Improving the outcomes of oesophageal interventions through novel x-ray based imaging methods

食管癌已被CRUK和其他机构确定为“未满足需求的癌症”；几十年来，存活率并没有显著提高。在英格兰和威尔士，这一比例在10年或更长时间内只有12%。在监测/分期/治疗的所有阶段（以下称为“流程”1-3）都可以发现缺陷。我们相信，具有显微分辨率的高灵敏度室内实时成像可以解决所有流中的缺陷，从而改善治疗效果。我们项目的目标是通过开发新的室内分析成像工具来提高食管癌患者的预期寿命和生存率，从而有效地指导治疗。流1是指在内窥镜下收集的活检，这些活检被送到组织病理学实验室，使用100年来没有改变的组织染色方法进行专家评估。周转时间长达一个月，导致治疗计划的延误，在此期间癌前病变可能发展成癌症。实时分析，因为他们收集将允许即时的室内治疗，显著改善患者管理。流2是指内镜下粘膜切除术（EMRs），这可能是完全治愈早期癌症的充分治疗方法。关键的问题是整个肿瘤是否已经被切除，或者肿瘤是否已经深入到食道壁。这将改变治疗途径。如果需要，实时分析将允许立即重复电子病历，最大限度地减少以后必须返回的患者数量（这使得重复电子病历更难执行）；它还将减少需要进行大手术切除整个食道（食道切除术）的患者数量。流3是指食道切除术，是指局部晚期癌症尚未扩散到局部以外，可以手术切除的患者。成功与否取决于获得明确的界限：为此，冷冻切片的收集和分析过程可能需要一个多小时，而我们的技术会实时显示这一点。另一个需要是确定周围淋巴结的数量、位置和浸润状态。有时收集到的淋巴结数量不足，直到后来才发现，这再次影响了治疗途径（例如，手术后需要化疗）。我们的团队开发了一种新的x射线成像方法，称为x射线相衬成像（XPCI）。它使用不同的物理原理（折射和干涉）来产生图像对比度，而不是x射线衰减，这是自伦琴以来存在的每个系统都在使用的。由于这一点，XPCI可以揭示传统x射线无法看到的特征，特别是软组织中微弱的结构变化。我们已经证明，与传统x射线不同，XPCI具有足够的灵敏度来区分食道壁的层数，这与本项目非常相关。我们还证明了XPCI可以在几分钟内完成全3D（“计算机断层扫描”）扫描，并且在使用传统x射线源时达到1微米的分辨率。我们相信，有针对性的XPCI实现可以满足所有上述流的实时分析需求（尽管可能需要两个具有不同视场和分辨率的独立仪器），我们已经组建了一个由工程师、物理学家、临床医生和实业家组成的团队来解决这个问题。工程师和物理学家将使用临床医生的输入来设计和构建成像系统；该系统将用于对来自所有溪流的足够数量的标本进行成像，从而得出关于临床益处的重要结论。实业家将监督这一过程，以确保与工业流程和法规遵从性的兼容性，并最终使研究进入临床利用。

Oesophageal cancer has been identified by CRUK and other institutions as a "cancer of unmet need"; survival rates have not improved significantly for decades. In England and Wales, these are of only 12% for 10 or more years. Pitfalls can be identified at all stages of surveillance/staging/treatment (referred to in the following as "streams" 1-3). We believe that highly sensitive, in-room, real-time imaging with microscopic resolution could address pitfalls in all streams, consequently improving treatment outcomes. The objective of our project is to increase life expectancy and survival rates of patients with oesophageal cancer by developing novel imaging tools for in-room analysis that can guide treatment effectively.Stream 1 refers to biopsies collected at endoscopy, which are sent to the histopathology lab for expert evaluation using a tissue staining method that has not changed for 100 years. The turnaround time is up to one month, leading to delays in scheduling therapy during which pre-cancerous lesions can develop into cancer. Real time analysis as they are collected will allow for immediate in-room therapy, significantly improving patient management.Stream 2 refers to Endoscopic Mucosal Resections (EMRs) which may be sufficient treatment for complete cure of early stage cancers. The crucial questions are whether the entire tumour has been removed, or whether the tumour has extended deep into the wall of the oesophagus. This would change the treatment pathway. Real-time analysis would allow for immediate repeat EMR if needed, minimising the number of patient having to return later (which makes repeat EMR harder to perform); it would also reduce the number of patients requiring major surgery to remove the entire oesophagus (oesophagectomy).Stream 3 refers to oseophagectomy, undergone by patients with locally advanced cancer that has not spread beyond the local area that can be removed surgically. Success depends on achieving clear margins: for this, frozen sections are collected and analysed through a procedure that can take over an hour, while our technology would reveal this in real time. Another need is identification of the number, position and infiltration state of surrounding lymph nodes. An insufficient number of lymph nodes is sometimes collected, which is not found out until later - again with implications for treatment pathways (e.g. need for chemotherapy after surgery).Our team has developed a new approach to x-ray imaging called x-ray phase contrast imaging (XPCI). It uses a different physical principle (refraction and interference) to generate image contrast, instead of x-ray attenuation which is what every system in existence has been using since Roentgen. Thanks to this, XPCI can reveal features considered invisible to conventional x-rays, notably faint structural changes in soft biological tissue. We have already proven that XPCI, unlike conventional x-rays, has sufficient sensitivity to distinguish between layers of the wall of the oesophagus, which is very relevant to this project. We have also demonstrated that XPCI can perform full 3D ("computed tomography") scans in minutes, and reach resolution of 1 micron while using conventional x-ray sources. We believe that targeted implementations of XPCI can fulfil the needs of real-time analysis for all above streams (albeit possibly through two separate instruments with different field-of-view and resolution), and we have assembled a team of engineers, physicists, clinicians and industrialists to tackle this problem. Engineers and physicist will design and build the imaging systems using input from the clinicians; the systems will be used to image a sufficient number of specimens from all streams to allow drawing significant conclusions on the clinical benefits. The industrialists will oversee the process to ensure compatibility with industrial processes and regulatory compliance, and ultimately take the research into clinical exploitation.