Sensitive detection of malignancy in primary acquired melanosis by advanced optical imaging

项目摘要 眼表肿瘤如结膜黑色素瘤和眼表鳞状细胞瘤是 由结膜或角膜利姆布斯引起的眼睛的潜在致盲或致命损伤。早期检测 治疗对成功的结果很重要，在癌前病变发生之前治疗高危癌前病变， 变坏是有利的。然而，建立临床诊断通常并不简单， 不同病变类型的外观重叠。此外，临床上良性病变，如原发性 获得性黑变病（PAM）可能潜在地隐藏显微镜下的细胞色素沉着，这赋予了显著的风险， 转化为黑素瘤目前唯一可靠区分良性和癌前病变的方法 病变是切除病变进行活检，这导致许多良性病变被切除， 漏掉任何恶性肿瘤存在局部化疗选择，但其适当使用取决于 准确的诊断和监测的条件，这强调了一个可靠的， 敏感的非侵入性成像工具，以检测眼表恶性肿瘤。为了满足这一需求，我们建议 一种新的光学相干层析成像（OCT）模式，双波段双扫描逆光谱OCT （D2ISOCT），以提供微血管造影、微血管 氧化和纳米级的超微结构特性。没有其他现有技术能够实现这种 测量.以前的研究已经检测到增加的氧饱和度和超微结构的改变， 癌前组织我们还对人结膜活检进行了体外研究，结果显示 组织超微结构改变的ISOCT标记物以及代谢标记物的变化增加 双光子内源性荧光显微镜检测结果与眼表恶性肿瘤相关。 我们假设ISOCT超微结构标记物、微血管密度和sO2是敏感的标记物 用于检测眼表面恶性肿瘤和癌前状态。我们有两个具体目标。1)我们将 开发了一种新型的双波段双扫描ISOCT（D2ISOCT）系统，用于人眼的活体分析 面2)我们将进行一项试点临床研究，以验证D2ISOCT系统用于检测恶性肿瘤和 人类受试者眼表病变的癌前变化。对公众健康的影响：1） 该项目的成功将导致一个突破性的新的成像设备的病变的评估， 眼表该技术可能有助于指导患者的适当治疗，并改善其 结果。2)该成像方法的有效性可能会导致进一步的临床研究预测成像 眼睛的其他恶性病变的标志物，包括虹膜和视网膜肿瘤。

PROJECT SUMMARY Ocular surface neoplasms such as conjunctival melanoma and ocular surface squamous neoplasia are potentially blinding or fatal lesions of the eye that arise from the conjunctiva or corneal limbus. Early detection and treatment is important for successful outcomes, and treating high-risk pre-malignant lesions before they become malignant is favorable. However, establishing a clinical diagnosis is often not straightforward due to overlap in the appearance of different lesion types. Furthermore, a clinically benign lesion such as primary acquired melanosis (PAM) can potentially harbor microscopic cellular atypia, which confers a significant risk of conversion to melanoma. The only currently available method to reliably distinguish benign from pre-malignant lesions is to excise the lesion for biopsy, which results in many benign lesions being removed in order not to miss any malignant ones. Topical chemotherapeutic options exist, but their appropriate use depends upon accurate diagnosis and monitoring of the condition, which underscores the importance of a reliable and sensitive non-invasive imaging tool to detect ocular surface malignancy. To address this need, we propose a new optical coherence tomography (OCT) modality, dual-band dual-scan inverse spectroscopic OCT (D2ISOCT), to provide sensitive and comprehensive quantification of both microangiography, microvascular oxygenation and nanoscale ultra-structural properties. No other existing technology enables such measurements. Previous studies have detected increased oxygen saturation and ultrastructural alterations in pre-malignant tissue. We have also conducted an ex vivo study from human conjunctival biopsies, showing that increases in an ISOCT marker of tissue ultra-structure alteration, as well as changes in metabolic markers detected by two photon intrinsic autofluorescence microscopy were correlated with ocular surface malignancy. We then hypothesize that ISOCT ultra-structural markers, microvascular density and sO2 are sensitive markers for the detection of ocular surface malignancy and pre-malignant states. We have two specific aims. 1) We will develop a novel dual-band dual-scan ISOCT (D2ISOCT) system for in vivo analysis of the human ocular surface. 2) We will conduct a pilot clinical study to validate the D2ISOCT system for detecting malignant and pre-malignant changes in ocular surface lesions in human subjects. IMPACT ON PUBLIC HEALTH: 1) The success of this project will lead to a groundbreaking new imaging device for the evaluation of lesions of the ocular surface. The technique may help to guide appropriate treatment for patients and improve their outcomes. 2) The validity of the imaging method could lead to further clinical study on predictive imaging markers for other malignant lesions of the eye, including iris and retinal tumors.