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An automated tool for reliable detection of seizures in rodent models of epilepsy
Armen Sargsyan1, Dmitri Melkonian1, Pablo M. Casillas-Espinosa2, Terence J. O’Brien2 1 Kaoskey Pty. Ltd. Sydney, Australia 2 Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia
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in pre-clinical drug development of new therapies, eg
Prolonged video-EEG monitoring in chronic epilepsy rodent models has become an important tool in pre-clinical drug development of new therapies, eg anti-epileptogenesis, disease modification and drug resistant epilepsy. Many researches still prefer to identify the seizures by themselves by visually inspecting the video and EEG and tedious process very time-consuming
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Spectral Band Index Tool (SBIT)
An easy to use & reliable computational tool for detection of electrographic seizures in prolonged EEG recordings in rodent models of epilepsy SBIT is based on advanced time-frequency analysis detects the episodes of EEG with excessive activity in certain frequency bands
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The tool was tested on two acquired and two genetic spontaneously seizing, chronic epilepsy rat models Animal models Notation Acquired Post-status epilepticus model of temporal lobe epilepsy Post-SE Fluid percussion injury model of post-traumatic epilepsy PTE Genetic Genetic Absence Epilepsy Rat from Strasbourg GAERS Wistar Albino Glaxo/Rijswijk model of absence epilepsy WAG/Rij
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The ictal EEG in these models contains a strong component with frequency around 21 Hz, which is specific for seizures only SBI = max { Power spectrum in the frequency band [f1, f2] } Spectral Band Index: SBI calculated for frequency band 20 – 23 Hz (narrow band around 21 Hz) Post-SE, animal Z38, 12 days-long recording 12 days Seizures SBI calculated for frequency band 1 – 40 Hz (wide band)
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Examples of single and averaged spike-wave complexes and their amplitude frequency characteristics from four rat models Average SW (over one seizure) 0.00 0.05 0.10 Time, s Model Sample SW 0.00 0.05 0.10 Time, s 1 10 100 AFC Peak frequency, Hz: 18.33 19.82 21.11 20.23 Frequency, Hz 20 1 10 100 AFC 17.64 24.12 19.21 20.29 Peak frequency, Hz: Frequency, Hz 20 Post-SE PTE GAERS WAG/Rij Note that all peaks are within the Hz band, with mean around Hz
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SBI plot for an artefact-free recording (model: Post-SE; animal: 27)
00:00 48:00 96:00 144:00 192:00 240:00 288:00 SBI, relative units Time, hh:mm (12 days) SBI plot for an artefact-free recording (model: Post-SE; animal: 27) Seizure 2 Seizure 3 Seizure 4 Seizure 1 Largest inter-ictal SBI 00:00 48:00 96:00 144:00 192:00 240:00 288:00 SBI, relative units Time, hh:mm (12 days) SBI Plot for recording containing strong artefacts (model: Post-SE; animal: Z40) Seizure 1 Seizure 2 Seizure 3 Seizure 4 Seizure 5 Artefacts
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Processing results Number of animals Number of seizures Model
Annotated Detected Verified Post-SE 39 120 124 (+4) 124 PTE 5 43 49 (+6) 49 GAERS 41 8733 8733 8733 WAG/Rij 14 825 825 825 Total 99 9721 9731 9731 All annotated seizures plus some missed by experts were detected (no false-negatives, 100% sensitivity)
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Average reduction of processing time
Max processing time per 1 day record 5 min Min processing time per 1 day record 0.1 min Average processing time per 1 day record 1 min Approximate time spent by expert for visual examination of 1 day record 60 min 60 times Average reduction of processing time (saves 98.3% of time)
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Two major factors ensured such effective performance :
1. An advanced technique of short term spectral analysis based on original Similar Basis Function (SBF) algorithm, which, unlike conventional FFT - is applicable to short time windows - may calculate the Fourier transform within arbitrary frequency band of interest - with arbitrary frequency resolution 2. Discovery of frequency component that is specific for rat ictal EEG
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Conclusions SBIT significantly reduces processing time,
still leaving the final decisions to the expert SBIT is reliable – no false negatives SBIT is easy to use – the default parameters work well and there will be no or little need to change them when applied to rats SBIT will be a substantial aid to researchers in seizure identification in long-term EEG recordings in rats (e.g., pre-clinical research and therapy development)
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Thank you Acknowledgments
We thank Prof. Gilles van Luijtelaar (Radboud University Nijmegen, The Netherlands ) for kindly providing the WAG/Rij rat data.
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