www.spiedigitallibrary.org/conference-proceedings-of-spie on 11/20/2017 Terms of Use: https://www.spiedigitallibrary.org/terms-of-use

250

+ Peak values

-Averaged A -lines

200 +

150

+

II

1¡

I.

100 50 0

15

0.5

2.5

Depth (mm) 20

F.+ Peak values

+ ++

Of5

15

1

2

25

3

Depth (mm)

Figure. 2 Plot showing change in intensity of averaged A lines acquired from 1 mm thick optical blank with depth for SS- OCT system. The sensitivity is calculated using 10 log10 (Imax / Noise mean)

2.2 cmOCT processing technique The cmOCT algorithm uses the magnitude of the extracted OCT signal to reconstruct the flow map from the static tissue background. cmOCT algorithm10 is given by Eq.1. 𝑁 𝑐𝑚𝑂𝐶𝑇(𝑥, 𝑦) = ∑𝑀 𝑝=0 ∑𝑞=0

̅̅̅̅̅̅̅̅̅̅ [𝐼𝐴 (𝑥+𝑝,𝑦+𝑞)−𝐼̅̅̅̅̅̅̅̅̅̅̅ 𝐴 (𝑥,𝑦)] [𝐼𝐵 (𝑥+𝑝,𝑦+𝑞)−𝐼𝐵 (𝑥,𝑦)] 2 2 √[(𝐼𝐴 (𝑥+𝑝,𝑦+𝑞)−𝐼̅̅̅̅̅̅̅̅̅̅̅̅ 𝐴 (𝑥,𝑦))] [(𝐼𝐵 (𝑥+𝑝,𝑦+𝑞)−𝐼̅̅̅̅̅̅̅̅̅̅̅̅ 𝐵 (𝑥,𝑦))]

(1)

where IA and IB are the OCT intensity images at 2 successive images at same location and M and N are the kernel size. For our experiments, 5 x 5 grid size was chosen. This grid is then shifted across the entire XY image and a 2D correlation map is generated. The resulting correlation map contains values in the range of 0 ± 1 indicating weak correlation and strong correlation respectively. For all the data sets acquired, cmOCT technique was applied to the adjacent frames over the 8 frames at each location and then averaged to produce a flow map as given by Eq. (2). 𝐴𝑣𝑒𝑟𝑎𝑔𝑒𝑑𝑐𝑚𝑂𝐶𝑇 (𝑥, 𝑦) =

1 𝐾

∑7𝐾=1 𝑐𝑚𝑂𝐶𝑇 (𝑥, 𝑦)

(2)

3. RESULTS & DISCUSSION To demonstrate cmOCT for high speed swept source OCT, experiments were first carried out using capillary tubes filled with intralipid solution to detect the Brownian motion of particles. The capillary tube with an inner diameter ∼300 μm was embedded in synthetic clay to simulate tissue optical heterogeneity. The capillary tube was filled with intralipid solution. M-B mode scanning protocol acquired 3 D volumetric data over an imaging area of 3 x 5 mm2. In the Y- scan direction, 200 scans were acquired over a distance of 5 mm, thus generating a total volume of 1600 images with 1000 A- lines per B frame using the M-B scan protocol. Fig. 3 shows the result of modified scanning protocol based cmOCT algorithm on the capillary phantom.


(A)

(B)

(C) Figure 2 (A) OCT structural image showing capillary embedded in synthetic clay, (B) Flow image with cmOCT using modified scanning protocol, (C) Maximum intensity projection through the cmOCT volumetric data over an imaging area of 5 mm 3 mm x 3mm.

Further, to demonstrate the suitability of proposed technique for in vivo imaging applications, measurements were taken from nail fold of a healthy adult volunteer. OCT images are acquired from the dorsal skin over the distal phalanx of the little finger. The same scanning protocol was used as mentioned in section 2.1 over an imaging area of 5 x 3 mm2. The maximum intensity projection through the cmOCT volumetric data from the nail fold capillary is shown in Fig 3.

