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

通过先进光学成像灵敏检测原发性获得性黑变病的恶性肿瘤

• 批准号: 10251585
• 负责人: Ji Yi
• 金额: $ 12.55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251585
• 关键词: Sensitive; detection; malignancy; primary; acquired

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.

项目概要 眼表肿瘤如结膜黑色素瘤、眼表鳞状细胞瘤等 结膜或角膜缘引起的潜在致盲或致命的眼睛损伤。早期发现 治疗对于成功的结果很重要，并且在高危癌前病变发生之前对其进行治疗 恶变是有利的。然而，由于以下原因，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，临床上的良性病变，例如原发性病变 获得性黑变病 (PAM) 可能存在微观细胞异型性，这会带来显着的风险 转化为黑色素瘤。目前唯一可用的可靠区分良性与癌前病变的方法 病变就是切除病灶进行活检，这样就导致很多良性病灶被切除，以免 错过任何恶性的。存在局部化疗方案，但其适当使用取决于 准确诊断和监测病情，这强调了可靠和可靠的方法的重要性 用于检测眼表恶性肿瘤的灵敏非侵入性成像工具。为了满足这一需求，我们提出了 新的光学相干断层扫描 (OCT) 模式，双波段双扫描逆光谱 OCT (D2ISOCT)，提供微血管造影、微血管造影和微血管造影的灵敏且全面的量化 氧化和纳米级超结构特性。没有其他现有技术能够实现这样的 测量。先前的研究已经检测到氧饱和度增加和超微结构改变 癌前组织。我们还对人类结膜活检进行了离体研究，表明 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 通过两个光子固有自发荧光显微镜检测到的与眼表恶性肿瘤相关。 然后我们假设 ISOCT 超微结构标志物、微血管密度和 sO2 是敏感标志物 用于检测眼表恶性肿瘤和癌前状态。我们有两个具体目标。 1）我们会 开发一种新型双波段双扫描 ISOCT (D2ISOCT) 系统，用于人眼的体内分析 表面。 2) 我们将进行一项试点临床研究，以验证 D2ISOCT 系统检测恶性和恶性肿瘤的能力。 人类受试者眼表病变的癌前变化。对公众健康的影响： 1) 该项目的成功将带来一种突破性的新型成像设备，用于评估皮肤病变 眼表面。该技术可能有助于指导患者适当的治疗并改善他们的症状 结果。 2）成像方法的有效性可以促进预测成像的进一步临床研究 眼睛其他恶性病变的标志物，包括虹膜和视网膜肿瘤。