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

通过基于 X 射线的新型成像方法改善食管干预的结果

• 批准号: EP/P023231/1
• 负责人: Alessandro Olivo
• 金额: $ 120.86万
• 依托单位: University College London
• 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%2FP023231%2F1
• 关键词: Improving; outcomes; oesophageal; interventions; through

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.

食管癌已被CRUK和其他机构确定为“未满足需求的癌症”;几十年来生存率没有显着提高。在英格兰和威尔士，10年或更长时间的失业率仅为12%。在监测/分期/治疗的所有阶段（以下称为“流程”1-3）都可以发现陷阱。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。本项目的目标是通过开发新型影像学工具，在室内分析中有效指导治疗，从而提高食管癌患者的预期寿命和生存率。流1是指在内窥镜下收集的活检标本，将其送至组织病理学实验室，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，导致治疗计划的延迟，在此期间，癌前病变可能发展为癌症。当它们被收集时的真实的时间分析将允许立即的室内治疗，显著地改进患者管理。流2指的是内窥镜粘膜切除术（EMR），其可能是完全治愈早期癌症的足够治疗。关键的问题是是否整个肿瘤已经被切除，或者肿瘤是否已经深入到食管壁。这将改变治疗途径。实时分析将允许在需要时立即重复EMR，最大限度地减少以后必须返回的患者数量（这使得重复EMR更难执行）;它还将减少需要大手术切除整个食管（食管切除术）的患者数量。流3指的是食管切除术，用于局部晚期癌症患者，这些癌症尚未扩散到可以手术切除的局部区域。成功取决于获得清晰的边缘：为此，通过一个可能需要一个多小时的程序收集和分析冷冻切片，而我们的技术将在真实的时间内揭示这一点。另一个需要是识别周围淋巴结的数量、位置和浸润状态。有时收集的淋巴结数量不足，直到后来才被发现-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射线相位衬度成像（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射线不可见的特征，特别是软生物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管壁的层，这与该项目非常相关。我们还证明了XPCI可以在几分钟内进行全3D（“计算机断层扫描”）扫描，并在使用传统X射线源时达到1微米的分辨率。我们相信，XPCI的目标实现可以满足所有上述流的实时分析需求（尽管可能通过两种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，临床医生和工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设计和构建成像系统;该系统将用于对所有流中的足够数量的标本进行成像，以便得出有关临床受益的重要结论。工业家将监督这一过程，以确保与工业流程和法规合规性的兼容性，并最终将研究纳入临床开发。

项目成果

The transition from refraction to ultra-small-angle x-ray scattering (USAXS) in a laboratory phase-based x-ray microscope for soft tissue imaging

用于软组织成像的实验室相基 X 射线显微镜从折射到超小角度 X 射线散射 (USAXS) 的转变

• DOI: 10.1063/5.0169649
• 发表时间: 2023
• 作者: Esposito M

P239 X-ray phase contrast imaging for staging oesophageal tumours: preliminary results from the VIOLIN study

P239 用于食管肿瘤分期的 X 射线相差成像：VIOLIN 研究的初步结果

• DOI: 10.1136/gutjnl-2020-bsgcampus.313
• 发表时间: 2021
• 作者: Wolfson P

Freestanding high-aspect-ratio gold masks for low-energy, phase-based x-ray microscopy.

• DOI: 10.1088/1361-6528/ac9b5f
• 发表时间: 2022-11-07
• 期刊: Nanotechnology
• 影响因子: 3.5

Monochromatic Propagation-Based Phase-Contrast Microscale Computed-Tomography System with a Rotating-Anode Source

• DOI: 10.1103/physrevapplied.11.034004
• 发表时间: 2019-03-04
• 期刊: PHYSICAL REVIEW APPLIED
• 影响因子: 4.6
• 作者: Brombal, L.;Kallon, G.;Endrizzi, M.
• 通讯作者: Endrizzi, M.

Laboratory-based x-ray dark-field microscopy

基于实验室的 X 射线暗视野显微镜

• DOI: 10.1103/physrevapplied.20.064039
• 发表时间: 2023
• 期刊: Physical Review Applied
• 影响因子: 4.6
• 作者: Esposito M