Structural correlates of active-staining following magnetic resonance microscopy in the mouse brain.
Structural correlates of active-staining following magnetic resonance microscopy in the mouse brain.
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DOI：
10.1016/j.neuroimage.2011.01.082
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发表时间：
2011-06-01
期刊：
影响因子：
5.7
通讯作者：
Lythgoe, Mark F.
中科院分区：
文献类型：
--
作者：
Cleary, Jon O.;Wiseman, Frances K.;Norris, Francesca C.;Price, Anthony N.;Choy, ManKin;Tybulewicz, Victor L. J.;Ordidge, Roger J.;Brandner, Sebastian;Fisher, Elizabeth M. C.;Lythgoe, Mark F.
关键词：
全世界正在进行广泛的努力，为大约25,000个小鼠基因中的每一个基因生产敲除小鼠，这可能为神经系统疾病的潜在病理生理学提供新的见解。显微磁共振成像（μMRI）是一种非侵入性形态学表型的关键方法，能够在MR造影剂固定后产生离体大脑的高分辨率3D图像。这些药物被认为是活性染色剂，可以增强MRI上不可见的结构。在这项研究中，我们研究了Gd-DTPA MRI剂的结构相关性，以及用于小鼠大脑对比增强梯度回声成像的最佳制备和扫描参数。我们观察到，由于提取损伤程度的不同，原位制备优于非原位制备。通过优化的参数对大脑进行原位扫描，使图像具有高信噪比（SNR ~ 30）和全面的解剖描绘。磁共振脑结构与组织学的直接相关性，皮层、小脑、嗅球和海马的详细精细组织结构。神经丝染色显示MR阴性区域与髓鞘白质结构密切相关，而MR阳性结构与灰质含量高的区域相对应。我们能够识别出许多亚区域，特别是在海马体中，例如无髓苔藓纤维（透明层）及其在金字塔层中的突触区域，以及齿状回的颗粒层，这是一个密集堆积的细胞体区域，作为一个高强度区域清晰可见。这表明细胞结构影响MR造影剂的位置特异性分布，导致T2*的局部变化，从而导致组织识别增强。我们的发现不仅提供了对MR活性染色的细胞分布和机制的见解，而且还允许进行三维分析，从而能够解释磁共振显微镜下的大脑数据，并突出细胞结构，以研究疾病发展和疾病过程。►研究对比增强小鼠脑成像的制备和MR参数。►还研究了活性染色对小鼠大脑优化成像的相关性。►用优化的参数对大脑进行原位扫描，可以获得详细的高信噪比图像。►将MR脑结构与组织学相关联，详细显示精细的组织结构。我们的发现可能为MR活性染色的细胞分布提供见解。
Extensive worldwide efforts are underway to produce knockout mice for each of the ~ 25,000 mouse genes, which may give new insights into the underlying pathophysiology of neurological disease. Microscopic magnetic resonance imaging (μMRI) is a key method for non-invasive morphological phenotyping, capable of producing high-resolution 3D images of ex-vivo brains, after fixation with an MR contrast agent. These agents have been suggested to act as active-stains, enhancing structures not normally visible on MRI. In this study, we investigated the structural correlates of the MRI agent Gd-DTPA, together with the optimal preparation and scan parameters for contrast-enhanced gradient-echo imaging of the mouse brain. We observed that in-situ preparation was preferential to ex-situ due to the degree of extraction damage. In-situ brains scanned with optimised parameters, enabled images with a high signal-to-noise-ratio (SNR ~ 30) and comprehensive anatomical delineation. Direct correlation of the MR brain structures to histology, detailed fine histoarchitecture in the cortex, cerebellum, olfactory bulb and hippocampus. Neurofilament staining demonstrated that regions of negative MR contrast strongly correlated to myelinated white-matter structures, whilst structures of more positive MR contrast corresponded to areas with high grey matter content. We were able to identify many sub-regions, particularly within the hippocampus, such as the unmyelinated mossy fibres (stratum lucidum) and their region of synapse in the stratum pyramidale, together with the granular layer of the dentate gyrus, an area of densely packed cell bodies, which was clearly visible as a region of hyperintensity. This suggests that cellular structure influences the site-specific distribution of the MR contrast agent, resulting in local variations in T2*, which leads to enhanced tissue discrimination. Our findings provide insights not only into the cellular distribution and mechanism of MR active-staining, but also allow for three dimensional analysis, which enables interpretation of magnetic resonance microscopy brain data and highlights cellular structure for investigation of disease processes in development and disease. ► Investigated preparation and MR parameters for contrast-enhanced mouse brain imaging. ► Also investigated correlates of active-staining for optimised imaging of mouse brain. ► In-situ brains scanned with optimised parameters enabled detailed, high SNR images. ► Correlated MR brain structures to histology, detailing fine histoarchitecture visible. ► Our findings may provide insights into the cellular distribution of MR active-stains.
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