光学相干成像及临床应用研究

Optical Coherence Imaging for Clinical Applications

精准识别肿瘤边界对于提高切除率、降低复发率、改善患者预后具有极其重要的意义,但目前仍缺乏术中及时、精准识别肿瘤边界及肿瘤侵袭性的成像方式。光学相干层析成像(OCT)作为一种无创、无标记、高分辨率的三维光学层析成像技术,不但可以获得组织的三维断层形貌特征,还能实现组织的三维微循环网络可视化。光学活性快速病理成像是一种不需要对术中新鲜组织进行任何预处理即可获得类似病理切片信息的高分辨率高对比度光学相干成像技术。本文将介绍推进光学相干成像在术中应用的系列研究工作,包括自适应肿瘤血管算法、机器人辅助OCT、显微镜集成OCT、超高速扫描激光器、术中实时三维OCT成像以及光学活性快速病理成像的研究和开发,以实现在肿瘤切除前获取肿瘤血管及其微循环信息,肿瘤切除后通过光学活性快速病理成像进行快速病理检测。这些研究将有利于提高肿瘤全切率、降低肿瘤复发率、改善胶质瘤患者预后,推进精准医学的发展。

Significance Optical coherence tomography(OCT)plays a pivotal role in medical imaging,particularly in enhancing the tumor resection accuracy.The significance of this technology lies in its ability to improve patient prognosis by providing real-time,detailed visualization of tumor boundaries and invasiveness,thereby reducing recurrence rates and aiding the precise removal of malignant tissues.Progress We introduced a series of research efforts to advance the intraoperative application of optical coherence imaging.Vascular characteristics are an important basis for intraoperative pathological assessment.We first introduced OCT angiography with adaptive multi-time intervals,which proposes a time-efficient scanning protocol by adaptive optimization of the weights of different timeinterval B-scan angiograms.This novel OCTA technique achieved better performance,with a visible vascular density increase of approximately 67%and a signal-to-noise ratio enhancement of approximately 11.6%(Figs.2 and 3).In the context of intraoperative applications,we introduced robot-assisted OCTA,which integrated a high-resolution OCT system with a 6-degree of freedom robotic arm(Fig.4).Robot-assisted OCTA can achieve wide-field imaging of artificially determined scanning paths.High-resolution vascular imaging of the mouse brain by robot-assisted OCTA successfully confirmed the effect of unevenly distributed resolution and fall-off caused by the large-curvature sample(Fig.5).Thereafter,we introduced a microscope-integrated OCT system that can be well integrated with current intraoperative equipment and does not need to pause the surgical process(Figs.6 and 7).Providing real-time tissue depth information to a doctor can help improve their decision-making ability in delicate surgical procedures such as ophthalmology and nervous system surgery.Intraoperative three-dimensional(3D)real-time imaging requires an OCT system with high imaging and processing speeds.Thereafter,we introduced the 10.3 MHz ultra-high speed scanning laser with stretch pulse modelocked based on polarization isolation(Fig.8),which employs a simple and low-cost approach to suppress the transmitted light and achieves an effective duty cycle of~100%with only one CFBG and no need for intra-cavity semiconductor optical amplifier(SOA)modulation,extra-cavity optical buffering,and post amplification(Fig.9).Real-time 3D OCT imaging is necessary for practical intraoperative applications,and a series of studies have been conducted to achieve this goal.A home-built 3.28 MHz FDML based OCT system combined with GPUs(NVIDIA,GeForce GTX690,and GeForce GTX680,USA)achieved real-time processing and visualization of 3D OCT data(Fig.10).The imaging range and longitudinal resolution can be flexibly adjusted by changing the spectral rangeof the output.Although OCT offers high-quality structural and vascular imaging,it lacks cellular resolution,which limits detailed tumor analysis.Dynamic full-field OCT(D-FFOCT)is an optically active rapid pathological imaging technology based on array interference detection that captures subcellular metabolic motion at millisecond temporal and nanometer spatial scales,and significantly enhances tumor diagnostics by providing detailed insights beyond conventional OCT capabilities(Fig.11).Normal and diseased tissues can be accurately distinguished by analyzing the temporal characteristics of dynamic signals,such as amplitude,frequency,and standard difference.Through the use of high-power objective lenses and broadband light sources,the resolution can reach sub-microns,and as an imaging tool for intraoperative tissue sections,it is fast,easy(no freezing or staining is required),and highly accurate.Freshly isolated mouse brain glioma sections were imaged using the D-FFOCT system,which showed a clear boundary,distinct cell structure,and dynamic intensity between the glioma and normal brain tissue(Fig.12).Conclusions and Prospects Advancements in OCT technology,including the significantly increased sweep speed of the light source,improvement of the probe for the intraoperative scene,optimization of the blood flow algorithm,and high-speed data processing capability supported by the GPU,make real-time intraoperative 3D tomography possible.D-FFOCT imaging with a cellresolving ability is an important step forward in the timely pathology of tumor resection.The integration of advanced OCT technologies into clinical practice heralds a new era of precision medicine in which surgical accuracy is significantly enhanced and tumor recurrence is minimized.Future studies should focus on further refining OCT capabilities,integrating these advanced technologies to improve clinical practicability,expanding their applications across different types of cancer,and integrating Al to automate and enhance diagnostic accuracy.This vision foresees OCT not only as a tool for improved surgical interventions but also as a pivotal element in the broader strategy of personalized and targeted treatment approaches,offering a beacon of hope for more effective cancer management and patient recovery paths.The ultimate goal is to establish OCT as an indispensable tool for tumor surgery and management,revolutionizing patient care and outcomes.