Background

Tissue microarrays (TMAs), where each block (and thus section) contains multiple tissue cores from multiple blocks potentially allow more efficient use of tissue, reagents and time in neuropathology.

New method

The relationship between data from TMA cores and whole sections was investigated using ‘virtual’ TMA cores. This involved quantitative assessments of microglial pathology in white matter lesions and motor neuron disease, alongside qualitative TDP-43 inclusion status in motor neuron disease cases. Following this, a protocol was developed for TMA construction.

Results

For microglial pathology we found good concordance between virtual cores and whole sections for volume density using one 1.75 mm core (equivalent to a 2 mm core after accounting for peripheral tissue loss). More sophisticated microglial cell size and measures required two cores. Qualitative results of pTDP-43 pathology showed use of one 1.75 mm core gave a 100 % sensitivity and specificity within grey matter, and 88.3 % sensitivity and 100 % specificity within white matter. A method of producing the TMAs was suitable for immunohistochemistry both manually and by autostainer, with the minimal core loss from the microscope slide.

Comparison with existing methods

TMAs have been used infrequently in post mortem neuropathology research. However, we believe TMAs give comparable tissue assessment results and can be constructed, sectioned and stained with relative ease.

Conclusions

We found TMAs could be used to assess both quantitative (microglial pathology) and qualitative pathology (TDP-43 proteinopathy) with greatly reduced quantities of tissue, time and reagents. These could be used for further work to improve data acquisition efficiency.

中文翻译：

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组织微阵列（TMA）在验尸神经病理学中的应用

背景

组织微阵列（TMA），其中每个块（以及每个切片）都包含来自多个块的多个组织核心，可能使神经病理学更有效地利用组织，试剂和时间。

新方法

使用“虚拟” TMA内核研究了来自TMA内核和整个部分的数据之间的关系。这涉及定量评估白质病变和运动神经元疾病中的小胶质细胞病理，以及运动神经元疾病病例中定性的TDP-43包涵状态。此后，开发了用于TMA构建的协议。

结果

对于小胶质细胞病理学，我们使用一个1.75 mm的芯（考虑到周围组织的损失，相当于2 mm的芯）在虚拟芯和整个切片之间发现了良好的体积密度一致性。更复杂的小胶质细胞大小和测量需要两个核心。pTDP-43病理学的定性结果显示，使用一个1.75 mm核芯在灰质中给出了100％的灵敏度和特异性，在白质中给出了88.3％的灵敏度和100％特异性。制备TMA的方法适用于手动和自动染色的免疫组织化学，显微镜载玻片的核心损失最小。

与现有方法的比较

在死后神经病理学研究中很少使用TMA。但是，我们相信TMA可以提供可比的组织评估结果，并且可以相对容易地进行构建，切片和染色。

结论

我们发现TMA可用于评估定量（小胶质细胞病理）和定性病理（TDP-43蛋白病），同时大大减少了组织，时间和试剂的用量。这些可以用于进一步的工作，以提高数据采集效率。