光學影像實驗室 Optical Imaging Lab.

Novel imaging technologies for biomedical applications.

Technologies of Optical Coherence Tomography (OCT)

光學同調斷層掃描術

光學同調斷層掃瞄技術所得到的影像結果,如同一般病理切片所得到的結果,所以又被稱做光學病理切片。此技術是利用一光學干涉儀作為主要架構,再搭配光束掃瞄機制,來重建組織的二維或三維結構,加上軟體的影像處理技術,可將掃瞄影像以3D立體方式成像,便於觀察者以任意方向針對結果作判讀。其影像解析度取決於所使用的光源頻寬、波長及光學元件。對於不同光源及光學元件,縱向及橫向解析度可從幾十um到um等級。另外在掃瞄深度方面,受限於生物組織內的水分子及黑色素吸收,不同的組織會有不同的掃瞄深度,一般而言,可達到幾百um至幾個mm左右。

在早期光學同調斷層掃瞄技術,著重於時域技術發展,其掃瞄速度最快可達到10 frames/s的輸出,漸漸隨著CCD及光源技術的發展,近年來著重於頻域光學同調斷層掃瞄技術,主要優於時域技術的好處是,造影速度的提升以及系統靈敏度也大幅的獲得改善。因此,就頻域光學同調斷層掃瞄技術而言,造影速度可達40 frames/s,使得成像可以以vedio-rate方式成像,提供醫師更及時的掃瞄及判斷。

除了一般二維或三維的造影方式,光學同調斷層掃瞄技術也提供了其他更有力的分析,例如Doppler-OCT可以用來量測血流並及時造影,觀看血流速度及血管厚度; Polarization-Sensitive OCT是針對某些組織具有光的雙折射性,如肌肉組織,肝組織等,可以分析在組織中其他物質的成分及厚度,本實驗室也利用此方法,與台大醫院合作,針對脂肪肝來作分析研究,並有相當不錯的結果;Second- Harmonic OCT是針對某些組織部位具有二倍頻效果,此方法可應用於一些組織介面變異的研究。Spectroscopic OCT乃利用不同波段的光源來針對相同的組織作研究,根據不同波段的光源針對同一組織具有不同的散射及吸收係數,由此可以分析組織的結構及成分。


Development of functional optical coherence tomography for dermatology study

Abstract:

We demonstrated a portable, functional optical coherence tomography (OCT) system for dermatology study. To miniaturize the size of the scanning probe for the OCT system and to scan arbitrary locations of skin, we used SolidWorks software to design the mechanical components of probe and to use 3D printer to fabricate mechanical components to integrate the electrical devices and optical components. In addition, the developed OCT system can reconstruct 3D structural OCT images and 3D vascular patterns of skin, simultaneously. This system can be implemented for diagnoses of skin diseases and for studies on cosmetics. Also, the developed system was used for the study on hair follicles and papilla of facial skin. From the results, the sizes and distribution of follicles and papilla can be identified, which can be used as the indicators for diagnosis of skin diseases.

Figure 1. Photos of the probe for skin scanning and In vivo OCT images of human skin.
  • Meng-Tsan Tsai*, and Feng-Yu Chang, “Visualization of hair follicles using high-speed optical coherence tomography based on a Fourier domain mode locking laser,” Laser physics 22, 791-796 (2012).

  • Meng-Tsan Tsai*, Chih Hsun Yang, Su-Chin Shen, Feng-Yu Chang, Je-Yun Yi, and Cheng-Hiang Fan, “Noninvasive characterization of fractional photothermolysis induced by ablative and non-ablative lasers with optical coherence tomography,” Laser Physics 23, 075604 (2013).

  • Meng-Tsan Tsai, Chih-Hsun Yang, Su-Chin Shen, Ya-Ju Lee, Feng-Yu Chang, and Cheng-Shin Feng, “Monitoring of wound healing process of human skin after fractional laser treatments with optical coherence tomography,: Biomed. Opt. Express 4, 2362-2375 (2013).

