OFFICE BASED IMAGING OF EARLY LARYNGEAL CANCER USING HIGH-SPEED FD-OCT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 上呼吸道癌症与长期吸烟和饮酒的综合作用有着千丝万缕的联系。喉癌在不吸烟的人中非常罕见，而且风险随着每天吸烟的数量增加而增加。每年约有15,000人被诊断为喉癌，约占所有新诊断癌症的1.2%。在过去的十年里，初级保健医生对喉癌体征和症状的更多认识导致了喉癌的早期诊断，这种癌症在早期阶段表现得相当微妙，主要症状是声音改变，特别是声音嘶哑。由于早期诊断喉癌的治愈率(90%)比晚期疾病(60%)高得多，临床医生在获得声带活检方面非常积极，即使这意味着许多活检会得出非癌症的诊断。声带活检并不是无害的，由于切除了脆弱的粘弹性结缔组织，经常会导致不可逆转的发音困难和声音嘶哑。侵袭性喉癌的定义是声带癌向同一组织扩散。 在没有活检的情况下诊断喉部侵袭性肿瘤的存在或高可能性，将为外科医生提供更好地确定哪些患者适合接受手术内窥镜和活检的能力。同样，许多患者可以避免与声带活检相关的并发症。需要一种基于办公室的非接触技术来获得声带微结构的实时横断面图像，从而帮助区分侵袭性和非侵袭性肿瘤。这种设备可以相对简单地对喉癌高危或怀疑患有喉癌的患者进行诊断筛查，并可以评估与二手烟烟雾暴露有关的慢性喉部疾病。我们建议通过开发一种先进的基于光学相干层析成像(OCT)的仪器来完成这项任务，该仪器可以在办公室对喉部进行成像，而不需要麻醉或镇静。OCT是一种新兴的光学成像设备，它使用光在组织中产生横断面图像，在我们的领导下，我们已经在300多名患者中率先使用这种设备在手术环境中对上消化道进行成像。 这项拟议的研究将设计和开发OCT探头，与现有的基于办公室的传统喉镜系统协同工作。我们相信，这项新兴技术的使用最终将1)提供一种筛查早期喉癌患者的手段，并最大限度地减少为诊断早期喉癌而进行的不必要的活检次数，从而减少医源性发音困难；2)在显微外科手术期间，引导耳鼻咽喉科医生将活组织检查重点放在微侵袭性癌症的高危区域；以及3)实现声带横断面图像的存档存储，可用于确定声带显微解剖和结构随时间的变化，从而增强传统的静态二维喉部照片。我们坚信，OCT有可能成为与CT和MRI一样重要的头颈部恶性肿瘤治疗方法，因为它提供了关于组织微结构的精细细节；与这些传统成像方式不同，在办公室进行喉部OCT成像仍然是一项重大的技术挑战，因此现在是我们研究的主要重点。我们的建议是临床驱动的，重点是将先进的喉部成像设备应用于临床实践和大规模评估。设备设计中的技术挑战在于内科、外科和生物医学工程的结合。 具体目标是 1.设计并制作了可与办公室喉镜成像系统集成的OCT探头。 2.对喉癌高危患者进行大规模筛查，并将F-OCT图像与临床表现和常规视频内窥镜图像进行对照。 3.将OCT声带图像与喉癌显微手术患者的声带活检结果相关联。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer of the upper aerodigestive tract is inextricably linked to the combined effect of chronic tobacco and alcohol use. Laryngeal cancer is very rare in nonsmokers, and the risk increases with numbers of cigarettes smoked per day. Approximately 15,000 laryngeal cancers are diagnosed each year, representing about 1.2% of all newly diagnosed cancers. Greater awareness of the signs and symptoms of laryngeal cancer by primary care physicians over the past decade has led to earlier diagnosis of laryngeal cancer, which presents quite subtly at earlier stages, with the cardinal symptom being voice change, specifically hoarseness. Since early diagnosis of laryngeal cancer results in a much higher cure rate (>90%) than late-stage disease (<60%), clinicians are aggressive with respect to obtaining vocal cord biopsies, even though this means many biopsies will yield a diagnosis that is not cancer. Vocal cord biopsy is not innocuous, and frequently leads to irreversible dysphonia and hoarseness as a consequence of removing the delicate viscoelastic connective tissues. Invasive laryngeal cancer is defined as the spread of vocal cancer into this same tissue. Diagnosing the presence or high likelihood of an invasive laryngeal tumor without biopsy would provide surgeons with the ability to better determine which patients are candidates for surgical endoscopy and biopsy. Likewise, many patients may be spared the morbidity associated with a vocal cord biopsy. An office-based, non-contact technique is needed to obtain real-time cross-sectional images of the vocal cord microstructure and hence aid in distinguishing invasive from non-invasive tumors. Such a device would allow relatively simple diagnostic screening of patients at high risk of or suspected as having laryngeal cancer and would allow evaluation of chronic laryngeal disease related to second-hand tobacco smoke exposure. We propose to accomplish this task by developing an advanced Optical Coherence Tomography (OCT)-based instrument to image the larynx in the office without the need for anesthesia or sedation. OCT is an emerging optical imaging modality that uses light to produce crosssectional images in tissue, which under we have pioneered use in more than 300 patients to image the upper aero-digestive tract in operative settings. The proposed research will design and develop OCT probes that will work in tandem with existing conventional office-based laryngeal endoscopy systems. We believe use of this emerging technology will ultimately 1) provide a means to screen patients for early laryngeal cancer and minimize the number of unnecessary biopsies performed to diagnose early laryngeal cancer, thus reducing iatrogenic dysphonia; 2) guide otolaryngologists during microsurgery to focus biopsies on regions with a higher probability of microinvasive cancer; and 3) allow archival storage of cross-sectional images of the vocal cord which can be used to determine changes in cord microanatomy and structure over time, augmenting conventional static two-dimensional laryngeal photographs. We firmly believe OCT has the potential to become as vital as CT and MRI for managing head and neck malignancies since it provides such exquisite detail on tissue microstructure; unlike these traditional imaging modalities, performing laryngeal OCT imaging in the office remains a major technical challenge, and therefore is now the main focus of our research. Our proposal is clinically driven and focuses bringing an advanced laryngeal imaging device into clinical practice and large scale evaluation. The technical challenges in device design lie at the nexus of medicine, surgery, and biomedical engineering. The specific aims are 1. Design and construct OCT probe that can be integrated with an office-based laryngeal endoscopy imaging system. 2. Perform large-scale screening of patients at risk of laryngeal cancer, and correlate F-OCT images with clinical findings and conventional video endoscopic images. 3. Correlate OCT vocal cord images with biopsies in the subset of patients undergoing microlaryngeal surgery for cancer diagnosis.