An integrated MRI tool to map brain microvascular and metabolic function: improving imaging diagnostics for human brain disease

绘制大脑微血管和代谢功能的集成 MRI 工具：改善人脑疾病的成像诊断

• 批准号: EP/S025901/1
• 负责人: Richard Wise
• 金额: $ 115.9万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS025901%2F1
• 关键词: integrated; MRI; tool; map; brain

Brain diseases such as tumours, head injury, epilepsy, multiple sclerosis and dementias have considerable personal, social and economic costs for the sufferers and their carers. While magnetic resonance imaging (MRI) has revolutionised the management of many brain conditions in the last 40 years, there is a need for better tools for quantifying the brain's supply of energy in terms of blood flow and vascular function and it use of energy in terms of metabolic function. For example, in the case of the most common forms of brain tumour, glioma, we lack detailed information about the heterogeneity of tissue function that could help guide better treatments such as more targeted and individualised combined radiotherapy and drug programmes. Understanding more about the tumour microenvironment will also promote the development of more effective treatments. For high-grade gliomas, particularly glioblastoma, the prognosis remains poor, highlighting an urgent clinical need.Recently, we at Cardiff University Brain Research Imaging Centre (CUBRIC), and others, have developed MRI-based tools (termed dual calibrated fMRI) to map across the human brain, with a spatial resolution of a few millimetres, the amount of oxygen that the brain is consuming (known as CMRO2) along with measures of the efficiency of blood supply. CMRO2 reflects neural activity and can be altered with disease such as tumour where there is cell proliferation and energy metabolism is changed. Knowing also the functional properties of brain blood vessels and the oxygen status of brain tissue is important for understanding whether blood supply is sufficient or the vasculature is abnormal as is often seen in tumours where vessels proliferate. Our newly developed methods have shown promise in revealing abnormalities of brain tissue energy consumption in multiple sclerosis and epilepsy. In epilepsy they may offer an alternative to the use of radiation-based PET scans in the evaluation of patients for brain surgery by identifying areas in the brain with abnormally low metabolism.However, to produce a wider clinical impact it is necessary to advance the MRI and data analysis further, such that they could then be taken forward for commercial development and routine clinical use, initially within clinical trials. Two-thirds of the proposed project will address engineering and physical science challenges to (i) speed up data acquisition to about 10 mins, a clinically feasible time, by optimising the MRI data acquisition and analysis, (ii) widen the range of tissue pathology that we can reliably measure through collection of additional MRI information and detailed biophysical modelling of tissue properties and (iii) implement efficient artificial intelligence (neural network) based data analysis that can rapidly feed the images to the clinician at the MRI scanner. The remaining one-third of the project will demonstrate the feasibility of the method and its value in application to brain tumour (glioma). We aim to show that we can map the heterogeneity of tumour tissue that can reveal the type of tumour, where it is actively growing, where it is and is not responding to treatment and where radiotherapy may be damaging healthy tissue, all helping to guide treatment decisions for maximum efficacy.Central to the success of our proposal are our partnerships with industry and the NHS. Siemens will contribute the expertise of its onsite scientist at CUBRIC for the development of the MRI technology. The Velindre Cancer Centre, South Wales' principal centre for oncology, will partner on the clinical pilot studies and help to evaluate imaging for future patient benefit. Our partners will help us to bring the methods to the point within this project, if successful, of commercial development for healthcare benefit and larger scale clinical trials to demonstrate how the methods may be used in clinical practice for diagnosis, treatment planning and monitoring.

肿瘤、头部损伤、癫痫、多发性硬化症和痴呆等脑部疾病给患者及其护理人员带来了相当大的个人、社会和经济成本。虽然磁共振成像 (MRI) 在过去 40 年里彻底改变了许多大脑疾病的管理，但仍需要更好的工具来量化大脑在血流和血管功能方面的能量供应以及在代谢功能方面的能量使用。例如，对于最常见的脑肿瘤神经胶质瘤，我们缺乏有关组织功能异质性的详细信息，这些信息可以帮助指导更好的治疗，例如更有针对性和个体化的联合放射治疗和药物方案。更多地了解肿瘤微环境也将促进更有效治疗方法的开发。对于高级别神经胶质瘤，特别是胶质母细胞瘤，预后仍然很差，这凸显了迫切的临床需求。最近，卡迪夫大学大脑研究成像中心 (CUBRIC) 和其他机构开发了基于 MRI 的工具（称为双校准 fMRI），以几毫米的空间分辨率绘制整个人脑的图谱，显示大脑消耗的氧气量（称为 CMRO2）以及 血液供应效率的衡量标准。 CMRO2 反映神经活动，并且会随着疾病（例如肿瘤）而改变，其中细胞增殖和能量代谢发生变化。了解脑血管的功能特性和脑组织的氧气状态对于了解血液供应是否充足或脉管系统是否异常（如血管增殖的肿瘤中常见）非常重要。我们新开发的方法有望揭示多发性硬化症和癫痫症的脑组织能量消耗异常。对于癫痫症，它们可以通过识别大脑中新陈代谢异常低下的区域，为评估脑部手术的患者提供基于辐射的 PET 扫描的替代方案。然而，为了产生更广泛的临床影响，有必要进一步推进 MRI 和数据分析，以便随后可以将其用于商业开发和常规临床使用（最初在临床试验中）。拟议项目的三分之二将解决工程和物理科学挑战，以（i）通过优化 MRI 数据采集和分析，将数据采集速度加快到约 10 分钟（临床上可行的时间），（ii）通过收集额外的 MRI 信息和组织特性的详细生物物理建模，扩大我们可以可靠测量的组织病理学范围，以及（iii）实施基于高效人工智能（神经网络）的数据分析，可以 通过 MRI 扫描仪将图像快速传送给临床医生。该项目剩下的三分之一将展示该方法的可行性及其在脑肿瘤（神经胶质瘤）中的应用价值。我们的目标是展示我们可以绘制肿瘤组织的异质性图谱，从而揭示肿瘤的类型、肿瘤在何处活跃生长、何处对治疗有反应和没有反应以及放射治疗可能会损害健康组织，所有这些都有助于指导治疗决策以实现最大疗效。我们提案成功的核心是我们与行业和 NHS 的合作。西门子将贡献其 CUBRIC 现场科学家的专业知识来开发 MRI 技术。南威尔士的主要肿瘤学中心 Velindre 癌症中心将合作开展临床试点研究，并帮助评估影像学以提高未来患者的利益。如果成功的话，我们的合作伙伴将帮助我们在该项目中将这些方法引入医疗保健效益的商业开发和更大规模的临床试验，以展示这些方法如何在临床实践中用于诊断、治疗计划和监测。

项目成果

Quantitative mapping of cerebral oxygen metabolism using breath-hold calibrated fMRI

• DOI: 10.1101/2021.04.08.438939
• 发表时间: 2021-04
• 期刊: bioRxiv
• 作者: M. Germuska;RC Stickland;AM Chiarelli;H. Chandler;R. Wise

Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data

• DOI: 10.1016/j.neuroimage.2023.120492
• 发表时间: 2023-12-09
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Biondetti，Emma;Chiarelli，Antonio Maria;Wise，Richard G.
• 通讯作者: Wise，Richard G.

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI.

氧气输送的流动扩散模型，用于通过单一气体校准的功能磁共振成像定量绘制脑氧代谢率 (CMRO2)。

• DOI: 10.1177/0271678x221077332
• 发表时间: 2022
• 期刊: official journal of the International Society of Cerebral Blood Flow and Metabolism
• 作者: Chiarelli AM