  • Meng-Tsan Tsai, Jeng-Jie Hung, and Ming-Che Chan, “Ultrahigh resolution optical coherence tomography with LED-Phosphor-based broadband light source, Appl. Phys. Express 6, 122502 (2013).

  • Meng-Tsan Tsai, and Ming-Che Chan, “Simultaneous 0.8, 1.0, and 1.3 μm multi-spectral and common-path broadband source for optical coherence tomography,” Optics Letters 39(4), 865-868 (2013).

  • Cheng-Kuang Lee, Meng-Tsan Tsai*, Feng-Yu Chang, Chih-Hsun Yang, Su-Chin Shen, Ouyang Yuan, and Chih-He Yang, “Evaluation of moisture-related attenuation coefficient and water diffusion velocity in human skin using optical coherence tomography,” Sensors 13, 4041-4050 (2013)


Observation of drug delivery with speckle-variance optical coherence tomography

Abstract:

Transdermal drug delivery systems (TDDS) have been an attracting field in drug delivery because of its benefit over parenteral and oral administration. In this study, we used OCT to observe the dissolution process of MNs and to investigate the temporal effects on mouse skin induced by MNs, including the morphological and vascular changes. To observe the dissolving process of polymer MNs, time-series OCT images were acquired to estimate the sizes of MNs at different skin depth. Moreover, the changes in skin morphology and vessels can be studied with OCT imaging as well as the recovery process of skin. Here, we proposed a new method to evaluate the cross-correlation relationship between sequential 2D OCT images obtained at same skin location to observe the variation of the backscattered intensities in OCT images due to the diffusion of Rhodamine. From the results, Rhodamine diffusion process from MNs into surrounding skin can be quantitatively evaluated.

Figure 2.
Upper figures: Time-series en-face images at three different depths of the mouse ear skin obtained after the insertion of MN patch for (a), (f), (k) 20 mins, (b), (g), (l) 60 mins, (c), (h), (m) 100 mins, and (d), (i), (n) 140 mins, and (e), (j), (o) 180 mins.
Lower figures: (a)-(f) Projection view of OCT angiography obtained (a) before insertion of MN patch and after removing the MN patch for (b) 0 hr, (c) 12 hrs, (d) 24 hrs, (e) 36 hrs, and (f) 48 hrs. (g) the photo of mouse ear before insertion of MN patch, and (h) the photo of mouse ear after insertion of MN patch by using Evans blue as a contrast agent for identification of blood leakage.
  • I.-Chi Lee, Jheng-Siou He, Meng-Tsan Tsai*, and Kai-Che Lin, “Fabrication of a novel partially dissolving polymer microneedle patch for transdermal drug delivery,” Journal of Materials Chemistry B, 3, 276-285 (2015).

  • Chih-Hsun Yang, Meng-Tsan Tsai*, Su-Chin Shen, Chau Yee Ng, and Shih-Ming Jung, “Feasibility of ablative fractional laser-assisted drug delivery with optical coherence tomography,” Biomedical Optical Express 5(11) 3949–3959 (2014).


OCT-guided laser microsurgery for blood coagulation and tissue ablation

Abstract:

In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT.

Figure 3. Depth-encoded projection view of OCT angiography, top view of 3D OCT images, and 3D OCT images recorded (a, g, m) before blood leakage was induced by a needle, (b, h, n) during blood leakage, (c, I, p) after exposure to 532-nm laser for 5 s, (d, j, p) after exposure to 532-nm laser for 10 s, (d, j, p) after exposure to 532-nm laser for 15 s, (e, k, q) after exposure to 532-nm laser for 20 s, and (f, l, r) after exposure to 532-nm laser for 25 s. The white arrows represent the region of leaked blood.

  • Feng-Yu Chang, Meng-Tsan Tsai*, Zu-Yi Wang, Chun-Kai Chi, Cheng-Kuang Lee, Chih-Hsun Yang, and Ming-Che Chan, “Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode,” Scientific Reports 2015 (Revised).


