Improving Sensitivity and Spatial Coverage of Myocardial Arterial Spin Labeling

摘要

Magnetic resonance imaging (MRI) is a medical imaging technique invented by Paul Lauterbur in 1971 that uses the principles of nuclear magnetic resonance to generate images. Widely touted as the most important medical invention in the last 50 years, MRI has transformed the medical landscape by providing high resolution anatomic images with excellent soft tissue contrast. MRI is important for identifying neuropathology, assessing cardiovascular function, evaluating spinal and joint disease, and diagnosing and staging cancer both pre-and-post-operatively. The power of MRI lies in its ability to generate novel contrast mechanisms, which has expanded the scope of MRI beyond anatomic imaging into quantitative imaging of an array of both physical and physiological processes, including diffusion, spectroscopy, blood flow, and perfusion.;In this dissertation, I focus specifically on perfusion imaging of the heart. Many techniques asides from MRI are also sensitive to perfusion, such as SPECT, PET, CT, and ultrasound. We believe MRI has the potential to supersede these various modalities because it can offer high spatial resolution without ionizing radiation and can even avoid injected contrast agents through a novel technique called arterial spin labeling. The benefits of using ASL MRI are two-fold. One, ASL can be used repeatedly in patients for long-term evaluation of perfusion defects, which may be useful to assess disease progression. Two, ASL is contrast free and can be tolerated in a large population of patients with renal disease. This population is more susceptible to coronary artery disease than the general population and have the most to gain from a clinically viable cardiac ASL protocol.;Therefore, the focus of this work is to take the necessary steps to make ASL clinically viable. In its current implementation, ASL has poor sensitivity and limited spatial coverage. Poor sensitivity is unavoidable because without contrast agents, the perfusion signal in ASL is low, on the order of 12% of the background signal from the heart itself. This makes maximizing the sensitivity of the ASL signal all the more important. Our first step was to determine how imaging parameters influence the sensitivity of not only ASL, but quantitative cardiac MRI in general. The metric we used to quantify sensitivity was the variability of cardiac images over time, or in technical terms, the temporal signal to noise ratio. If certain imaging parameters lead to large fluctuations in the cardiac images, there would be no hope of unmasking a small 1--2% ASL signal change. Through this study, I made the important finding that there is a fundamental limit towards minimizing these fluctuations, at which point further increases in the raw signal strength become unnecessary.;With suitable imaging parameters at hand, I turned my attention towards the ASL pulse sequence itself. Traditionally, ASL labels arterial blood using a magnetization preparation upstream of the tissue of interest and images after a post labeling delay to allow the labeled blood to enter the tissue. The amount of time it takes the labeled blood to reach the imaged tissue, called the transit delay, is a critical determinant of the sensitivity of the ASL signal because labeled blood decays over time. In an extreme example, if the labeled blood signal has completely decayed before its arrival, ASL would have zero sensitivity. To counteract transit delay, I opted to use velocity selective labeling, which labels arterial blood based on its velocity as opposed to its spatial position. In theory, blood within small arterioles within the imaging slice can be labeled to eliminate transit delay completely. In practice, blood further upstream the arterial tree is typically targeted to minimize the transit time. The choice of velocity selective parameters determines how far upstream and in which direction labeling occurs in the arterial tree. These parameters were systematically varied and resulting perfusion estimate were compared with those obtained from the standard spatially selective FAIR ASL. Through this study, I found suitable velocity selective parameters and demonstrated the feasibility of VSASL.;Lastly, I sought to increase spatial coverage of ASL. Simple sequential multi-slice imaging is not possible due to the limited scan times (~ 3 min) required for ASL under pharmacologically induced stress. 3D imaging may have superior slice coverage, but has long scan times and is unnecessary; three axial slices of the heart is sufficient for clinical evaluation. Instead, I chose simultaneous multi-slice imaging because of its fast imaging time. In SMS imaging, multiple slices are simultaneously excited and shifted with respect to each other to ease their reconstruction. While still preliminary, I demonstrated that two slices can be simultaneously excited and reconstructed to obtain perfusion similar with single slice cardiac ASL.