Optical coherence tomography for cross-sectional imaging of neural activity.

We report a functional optical coherence tomography cross-sectional scanner to detect neural activity using unmyelinated nerves dissected from squid. The nerves, unstained or stained with a voltage-sensitive dye, were imaged in a nerve chamber. Transient phase changes from backscattered light were detected during action potential propagation. The results show that the scanner can provide high spatiotemporal resolution cross-sectional images of neural activity ([Formula: see text]; [Formula: see text]; [Formula: see text] in [Formula: see text]). The advantage of this method compared to monitoring a single depth profile [Formula: see text] is a dramatic increase in the number of available sites that can be measured in two spatial dimensions [Formula: see text] with lateral scanning; therefore, the study demonstrates that two-dimensional monitoring of small-scale functional activity would also be feasible.

Exponential sum-fitting of dwell-time distributions without specifying starting parameters.

Fitting dwell-time distributions with sums of exponentials is widely used to characterize histograms of open- and closed-interval durations recorded from single ion channels, as well as for other physical phenomena. However, it can be difficult to identify the contributing exponential components. Here we extend previous methods of exponential sum-fitting to present a maximum-likelihood approach that consistently detects all significant exponentials without the need for user-specified starting parameters. Instead of searching for exponentials, the fitting starts with a very large number of initial exponentials with logarithmically spaced time constants, so that none are missed. Maximum-likelihood fitting then determines the areas of all the initial exponentials keeping the time constants fixed. In an iterative manner, with refitting after each step, the analysis then removes exponentials with negligible area and combines closely spaced adjacent exponentials, until only those exponentials that make significant contributions to the dwell-time distribution remain. There is no limit on the number of significant exponentials and no starting parameters need be specified. We demonstrate fully automated detection for both experimental and simulated data, as well as for classical exponential-sum-fitting problems.

Detection of Neural Action Potentials Using Optical Coherence Tomography: Intensity and Phase Measurements with and without Dyes.

We review the use of optical coherence tomography (OCT) for detection of neural activity, and present a new approach for depth-localization of neural action potentials (APs) using voltage-sensitive dyes as contrast agents in OCT. A stained squid giant axon is imaged by spectral-domain OCT. Changes in the intensity and phase of back-scattered light coming from regions around the membrane are measured during AP propagation. The depth-resolved change in back-scattered intensity coincides with the arrival of AP at the measurement area, and is synchronous with the changes in transmitted light intensity and reflection-mode cross-polarized light intensity measured independently. The system also provides depth-resolved phase changes as an additional indication of activity. With further investigation our results could open a new era in functional imaging technology to localize neural activity at different depths in situ.

Low coherence interferometer for sensing retardance change during neural activity.

A variety of optical measurements, including retardance/birefringence change, have revealed transient optical and structural changes associated with action potential propagation. Those changes can be understood better by developing new techniques and improving the current approaches. To detect transient retardance changes in a stimulated nerve, we propose a differential phase technique utilizing two orthogonal polarization channels of a polarization-maintaining fiber based interferometer. The superior sensitivity of the system (10.4 pm) is promising to achieve a non-contact optical measurement of action potential propagation in reflection mode, and to study the transient retardance changes during neural activity.

Optical coherence tomography phase measurement of transient changes in squid giant axons during activity.

Noncontact optical measurements reveal that transient changes in squid giant axons are associated with action potential propagation and altered under different environmental (i.e., temperature) and physiological (i.e., ionic concentrations) conditions. Using a spectral-domain optical coherence tomography system, which produces real-time cross-sectional images of the axon in a nerve chamber, axonal surfaces along a depth profile are monitored. Differential phase analyses show transient changes around the membrane on a millisecond timescale, and the response is coincident with the arrival of the action potential at the optical measurement area. Cooling the axon slows the electrical and optical responses and increases the magnitude of the transient signals. Increasing the NaCl concentration bathing the axon, whose diameter is decreased in the hypertonic solution, results in significantly larger transient signals during action potential propagation. While monophasic and biphasic behaviors are observed, biphasic behavior dominates the results. The initial phase detected was constant for a single location but alternated for different locations; therefore, these transient signals acquired around the membrane appear to have local characteristics.