Optical imaging methods have become very powerful tools in biomedical research since they can achieve both high spatial and temporal resolutions. However, due to the effects of light scattering, the penetration depth of optical imaging methods is usually limited. Gradient refractive index (GRIN) lens that are 350–2,000 μm in diameter and provide micron-scale resolution have been shown to enable minimally invasive in vivo imaging of deep tissues. Based on GRIN lens, we developed a small hand-held optical coherence tomography (OCT) forward-imaging needle device for real-time epidural anesthesia surgery guidance and demonstrated its feasibility through ex vivo and in vivo animal experiments. Besides, to access subcortical brain structures, we combined voltage-sensitive dye imaging (VSDi) with GRIN lens to image neural activities evoked in thalamic barreloids by deflection of whiskers in vivo in the whisker system of rodents.