System Design Of Miniature Head-mounted Brain Functional Optical Imagers In Freely Moving Animals

The functional brain imaging has provided an unprecedented method to study brain organization and functional disruption due to various neurological diseases.The conventional brain imaging techniques require animals to be anesthetized and restrained,in order to minimize motion artifacts.However,anesthetics have confounding effects on physiologic condition,neural activity,brain metabolism,cerebral blood flow and many other parameters,and thus limit the in vivo brain function study.Therefore,head-mounted imaging systems which could be applied to freely-moving animals were designed and developed in the past decade.Optical imaging technologies,especially endogenous optical imaging methods,have shown great advantage in these applications,including high temporal and spatial resolution,relatively simple system setup and non-invasiveness without injection of exogenous contrast agents.With the development in optics and electrical engineering,several miniature endogenous optical imaging systems that can be applied to freely moving rats.However,these systems are still too large and heavy for small animals,which constrains their applications.The fiber-optic-based imager,on the other hand,would induce dense grid and information loss.In this study,we designed two miniature imagers based on two full-field endogenous optical imaging methods,i.e.,Laser Speckle Contrast Imaging(LSCI)and Optical Intrinsic Signal Imaging(OISI),respectively.The LSCI imager(4.5 g in weight,2.2 cm in height)could monitor the real-time cerebral blood flow changes for an area of ~ 8.4 mm ×6 mm in awake animals.The major components include a micro CMOS chip(frame rate: 46 fps;field of interest: 300×420 pixels),a microlens system fixed onto a 3D-printed nylon supporting frame and a fiber bundle for illumination.The OISI imager can investigate the real time concentration variations of oxyhemoglobin(HbO)and deoxyhemoglobin(HbR)in freely-moving animals with high resolution.For multi-wavelength imaging,two separate optical fiber bundles transmit the lights from light emitting diodes(LEDs)sources with 590-nm and 625-nm wavelength,respectively.The light sources were triggered by Single Chip Microcomputer in order to alternately illuminate the region of interest.The high-speed switch was strictly controlled by the dual-thread program.The imager is light and tiny(weight: ~3 g;height: ~1.2 cm)with good performance(frame rate: 25 fps;field of interest: 250×250 pixels).As an application and demonstration,we studied the hemodynamic change during the photothrombotic focal cerebral cortex ischemic lesion model of rat.