Using Drosophila as an experimental model for the study on heart diseases with optical coherence tomography

Abstract:

To study cardiovascular diseases, we use Drosophilae as an experiment model, which has a high degree of similarity of human genes. In this study, we use swept-source optical coherence tomography (SS-OCT) to observe the cardiac dynamics of Drosophilae, due to the advantages of high resolution, high sensitivity and real-time imaging. With OCT, the entire heart chambers of fly including conical chamber and four ostia portions can be observed. In addition, to remove the motion artifact resulting from heart contraction and body movement, a motion-corrected algorithm for OCT images was proposed. Then, such OCT system with the motion-corrected algorithm was used for investigation of age-associated heart dysfunction. In our experiments, three groups with different ages were included including 2-week-old, 4-week-old, and 6-week-old flies. Finally, three indicators are proposed to evaluate the heart function, heart beating rate, time delay between chambers, and the ratio of diastolic and systolic dimension (D/S ratio).

Figure 4.
Upper figures: beating pattern of four heart chambers after motion correction.
Lower figures: statistical results of beat rate and beating delay of three groups (2-week-old, 4-week-old, and 6-week-old).
  • Meng-Tsan Tsai*, et al., “Observations of Cardiac Beating Behaviors of Wild-type and Mutant Drosophilae with Optical Coherence Tomography,” Journal of Biophotonics 4, 610-618 (2011).

  • Meng-Tsan Tsai*, Cheng-Kuang Lee, Feng-Yu Chang, June-Tai Wu, Chung-Pu Wu, Ting-Ta Chi, and Chih-Chung Yang, “Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography,” J. Biophotonics.6, 708-717 (2013). (Selected as the journal cover page)


Investigation of Focused ultrasound-induced temporal effects on vessels with optical coherence tomography

Abstract:

Focused ultrasound (FUS) can be used to locally and temporally enhance vascular permeability, improving the efficiency of drug delivery from the blood vessels into the surrounding tissue. However, it is difficult to evaluate in real time the effect induced by FUS and to noninvasively observe the permeability enhancement. In this study, speckle-variance optical coherence tomography (SVOCT) was implemented for the investigation of temporal effects on vessels induced by FUS treatment. With OCT scanning, the dynamic change in vessels during FUS exposure can be observed and studied. Moreover, the vascular effects induced by FUS treatment with and without the presence of microbubbles were investigated and quantitatively compared. Additionally, 2D and 3D speckle variance images were used for quantitative observation of blood leakage from vessels due to the permeability enhancement caused by FUS, which could be an indicator that can be used to determine the influence of FUS power exposure. In conclusion, SVOCT can be a useful tool for monitoring FUS treatment in real time, facilitating the dynamic observation of temporal effects and helping to determine the optimal FUS power.

Figure 5.
Upper figures: FA images of the mouse ear obtained using various exposure powers of 1, 4, and 10 W. The images were captured 2 min after the injection of fluorescence images.
Central figures: Projection view of SVOCT images of the mouse ear, which were obtained (a) before FUS exposure and after FUS exposures of (b) 1 W, (c) 5 W, (d) 10 W, and (e) 15 W in the presence of microbubbles. Media 1 demonstrate the 3D animation of SVOCT images before and after FUS exposure of 15 W.
Lower figures: 3D OCT angiographies obtained (a) before and after FUS exposure for (b) 5, (c) 10, and (d) 15 s, respectively.
  • Meng-Tsan Tsai*, Ting-Da Chi, Hao-Li Liu, Feng-Yu Chang, Chih-Hsun Yang, Cheng-Kuang Lee, and C. C. Yang, “Microvascular imaging using swept-source optical coherence tomography,” Appl. Phys. Express 4, 097001 (2011).