DO

Figure 3 (A) and (B) Maximum intensity projection through the cmOCT volumetric data from 2 regions of the dorsal distal skin of little finger for an area of 5 3 mm2.

Also to evaluate the proposed method for ocular studies, angiographic studies on a rat model that had undergone a corneal transplant is further investigated. cmOCT angiographic images obtained for a normal rat eye and a transplanted eye is shown in Fig. 4 and Fig. 5 respectively.


m

â

Figure. 4 (A) Volumetric reconstruction of rat eye from OCT intensity with a volume of area of 6 mm x 6 mm x 3mm. (B) Maximum intensity projection of cmOCT map through the 3 - D volume.

Figure 5 (A) Volumetric reconstruction of rat eye with transplanted cornea showing corneal angiogenesis following the transplant imaged over a volumetric area of 6 mm x 6 mm x 3mm. (B) Maximum intensity projection of cmOCT map through the 3D volume.

In this study, we described and presented a high-speed cmOCT based microcirculation imaging using a modified scanning protocol acquiring multiple scans at each location. We optimized the cmOCT algorithm to obtain microcirculation maps at an A scan rate of 200 kHz.


ACKNOWLEDGMENTS This work was supported by the National Biophotonics Imaging Platform Ireland funded under the Higher Education Authority PRTLI Cycle 4, cofunded by the Irish Government and the European Union–Investing in your future.

REFERENCES [1] Schmitt, Joseph M. "Optical coherence tomography (OCT): a review." Selected Topics in Quantum Electronics, IEEE Journal of 5(4) 1205-1215 (1999). [2] Jonathan, Enock, Joey Enfield, and Martin J. Leahy. "Correlation mapping method for generating microcirculation morphology from optical coherence tomography (OCT) intensity images." Journal of biophotonics 4(9), 583-587 (2011). [3] Enfield, Joey, Enock Jonathan, and Martin Leahy. "In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT)." Biomedical optics express 2 (5), 1184-1193 (2011). [4] Mariampillai, Adrian, et al. "Speckle variance detection of microvasculature using swept-source optical coherence tomography." Optics letters 33 (13), 1530-1532 (2008). [5] Jia, Yali, et al. "Split-spectrum amplitude-decorrelation angiography with optical coherence tomography." Optics express 20(4), 4710-4725 (2012). [6] Chen, Zhongping, et al. "Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography." Optics letters 22 (14), 1119-1121 (1997). [7] Leitgeb, Rainer, et al. "Real-time assessment of retinal blood flow with ultrafast acquisition by colour Doppler Fourier domain optical coherence tomography "Optics Express 11 (23), 3116-3121 (2003). [8] Kim D. Y. et al., “In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography,” Biomed. Opt. Express. 2 (6), 1504 –1513 (2011). [9] Motaghiannezam, SM Reza, David Koos, and Scott E. Fraser. "Differential phase-contrast, swept-source optical coherence tomography at 1060 nm for in vivo human retinal and choroidal vasculature visualization." Journal of biomedical optics 17 (2), 0260111-0260115 (2012). [10] Wang, Ruikang K., and Lin An. "Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo." Optics express 17 (11) 8926-8940 (2009). [11] Wang, Ruikang K., et al. "Optical microangiography provides depth-resolved images of directional ocular blood perfusion in posterior eye segment." Journal of biomedical optics 15 (2), 020502-020502 (2010). [12] Subhash, Hrebesh M., and Martin J. Leahy. "Microcirculation imaging based on full-range high-speed spectral domain correlation mapping optical coherence tomography." Journal of biomedical optics 19 (2), 021103-021103 (2014). [13] Subhash, H.M. and Leahy, M., “High-speed high-sensitivity spectral domain correlation mapping optical coherence tomography based modified scanning protocol” Proc. SPIE 8571 (2013) [14] Choma, Michael A., et al. "Sensitivity advantage of swept source and Fourier domain optical coherence tomography." Optics express 11 (18) 2183-2189 (2003).
