In vivo detection of cortical optical changes associated with seizure activity with optical coherence tomography

Abstract

The most common technology for seizure detection is with electroencephalography (EEG), which has low spatial resolution and minimal depth discrimination. Optical techniques using near-infrared (NIR) light have been used to improve upon EEG technology and previous research has suggested that optical changes, specifically changes in near-infrared optical scattering, may precede EEG seizure onset in in vivo models. Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth resolved cross-sectional images. In this study, OCT was used to detect changes in optical properties of cortical tissue in vivo in mice before and during the induction of generalized seizure activity. We demonstrated that a significant decrease (P < 0.001) in backscattered intensity during seizure progression can be detected before the onset of observable manifestations of generalized (stage-5) seizures. These results indicate the feasibility of minimally-invasive optical detection of seizures with OCT.

Keywords: (100.2960) Image analysis; (110.4500) Optical coherence tomography; (170.3880) Medical and biological imaging.

Fig. 1

Schematic of the SD-OCT system. SLD: superluminescent diode, lsc: line scan camera, gm: galvanometer.

Fig. 2

Reduction in intensity during seizure progression. (A) OCT images of mice brain, one for each experiment, acquired in vivo with axial and lateral resolutions of 8 µm and 20 µm respectively. The red boxes indicate the ROIs used for average intensity calculations. The scale bar is 0.5 mm. (B) Plots of normalized intensity (NI) from the ROIs on left over time. The occurrences of the experimental steps are indicated: S: Saline injection (first red bar), PTZ: PTZ injection (second red bar), FMJ: Facial myoclonic jerks (green dashed line), FS: Full stage-5 seizure (blue dashed line). The gray region is the 2SD interval above and below the mean of the 10 min baseline.

Fig. 3

OCT-detected “optical threshold” precedes myoclonic jerks and full seizure. Latency from PTZ injection (min) displayed for optical threshold (defined as 2SD change in intensity), myoclonic jerks, and full stage-5 (generalized tonic-clonic) seizure. Optical threshold crossing preceded both myoclonic jerks (focal seizure) and generalized seizure, indicating the ability of OCT to optically detect pre-seizure state.

Fig. 4

Plot of the three average slopes: Baseline, Post saline injection, and Post PTZ injection. The average slopes were calculated from four seizure experimental data sets. The interval bars were calculated with a 90% confidence interval using the t-distribution. NI: Normalized Intensity, t: time (min), Inj.: Injection.