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Transcript of 1 Seizure Time Series Analysis I: Seizure Detection, Optimization and Assessment of Seizure...
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Seizure Time Series Analysis I:Seizure Detection, Optimization and
Assessment of Seizure Detection Algorithms
Sridhar Sunderam, Ph.D.Center for Neural Engineering
The Pennsylvania State University
4th Intl. Workshop on Seizure PredictionKansas City, MOJune 4, 2009
1. What to detect, and why:Targets
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Markers of epilepsy Interictal spikes Ripples, Fast ripples High frequency oscillations
Electrographic seizures Clinical seizures
Seizure precursor/Preictal state States of vigilance (?)
Fast ripples or HFOs: 80-500 Hz
Andrzejak et al
Staba et al., 2002
Clinical seizure
1. What to detect, and why:Applications
Treatment GoalsSeizure controlImproved QOL
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www.clevelandclinicmeded.com
TargetsIon channelsReceptors
Antiepileptic drugs
Side-effectsCognitionAllergiesInteractions
SurgeryLocalizationFunction mapping
Electrical stimulation
Uses of detection Diagnose seizure
types and foci Evaluate for surgery Seizure warning Responsive therapy Treatment evaluation
1. What to detect, and why: Performance goals
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All of the above:
Early detection
Sensitivity: frequent hits
Specificity: rare misses
Low false alarm rate: patient anxiety, treatment dose
Low cost (computation/power): implanted devices
Quantitative description:
Not just onset: intensity, duration, spread, dynamics
2. Seizure detection:The jungle out there…
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Any sufficiently advanced technology is indistinguishable from magic
- Arthur C. Clarke
2. Seizure detection:What you really want…
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Signal source Cohort
Focus/semiology Performance
2. Seizure detection:General Framework
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Source
Daly and Wolpaw Lancet Neurology 2008
EEG
ECoG
LFP andspikes
SIGNALCONDITIONING
FEATUREEXTRACTION
SEIZUREFILTERING
POST-PROCESSING
DETECTION
THRESHOLDSEIZURE!
TASKS Source selection Feature selection Filter design Detector design Performance evaluation
2. Seizure detection:Signal conditioning
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SIGNALCONDITIONING
Amplification Antialiasing/bandpass (e.g., 0.5-80 Hz) Sampling (e.g., 200 Hz) Artifact rejection:
Line noise, motion, stim, etc.
Here comes the good data!
Signal
Gotman EEG & Clin Neurophysiol 1982
Elimination of line noise
(Topic of Litt lecture)
2. Seizure detection:Feature extraction
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FEATUREEXTRACTION
One or more features that “look” different during seizure
Good data
Example features
Wave morphology:
Amplitude
Shape…
Spectral characteristics:
Band power
Edge frequency…
Statistics:
Rhythmicity
Entropy…
Seizure Interictal
Mormann et al. Epilepsia 2005
Analysis window
Half wave geometryGotman EEG & Clin Neurophysiol 1982
Line length featureEsteller et al. IEEE-EMBC 2001
2. Seizure detection:Seizure filtering
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SEIZUREFILTERING
Features
Correlate ofSeizure content
Example 1: Wavelet-based FIR filtersOsorio et al, 1998-2007
x(t) * b(t)
X(f) x B(f)
2. Seizure detection:Seizure filtering
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SEIZUREFILTERING
Features
Correlate ofSeizure content
Example 2: Spectrographic signatures of epileptic seizures Schiff et al., Clin Neurophysiol 2000
“Brain chirps”
Stacked in sequential windows
Correlation with seizure chirp
template
2. Seizure detection:Post-processing
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POST-PROCESSING
Seizure contentWell-behaved
output
Background estimationMedian filtering
Meng et al. Med Eng Phys 2004Osorio et al.
Epilepsia 1998
Gotman EEG & Clin Neurophysiol 1982
2. Seizure detection:Detection/Classification
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DETECTION
SEIZURE!
