Imaging brain activity during seizures in freely behaving rats using a miniature multi-modal imaging system.

Iliya Sigal,Raanan Gad,Melanie Jeffrey,Bojana Stefanovic,Ofer Levi,Peter L Carlen,Dene Ringuette,Margaret M Koletar

doi:10.1364/boe.7.003596

Abstract

We report on a miniature label-free imaging system for monitoring brain blood flow and blood oxygenation changes in awake, freely behaving rats. The device, weighing 15 grams, enables imaging in a ∼ 2 × 2 mm field of view with 4.4 μm lateral resolution and 1 - 8 Hz temporal sampling rate. The imaging is performed through a chronically-implanted cranial window that remains optically clear between 2 to > 6 weeks after the craniotomy. This imaging method is well suited for longitudinal studies of chronic models of brain diseases and disorders. In this work, it is applied to monitoring neurovascular coupling during drug-induced absence-like seizures 6 weeks following the craniotomy.

Highlights

Monitoring neurovascular coupling (NVC), or the response of the brain vasculature to the changes in neuronal activity, is key to understanding various brain diseases and disorders such as epilepsy [1, 2], stroke [3], and Alzheimer’s disease [4]
A common challenge in monitoring NVC in animal disease models is the presence of anaesthesia, which confounds NVC [9], strongly perturbs neuronal activity, cerebral blood flow, cerebral metabolic rate of oxygen consumption, and prevents neuroimaging during animal behavior
In this paper we demonstrate a novel head-mounted device for wide field imaging of brain blood flow and brain blood oxygenation changes in awake, freely-moving rats with high spatiotemporal resolution, using a chronically-implanted cranial window

Summary

Introduction

Monitoring neurovascular coupling (NVC), or the response of the brain vasculature to the changes in neuronal activity, is key to understanding various brain diseases and disorders such as epilepsy [1, 2], stroke [3], and Alzheimer’s disease [4]. NVC, which can serve as surrogate to neuronal activity, can be monitored by a wide range of optical techniques that measure changes in brain blood flow and oxygenation, including Diffuse Optical Tomography (DOT) [5], Diffuse Correlation Spectroscopy (DCS) [6], Intinsic Optical Signal Imaging (IOSI) [7], and Laser Speckle Contrast Imaging (LSCI) [8]. In response to the aforementioned challenge, significant effort has been made to miniaturize brain imaging systems that are mounted on, or implanted in, rodents’ heads [10, and references therein]. Most such systems were designed to image fluorescently-labeled neuronal activation or ion dynamics, and relatively few studies showed in-vivo imaging of vascular dynamics in awake rat brains. Et al, [13] and Lu, et al, [14] combined LSCI with IOSI for simultaneous measurement of cortical blood flow speeds and changes in oxygenated and deoxygenated hemoglobin (HbO and HbR, respectively) concentrations in tissue and vessels

Methods

Results

Conclusion