Combined raman spectroscopy-optical tomagraphy for complete diagnosis of skin can

拉曼光谱-光学断层扫描相结合，可对皮肤进行全面诊断

• 批准号: 7623181
• 负责人: Anita Mahadevan-Jansen
• 金额: $ 13.12万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623181
• 关键词: Anxiety; Appearance; Area; Basal cell carcinoma; Benchmarking; Benign; Biochemical; Biopsy; Breast; Cancer Detection; Cancerous; Cervix Uteri; Clinic Visits; Clinical; Clinical Course of Disease; Confocal Microscopy; Data; Data Set; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Differential Diagnosis; Diffuse; Discrimination; Disease; Disease Management; Early Diagnosis; Ensure; Epithelial; Evaluation; Excision; Fluorescence; Foundations; Gastrointestinal tract structure; Goals; Healthcare; Histology; Histopathology; Image; Imaging Techniques; In Vitro; Incidence; Individual; Lasers; Lesion; Location; Malignant - descriptor; Malignant Neoplasms; Maps; Measurement; Measures; Medicine; Methods; Microscopic; Modality; Molecular; Monitoring for Recurrence; Nature; Noise; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Organ; Output; Ovary; Pathology; Pathology Report; Patient Care; Patients; Perception; Performance; Phase; Physical Examination; Physicians; Pigments; Pilot Projects; Prostate; Protocols documentation; Radar; Raman Spectrum Analysis; Reporting; Research; Resolution; Risk; Sampling; Screening for Skin Cancer; Screening procedure; Signal Transduction; Site; Skin; Skin Cancer; Source; Specificity; Spectrum Analysis; Speed; Staging; Surface; System; Techniques; Technology; Testing; Thick; Time; Tissue Sample; Tissues; Training; Underserved Population; Upper arm; Validation; Visible Radiation; Work; cancer diagnosis; clinical practice; cost effectiveness; data acquisition; design; detector; flexibility; follow-up; imaging modality; improved; in vivo; innovation; instrument; interest; meetings; miniaturize; novel; optical imaging; outcome forecast; public health relevance; rapid detection; skin lesion; spectroscopic imaging; success; tool

DESCRIPTION (provided by applicant): The incidence of skin cancer has been on the rise in recent years and as in most cancers, early diagnosis and thorough treatment (i.e., complete resection) are the keys to gain a favorable prognosis. Current diagnostic methods for skin cancers rely on physical examination in conjunction with skin biopsy, methods that have limited accuracy in early diagnosis. Hence there is considerable interest in developing a non-invasive diagnostic and screening tool, which can accurately recognize skin cancer in its early stages. Such a tool would not only detect early signs of malignancy, it will also reduce unnecessary diagnostic surgical procedures, facilitate complete excision of skin cancers by accurately delineating the skin cancer margins prior to and during the surgery, and allow treated patients to be monitored for recurrence. In this proposal we present a method that combines Optical Coherence Tomography (OCT), an imaging technique that visualizes tissue microstructure, with Raman spectroscopy, a spectroscopy technique that provides a tissue biochemical map in a single portable instrument for the effective detection of skin lesions. The real-time non-invasive nature of this combined technique can enable a "see and treat" protocol that would decrease the number of return clinic visits and patient anxiety as the long waits for histopathology diagnoses would be eliminated. Thus, the technology has the potential to increase access to underserved populations where follow-up to screening may not be available. The technology poses no known risks to the patient, and therefore could be a safe alternative to current screening methods. PUBLIC HEALTH RELEVANCE: The incidence of skin cancer has been on the rise in recent years and as in most cancers, early diagnosis and thorough treatment (i.e., complete resection) are the keys to gain a favorable prognosis. Current diagnostic methods for skin cancers rely on physical examinations in conjunction with skin biopsy, methods that have limited accuracy for early diagnosis. Hence there is considerable interest in developing a non- invasive diagnostic and screening tool, which can accurately recognize skin cancer in its early stages. Such a tool would not only detect early signs of malignancy, it could also reduce unnecessary diagnostic surgical procedures, facilitate complete excision of skin cancers by accurately delineating the skin cancer margins prior to and during the surgery, and allow treated patients to be monitored for recurrence. Initial reports have identified the practical limitations of non-invasive optical devices using either imaging or spectroscopy to evaluate the diverse clinical appearance of normal skin, benign lesions, and malignancy. In this proposal, we describe the design of a device that is specifically geared towards thorough non-invasive analysis of both the underlying microstructure and biochemical composition of the skin. The challenge presented by the variability of skin and skin cancers present the ideal test organ and pathology for the proposed multi-modal device. This R21 proposal seeks to validate the hypothesis that a device that combines morphological imaging with optical coherence tomography (OCT) and biochemical evaluation with Raman spectroscopy (RS) increases the diagnostic information available to the physician and could improve the diagnostic performance of each technique alone. The feasibility phase of this project is designed towards the development of a combined RSOCT system and the validation of such a combined imaging method for the detection of skin cancers. The specific aims are designed towards quantifiable and achievable milestones that will demonstrate the potential of such an approach towards cancer diagnosis in general and skin cancer detection in particular. Specific Aim #1: Develop and test a benchtop combined RS-OCT system: A benchtop version of the combined system will be developed on the platform of a Fourier Domain-OCT spectral radar system consisting of two sources but a single detector and sample arm. The performance of both OCT and RS will each be compared with benchmark values of existing in vivo systems. Specific Aim #2: Develop an RSOCT handheld probe for in vivo application: In order to test the utility of such a multi-modal system in vivo, a handheld probe will be developed and the entire system made portable to allow for flexibility of measurements from hard to reach lesion sites. The performance of both OCT and RS will each be compared with benchmark values of the benchtop system. Specific Aim #3: Conduct a pilot study on 30 patients with suspected basal cell carcinomas (BCCs) to demonstrate the utility RS-OCT: A small pilot study will evaluate the validity of the combined device in clinical practice where lesions suspected of BCCs will be assessed with RS alone, OCT alone, and combined RS-OCT. The ability of RS to discriminate between normal benign and malignant lesions will be compared with OCT guided RS. The specific aims described above will demonstrate the potential of RSOCT for the diagnosis and possible screening of skin cancers. The proposed work will have a significant impact on health care by providing the potential for complete disease management with a single detection tool. This would result in improved patient care and cost-effectiveness. With the success of this technique, RSOCT can be applied to other organ sites such as the breast, prostate and ovary as well as other diseases thus impacting a broader field in medicine.

