Quantitative OCT-Raman spectral imaging for intra-operative detection of positive margins in breast conserving surgery

乳腺癌是女性中最常见的癌症，英国每年有5.5万名新患者被确诊。保乳手术是最广泛使用的切除癌症的手术。手术的目的是用尽可能小的疤痕切除整个癌症。为了将癌症复发的风险降至最低，外科医生切除了癌症，包括一块看起来正常的组织边缘。然而，在手术时，通常很难知道应该切除多少正常组织。太大的边际会增加对附近组织的损害风险，并导致更大的疤痕。削减太小的利润率可能会留下一些癌细胞，这会增加癌症重新生长的风险。在手术过程中，外科医生在肿瘤结束的地方工具有限，主要依靠他们的手指来判断应该切除多少组织。为了确认整个癌症是否被成功切除，切除的组织被转移到组织学实验室，在那里将其切成薄片，用一些特殊的模具染色，然后由专业的组织病理学专家在显微镜下观察。然而，这需要很长的时间(几天到一周)，因此不能在手术期间完成。如果组织病理学发现切除组织表面的癌细胞(阳性边缘)，患者将被重新安排进行另一次手术。目前，在英国，每五名接受保乳手术的患者中就有一人(每年约一万人)需要再次手术；这一数字与欧洲和美国的其他国家相似。如果外科医生能够在患者在手术室时检查整个癌症是否已经切除，乳腺癌手术的结果将显著改善，二次手术的需要将减少。在过去的十年里，我们的团队开发了一种新的成像技术，可以区分健康的乳房组织和癌症。这项技术被称为拉曼光谱，它测量乳房组织的分子特性，并检测与癌症有关的变化。通过将拉曼光谱与光学相干断层扫描技术相结合，我们计划开发一种新的仪器，可以扫描整个乳房组织样本的表面，并建立图像，甚至可以识别外科医生通常感觉不到的微小肿瘤区域。光学相干断层扫描技术可以快速扫描整个边缘并识别高危区域。因此，这种新的仪器对外科医生来说可能是一个非常有用的工具，因为他们可以分析手术过程中切割的乳房组织，而患者仍然在手术室的麻醉下。如果检测到任何癌细胞，他们可以当场移除额外的组织，并重复这一过程，直到整个癌症消失。在这个项目中，我们希望在我们长达十年的研究基础上，开发一种可供外科医生在手术室使用的第一代器械。为了实现这一目标，我们组建了一支由光学、显微镜和高级数据处理方面的专家、乳腺癌外科医生和患者组成的团队，以设计一种可以集成到手术室并随后在整个NHS采用的具有成本效益的仪器。如果成功，这项新技术将有助于在一次手术中最大限度地增加彻底切除癌症的机会，从而改变乳腺癌手术的方方面面。我们知道，额外的手术会给患者带来巨大的情绪压力，往往会导致较差的美容效果，延误其他治疗，需要患者更长的恢复时间，并增加NHS的成本。

Breast cancer is the most common cancer among women, with 55,000 new patients diagnosed each year in the UK. Breast conserving surgery is the most widely used procedure for cutting the cancer out. Surgery aims to remove the entire cancer with the smallest scar possible. To minimise the risks of the cancer returning, the surgeon cuts the cancer out including a margin of normal-looking tissue. However, at the time of surgery it is often difficult to know how much normal tissue to remove. Too wide a margin increases the risk of damage to nearby tissue and leads to a larger scar. Cutting too narrow margins may leave some cancer cells behind, which increases the risk of the cancer to re-grow. During the operation, surgeons have limited tools where the tumour ends, and mainly rely on their fingers to judge how much tissue to cut out. To confirm whether the whole cancer was cut out successfully, the removed tissue is transferred to the histology laboratory where it is cut into thin sections, stained with some special dies, and then observed under a microscope by a specialist histopathologist. However, this take long time (several days to one week) and therefore cannot be done during the surgery. If histopathology identifies cancer cells at the surface of the cut out tissue (positive margins), the patient is rescheduled for another surgery. Currently, one in five patients (~10,000 per year) undergoing breast conserving surgery in England needs a re-operation; this number is similar to other countries in Europe and the USA.The outcome of breast cancer surgery could be significantly improved, and the need of second operation reduced, if surgeons were able to check while the patients is in the operating room whether the entire cancer is out or not. In the last decade our team has developed a new imaging technique that can discriminate between healthy breast tissue and cancer. This technique, called Raman spectroscopy, measures molecular properties of breast tissue and detects changes related to cancer. By combining Raman spectroscopy with optical coherence tomography, a technique that can scan quickly the whole margins and identify high risk areas, we plan to develop a new instrument that could scan the surface of whole breast tissue specimen and build images that can identify even small regions of tumour, that often may not be felt by surgeons. Thus, this new instrument could be a very useful tool for surgeons as they could analyse the breast tissue cut during the surgery, while the patient is still under anaesthesia in the operating room. If any cancer cells are detected, they could on the spot remove additional tissue, and repeat this procedure until the whole cancer is out. In this project we want to build on our decade-long research and develop a first-generation instrument that can be used by surgeons in the operating room. To achieve this, we have assembled a team of scientists specialists in optics, microscopy and advance data processing, breast cancer surgeons and patients, to design a cost effective instrument that can be integrated in the operating room and then be adopted across the NHS. If successful, the new technology could lead to a step-change in breast cancer surgery by helping to maximise the chances for complete cancer removal in a single operation. We know that additional surgery causes huge emotional stress to patients, often leads to poorer cosmetic outcome, delays other treatment, require longer recovery times for patients, and increases costs to the NHS.