PMID- 22732566 OWN - NLM STAT- MEDLINE DCOM- 20121210 LR - 20240321 IS - 1095-9572 (Electronic) IS - 1053-8119 (Print) IS - 1053-8119 (Linking) VI - 62 IP - 3 DP - 2012 Sep TI - A quantitative analytic pipeline for evaluating neuronal activities by high-throughput synaptic vesicle imaging. PG - 2040-54 LID - 10.1016/j.neuroimage.2012.06.020 [doi] AB - Synaptic vesicle dynamics play an important role in the study of neuronal and synaptic activities of neurodegradation diseases ranging from the epidemic Alzheimer's disease to the rare Rett syndrome. A high-throughput assay with a large population of neurons would be useful and efficient to characterize neuronal activity based on the dynamics of synaptic vesicles for the study of mechanisms or to discover drug candidates for neurodegenerative and neurodevelopmental disorders. However, the massive amounts of image data generated via high-throughput screening require enormous manual processing time and effort, restricting the practical use of such an assay. This paper presents an automated analytic system to process and interpret the huge data set generated by such assays. Our system enables the automated detection, segmentation, quantification, and measurement of neuron activities based on the synaptic vesicle assay. To overcome challenges such as noisy background, inhomogeneity, and tiny object size, we first employ MSVST (Multi-Scale Variance Stabilizing Transform) to obtain a denoised and enhanced map of the original image data. Then, we propose an adaptive thresholding strategy to solve the inhomogeneity issue, based on the local information, and to accurately segment synaptic vesicles. We design algorithms to address the issue of tiny objects of interest overlapping. Several post processing criteria are defined to filter false positives. A total of 152 features are extracted for each detected vesicle. A score is defined for each synaptic vesicle image to quantify the neuron activity. We also compare the unsupervised strategy with the supervised method. Our experiments on hippocampal neuron assays showed that the proposed system can automatically detect vesicles and quantify their dynamics for evaluating neuron activities. The availability of such an automated system will open opportunities for investigation of synaptic neuropathology and identification of candidate therapeutics for neurodegeneration. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Fan, Jing AU - Fan J AD - The Ting Tsung and Wei Fong Chao Center for Bioinformatics Research and Imaging for Neurosciences, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX 77030, USA. FAU - Xia, Xiaofeng AU - Xia X FAU - Li, Ying AU - Li Y FAU - Dy, Jennifer G AU - Dy JG FAU - Wong, Stephen T C AU - Wong ST LA - eng GR - R01 AG028928/AG/NIA NIH HHS/United States GR - R01 LM009161/LM/NLM NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120623 PL - United States TA - Neuroimage JT - NeuroImage JID - 9215515 SB - IM MH - Algorithms MH - Animals MH - Brain/physiology MH - Cells, Cultured MH - Diagnostic Imaging/*methods MH - High-Throughput Screening Assays/*methods MH - Image Processing, Computer-Assisted/*methods MH - Mice MH - Mice, Inbred C57BL MH - Neurons/*physiology MH - Synaptic Vesicles PMC - PMC3437259 MID - NIHMS394125 EDAT- 2012/06/27 06:00 MHDA- 2012/12/12 06:00 PMCR- 2013/09/01 CRDT- 2012/06/27 06:00 PHST- 2012/02/27 00:00 [received] PHST- 2012/06/12 00:00 [accepted] PHST- 2012/06/27 06:00 [entrez] PHST- 2012/06/27 06:00 [pubmed] PHST- 2012/12/12 06:00 [medline] PHST- 2013/09/01 00:00 [pmc-release] AID - S1053-8119(12)00634-9 [pii] AID - 10.1016/j.neuroimage.2012.06.020 [doi] PST - ppublish SO - Neuroimage. 2012 Sep;62(3):2040-54. doi: 10.1016/j.neuroimage.2012.06.020. Epub 2012 Jun 23.