Çimen Yetiş Sibel, Çapar Abdulkerim, Ekinci Dursun A, Ayten Umut E, Kerman Bilal E, Töreyin B Uğur
Yildiz Technical University, Dept. of Electronics and Communication Engineering, Istanbul, Turkey.
Istanbul Technical University, Informatics Institute, Istanbul, Turkey.
J Neurosci Methods. 2020 Dec 1;346:108946. doi: 10.1016/j.jneumeth.2020.108946. Epub 2020 Sep 12.
The myelin sheath produced by glial cells insulates the axons, and supports the function of the nervous system. Myelin sheath degeneration causes neurodegenerative disorders, such as multiple sclerosis (MS). There are no therapies for MS that promote remyelination. Drug discovery frequently involves screening thousands of compounds. However, this is not feasible for remyelination drugs, since myelin quantification is a manual labor-intensive endeavor. Therefore, the development of assistive software for expedited myelin detection is instrumental for MS drug discovery by enabling high-content image-based drug screens.
In this study, we developed a machine learning based expedited myelin detection approach in fluorescence microscopy images. Multi-channel three-dimensional microscopy images of a mouse stem cell-based myelination assay were labeled by experts. A spectro-spatial feature extraction method was introduced to represent local dependencies of voxels both in spatial and spectral domains. Feature extraction yielded two data set of over forty-seven thousand annotated images in total.
Myelin detection performances of 23 different supervised machine learning techniques including a customized-convolutional neural network (CNN), were assessed using various train/test split ratios of the data sets. The highest accuracy values of 98.84±0.09% and 98.46±0.11% were achieved by Boosted Trees and customized-CNN, respectively.
Our approach can detect myelin in a common experimental setup. Myelin extending in any orientation in 3 dimensions is segmented from 3 channel z-stack fluorescence images.
Our results suggest that the proposed expedited myelin detection approach is a feasible and robust method for remyelination drug screening.
神经胶质细胞产生的髓鞘可使轴突绝缘,并支持神经系统的功能。髓鞘变性会导致神经退行性疾病,如多发性硬化症(MS)。目前尚无促进髓鞘再生的MS治疗方法。药物研发通常需要筛选数千种化合物。然而,对于髓鞘再生药物来说这并不可行,因为髓鞘定量是一项人工劳动强度大的工作。因此,开发用于快速检测髓鞘的辅助软件,通过基于高内涵图像的药物筛选,对MS药物研发具有重要意义。
在本研究中,我们开发了一种基于机器学习的方法,用于在荧光显微镜图像中快速检测髓鞘。专家对基于小鼠干细胞的髓鞘形成试验的多通道三维显微镜图像进行了标注。引入了一种光谱空间特征提取方法,以表示体素在空间和光谱域中的局部依赖性。特征提取总共产生了两个数据集,包含超过四万七千张标注图像。
使用数据集的各种训练/测试分割比例,评估了包括定制卷积神经网络(CNN)在内的23种不同监督机器学习技术的髓鞘检测性能。提升树和定制CNN分别取得了98.84±0.09%和98.46±0.11%的最高准确率。
我们的方法可以在常见的实验设置中检测髓鞘。从三通道z-stack荧光图像中分割出在三维空间中任意方向延伸的髓鞘。
我们的结果表明,所提出的快速髓鞘检测方法是一种用于髓鞘再生药物筛选的可行且稳健的方法。