Quantitative MRI/PET bimodal pharmacokinetic modeling to improve diagnostic accuracy in medical imaging

在临床上，各种成像技术被用来检查病人的身体，找出“哪里出了问题”。PET/MRI是一种新的可用技术，它结合了两种已建立的成像技术，磁共振成像（MRI）和正电子发射断层扫描（PET）。PET/MRI扫描仪正在进入加拿大的医院，一些研究已经提出了PET/MRI相对于单独的PET和MRI扫描仪的一些优势。然而，PET/MRI扫描仪非常昂贵，为了确保加拿大人从这项投资中获得高回报，我们必须探索这项技术的全部潜力。我们的研究重点是分子成像，这是成像的一个特定分支，可以量化生理过程并以非常精细的细节表征组织。为了做到这一点，我们注入分子“探针”，可以在成像过程中监测。例如，PET可用于使用可追踪的糖来检测细胞的糖消耗，MRI可用于使用对比生成探针来检测流向肿瘤的血流。这种信息可用于临床规划和监测抗癌治疗，并诊断病理。然而，分子成像并不容易。困难在于，注射探针在体内的分布取决于其预期目标（我们正在寻找的目标）以及它与身体的任何其他相互作用。想象一下，有一个有许多房间的建筑物，病人需要治疗。注射探针就像让护士和医生进去，他们的目标是照顾这些病人。想象就像透过窗户看。一个观察者如何知道一个医生在一个房间里是因为他/她发现了一个病人，还是因为他/她正在寻找一个病人？如果医生停止移动，他/她可能只是被困在房间里，因为房间非常忙碌。他/她也可能与健康的人讨论。分子成像是类似的：我们注射一个探针来检测肿瘤，我们在身体的某个地方检测探针。然而，我们永远无法确定探针是否真的找到了它的预定目标，或者它在那里只是因为它正在探索身体“寻找”它的目标。这个问题的解决方案相当简单：我们派出另一个团队，他们的唯一目标是走进大楼，探索房间，而不是停下来照顾病人。最后，我们比较了两个团队的位置，差异表明了患者的位置。这就是PET/MRI派上用场的地方：我们有两个观察者（成像技术），每个人都能检测到一个探头。第一探针被靶向（例如，朝向肿瘤），第二个是非靶向的，并指示第一个探针如果只是“探索”身体的话会在哪里。两者之间的差异表明目标位于何处。到目前为止，由于这里描述的问题，临床中的分子成像领域受到限制。我们的工作将消除这种限制。使用PET/MRI，我们将开发监测两个探头的方法。除其他外，我们将能够区分图像中的非靶向（非特异性）和靶向（特异性）信号，这将使我们能够更准确地表征组织，并在分子水平上提供真实的、可靠的和定量的信息，临床医生可以使用这些信息来诊断和监测疾病。

In the clinic, various imaging technologies are used to look inside patients and find out “what’s wrong”. PET/MRI is a newly available technology which combines two established imaging technologies, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). PET/MRI scanners are making an entry into Canadian hospitals, and several studies have presented some of the advantages of PET/MRI over separate PET and MRI scanners. However, PET/MRI scanners are very expensive, and to make sure Canadians get a high return from this investment, we must explore the full potential of this technology.Our research focuses on molecular imaging, a specific branch of imaging that quantifies physiological processes and characterizes tissues in very fine detail. To do this, we inject molecular “probes” that can be monitored during imaging. For example, PET can be used to detect the sugar consumption of cells using a traceable sugar, and MRI can be used to detect blood flow to a tumor using a contrast generating probe. This kind of information can be used in the clinic to plan and monitor anti-cancer therapy, and diagnose pathologies. However, molecular imaging is not easy. A difficulty is that distribution of an injected probe inside the body depends on both its intended target (what we are looking for) and any other interaction it has with the body. Imagine a building with many rooms where patients require treatment. Injecting a probe is like sending nurses and physicians inside whose goal is to attend to these patients. Imaging is like watching through the windows. How can an observer know whether a physician is inside a room because he/she has found a patient, or because he/she is looking for one? If a physician stops moving, he/she might simply be stuck in a room because the room is very busy. He/She might also be discussing with someone healthy. Molecular imaging is similar: We inject a probe to detect a tumor, and we detect the probe somewhere in the body. Yet, we can never be certain if the probe has indeed found its intended target, or if it is there simply because it is exploring the body “searching” for its target. The solution to this problem is fairly simple: We send another team, whose only goal is to walk inside the building and explore the rooms without stopping to attend to patients. At the end, we compare the location of both teams, and the difference indicates where the patients are. This is where PET/MRI comes in handy: we have two observers (imaging technologies) capable of detecting one probe each. The first probe is targeted (e.g., toward a tumor), and the second one is untargeted, and indicates where the first probe would be if it was just “exploring” the body. The difference between the two indicates where the target is located. As of now, the field of molecular imaging in the clinic is limited because of the problem described here. Our work will remove this limitation. Using PET/MRI, we will develop methods to monitor two probes. We will, among other things, be able to make the difference between untargeted (unspecific) and targeted (specific) signal in images, which will enable us to characterize tissues more accurately, and provide real, solid and quantitative information at the molecular level that clinicians can use to diagnose and monitor diseases.