Technologies for 3D histologically-detailed reconstruction of individual whole hearts

个体全心脏 3D 组织学详细重建技术

• 批准号: BB/E003443/1
• 负责人: Peter Kohl
• 金额: $ 77.45万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE003443%2F1
• 关键词: Technologies; 3D; histologically; detailed; reconstruction

The heart is an electrically controlled mechanical pump, whose dysfunction is incompatible with life. Both normal and disturbed activity are closely associated with the fine architectural detail of the tissue that makes up the heart. Thus, electrical signals for contraction must first travel along every single of the millions of muscle cells in the heart, before each individual fibre will shorten at its prescribed timing. Similarly, the forces produced by individual cells are largely transmitted in the direction of muscle fibres. Furthermore, muscle fibres are ordered in complex units, joined together by non-muscle 'connective' tissue, and this arrangement allows the muscle not only to shorten, but also to thicken, in order to push blood out of the cardiac chambers and into the arteries that supply all organs of the body. A precise understanding of detailed cardiac tissue architecture would be of great importance for the diagnosis of cardiac diseases, prediction of their progression, identification of treatment strategies, and even for doctors' teaching and training (the heart is one of the organs where 'learning by mistake' is not an option!). This clinical relevance is contrasted by the fact that, traditionally at least, establishing architecture of any tissue meant 'cutting it open' (not an option either). Recent improvements in non-invasive techniques, such as Magnetic Resonance Imaging (MRI), have started to provide increasingly detailed insight into organ structure and function. Even though the detail contained in these recordings is not yet sufficient to reliably identify fibre orientation in a patient's heart, clearly the technology is moving in that direction, and it is important that we start now to develop the tools required to handle the vast amount of data that doctors will be able to extract from high resolution MRI or similar techniques. This is a major challenge. It requires a combination of skills and expertise not usually present in a single lab or clinic. These include: automated image registration, analysis, and alignment; creation of computationally usable three-dimensional (3D) data sets; comprehensive validation using histology to obtain very high resolution detail for the whole organ; establishment of a 'reference atlas' from which individual anatomies can subsequently be 'morphed'; integration of all data into computer models of the beating heart; 3D visualisation; and the subsequent application of all the above to an individual within a time-frame that makes 'clinical sense' (hours, not months). This project undertakes to develop exactly this technology, combining the expertise of leading teams in cardiac MRI (Cardiovascular Medicine at the John Radcliffe Hospital Oxford), bio-medical studies (Oxford University Department of Physiology, Anatomy & Genetics), and computing (Oxford University Computing Laboratory). These teams will jointly implement and validate the whole range of tools required to efficiently reconstruct individual beating hearts from entirely non-invasive imaging techniques, based on proof-of-principle in small rodents, taking care that all algorithms are scalable to be adapted, in future, to the significantly larger organ sizes required for clinical application. The longer-term vision is that after a clinically-indicated cardiac MRI, doctors will be able to look at a 3D holographic projection of the patient's heart, zoom-in on any relevant detail (a coronary vessel blockage or a damaged part of tissue), assess treatment modalities, predict outcomes, and / using advanced force-feedback instruments / conduct 'mock surgery' on that heart before the patient even enters the theatre. Much of this vision is still far ahead. Nonetheless, this proposal will make an important step by developing the technology to link non-invasive cardiac imaging to data extraction and integration into anatomically-detailed, functional 3D models of individual hearts.

心脏是一个电控机械泵，其功能障碍与生命格格不入。正常和紊乱的活动都与构成心脏的组织的精细结构细节密切相关。因此，用于收缩的电信号必须首先沿着心脏中数百万个肌肉细胞中的每一个传播，然后每个单独的纤维都会在规定的时间缩短。类似地，单个细胞产生的力主要沿肌肉纤维的方向传递。此外，肌肉纤维以复杂的单位排列，通过非肌肉“结缔”组织连接在一起，这种排列不仅使肌肉缩短，而且使肌肉变厚，以便将血液从心室推出并进入供应身体所有器官的动脉。准确了解详细的心脏组织结构对于心脏病的诊断、预测其进展、确定治疗策略，甚至对于医生的教学和培训都具有非常重要的意义（心脏是不能“通过错误学习”的器官之一！）。这种临床相关性与以下事实形成鲜明对比：至少在传统上，建立任何组织的结构都意味着“将其切开”（也不是一种选择）。磁共振成像 (MRI) 等非侵入性技术的最新改进已开始提供对器官结构和功能越来越详细的了解。尽管这些记录中包含的细节还不足以可靠地识别患者心脏中的纤维方向，但显然该技术正在朝这个方向发展，重要的是我们现在开始开发处理大量数据所需的工具，医生将能够从高分辨率 MRI 或类似技术中提取这些数据。这是一个重大挑战。它需要通常在单个实验室或诊所中不具备的技能和专业知识的结合。其中包括：自动图像配准、分析和对齐；创建计算上可用的三维 (3D) 数据集；使用组织学进行综合验证，以获得整个器官的高分辨率细节；建立“参考图集”，随后可以对个体解剖结构进行“变形”；将所有数据整合到跳动心脏的计算机模型中； 3D 可视化；以及随后在具有“临床意义”的时间范围内（数小时，而不是数月）将上述所有内容应用于个人。该项目致力于开发这项技术，结合了心脏 MRI（牛津约翰拉德克利夫医院心血管医学）、生物医学研究（牛津大学生理学、解剖学和遗传学系）和计算（牛津大学计算实验室）领域领先团队的专业知识。这些团队将基于小型啮齿类动物的原理验证，共同实施和验证通过完全非侵入性成像技术有效重建个体跳动心脏所需的全部工具，并注意所有算法都可以扩展，以便将来适应临床应用所需的更大的器官尺寸。长期愿景是，在进行临床指示的心脏 MRI 后，医生将能够查看患者心脏的 3D 全息投影，放大任何相关细节（冠状血管阻塞或组织受损部分），评估治疗方式，预测结果，和/使用先进的力反馈仪器/在患者进入手术室之前对该心脏进行“模拟手术”。这一愿景的大部分内容仍然遥不可及。尽管如此，该提案将通过开发将非侵入性心脏成像与数据提取联系起来并集成到个体心脏的解剖详细、功能性 3D 模型中的技术来迈出重要的一步。