描述(申请人提供)：皮肤癌的发病率近年来呈上升趋势，与大多数癌症一样，早期诊断和彻底治疗(即完全切除)是获得良好预后的关键。目前皮肤癌的诊断方法依赖于体检和皮肤活检，这些方法在早期诊断中的准确性有限。因此，人们对开发一种非侵入性的诊断和筛查工具非常感兴趣，这种工具可以在皮肤癌的早期阶段准确地识别。这样的工具不仅可以发现早期的恶性肿瘤迹象，还可以减少不必要的诊断性外科手术，通过准确描绘手术前和手术中的皮肤癌边缘，促进皮肤癌的完全切除，并允许监测接受治疗的患者是否复发。在这项建议中，我们提出了一种结合光学相干层析成像(OCT)和拉曼光谱技术的方法，光学相干断层成像(OCT)是一种可视化组织微结构的成像技术，拉曼光谱技术是一种在单个便携式仪器中提供组织生化图谱的光谱技术，用于有效检测皮肤损伤。这种组合技术的实时非侵入性特性可以实现一种“即看即治”方案，该方案将减少返回诊所的次数和患者的焦虑，因为将消除等待组织病理学诊断的漫长等待。因此，这项技术有可能增加对那些可能无法获得筛查后续行动的服务不足人群的接触。这项技术对患者没有已知的风险，因此可能是目前筛查方法的安全替代方案。 公共卫生相关性：皮肤癌的发病率近年来一直在上升，与大多数癌症一样，早期诊断和彻底治疗(即完全切除)是获得良好预后的关键。目前皮肤癌的诊断方法依赖于体检和皮肤活检，这些方法对早期诊断的准确性有限。因此，人们对开发一种非侵入性的诊断和筛查工具非常感兴趣，这种工具可以在皮肤癌的早期阶段准确地识别。这样的工具不仅可以发现早期的恶性肿瘤迹象，还可以减少不必要的诊断性外科手术，通过准确描绘手术前和手术中的皮肤癌边缘，促进皮肤癌的完全切除，并允许监测接受治疗的患者是否复发。最初的报告已经确定了非侵入性光学设备的实际局限性，使用成像或光谱学来评估正常皮肤、良性病变和恶性肿瘤的不同临床表现。在这项建议中，我们描述了一种专门针对皮肤潜在微结构和生化成分的彻底非侵入性分析的设备的设计。皮肤癌和皮肤癌的变异性带来的挑战为拟议的多模式设备提供了理想的测试器官和病理学。R21建议试图验证这样一种假设，即将形态成像与光学相干断层扫描(OCT)和生化评估与拉曼光谱(RS)相结合的设备增加了医生可用的诊断信息，并且可以单独提高每种技术的诊断性能。该项目的可行性阶段旨在开发一种综合的RSOCT系统，并验证这种用于皮肤癌检测的综合成像方法。具体目标旨在实现可量化和可实现的里程碑，这些里程碑将证明这种方法在一般癌症诊断，特别是皮肤癌检测方面的潜力。具体目标#1：开发和测试台式RS-OCT组合系统：将在傅立叶域-OCT光谱雷达系统平台上开发组合系统的台式版本，该系统由两个源组成，但只有一个探测器和样品臂。OCT和RS的性能将分别与现有活体系统的基准值进行比较。具体目标#2：开发一种用于活体应用的RSOCT手持式探头：为了测试这种多模式系统在体内的实用性，将开发一种手持式探头，并使整个系统变得便携，以便从难以到达的病变部位进行灵活的测量。OCT和RS的性能将分别与台式系统的基准值进行比较。具体目标#3：对30名疑似基底细胞癌(BCC)患者进行一项先导性研究，以证明RS-OCT的有效性：一项小型先导性研究将评估联合设备在临床实践中的有效性，其中疑似BCC的病变将单独使用RS、OCT和联合RS-OCT进行评估。与OCT引导下的RS相比，RS对正常、良、恶性病变的鉴别能力更强。以上描述的具体目的将展示RSOCT在皮肤癌诊断和可能的筛查中的潜力。拟议的工作将对卫生保健产生重大影响，因为它提供了利用单一检测工具进行全面疾病管理的可能性。这将带来更好的病人护理和成本效益。随着这项技术的成功，RSOCT可以应用于其他器官部位，如乳房、前列腺和卵巢以及其他疾病，从而影响到更广泛的医学领域。