The development of label-free imaging technologies that directly assess neural activity remains a pressing need. Among a variety of techniques that aim to detect transient signals associated with action potential (AP) propagation, optical techniques have the potential for revealing and locating APs with high spatio- temporal resolution. For instance, differential-phase interferometry and then phase-sensitive measurements of spectral-domain optical coherence tomography (OCT) have allowed us to detect AP- related nanometer-scale transient structural changes from unmyelinated invertebrate axons. To obtain useful tests of nerve function, however, investigations on contrast enhancement methods for both myelinated and unmyelinated nerve fibers are needed. The long term goal of this project is to provide non- contact depth-resolved optical measurements of nerve function that are useful in basic scientific research. The overall objective of this project is to use multi-contrast OCT and contrast enhancement methods for depth-resolved label-free imaging of neural activity in myelinated and unmyelinated nerve models. The hypothesis behind the work is that a properly directed external static magnetic field generates Lorentz force in functioning nerve (due to ionic movements / action currents), which consequently induces a mechanical wave accompanying AP propagation and facilitates the optical imaging of neural activity. Phase-sensitive OCT is well poised to locate such transient signals with sub-nanometer sensitivity. We will also monitor the intensity (reflectivity) and birefringence (retardance) signals as additional indications of neural activity. To achieve the objective of this application, we will pursue optical imaging of neural activity based on Lorentz effect in ex-vivo preparations (Specific Aim 1) and in-vivo visual cortex (Specific Aim 2). With successful completion of the proposed work, we will achieve the following outcomes. The feasibility of using Lorentz effect to aid label-free optical imaging of APs will be revealed. This will also inform people in related imaging fields to determine whether the Lorentz effect imaging is within the capabilities of current technology. If our work is shown to be useful, it will support functional neural investigations in laboratory setting. The results may also suggest more challenging in-vivo applications that require incorporation of active tracking systems for the needed stability.
The proposed research is relevant to providing label-free depth-resolved optical imaging of nerve function. The results are expected to advance scientific studies and to help assess feasibility of the technique for its use in research and practice.
