A Novel Deep Raman Spectroscopy Platform for Non-Invasive In-Vivo Diagnosis of Breast Cancer

用于乳腺癌非侵入性体内诊断的新型深度拉曼光谱平台

• 批准号: EP/P012442/1
• 负责人: Nicholas Stone
• 金额: $ 152.78万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FP012442%2F1
• 关键词: Novel; Deep; Raman; Spectroscopy; Platform

Recently, we have pioneered a portfolio of revolutionary optical technologies in the area of laser spectroscopy, namely deep Raman spectroscopy, for non-invasive molecular probing of biological tissue. The developments have the potential of making a step-change in many fields of medicine including cancer diagnosis. The techniques comprise spatially offset Raman spectroscopy (SORS) and Transmission Raman (both patented by the applicants). The methods are described in detail in a tutorial review: http://pubs.rsc.org/en/content/articlelanding/2016/cs/c5cs00466g. There is an urgent clinical need for early objective diagnosis and prediction of likely treatment outcomes for many types of subsurface cancers. This is not addressed by existing technologies. There are numerous steps along the cancer clinical pathway where real-time, in vivo, molecular specific disease analysis would have a major impact. This would significantly reduce needle biopsy, in around 80% of those recalled following mammographic screening this step is unnecessarily - ie leading to the diagnosis of benign lesions. Our novel approach would allow for more accurate and immediate diagnosis in conjunction with mammography at first presentation by improving screening or surveillance techniques, leading to earlier diagnosis and better treatment outcomes. Secondly it would allow surgical margin assessment and treatment monitoring in real-time and thirdly identification of metastatic invasion in the lymphatic system during routine surgery. There are numerous other areas where a rapid molecular analysis of a tissue sample in the clinic or theatre environment would allow improved clinical decision-making, for example when pre- operatively staging the disease and particularly when non-invasively monitoring tumour response during chemo/radiotherapy. Clearly these approaches would be beneficial to the patient by reducing cancer recurrence rates; but also by minimising the numbers of invasive procedures required, thus reducing costs and patient anxiety.Raman spectroscopy is a highly molecular-specific method, which itself has proven to be a useful tool in early epithelial cancer diagnostics, although in its conventional form it has been restricted to sampling the tissue surface of much less than 1 mm deep. The new technology unlocks unique access to tissue abnormalities of up to several cm's deep, i.e. at depths one to two orders of magnitude higher than those previously possible with Raman.Following on from our previous project, where we were able to demonstrate conceptually a ~100x improvement in signal recovery compared to our early feasibility work, we are now able to rapidly develop a platform for real-clinical tools using this approach. We propose to make major breakthroughs in this area and advance diagnostics particularly focussed on breast cancer and lymph node metastasis initially as focused case studies and then potentially applied to prostate cancers (outside the scope of this proposal). This will be explored as a joint cross-disciplinary research venture between Profs Stone and Matousek, the two key researchers in this area. We now seek funding to progress this work in a timely manner by developing a novel medical diagnostic platform of major societal impact. We propose to bring together key players from multidisciplinary areas covering physical sciences, spectroscopy, radiology, cancer diagnostic and therapeutic surgery, and histopathology to exploit all of the relevant skills and develop a critical mass of expertise to tackle these challenging issues.

最近，我们在激光光谱领域开创了一系列革命性的光学技术，即深度拉曼光谱，用于生物组织的非侵入性分子探测。这些进展有可能使包括癌症诊断在内的许多医学领域发生重大变化。这些技术包括空间偏移拉曼光谱（SORS）和透射拉曼（均由申请人申请专利）。这些方法在教程评论中有详细描述：http://pubs.rsc.org/en/content/articlelanding/2016/cs/c5cs00466g。临床迫切需要对多种类型的皮下癌症进行早期客观诊断和预测可能的治疗结果。现有技术无法解决这个问题。癌症临床路径中有许多步骤，实时体内分子特异性疾病分析将产生重大影响。这将显着减少针吸活检，在乳房X线照相筛查后回忆的大约80%的人中，这一步骤是不必要的——即导致良性病变的诊断。我们的新方法将通过改进筛查或监测技术，在首次就诊时结合乳房X光检查进行更准确、更即时的诊断，从而实现更早的诊断和更好的治疗结果。其次，它可以实时评估手术切缘和治疗监测，第三，在常规手术过程中识别淋巴系统的转移侵袭。在许多其他领域，在诊所或手术室环境中对组织样本进行快速分子分析将有助于改善临床决策，例如在术前对疾病进行分期时，特别是在化疗/放疗期间非侵入性监测肿瘤反应时。显然，这些方法将通过降低癌症复发率而对患者有益。拉曼光谱是一种高度分子特异性的方法，其本身已被证明是早期上皮癌诊断的有用工具，尽管其传统形式仅限于对深度小于 1 毫米的组织表面进行采样。这项新技术解锁了对深达几厘米的组织异常的独特途径，即深度比以前使用拉曼可能实现的深度高一到两个数量级。在我们之前的项目中，我们能够从概念上证明与我们早期的可行性工作相比信号恢复有约 100 倍的改进，我们现在能够使用这种方法快速开发一个用于实际临床工具的平台。我们建议在这一领域取得重大突破，并推进诊断，特别是针对乳腺癌和淋巴结转移，最初作为重点案例研究，然后可能应用于前列腺癌（超出本提案的范围）。该领域的两位主要研究人员 Stone 教授和 Matousek 教授将作为跨学科联合研究项目对此进行探索。我们现在寻求资金，通过开发具有重大社会影响的新型医疗诊断平台来及时推进这项工作。我们建议将来自物理科学、光谱学、放射学、癌症诊断和治疗手术以及组织病理学等多学科领域的关键参与者聚集在一起，利用所有相关技能并发展大量的专业知识来解决这些具有挑战性的问题。

项目成果

Noninvasive Determination of Depth in Transmission Raman Spectroscopy in Turbid Media Based on Sample Differential Transmittance

• DOI: 10.1021/acs.analchem.7b01469
• 发表时间: 2017-09-19
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Gardner, Benjamin;Stone, Nicholas;Matousek, Pavel
• 通讯作者: Matousek, Pavel

Guided principal component analysis (GPCA): a simple method for improving detection of a known analyte

引导主成分分析 (GPCA)：一种改进已知分析物检测的简单方法

• DOI: 10.1039/d3an00820g
• 发表时间: 2023
• 期刊: The Analyst
• 作者: Gardner B

Sensitivity of Transmission Raman Spectroscopy Signals to Temperature of Biological Tissues.

• DOI: 10.1038/s41598-018-25465-x
• 发表时间: 2018-05-30
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ghita A;Matousek P;Stone N
• 通讯作者: Stone N

Noninvasive simultaneous monitoring of pH and depth using surface-enhanced deep Raman spectroscopy

• DOI: 10.1002/jrs.5875
• 发表时间: 2020-03-20
• 期刊: JOURNAL OF RAMAN SPECTROSCOPY
• 影响因子: 2.5
• 作者: Gardner, Benjamin;Stone, Nicholas;Matousek, Pavel
• 通讯作者: Matousek, Pavel