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

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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.