Adam J. Black

Reconstructing micrometer-scale fiber pathways in the brain: Multi-contrast optical coherence tomography based tractography

Comprehensive understanding of connective neural pathways in the brain has put great challenges on the current imaging techniques, for which three-dimensional (3D) visualization of fiber tracts with high spatiotemporal resolution is desirable. Here we present optical imaging and tractography of rat brain ex-vivo using multi-contrast optical coherence tomography (MC-OCT), which is capable of simultaneously generating depth-resolved images of reflectivity, phase retardance, optic axis orientation and, for in-vivo studies, blood flow images. Using the birefringence property of myelin sheath, nerve fiber tracts as small as a few tens of micrometers can be resolved and neighboring fiber tracts with different orientations can be distinguished in cross-sectional optical slices, 2D en-face images and 3D volumetric images. Combinational contrast of MC-OCT images enables visualization of the spatial architecture and nerve fiber orientations in the brain with unprecedented detail. The results suggest that optical tractography, by virtue of its direct accessibility to nerve fibers, has the potential to validate diffusion magnetic resonance images and investigate structural connections in normal brain and neurological disorders. In addition, an endoscopic MC-OCT may be useful in neurosurgical interventions to aid in placement of deep brain stimulating electrodes.

Optical coherence tomography for cross-sectional imaging of neural activity

Abstract. 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 (15  μs/A-line; 0.25  ms/B-scan; ∼8.5×5.5  μm2 in xz). The advantage of this method compared to monitoring a single depth profile z is a dramatic increase in the number of available sites that can be measured in two spatial dimensions xz with lateral scanning; therefore, the study demonstrates that two-dimensional monitoring of small-scale functional activity would also be feasible.

Quantifying three-dimensional optic axis using polarization-sensitive optical coherence tomography.

The optic axis of birefringent samples indicates the direction of optical anisotropy, which should be described in three-dimensional (3-D) space. We present a method to quantify the complete 3-D optic axis orientation calculated from in-plane optic axis measurements from a polarization-sensitive optical coherence tomography system. The in-plane axis orientations with different illumination angles allow the calculation of the necessary polar angle. The method then provides the information to produce the actual birefringence. The method and results from a biological sample are presented.

New System for Digital to Analog Transformation and Reconstruction of 12-Lead ECGs

Introduction We describe initial validation of a new system for digital to analog conversion (DAC) and reconstruction of 12-lead ECGs. The system utilizes an open and optimized software format with a commensurately optimized DAC hardware configuration to accurately reproduce, from digital files, the original analog electrocardiographic signals of previously instrumented patients. By doing so, the system also ultimately allows for transmission of data collected on one manufacturers 12-lead ECG hardware/software into that of any other. Materials and Methods To initially validate the system, we compared original and post-DAC re-digitized 12-lead ECG data files (∼5-minutes long) in two types of validation studies in 10 patients. The first type quantitatively compared the total waveform voltage differences between the original and re-digitized data while the second type qualitatively compared the automated electrocardiographic diagnostic statements generated by the original versus re-digitized data. Results The grand-averaged difference in root mean squared voltage between the original and re-digitized data was 20.8 µV per channel when re-digitization involved the same manufacturers analog to digital converter (ADC) as the original digitization, and 28.4 µV per channel when it involved a different manufacturers ADC. Automated diagnostic statements generated by the original versus reconstructed data did not differ when using the diagnostic algorithm from the same manufacturer on whose device the original data were collected, and differed only slightly for just 1 of 10 patients when using a third-party diagnostic algorithm throughout. Conclusion Original analog 12-lead ECG signals can be reconstructed from digital data files with accuracy sufficient for clinical use. Such reconstructions can readily enable automated second opinions for difficult-to-interpret 12-lead ECGs, either locally or remotely through the use of dedicated or cloud-based servers.

Spectral-domain low-coherence interferometry for phase-sensitive measurement of Faraday rotation at multiple depths

We describe a method for differential phase measurement of Faraday rotation from multiple depth locations simultaneously. A polarization-maintaining fiber-based spectral-domain interferometer that utilizes a low-coherent light source and a single camera is developed. Light decorrelated by the orthogonal channels of the fiber is launched on a sample as two oppositely polarized circular states. These states reflect from sample surfaces and interfere with the corresponding states of the reference arm. A custom spectrometer, which is designed to simplify camera alignment, separates the orthogonal channels and records the interference-related oscillations on both spectra. Inverse Fourier transform of the spectral oscillations in k-space yields complex depth profiles, whose amplitudes and phase difference are related to reflectivity and Faraday rotation within the sample, respectively. Information along a full depth profile is produced at the camera speed without performing an axial scan for a multisurface sample. System sensitivity for the Faraday rotation measurement is 0.86 min of arc. Verdet constants of clear liquids and turbid media are measured at 687 nm.

Quantifying axis orientation in 3D using polarization-sensitive optical coherence tomography(Conference Presentation)

The optic axis of birefringent tissues indicates the direction of structural anisotropy. Polarization-sensitive Optical Coherence Tomography (PS-OCT) can provide reflectivity contrast as well as retardance and optic axis orientation contrasts that originate from tissue birefringence. We introduce imaging 3D tissue anisotropy by using a single-camera and polarization-maintaining fiber (PMF) based PS-OCT, which utilizes normal and angled illuminations. Because environmental factors such as the movement of PMF and temperature fluctuations induce arbitrary phase changes, the optic axis orientation measurement has a time-varying offset. In order to measure the absolute axis orientation, we add a calibration path which dynamically provides the arbitrary offset to be subtracted from the relative axis orientation values. The axis orientation on the normal plane is the 2D projection of the fiber direction in 3D space. We propose to characterize the axis orientation in different planes (xy, xy’ and x’y planes) by using normal and angled illuminations. This allows calculation of the polar angle that completes the orientation information in 3D. Polarization-based optical systems relying on one illumination angle measure the “apparent birefringence” that light encounters rather than the “true birefringence”. Birefringence as a measure of anisotropy is quantified with the orientation information in 3D. The method and validation with a biological tissue are presented. The study can facilitate imaging and mapping the structural connections in anisotropic tissues including the brain.

Polarization-based balanced detection for spectral-domain optical coherence tomography

We present a new design for spectral-domain optical coherence tomography that allows balanced detection using a single camera. The design uses polarization optics to encode the light in reference and sample arms. Two parallel and highly aligned spectra, which carry out-of-phase interference signals, in-phase common noise, and auto-interference terms, are focused on the camera, which performs the digital balanced detection for each wavelength. The optical system is characterized and tested for tissue imaging. Results demonstrate consistent signal gains in depth and suppression of DC and sample auto-interference. The design could be further amended for polarization-sensitive imaging and might demonstrate a market for manufacturing dual-line cameras with analog-balanced detection capability.