Automated algorithm for GI spike burst detection and demonstration of efficacy in ischemic small intestine

Abstract

We present a novel, fully-automated gastrointestinal spike burst detection algorithm. Following pre-processing with SALPA (Wagenaar and Potter, J. Neurosci. Methods 120:113-120, 2002) and a Savitzky-Golay filter to remove unwanted low and high frequency components, candidate spike waveforms are detected utilizing the non-linear energy operator. Candidate waveforms are classified as spikes or artifact by a support vector machine. The new method achieves highly satisfactory performance with >90% sensitivity and positive prediction value. We also demonstrate an application of the new method to detect changes in spike rate and spatial propagation patterns upon induction of mesenteric ischemia in the small intestine. Spike rates were observed to transiently increase 10-20 fold for a duration of ≈600 s, relative to baseline conditions. In ischemic conditions, spike activity propagation patterns included retrograde-longitudinal wavefronts with occasional spontaneous conduction blocks, as well as self-terminating concentric-circumferential wavefronts. Longitudinal and circumferential velocities were 6.8-8.0 cm/s and 18.7 cm/s, respectively.

Figure 1

Top: Representative raw electrode signal (gray trace) and SALPA + SG filtered signal (black trace). Bottom: Energy signal. The dash-dotted line marks the energy detection threshold. The window in which SVM features are computed is demarcated by the horizontal line terminating in squares. The lower threshold is indicated by the dotted line, and the horizontal bars terminating in left and right triangles demarcate the on and off time search windows, respectively. A spike burst occurs from ≈ 3.4 - 4.7 s. Regular cardiac artifacts are seen in the signals at approximately 0.75 s intervals.

Figure 2

Spike bursts with automated marks for on and off times (green and red vertical dashes). SALPA + SG-filtered traces are shown in black, with selected raw signals shown in gray. Tick marks on the abscissa are spaced at 2 s. Green and red vertical dashes indicate a 70 μV scale. Three successive waves of spike activity occur at intervals of approximately 8 s. All marks are validated as true positives, except two false negatives occurred during the 3rd wave of activity on 5th and 7th traces from top, likely due to their relatively small amplitude. The effect of the SALPA filter removing the baseline wander and (possibly) SWs indicated by sharper transients (e.g. 1st and 3rd traces, 2 s prior to 2nd wave of activity) is evident. The effect of the SG removing high frequency noise is illustrated in the 10th trace. Spike burst detection results shown are for δt = 0.5 s.

Figure 3

Sensitivity (Sens.) and positive prediction value (PPV) vs. NEO detection threshold parameter, η, for the five data sets (Vanderbilt: blue, red, and black; Auckland: green and magenta). Only results for η ≥ 3 are shown for clarity. Sens. decreases with increasing η due to an increasing rate of false negatives. PPV remains fairly constant with increasing η due to SVM classification. Data shown for δt = 1.5, λ = 2. The metrics averaged across all 5 data sets are also shown (right-most panel). Mean ± s.d. are plotted.

Figure 4

Array-wide spike burst rate for localized total ischemia demonstration study. Results for three separate experiments are shown. The ordinate values (“Num. Spikes”) indicate the total number spike bursts observed across the entire electrode array during a 30 s window. Results are aligned on the abscissa such that, following a baseline period, 100% ischemia was induced at 0 s. Typically, the spike rate showed a marked increase followed by a decrease to near-baseline levels. For two experiments (red and black traces), there was a delay time of about 150 s before the spike rate started to increase; no such lag was observed for the other experiment (blue trace).

Figure 5

Array-wide spike burst rate for progressive ischemia, normalized to the maximum spike rate observed (at about 3900 s). Baseline period: 0–1800s. Arrowheads indicate times at which 50, 75, 90, 100% ischemia were induced, respectively. A 2 to 4-fold transient increase in spike rate lasting about 210 s was observed for upon inducing each successively more severe level of ischemia.

Figure 6

Isochrone activation map and representative electrograms. During the experiment, the 32×128 mm array (4 mm inter-electrode spacing), shown here in planar projection, was wrapped around the circumference of the small intestine such that the left and right borders were nearly adjacent, positioned on either side of the mesenteric blood supply arcade. Red and blue colors indicate the earliest and latest spike activity on times, respectively. Isochrone contours are drawn at 100 ms intervals. A longitudinal wave propagates in the retrograde direction with an average velocity of about 8 cm/s over a segment ≈ 92 mm in length. Electrode sites are marked by a black dot if a spike burst was detected at that location, or colored white with red perimeter if no spike was detected. Larger black circles indicate sites corresponding to SALPA + SG-filtered electrograms shown at right. Tick marks on abscissa indicate 500 ms intervals. Spike burst on and off times are marked with green and red vertical dashes. The dashed arrow highlights the retrograde propagation pattern.

Figure 7

Longitudinal and circumferential propagation of spike burst activity in fully ischemic small intestine and representative electrograms. Tick marks on abscissa indicate 500 ms intervals. Triangle and circle symbols at left of each electrogram are keyed to the electrode locations marked in the right most frames of the animation sequence. Downward-pointing arrowhead on abscissa marks the first spike burst on-time; numeric values at bottom of each frame indicate relative elapsed time in units of ms. Line of conduction block and dotted arrow correspond to two main waves of spike activity illustrated in frame sequences below. The on-time of a spike burst at a single electrode is indicated by a bright red pixel, set to progressively fade to white in 250 ms, in order to help visualize the propagation pattern. Square edge length represents 4 mm. Top row of frames (0–350 ms) shows a longitudinal wave of spike activity that propagated at 6.8 cm/s in the retrograde direction, self-terminating after covering a distance of 24 mm. Corresponding line of conduction block is indicated in electrograms 5–12, toward left. Bottom row of frames (1725–2075 ms) illustrates concentric-circumferentially propagating spike activity initiated on the edge of the electrode array adjacent to the mesenteric blood supply arcade (denoted by “M”) traveling around the entire electrode array (outer diameter of a intestinal segment) with a velocity of 18.7 cm/s. Dotted arrow overlaid on bottom 8 electrograms highlights this propagation pattern.