【作者】 张宁；

【导师】 薛平；

【作者基本信息】 清华大学 ， 物理学， 2014， 博士

【摘要】 癌症肿瘤是威胁广大人民群众生命的最严重的疾病之一，而早诊断、早治疗是治疗癌症肿瘤的关键。目前癌症诊断的黄金标准依然是活体切片法，但是容易出现错检、漏检、污染等，影响诊断的正确性和有效性。因此发展一种新型癌症早期诊断在体成像检测方法，将大大有助于上述问题的解决。光学相干层析（Optical Coherence Tomography，OCT）是一种利用生物组织散射光相干原理成像的微米尺度活体组织高分辨断层成像手段。该技术因其无损伤、微米分辨率、高速等特点对于癌症的早期诊断具有重大意义和应用价值。本论文以频域OCT（Spectral Domain OCT，SD-OCT）技术为基础，结合内窥OCT探头的研制，得到了一些有特色、有突破的研究成果。首先，在频域OCT技术的研究方面，传统频域OCT一般需要通过数值插值等数据后处理过程将探测光谱从波长域转换到波数域，这样才能由傅里叶变换重构出高质量的OCT信号。但是，这一过程冗繁耗时，成为成像速度提升的瓶颈。本论文提出了两种新型的波数线性化方法：其一是首次提出了菲涅尔频域OCT技术，利用菲涅尔波带片的特性，直接由空间上获得波数域线性的光谱信号，省去了传统的插值过程，进而提升成像速度，同时装置简单易集成；二是首次提出了线性波数采样的压缩感知算法，通过在空间选取波数线性的少量原始光谱数据，再利用压缩感知算法重构出OCT图像，这一方法同样省去了插值过程，仅用约20%原始数据量即可较好恢复原始图像，图像信噪比还有提升。其次，在内窥OCT探头的设计方面，本论文针对两种不同扫描方式的探头，分别提出了新设计方案，解决了各自的问题。对于环形扫描探头，本论文提出了基于超小型中空超声马达的新型探头设计，通过该马达驱动特殊设计的光学镜头旋转，实现了360度无盲区、高分辨率内窥成像，并且封装后探头尺寸进一步缩小至1.5mm；对于前向扫描探头，本论文提出了基于压电管的反向安装型探头方案，与传统前向扫描探头方案相比，该方案有效缩短了探头硬端长度，同时保持了与传统前向扫描探头相似的扫描性能，具有很好的临床应用前景。本论文的研究表明，内窥频域OCT的研制将有助于实现高速实时监测、高分辨率、无损断层成像，在癌症的早期诊断方面具有重要的价值。更多还原

【Abstract】 Cancer is one of the most serious diseases to human and the key to cure the canceris early diagnosis and treatment. The biopsy, as the gold standard for diagnosis ofcancer in clinic, suffers from error or missing detection as well as possible pollution,which degrades its accuracy and effectiveness. Therefore, a novel and in vivo imagingmethod for cancer diagnosis will significantly contribute to solving these problems.Optical coherence tomography (OCT) performs non-invasive, micrometer-resolution,high-speed imaging of tissue pathology, showing a greatly significant value for earlydiagnosis of cancer.In this thesis, we studied the spectral domain OCT (SD-OCT) technology and thedevelopment of endoscopic OCT probe as well. The related results of interest aredemonstrated as following.First, the conventional SD-OCT generally requires converting the original detectedspectrum from the wavelength domain to the wavenumber domain by numericalinterpolation, so as to reconstruct a high quality OCT image via the Fourier transform.However, this process is time-consuming and become a bottleneck to enhance imagingspeed. This thesis presents two novel methods for wavenumber linearization. One is theFresnel SD-OCT equipped with a Fresnel spectrometer that utilizes a Fresnel zone plate(FZP) as both dispersion and focusing optics, obtaining a linear-in-wavenumberspectrum directly. It removes the conventional interpolation process and thus isfavorable for enhancing the imaging speed. Another method is compressed sensing withlinear-in-wavenumber sampling (k-linear CS). An array of points that is evenly spacedin wavenumber domain is sampled from an original interferogram by a pre-set k-linearmask. Then the compressed sensing is applied on these points to reconstruct an A-scandata. To get an OCT image, this method uses less than20%of the total data as requiredin the conventional process and gets rid of the spectral calibration with numericalinterpolation in traditional CS-OCT. Therefore k-linear CS is favorable for high speedimaging.In addition, for the endoscopic OCT probe, we proposed new designs to both thecircumferential-imaging and forward-imaging probes, respectively. For thecircumferential-imaging, we presented an endoscopic probe equipped with a miniaturized hollow ultrasonic motor that rotated the objective lens and provided aninternal channel for the fiber to pass through, enabling360deg unobstructedcircumferential scanning. This probe has an ultra-small outer diameter of1.5mm with acustomized aspheric right-angle lens, leading to high transverse resolution. For theforward-imaging, we developed a compact, optical fiber scanning piezoelectrictransducer (PZT) probe with a reverse-mount design which achieved a shorter rigidlength compared with conventional forward-mount fiber designs, while maintaining thescanning performance similar to the forward-mount one. Therefore this new designshows greater potential in clinical applications.Our studies demonstrate the feasibility of endoscopic SD-OCT in breaking thelimitations of conventional imaging method and helping to achieve real-time monitoringand high resolution imaging of early cancer. We believe that endoscopic SD-OCT is apromising technique for the early diagnosis of cancer.更多还原