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: 7533592
• 负责人: Anita Mahadevan-Jansen
• 金额: $ 22.11万
• 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 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7533592
• 关键词: Anxiety; Appearance; Area; Basal cell carcinoma; Benchmarking; Benign; Biochemical; Biopsy; Breast; Cancer Detection; Cancerous; Caring; Cervix Uteri; Characteristics; Class; Clinic Visits; Clinical; Clinical assessments; Collection; Confocal Microscopy; Data; Data Set; Dermatologist; Dermoscopy; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Differential Diagnosis; Diffuse; Disabled Persons; Discrimination; Disease; Disease Management; Distal; Early Diagnosis; Enrollment; Ensure; Epithelial; Evaluation; Excision; Face; Fluorescence; Foundations; Future; Gastrointestinal tract structure; Goals; Gold; Healthcare; Histologic; Histology; Histopathology; Image; Imaging Techniques; Imiquimod; In Vitro; Incidence; Individual; Invasive; Lasers; Lesion; Localized Lesion; Location; Malignant - descriptor; Malignant Neoplasms; Maps; Measurement; Measures; Medicine; Methods; Microscopic; Modality; Molecular; Monitor; Monitoring for Recurrence; Nature; Noise; Non-Malignant; Numbers; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Organ; Output; Ovary; Pathology; Patient Care; Patients; Performance; Phase; Physical Examination; Physicians; Pigments; Pilot Projects; Pliability; Probability; Process; Prostate; Protocols documentation; Public Health; Radar; Raman Spectrum Analysis; Rate; Recurrence; Reporting; Research; Resolution; Risk; Sampling; Sampling Errors; Scanning; Score; Screening for Skin Cancer; Screening procedure; Signal Transduction; Site; Skin; Skin Cancer; Source; Specificity; Spectrum Analysis; Speed; Staging; Standards of Weights and Measures; Surface; System; Techniques; Technology; Testing; Thick; Time; Tissue Sample; Tissues; Translating; Underserved Population; Upper arm; Validation; Visible Radiation; Visual; Work; base; cancer diagnosis; clinical Diagnosis; clinically relevant; cost effectiveness; data acquisition; design; detector; diagnosis standard; follow-up; improved; in vivo; innovation; instrument; interest; miniaturize; novel; optical imaging; outcome forecast; spectroscopic imaging; success; tomography; tool; tumor

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（由申请人提供）：近年来皮肤癌的发病率一直在上升，并且与大多数癌症一样，早期诊断和彻底治疗（即，完整切除）是获得良好预后的关键。目前皮肤癌的诊断方法依赖于结合皮肤活检的体格检查，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诊断和筛查工具非常感兴趣，这种工具可以在早期准确识别皮肤癌。这种工具不仅可以检测恶性肿瘤的早期迹象，还可以减少不必要的诊断性外科手术，通过在手术前和手术期间准确描绘皮肤癌边缘来促进皮肤癌的完全切除，并允许监测治疗患者的复发。在这个建议中，我们提出了一种方法，结合光学相干断层扫描（OCT），一种成像技术，可视化组织的微观结构，与拉曼光谱，光谱技术，提供了一个组织的生物化学地图在一个单一的便携式仪器，有效地检测皮肤病变。这种组合技术的实时非侵入性性质可以实现“看和治疗”协议，这将减少复诊次数和患者焦虑，因为组织病理学诊断的长时间等待将被消除。因此，该技术有可能增加对服务不足的人群的访问，这些人群可能无法进行筛查。该技术对患者没有已知的风险，因此可能是当前筛查方法的安全替代方案。 公共卫生相关性：近年来，皮肤癌的发病率一直在上升，与大多数癌症一样，早期诊断和彻底治疗（即，完整切除）是获得良好预后的关键。目前皮肤癌的诊断方法依赖于结合皮肤活检的体格检查，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皮肤癌。这种工具不仅可以检测恶性肿瘤的早期迹象，还可以减少不必要的诊断性外科手术，通过在手术前和手术期间准确描绘皮肤癌边缘来促进皮肤癌的完全切除，并允许监测治疗患者的复发。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。在这个提议中，我们描述了一种设备的设计，该设备专门面向对皮肤的底层微观结构和生化成分进行彻底的非侵入性分析。皮肤和皮肤癌的变异性所带来的挑战为所提出的多模态器械提供了理想的测试器官和病理学。本R21提案旨在验证以下假设：将形态成像与光学相干断层扫描（OCT）和生化评价与拉曼光谱（RS）相结合的器械可增加医生可用的诊断信息，并可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个综合RSOCT系统，并验证这种综合成像方法用于检测皮肤癌。具体目标旨在实现可量化和可实现的里程碑，这些里程碑将展示这种方法在癌症诊断特别是皮肤癌检测方面的潜力。具体目标1：开发和测试台式组合RS-OCT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体内系统的基准值进行比较。具体目标#2：开发用于体内应用的RSOCT手持式探头：为了测试这种多模式系统在体内的效用，将开发手持式探头，并使整个系统便携，以允许从难以到达的病变部位进行测量的灵活性。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例疑似基底细胞癌（BCC）患者进行初步研究，以证明RS-OCT的实用性：一项小型初步研究将评价组合器械在临床实践中的有效性，其中将单独使用RS、单独使用OCT和组合RS-OCT评估疑似BCC的病变。将比较RS与OCT引导的RS区分正常良性和恶性病变的能力。上述具体目标将证明RSOCT在诊断和可能筛查皮肤癌方面的潜力。拟议的工作将对卫生保健产生重大影响，通过单一检测工具提供全面疾病管理的潜力。这将改善患者护理和成本效益。随着这项技术的成功，RSOCT可以应用于其他器官部位，如乳腺，前列腺和卵巢以及其他疾病，从而影响更广泛的医学领域。