“Smooth” output
DecisionThreshold
SEIZURE
SLEEP
AWAKE
UNIVARIATE
MULTIVARIATE(and multiclass)
DecisionBoundary
3. Seizure Quantification:Why Quantify?
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Detection gives binary output: Is there a seizure (onset)? (Y/N)
There are seizures, and there are seizures… Finer distinctions may be useful
Treatment evaluation: Measures of intensity, duration, spread
Seizure dynamics: Mechanism of initiation, progression or generalization
3. Seizure Quantification:Using SDA output
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Already tracking “seizure content” – just use it
Combine measures to quantify relative severity
Caveat: Must capture the seizure, whole seizure, and nothing but!
Intensity
Duration
Spread
Osorio et al. Epilepsia 1998
3. Seizure Quantification:Time-frequency-energy analysis
18Jouny et al, Clin Neurophysiol 2003
(topic of Franaszczuk lecture)
4. SDA Assessment:Ground Truth
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Human expert scoring is the gold standard Reproducibility, inter-rater reliability less than perfect
Four experts score one event
Wilson et al, Clin Neurophysiol 2003
4. SDA Assessment:Performance Measures
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Spread Single event: Onset delay Offset time Area of spread
DelaySDAoutput TP TP TPFP TNFN
Multiple events:
Error rates: Sensitivity = TP/(TP+FN) Specificity = TN/(FP+TN) Positive prediction value = TP/(TP+FP)
Clustering events affects error rates
4. SDA Assessment:ROC Analysis
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http://www.anaesthetist.com/mnm/stats/roc/Findex.htm
Assess performance Optimize params for:
Early detection Quantification Specific event type Individual/cohort
TPF = Sensitivity FPF = 1-Specificity AUC = area under curve = performance
Non-seizure Seizure
SDA output
Detection threshold
4. SDA Assessment:Optimization
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1. Parameter sensitivity analysis 2. Seizure filter adaptation
Osorio et al. Epilepsia 1998
Haas et al. Med Eng Phys 2007
5. Practical issues:Artifacts
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Line noise, motion, saturation, drop-out, cross-talk…
Mask activity, corrupt background Contribute to false detections Cause information loss Conditioning must flag/remove artifact Detector must disregard artifact Artifacts must not corrupt assessment
Eye-blink
Chewing
Saab & Gotman Clin Neurophysiol 2005
Sun et al. Neurotherapeutics 2008
Stimulation
5. Practical issues:What is a True Negative?
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Specificity = Fraction of non-seizures avoided (some use PPV, or FP/hr) But what is a True Negative?
Whole interval between seizures? But duration varies Interictal epochs = seizure duration? But how selected? Only epochs with interictal activity? Stringent but fair?
Get a superset of detections by relaxing constraints
SDAoutput
Seizure IED
5. Practical issues:Problem with FPR
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FPR = FP per hour A common index of SDA performance
FPR is a practical measure BUT: FPR ≠ 1-Specificity FPR does not reflect seizure rate
Best used in addition to: Sensitivity = TP/(TP+FN) Specificity = TN/(FP+TN) PPV = TP/(TP+FP)
5. Practical issues:Dealing with nonstationarity
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Purves et al. 2001
EEG changes with state of vigilanceTherefore, SDA baseline is a moving target
5. Practical issues:Dealing with nonstationarity
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Malow et al. Epilepsia 1998
Interictal spiking increases with sleep depth in temporal lobe epilepsyState of vigilance monitoring would be useful
5. Practical issues:The price of failure
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Unwarranted anxiety and treatment: False alarms, triggered stimulations
Flawed treatment evaluation: Altered study design: e.g., closed-loop to open-loop stim
Altered statistical power: e.g., retrospective inclusion of FNs
TP FP TP FP TP TP FP TP FP TP
Before: TP FN TP FN TP TP FN TP FN TP
After: TP TP TP TP TP TP TP TP TP TP
Conclusion:Which SDA is the best?
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The bare necessities: Precedes clinical onset Enough lead time High specificity
Why? To avoid cognitive impairment, and… We don’t really know when seizures start
But treating subclinical events may be beneficial Ultimately:
What to detect, How, and WhyIS REALLY UP TO YOU! THANK YOU
Or at least good enough…