Functional MRI Readouts From BOLD and Diffusion Measurements Differentially Respond to Optogenetic Activation and Tissue Heating
Functional MRI Readouts From BOLD and Diffusion Measurements Differentially Respond to Optogenetic Activation and Tissue Heating
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DOI：
10.3389/fnins.2019.01104
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发表时间：
2019-10-24
影响因子：
4.3
通讯作者：
Faber, Cornelius
中科院分区：
文献类型：
--
作者：
Albers, Franziska;Wachsmuth, Lydia;Faber, Cornelius
功能性血氧水平依赖（BOLD）MRI提供了一个全脑的读数，取决于对神经元活动的血液动力学反应。扩散fMRI已被提议作为BOLD fMRI的替代方案，并被假定直接依赖于神经元活动。这些互补的功能读数是与光遗传学刺激相结合来研究大脑网络的通用工具。光遗传学操作的细胞特异性和时间精确性有望进一步研究fMRI信号的起源。反之亦然，扩散fMRI读出的信号特性可以更好地解决光遗传学刺激的网络效应。然而，光遗传学刺激所需的光应用伴随着组织内的热沉积。由于扩散和BOLD都对温度变化敏感，光的应用可能导致明显的激活混淆fMRI数据的解释。组织加热的程度，在不同的功能磁共振成像序列中的表观激活的外观和这些现象的起源还没有得到很好的理解。在这里，我们从感觉或光遗传学刺激后的生理激活中解开了大鼠BOLD和扩散测量中的表观激活。BOLD和弥散功能磁共振成像显示类似的信号形状后，感觉刺激，明显不同于那些加热。高强度光应用诱导的表观激活由T-2*-效应主导，并导致主要的负信号变化。我们估计，即使是用于光遗传学刺激的低强度光应用也会使靠近纤维的BOLD反应降低高达0.4%。弥散fMRI信号包含T-2、T-2* 和弥散成分。表观扩散系数反映了分离的扩散成分，在光遗传学和电前爪刺激后均显示出负变化。相比之下，高强度的光应用后检测到积极的变化，从而排除了加热作为一个主要的贡献者的扩散功能磁共振成像信号。
Functional blood-oxygenation-level-dependent (BOLD) MRI provides a brain-wide readout that depends on the hemodynamic response to neuronal activity. Diffusion fMRI has been proposed as an alternative to BOLD fMRI and has been postulated to directly rely on neuronal activity. These complementary functional readouts are versatile tools to be combined with optogenetic stimulation to investigate networks of the brain. The cell-specificity and temporal precision of optogenetic manipulations promise to enable further investigation of the origin of fMRI signals. The signal characteristics of the diffusion fMRI readout vice versa may better resolve network effects of optogenetic stimulation. However, the light application needed for optogenetic stimulation is accompanied by heat deposition within the tissue. As both diffusion and BOLD are sensitive to temperature changes, light application can lead to apparent activations confounding the interpretation of fMRI data. The degree of tissue heating, the appearance of apparent activation in different fMRI sequences and the origin of these phenomena are not well understood. Here, we disentangled apparent activations in BOLD and diffusion measurements in rats from physiological activation upon sensory or optogenetic stimulation. Both, BOLD and diffusion fMRI revealed similar signal shapes upon sensory stimulation that differed clearly from those upon heating. Apparent activations induced by high-intensity light application were dominated by T-2*-effects and resulted in mainly negative signal changes. We estimated that even low-intensity light application used for optogenetic stimulation reduces the BOLD response close to the fiber by up to 0.4%. The diffusion fMRI signal contained T-2, T-2* and diffusion components. The apparent diffusion coefficient, which reflects the isolated diffusion component, showed negative changes upon both optogenetic and electric forepaw stimulation. In contrast, positive changes were detected upon high-intensity light application and thus ruled out heating as a major contributor to the diffusion fMRI signal.