Magnetic resonance based quantitative assessment of myocardial microvascular and microstructural function using STEAM-tIVIM

心脏供血不足，经常在运动时引起胸痛，通常是由供应心肌的血管变窄引起的。然而，在这些患者中，约有一半的人在血管图片上没有明显的狭窄，疼痛通常是由于心脏血管的微观疾病引起的。这种情况被称为微血管功能障碍。我们将开发一种名为STEAM-tIVIM的新型MRI扫描，它可以提供微观血管中的血流和心肌微观结构的信息。这种方法可以检测到水分子在我们身体细胞内外的随机运动。由于心脏的微观血管在短距离内有许多曲折，因此血液的运动显得随机，也可以用STEAM-tIVIM检测到。我们将能够检测到血液流动的方向和砖状肌肉细胞指向的方向。没有其他方法可以在不取下心脏切片并在显微镜下研究的情况下提供这些信息。我们的核磁共振技术不使用辐射或染料注射。我们将评估我们的核磁共振扫描对血流变化的敏感性，方法是将显微镜下的血管添加到我们已经开发的显微镜下的心肌计算机模型中。这个模型将告诉我们，我们能够通过扫描检测到的血流量的最小变化是什么，以及扫描仪的最高灵敏度设置是什么。我们将编程核磁共振扫描仪来收集数据，并将这些数字流转换成图片，显示诸如微观血管内的血液流动、血管中有多少血液以及血管在心脏各处的方向变化等测量结果。从同样的扫描中，其他图片将显示心肌细胞是如何排列的。我们的程序将使用我们的计算机模型进行测试，然后通过扫描测试对象（瓶装水基液体），然后10名志愿者检查扫描在跳动的心脏中的效果如何。这些扫描大约需要一个小时，没有辐射，我们用心电图来监测心跳，这样我们就可以在心脏运动最少的时候扫描心跳的部分。为了证实核磁共振成像扫描图像对微观血管血流变化的敏感性，我们将扫描猪的心脏。这些心脏来自被屠宰的猪，否则就会被扔掉。我们会一边扫描一边将类似血液的液体泵入猪心脏的血管。通过改变液体的流量，我们可以检查我们的方法有多灵敏。我们还将在液体中添加一种药物，这种药物可以使健康心脏的动脉变宽，模拟运动，以检查当我们给这种药物时，我们能否通过核磁共振扫描图像检测到心脏中多余的血液。我们的新核磁共振扫描将与目前可用的另一种核磁共振扫描进行比较，但需要向心脏注射染料，因此对一些患者来说是不可能的。科学家们还担心，当患者多次使用这种染料进行扫描时，这种染料会在体内积聚。最后，我们将检查MRI扫描可以检测微血管功能障碍患者心肌血流的变化。许多被医生认为有微血管功能障碍的病人都进行了核磁共振扫描，这是他们正常护理的一部分，我们会邀请他们再来做第二次扫描。在第二次扫描中，我们将运行新的STEAM-tIVIM方法两次，一次是在患者注射用于模拟运动的药物的同时。我们将扫描20名患者，并扫描与患者年龄相近，男女比例相近的相同数量的志愿者。我们相信，当我们模拟运动时，在病人身上测量到的流向心脏肌肉的血流量会比志愿者小。

An inadequate blood supply to the heart, often causing chest pain during exercise, is typically caused by narrowing of the blood vessels that supply the heart muscle. However, in around half of these patients no severe narrowing is visible in pictures of the vessels and the pain is often due to disease in the microscopic blood vessels of the heart. This condition is known as microvascular dysfunction. We will develop a new type of MRI scan known as STEAM-tIVIM that provides information on both the blood flow in the microscopic vessels and the microscopic structure of the heart muscle. This method detects the random movement of water molecules as they move around inside and outside the cells of our bodies. As the microscopic vessels of the heart have many twists and turns in a short distance, the movement of blood appears random and can also be detected with STEAM-tIVIM. We will be able to detect the direction of blood flow and the direction that the brick-like muscle cells are pointing in. No other method exists that provides this information without removing a piece of the heart and studying it under a microscope. Our MRI technique uses no radiation or injection of dyes.We will assess how sensitive our MRI scan is to changes in blood flow by adding microscopic blood vessels to a computer model of the heart muscle on a microscopic scale that we have developed. This model will tell us what the smallest change in blood flow that we will be able to detect using our scans is and what the scanner settings for the highest sensitivity will be. We will programme the MRI scanner to collect the data and turn this stream of numbers into the pictures showing how measures such as the flow of blood within microscopic blood vessels, how much blood is in the vessels and the direction of the blood vessels vary across the heart. From these same scans, other pictures will show how the heart muscle cells are aligned. Our programmes will be tested using our computer model, then by scanning test objects (bottles of water-based liquids) and then 10 volunteers to check how well the scans work in a beating heart. These scans take around 1 hour, there is no radiation and we monitor the heartbeat using an ECG to allow us scan in the part of the heartbeat when the heart is moving least. To confirm how sensitive the MRI scan pictures are to changes in the flow of blood through the microscopic blood vessels we will scan pigs' hearts. The hearts come from butchered pigs and would otherwise be thrown away. We will pump blood-like liquid through the vessels of the pig hearts while we scan. By varying the flow of liquid we can check how sensitive our methods are. We will also add a medicine to the liquid which makes arteries wider in healthy hearts, mimicking exercise to check that we can detect the extra blood in the heart with our MRI scan pictures when we give this medicine. Our new MRI scan will be compared to another type of MRI scan that is available at the moment, but needs injection of a dye into the heart so is not possible in some patients. Scientists are also concerned about the build-up of this dye in the body when patients have many scans using it.Finally, we will check that the MRI scan can detect changes in blood flow in the heart muscle of patients with microvascular dysfunction. Many patients who doctors think have microvascular dysfunction have MRI scans as part of their normal care and we will invite them to come back for a second scan. In this second scan, we will run our new STEAM-tIVIM method twice, once while the patient is injected with the medicine used to simulate exercise. We will scan 20 patients and scan the same number of volunteers of a similar age and male to female ratio as the patients. We believe that when we simulate exercise, the increase in blood flow to the heart muscle measured in patients will be smaller than in the volunteers.