高性能光学相干层析成像的研究

Development of High-Performance Optical Coherence Tomography

介绍了光学相干层析成像在不断提升其性能方面的一些研究,其中主要包括在成像的分辨率、成像速度、成像探头等基础核心指标方面大幅提升的代表性工作。综述了清华大学物理系近二十多年来在光学相干层析成像研究方面的一系列重要进展,包括取得了纵向分辨率为0.64μm的高分辨率成像、E3.5长时间细胞活体的亚细胞分辨成像,成功研制了速度高达40 MHz的高速扫频激光器,实现了基于光计算的每秒1000万次轴向线扫描的超高速实时光学成像信息处理等。

Significance Optical coherence tomography(OCT)is a depth-resolved biomedical in vivo imaging technique providing cross-sectional and three-dimensional(3D)images of tissue microstructure with a micrometer-scale resolution.In the past few decades,OCT has been employed in various applications,including clinical and material research areas.In this paper,some studies on improving the performance of OCT are introduced.Among them,imaging resolution,imaging speed,and multifunctional integration are the basic core indicators of the imaging system.Recently,research on OCT conducted at the Department of Physics of Tsinghua University has achieved a series of important advances in improving imaging system performance.Progress For high-resolution imaging,we achieved ultrahigh-resolution OCT with a supercontinuum by coupling femtosecond pulses generated from a commercial Ti∶sapphire laser into an air-silica microstructure fiber.The visible supercontinuum from 450 to 700 nm centered at 540 nm was generated.A free-space axial OCT resolution of 0.64μm was achieved.The sensitivity of the OCT system was 108 dB with an incident light power of 3 mW at a sample,only 7 dB below the theoretical limit.For subcellular and long-time in vivo imaging,we developed a novel system of full-field OCT(FF-OCT)for label-free 3D subcellular in vivo imaging of preimplantation mouse embryos.As the sample received much less optical dose than in conventional confocal imaging,the preimplantation mouse embryos were alive even after several days’ live imaging.Various typical preimplantation stages,including zygote,two-cell,four-cell,and blastocyst(at embryonic day 3.5,E3.5 for short),were investigated with a spatial resolution of 0.7μm and imaging rate of 24 frame/s.These are the first in vivo studies with mammalian embryos at the beginning of their embryonic lives for understanding early patterning and polarity.For high-speed imaging,a high-speed swept source is necessary for system setup.Real-time 3 Dhigh-definition OCT imaging requires 1000 x-scan×1000 y-scan×30 times/s refresh rate,i.e.,1000×1000×30=30 MHz,implying that the laser should have a sweeping speed of at least 30 MHz.Therefore,we devised an all-optical swept source with an A-scan rate of 40 MHz,the fastest one thus far.The inertia-free swept source,having an output power of 41.2 mW,tuning range of 40 nm,and high scan linearity in wavenumber with a Pearson correlation coefficient r of 0.9996,comprised a supercontinuum laser,an optical band-pass filter,a linearly chirped fiber Bragg grating,an erbium-doped fiber amplifier,and two buffer stages.With a sensitivity of 87 dB and a 6-dB fall-off depth of 0.42 mm,ultrahigh-speed sweeping OCT based on sweep laser(SS-OCT)imaging of biological tissue in vivo was demonstrated.Ultrahigh-speed real-time optical imaging requires the real-time information processing of big image data.Realtime 3D high-definition OCT has a 1000 pixel(X)×1000 pixel(Y)×1000 pixel(Z)×30 times/s refresh rate,indicating that 30-Gbit/s data flow needs to be processed in real time.To address this challenge,we proposed a novel all-optical computing technique to process the signal in the spectral domain with a fiber-optics system other than compute interpolation based on fast Fourier transform algorithm(FFT)using an electronic computer,resulting in a significant reduction of processing time and enahancement of imagin speed.In the so-called optical computing OCT,the Fourier transform of the A-scan signal was optically processed in real time before the light was detected by aphotoelectric detector.Low-coherence continuous wave(CW)light centered at 1550 nm with an average power of 22 mW and a bandwidth of 40 nm was generated by a superluminescent diode.The CW light was modulated by a 10-GHz-bandwidth intensity modulator,known as the Mach-Zehnder modulator(MZM).The MZM was biased by apower supply and driven by a cos(at2)waveform signal generated by an arbitrary waveform generator(AWG).With this optical computing system,a processing rate of 107 A-scan per second was experimentally achieved,which is the highest speed for OCT imaging to the best of our knowledge.Because tiny endoscopic probes work as its sample arms,the applied range of the proposed OCT technique can be expanded to various internal organs such as arteries and esophagus.To further enhance the feasibility of the proposed OCT technique,we also proposed and fabricated a prototype focus-adjustable endoscopic probe with an outer diameter of 2.5 mm and a rigid length of 32 mm based on a two-way shape-memory-alloy(SMA)spring and an in-house hollow-core ultrasonic motor.This novel probe has adjustable focus and hence a larger scanning range,with high resolution and no sensitivity loss.The focus-adjustable range was more than 1.5 mm,with a 100.3-dB sensitivity and the best lateral resolution of~4μm.With the use of a hollow-core motor,the probe can provide an unobstructed 360°field of view.To the best of our knowledge,this is the first demonstration of a focus-adjustable probe for C-mode scanning in endoscopic OCT.We believe that this novel probe will be useful in future biomedical applications.Conclusion and Prospect This paper presents some remarkable research advances at Tsinghua University and is dedicated to celebrating the 110 th anniversary of Tsinghua University.