Mapping Auditory Brain Function with Mn-Enhanced MRI

描述(由申请人提供)： 为了分析具有明确神经解剖学和/或神经学缺陷的基因工程小鼠的脑功能变化，需要使用功能神经成像方法来绘制小鼠大脑中的神经活动图。在包括人类在内的大型啮齿动物和灵长类动物中，功能磁共振成像(FMRI)越来越多地被用于绘制主要感觉系统的大脑活动图。然而，有效的fMRI方法很难在小鼠身上实现，因为小鼠对空间分辨率的要求很高，而且在小鼠MRI使用的高磁场下存在显著的磁敏伪影。在感觉脑区域中，小鼠或较大哺乳动物的听觉系统很难用fMRI进行研究，因为较低的听觉中心存在严重的敏感性伪影，而且在将对特定声刺激的听觉反应与对MRI梯度线圈产生的背景噪声的反应分离方面存在固有的困难。我们最近研究了一种锰(Mn)增强磁共振成像(MEMRI)方法，该方法有可能提供在磁铁外清醒行为的小鼠中由明确的声刺激诱导的高分辨率听觉脑活动图。我们的初步结果表明，MEMRI可以检测到小鼠大脑听觉中枢的声音诱导神经活动，并且可以量化传导性听力损失小鼠增强/活动的变化模式。该项目的广泛目标是进一步开发这些方法，优化MEMRI方案，以绘制正常和耳聋小鼠的听神经活动图，从而能够对听觉小鼠大脑的发育和可塑性进行活体脑成像研究。 具体目标是： 1)建立一种检测小鼠听觉中脑神经活动的最佳MEMRI方法。2)建立小鼠听觉脑电地形图的MEMRI空间/频率分辨率。 3)明确和描述单侧耳聋小鼠MEMRI增强模式的改变。这些研究将为未来对正常和基因工程小鼠的大脑图谱研究奠定基础，为研究正常听力和听力障碍背后的遗传途径提供亟需的新神经成像工具。

DESCRIPTION (provided by applicant): Functional neuroimaging methods for mapping neural activity in the mouse brain are required to analyze altered brain function in genetically-engineered mice with defined neuroanatomical and/or neurological defects. In larger rodents and primates, including humans, functional magnetic resonance imaging (fMRI) has been used increasingly to map brain activity in the major sensory systems. However, effective fMRI approaches have been difficult to implement in mice because of the high spatial resolution requirements and the presence of significant susceptibility artifacts at the high magnetic fields used for mouse MRI. Among sensory brain regions, the auditory system has been difficult to study with fMRI in mice or larger mammals because of severe susceptibility artifacts in the lower auditory centers and because of the inherent difficulties in uncoupling the auditory response to a defined acoustic stimulus from the response to the background noise produced by the MRI gradient coils. We have recently investigated a Manganese (Mn)-Enhanced MRI (MEMRI) method with the potential to provide high resolution maps of auditory brain activity induced by defined acoustic stimulation in awake behaving mice outside the magnet. Our preliminary results show that sound-induced neural activity in auditory centers of the mouse brain can be detected with MEMRI, and that altered patterns of enhancement/activity can be quantified in mice with conductive hearing loss. The broad goals of this project are to further develop these approaches, optimizing MEMRI protocols for mapping auditory neural activity in normal and deafened mice, enabling in vivo brain imaging studies of the development and plasticity of the auditory mouse brain. The specific aims are: 1) To establish an optimal MEMRI protocol to detect neural activity in the mouse auditory midbrain. 2) To establish the spatial / frequency resolution of MEMRI for auditory brain mapping in the mouse. 3) To define and characterize altered patterns of MEMRI enhancement in unilaterally deaf mice. These studies will form the basis for future brain mapping investigations in normal and genetically-engineered mice, providing much needed new neuroimaging tools for studying the genetic pathways underlying normal hearing and hearing disorders.