Wavefront Corrected Multimodal Optical Coherence and Two-Photon Microscopy for Ra

Ra 的波前校正多模态光学相干和双光子显微镜

• 批准号: 8255740
• 负责人: Yuankai Kenny Tao
• 金额: $ 4.84万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2014-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8255740
• 关键词: Algorithms; Biological Markers; Blinded; Breast; Breast Cancer Detection; Breast-Conserving Surgery; Cancer Detection; Cancer Etiology; Cessation of life; Clinical; Collaborations; Collagen; Comb animal structure; Confocal Microscopy; Contrast Media; Cytokeratin; Detection; Development; Doctor of Medicine; Ductal Carcinoma; Evaluation; Excision; Feedback; Financial compensation; Fluorescence; Freezing; Frozen Sections; Gene Amplification; Histological Techniques; Histology; Histopathology; Hormone Receptor; Human; Image; Imaging Device; Immunohistochemistry; Interferometry; Israel; Laboratories; Lasers; Light; Light Microscope; Lobular Carcinoma; Lymph Node Dissections; Mammary Gland Parenchyma; Mammary Neoplasms; Mastectomy; Measurement; Measures; Medical center; Methods; Microscope; Microscopy; Modality; Molecular; Morbidity - disease rate; Multimodal Imaging; Nuclear; Operative Surgical Procedures; Optical Biopsy; Optical Coherence Tomography; Optics; Paraffin Embedding; Pathology; Patients; Penetration; Performance; Physiologic pulse; Platelet Factor 4; Postoperative Period; Process; Property; Radiation; Receptor Gene; Recurrence; Relative (related person); Repeat Surgery; Resolution; Sampling; Sensitivity and Specificity; Sentinel Lymph Node; Shapes; Signal Transduction; Source; Specificity; Specimen; Speed; Surgical margins; Survival Rate; System; Time; Tissue Sample; Tissues; Translating; Woman; base; cancer diagnosis; cancer surgery; clinical practice; design; fluorescence microscope; imaging modality; improved; in vivo; infiltrating duct carcinoma; light scattering; lobular breast carcinoma in situ; malignant breast neoplasm; medical schools; mortality; new technology; novel; optical imaging; tool; tumor; two-photon

DESCRIPTION (provided by applicant): Breast cancer is the second leading cause of cancer-related death and second most frequently diagnosed cancer in women in the United States1. Breast conserving surgery with radiation has emerged as the preferred method for treating breast cancer while preserving breast tissue and without compromising survival rates. Local recurrence following partial mastectomy is strongly correlated to the surgical margin2-4, but despite evaluation using a combination of intraoperative examination and post-operative histopathology, 40% of patients require surgical re-excision as a result of positive or close margins5, 6. Two-photon microscopy (TPM) has demonstrated significant resolution, molecular specificity, and light efficiency advantages over conventional white-light and fluorescence microscopes for imaging endogenous and exogenous contrast both in vivo and ex vivo7-9. However, scattering tissue severely degrades two-photon signals and resolution, limiting the fundamental imaging depth of TPM to ~100 <m10-13. Optical coherence tomography (OCT) is a method of utilizing low-coherence interferometry to detect the scattering properties of tissue down to penetration depths of ~1-2 mm14. The high detection sensitivity and coherence-gating of out-of-focus light of OCT has also been shown to enhance optical sectioning through highly scattering media when used in conjunction with confocal microscopy (optical coherence microscopy, OCM)15. OCM has recently demonstrated the capacity for optical biopsy by providing cellular-resolution images of freshly-excised bulk breast pathology specimens16. The current proposal emphasizes the development of a wavefront corrected multimodal OCM-TPM system to rapidly assess breast tumor margins. OCM-TPM will combine the advantages of complimentary contrast, depth penetration, and molecular-sensitivity of the respective modalities. A novel 10 fs pulsed laser source will be used to enhance two-photon fluorescence and allow for exquisite axial sectioning resolution using OCM. Further, the scattering wavefront will be compensated by using adaptive correction and feedback algorithms to improve the signal intensity and resolution of both OCM and TPM in scattering tissue. Concurrently, we propose to identify optimal intrinsic and extrinsic biomarkers and surrogates for optical evaluation of breast tumor margins, including nuclear size and shape and collagen orientation, as well as exogenous contrast sensitive to cytokeratins, hormone receptors, and gene amplification. The utility of OCM-TPM, relative to standard immunohistochemistry, will be assessed in a clinical setting to characterize cancer detection sensitivity and specificity. The proposed multimodal non-destructive optical imaging tool will allow for rapid intraoperative assessment of surgical margins as a means of reducing the morbidity and mortality associated with breast cancer.

描述（由申请人提供）：乳腺癌是与癌症相关死亡的第二大主要原因，在美国女性中被诊断出第二次最常见的癌症。用辐射保存乳房保存手术已成为治疗乳腺癌的首选方法，同时保存乳房组织并且没有损害存活率。部分乳房切除术后的局部复发与手术边缘2-4密切相关，但是尽管使用了术中检查和术后组织病理学的组合进行了评估，但40％的患者需要手术重新诊断，这是由于阳性或近距离的效果（6。白光和荧光显微镜，用于成像内源性和外源性对比度的体内和Ex Vivo7-9。但是，散射组织严重降解了两光子信号和分辨率，将TPM的基本成像深度限制在〜100 <m10-13。光学相干断层扫描（OCT）是一种利用低碳干涉法检测组织的散射特性至〜1-2 mm14的散射特性。当与共聚焦显微镜（光学相干显微镜，OCM）结合使用时，OCT偏心光的高检测灵敏度和相干门控可通过高度散射培养基增强光学切片。 OCM最近通过提供了新鲜研究的大量乳房病理标本16的细胞分辨率图像，证明了光学活检的能力。当前的建议强调了波前校正的多模式OCM-TPM系统的发展，以快速评估乳腺肿瘤的边缘。 OCM-TPM将结合相应方式的免费对比度，深度穿透和分子敏感性的优势。新型的10 FS脉冲激光源将用于增强两光子荧光，并允许使用OCM进行精美的轴向截面分辨率。此外，通过使用自适应校正和反馈算法来改善OCM和TPM在散射组织中的信号强度和分辨率来补偿散射波前。同时，我们建议确定最佳的内在和外在生物标志物和替代物，以对乳腺肿瘤边缘进行光学评估，包括核大小，形状和胶原蛋白方向，以及对细胞角蛋白，激素受体和基因扩增的外源性对比度。 OCM-TPM相对于标准免疫组织化学的实用性将在临床环境中进行评估，以表征癌症检测敏感性和特异性。提出的多模式非破坏性光学成像工具将允许对手术边缘进行快速术中评估，以减少与乳腺癌相关的发病率和死亡率。