  • Meng-Tsan Tsai, Cheng-Kuang Lee, Kung-Min Lin, Yu-Xiang Lin, Tzu-Han Lin, Ting-Chia Chang, Jiann-Der Lee, and Hao-Li Liu, “Quantitative observation of focused ultrasound induced vascular leakage and deformation via fluorescein angiography and optical coherence tomography,” Journal of Biomedical Optics 18(10), 101307 (2013).

  • Meng-Tsan Tsai, Feng-Yu Chang, Cheng-Kuang Lee, Cihun-Siyong Alex Gong, Yu-Xiang Lin, Jiann-Der Lee, Chih-Hsun Yang, and Hao-Li Liu, “Investigation of temporal vascular effects induced by focused ultrasound treatment with speckle-variance optical coherence tomography,” Biomed. Opt. Express 5(7), 2009–2022 (2014).


Diagnostics of oral precancer with functional optical coherence tomography

Abstract:

An OCT system was used to clinically scan oral lesions in different oral carcinogenesis stages, including normal oral mucosa control, mild dysplasia (MiD), moderate dysplasia (MoD), early-stage squamous cell carcinoma (ES-SCC), and well-developed SCC (WD-SCC), for diagnosis purpose. On the basis of the analyses of the SS-OCT images, the stages of dysplasia (MiD and MoD) and SCC (ES-SCC and WD-SCC) can be differentiated.

Figure 6.
Upper figures: 2D OCT images of buccal mucosa obtained from a 24-year-old male.
Lower figures: 3D OCT images and vascular images at various depths obtained from a 25-year-old male.
  • Meng-Tsan Tsai, et al., “Effective indicators for diagnosis of oral cancer using optical coherence tomography,” Opt. Express 16, pp. 15847-15862 (2008).

  • Meng-Tsan Tsai, et al., “Differentiating Oral lesions in Different Carcinogenesis stages with Optical Coherence Tomography.” J. Biomed. Opt., Vol. 14, No. 4, 044028 (2009).

  • Cheng-Kuang Lee, Meng-Tsan Tsai, Hsiang-Chieh Lee, Yih-Ming Wang, Hsin-Ming Chen, Chun-Pin Chiang, and C. C. Yang, “Diagnosis of Oral Submucous Fibrosis with Optical Coherence Tomography.” J. Biomed. Opt., Vol. 14, No. 5, September/October 2009 (2009).

  • Meng-Tsan Tsai, et al., “Delineation of an Oral Cancer Lesion with Swept-source Optical Coherence Tomography,” J. Biomed. Optics, Vol. 13, No. 4, 044012 (2008).

  • Meng-Tsan Tsai*, et al., “Differentiation of oral precancerous stages with optical coherence tomography based on the evaluation of optical scattering property,” Laser Physics 12 (2012).


Optical inspection of industrial products with optical coherence tomography

Abstract:
Figure 7. (a) The scanning electron microscope (SEM) image of the solar cell. The white bar and the stripe feature represent 100 μm in length and the electrode structure, respectively. (b) The optical coherence tomography (OCT) phase image of the solar cell. The white bar and the stripe feature represent 300 μm in length and the electrode structure, respectively. (c) The magnified image from the region marked by the red square in (b). (d) and (e) The cross-section SEM image and OCT phase image of the same solar cell. The corresponding location of (e) is indicated by the red-dash line in (c).
  • Meng-Tsan Tsai*, et al., “ Defect detection and property evaluation of indium tin oxide conducting glass using optical coherence tomography,” Opt. Express 19, 7559-7566 (2011).

  • Meng-Tsan Tsai, et al., “Quantitative phase imaging with swept-source optical coherence tomography for optical measurement,” IEEE Photonics Technology Letters 24, 640-642 (2012).

  • Meng-Tsan Tsai, Feng-Yu Chang, Yung-Chi Yao, Jie Mei, and Ya-Ju Lee, “Optical inspection of solar cells with phase-sensitive optical coherence tomography,” Solar Energy Materials and Solar Cells 136, 193-199, 2015.