Iron fMRI: Improving Sensitivty and localization

描述（由申请人提供）：本拨款提案“动物模型中的铁功能磁共振成像：提高灵敏度和空间定位”是RFA EB-03-002“小动物成像系统和方法”的R01申请。虽然BOLD fMRI的脑功能映射是人类常用的神经科学技术，但动物模型可以实现更有效的技术，这些技术尚未在人类中使用。特别是，氧化铁造影剂（iron fMRI）在功能磁共振成像（fMRI）灵敏度上有显著提高，似乎比BOLD方法提供更好的空间定位，但比BOLD方法的时间分辨率稍慢。拟建项目的目标是解决有关铁功能磁共振成像在动物模型中应用的主要遗留问题。也就是说，1)在非常高的磁场下，铁和BOLD功能磁共振成像的相对优点是什么，2)铁的时间反应对快速调节的大脑活动有什么影响，3)血容量是否比BOLD信号产生明显更好的空间定位？我们的假设是：1)铁方法将在不损失灵敏度的情况下提高图像质量，从而在高场功能磁共振成像中发挥关键作用；2)智能刺激策略将缓解铁时间响应缓慢的缺点，即使是快速刺激调制；3)铁方法将改善功能磁共振成像的空间定位。检测灵敏度和空间分辨率是在小动物模型中有效的功能磁共振成像最关键的实验因素。提出的实验解决了动物模型中关于铁功能磁共振成像的最重要的剩余问题，这些研究是这项强大技术从临床前研究到临床应用的最终进展的合乎逻辑的一步。

DESCRIPTION (provided by applicant): This grant proposal, "IRON fMRI in animal models: improving sensitivity and spatial localization", is an R01 application in response to RFA EB-03-002, "Systems & Methods for Small Animal Imaging". While functional brain mapping by BOLD fMRI is a common neuroscience technique in humans, animal models enable more effective techniques that are not yet available in humans. In particular, iron oxide contrast agents (IRON fMRI) offer remarkable improvements in fMRI sensitivity, appear to provide better spatial localization than the BOLD method, but suffer a somewhat slower temporal resolution than the BOLD method. The goal of the proposed project is to resolve the principal remaining issues concerning the application of IRON fMRI in animal models. Namely, 1) what are the relative merits and IRON and BOLD fMRI at very high magnetic fields, 2) what implications does the IRON temporal response have for rapidly modulated brain activity, and 3) does blood volume produce significantly better spatial localization than BOLD signal? Our hypotheses are 1) the IRON method will fill a critical role in high field fMRI by improving image quality without a loss of sensitivity, 2) intelligent stimulation strategies will mitigate disadvantages of the slow IRON temporal response even for rapidly stimulus modulations, and 3) the IRON method will improve spatial fMRI localization. Detection sensitivity and spatial resolution are among the most critical experimental factors for effective fMRI in small animal models. The proposed experiments address the most important remaining issues concerning IRON fMRI in animal models, and these studies are a logical step in the eventual progression of this powerful technique from pre-clinical studies to clinical utility.