title: Accurate detection of low signal-to-noise ratio neuronal calcium transient waves using a matched filter.
abstract: BACKGROUND
  Calcium imaging has become a fundamental modality for studying neuronal circuit dynamics both in vitro and in vivo. However, identifying calcium events (CEs) from spectral data remains laborious and difficult, especially since the signal-to-noise ratio (SNR) often falls below 2. Existing automated signal detection methods are generally applied at high SNRs, leaving a large need for an automated algorithm that can accurately extract CEs from fluorescence intensity data of SNR 2 and below.
  
  
  METHODS
  In this work we develop a Matched filter for Multi-unit Calcium Event (MMiCE) detection to extract CEs from fluorescence intensity traces of simulated and experimentally recorded neuronal calcium imaging data.
  
  
  RESULTS
  MMiCE reached perfect performance on simulated data with SNR ≥ 2 and a true positive (TP) rate of 98.27% (± 1.38% with a 95% confidence interval), and a false positive(FP) rate of 6.59% (± 2.56%) on simulated data with SNR 0.2. On real data, verified by patch-clamp recording, MMiCE performed with a TP rate of 100.00% (± 0.00) and a FP rate of 2.04% (± 4.10).
  
  
  CONCLUSIONS
  This high level of performance exceeds existing methods at SNRs as low as 0.2, which are well below those used in previous studies (SNR ≃ 5-10).
  
  
  CONCLUSIONS
  Overall, the MMiCE detector performed exceptionally well on both simulated data, and experimentally recorded neuronal calcium imaging data. The MMiCE detector is accurate, reliable, well suited for wide-spread use, and freely available at sites.uci.edu/aggies or from the corresponding author.
authors.affiliation: Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA. Electronic address: aszymans@uci.edu.
authors.forename: Agnieszka F
authors.initials: AF
authors.lastname: Szymanska
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: chi5.a1.ki6@gmail.com.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: hi.norimoto@gmail.com.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Norimoto
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: tomoe0178@gmail.com.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, Suita City, Osaka 565-0871, Japan. Electronic address: ikegaya@mol.f.u-tokyo.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikegaya
authors.affiliation: Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA. Electronic address: znenadic@uci.edu.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Nenadic
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology*; D061848:Optical Imaging / Q000379:methods*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D059629:Signal-To-Noise Ratio
chemical_list: D002118:Calcium
keywords: Calcium transients; Dendritic spines; Detection; Low SNR; Matched filter; Multineuron calcium imaging; Somatic calcium fluctuations