Development of MRI-guided radiation therapy

放射治疗包括向肿瘤发射高能X射线束，以杀死癌细胞。对于许多癌症患者来说，放射治疗非常有效，而且经常能治愈他们的疾病。不幸的是，在治疗肿瘤时，附近的正常组织不可避免地会受到一些辐射，这与副作用有关。这些副作用可以是轻微的、暂时的，完全消失的，也可以是严重的、危及生命的、永久性的，长期影响患者的生活质量。因此，在对患者进行放射治疗时，显然需要确保治疗尽可能准确地进行，以避免对正常组织进行不必要的治疗。在大多数情况下，放射治疗的计划是使用CT扫描来显示肿瘤的位置，但这通常只在治疗开始前进行一次。辐射准确传输的主要问题之一在于，很难准确确定肿瘤的位置，因为在标准的CT扫描中很难看到肿瘤。放射治疗通常以一系列剂量(称为分次)的形式在几周内进行，肿瘤可能每天处于略有不同的位置，或者在治疗过程中缩小，这一事实使问题变得更加复杂。让事情变得更加困难的是，肿瘤经常发生在移动的组织中。例如，当患者吸气和呼气时，肺肿瘤会有相当大的移动。因此，在计划放射治疗过程时，有必要在肿瘤周围留出较大的边缘，以确保辐射束不会偏离目标。因此，大量正常组织可能会受到不必要的高辐射剂量。在这项研究项目中，我们的目标是通过开发一种名为磁共振直线加速器(或磁共振引导的直线加速器)的新型机器来彻底改变提供放射治疗的技术。这台机器结合了最先进的辐射机(称为直线加速器)和磁共振成像(MRI)扫描仪。MRI扫描比CT扫描更能区分肿瘤和正常组织，而且不会使患者受到额外的辐射剂量。因此，这样的机器将使我们能够非常准确地看到肿瘤在放射治疗的每个部分的时间，它还将能够跟踪肿瘤在放射剂量期间在患者体内发生的实时运动。通过这些改进，我们的目标是能够在开始放射治疗之前减少我们在肿瘤周围放置的边缘，同时仍然相信我们一直都在达到肿瘤的目标。对于患者来说，这将有许多好处，包括更大的信心，即治疗将有效地治疗他们的疾病，副作用更少。更高水平的准确性和对正常组织的避免也意味着我们可能能够开出更高的肿瘤辐射剂量。对于临床医生和科学家来说，核磁共振扫描的诊断能力将使他们能够利用磁共振直线加速器开发新的方法来修改辐射传递模式，以便将额外的剂量储存在对患者构成最大威胁的肿瘤区域。这些区域可以使用核磁共振扫描仪上的所谓功能成像技术来识别。在MR引导的放射治疗成为现实之前，需要应对许多挑战，以确保能够准确和安全地提供治疗。这项提案中描述的研究计划将使我们能够使用核磁共振扫描仪获取肿瘤和正常组织的准确图像，同时提供精确的辐射剂量，甚至是移动的肿瘤目标。

Radiation therapy involves delivering high-energy X-ray beams to tumours in order to kill cancer cells. For many people with cancer, radiation therapy is very effective and frequently cures their disease. Unfortunately, when treating tumours, nearby normal tissues will inevitably receive some of the radiation and this is associated with side effects. These side effects can vary from mild, temporary changes that disappear completely to severe, life-threatening, permanent effects that chronically affect a patient's quality of life. Therefore, when treating patients with radiotherapy, there is a clear need to ensure that the treatment is delivered as accurately as possible in order to avoid unnecessary treatment of normal tissues. In most cases, radiotherapy is planned using a CT scan to show the position of the tumour, but this is usually only done once before the treatment starts. One of the major problems with accurate delivery of radiation lies in the fact that it can be very difficult to determine precisely where the tumour is, because it can be difficult to see on standard CT scans. The problem is compounded by the fact that radiation therapy is usually given as a series of doses (called fractions) divided over a period of weeks and the tumour may be in a slightly different position each day or may shrink during the course of treatment. To make matters even more difficult, tumours often occur in tissues that move. For example, lung tumours can move quite significantly as a patient breathes in and out. Therefore, when planning a course of radiation therapy, it is necessary to include a large margin around the tumour to make sure that the radiation beams do not miss their target. As a result, large volumes of normal tissues may receive unnecessarily high radiation doses.In this research project, we aim to revolutionise the technique for delivering radiation therapy by developing a new type of machine called an MR Linac (or magnetic resonance imaging-guided linear accelerator). This machine combines a state-of-the-art radiation machine (called a linear accelerator) with a magnetic resonance imaging (MRI) scanner. MRI scanning is better than CT scanning at being able to tell the difference between tumour and normal tissues and does not expose patients to additional radiation doses. Therefore, such a machine will allow us to see very accurately where the tumour is at the time of each fraction of radiation therapy and it will also be able to track the movements of a tumour as they occur in real-time within a patient during a dose of radiation. With these improvements, we aim to be able to reduce the margins we place around tumours before we start a course of radiation therapy and yet still be confident that we are hitting the tumour target all of the time. For patients, this will have a number of benefits including greater confidence that the treatment will be effective against their disease with fewer side effects. The greater level of accuracy and the avoidance of normal tissues also means that we may be able to prescribe higher radiation doses to the tumour. For clinicians and scientists, the diagnostic power of MRI scanning will allow them to use the MR Linac to develop new approaches to modify the pattern of radiation delivery such that extra dose can be deposited in tumour areas that pose the greatest threat to the patient. Such areas can be identified using so-called functional imaging techniques on an MRI scanner. Before MR-guided radiation therapy can become a reality, there are a number of challenges that need to be met to ensure that treatment can be delivered accurately and safely. The programme of research described in this proposal will enable us to use the MRI scanner to acquire accurate images of tumour and normal tissues while delivering precise radiation doses, even to moving tumour targets.