Emily J. McDowell

Methods and application areas of endoscopic optical coherence tomography

We review the current state of research in endoscopic optical coherence tomography (OCT). We first survey the range of available endoscopic optical imaging techniques. We then discuss the various OCT-based endoscopic methods that have thus far been developed. We compare the different endoscopic OCT methods in terms of their scan performance. Next, we examine the application range of endoscopic OCT methods. In particular, we look at the reported utility of the methods in digestive, intravascular, respiratory, urinary and reproductive systems. We highlight two additional applications--biopsy procedures and neurosurgery--where sufficiently compact OCT-based endoscopes can have significant clinical impacts.

An in vivo study of turbidity suppression by optical phase conjugation (TSOPC) on rabbit ear

We present a holography-based in vivo optical phase conjugation experiment performed on a living rabbit ear. The motion of live tissues caused the phase conjugate signal to decay with a consistent decay time of less than two seconds. We monitor the signal decay time variation after the ear is excised to postulate different mechanisms that cause the signal decay. The experimental findings address the minimum speed limit of a broad range of optical time reversal experiments for in vivo applications on tissues.

Characterization of light collection through a subwavelength aperture from a point source

We experimentally measure and theoretically model the light transmission characteristics of subwavelength apertures. The characterization consists of translating a point source at varying vertical height and lateral displacement from the aperture and measuring the resulting transmission. We define the variation of the transmission with lateral source displacement as the collection mode point spread function (CPSF). This transmission geometry is particularly relevant to subwavelength aperture based imaging devices and enables determination of their resolution. This study shows that the achieved resolutions degrade as a function of sample height and that the behavior of sensor devices based on the use of apertures for detection is different from those devices where the apertures are used as light sources. In addition, we find that the measured CPSF is dependent on the collection numerical aperture (NA). Finally, we establish that resolution beyond the diffraction limit for a nominal optical wavelength of 650 nm and nominal medium refractive index of 1.5 is achievable with subwavelength aperture based devices when the aperture size is smaller than 225 nm.

Turbidity suppression from the ballistic to the diffusive regime in biological tissues using optical phase conjugation

We describe the amplitude and resolution trends of the signals acquired by turbidity suppression through optical phase conjugation (TSOPC) with samples that span the ballistic and diffusive scattering regimes. In these experiments, the light field scattered through a turbid material is written into a hologram, and a time-reversed copy of the light field is played back through the sample. In this manner, the wavefront originally incident on the sample is reconstructed. We examine a range of scattering samples including chicken breast tissue sections of increasing thickness and polyacrylamide tissue-mimicking phantoms with increasing scattering coefficients. Our results indicate that only a small portion of the scattered wavefront (<0.02%) must be collected to reconstruct a TSOPC signal. Provided the sample is highly scattering, all essential angular information is contained within such small portions of the scattered wavefront due to randomization by scattering. A model is fitted to our results, describing the dependence of the TSOPC signal on other measurable values within the system and shedding light on the efficiency of the phase conjugation process. Our results describe the highest level of scattering that has been phase conjugated in biological tissues to date.

Spectral domain phase microscopy for local measurements of cytoskeletal rheology in single cells

We present spectral domain phase microscopy (SDPM) as a new tool for measurements at the cellular scale. SDPM is a functional extension of spectral domain optical coherence tomography that allows for the detection of cellular motions and dynamics with nanometer-scale sensitivity in real time. Our goal was to use SDPM to investigate the mechanical properties of the cytoskeleton of MCF-7 cells. Magnetic tweezers were designed to apply a vertical force to ligand-coated magnetic beads attached to integrin receptors on the cell surfaces. SDPM was used to resolve cell surface motions induced by the applied stresses. The cytoskeletal response to an applied force is shown for both normal cells and those with compromised actin networks due to treatment with Cytochalasin D. The cell response data were fit to several models for cytoskeletal rheology, including one- and two-exponential mechanical models, as well as a power law. Finally, we correlated displacement measurements to physical characteristics of individual cells to better compare properties across many cells, reducing the coefficient of variation of extracted model parameters by up to 50%.

Observation of polarization-gate based reconstruction quality improvement during the process of turbidity suppression by optical phase conjugation

We present experiments that study the impact of polarization selection on the phenomenon of turbidity suppression by optical phase conjugation. Counter to intuition, we discovered that the preferential utilization of multiply scattered light field components over their sparsely scattered counterparts via appropriate polarization selection can lead to better image reconstruction quality. This effect was observed with tissue phantoms and biological tissue sections. The physical origin of this effect and its dependence on scatterer properties are discussed.

Manual-scanning optical coherence tomography probe based on position tracking

A method based on position tracking to reconstruct images for a manual-scanning optical coherence tomography (OCT) probe is proposed and implemented. The method employs several feature points on a hand-held probe and a camera to track the devices pose. The continuous device poses tracking, and the collected OCT depth scans can then be combined to render OCT images. The tracking accuracy of the system was characterized to be about 6 microm along two axes and 19 microm along the third. A phantom target was used to validate the method. In addition, we report OCT images of a 54-stage Xenopus laevis tadpole acquired by manual scanning.

Molecular contrast optical coherence tomography: a pump-probe scheme using indocyanine green as a contrast agent

The use of indocyanine green (ICG), a U.S. Food and Drug Administration approved dye, in a pump-probe scheme for molecular contrast optical coherence tomography (MCOCT) is proposed and demonstrated for the first time. In the proposed pump-probe scheme, an optical coherence tomography (OCT) scan of the sample containing ICG is first acquired. High fluence illumination (approximately 190 kJ/cm2) is then used to permanently photobleach the ICG molecules--resulting in a permanent alteration of the overall absorption of the ICG. A second OCT scan is next acquired. The difference of the two OCT scans is used to determine the depth resolved distribution of ICG within a sample. To characterize the extent of photobleaching in different ICG solutions, we determine the cumulative probability of photobleaching, phi(B,cum), defined as the ratio of the total photobleached ICG molecules to the total photons absorbed by the ground state molecules. An empirical study of ICG photobleaching dynamics shows that phi(B,cum) decreases with fluence as well as with increasing dye concentration. The quantity phi(B,cum) is useful for estimating the extent of photobleaching in an ICG sample (MCOCT contrast) for a given fluence of the pump illumination. The paper also demonstrates ICG-based MCOCT imaging in tissue phantoms as well as within stage 54 Xenopus laevis.

Fundamental sensitivity limit imposed by dark 1/f noise in the low optical signal detection regime

The impact of dark 1/f noise on fundamental signal sensitivity in direct low optical signal detection is an understudied issue. In this theoretical manuscript, we study the limitations of an idealized detector with a combination of white noise and 1/f noise, operating in detector dark noise limited mode. In contrast to white noise limited detection schemes, for which there is no fundamental minimum signal sensitivity limit, we find that the 1/f noise characteristics, including the noise exponent factor and the relative amplitudes of white and 1/f noise, set a fundamental limit on the minimum signal that such a detector can detect.

A generalized noise variance analysis model and its application to the characterization of 1/f noise

We present a novel generalized model for the analysis of noise with a known spectral density. This model is particularly appropriate for the analysis of noise with a 1/f(a) distribution in a homodyne interferometer. The noise model reveals that, for alpha>1, 1/f(a) noise significantly impacts the homodyne signal-to-noise ratio (SNR) for integration times that near a characteristic time, beyond which the SNR will no longer significantly improve with increasing integration time. We experimentally verify our theoretical findings with a set of experiments employing a quadrature homodyne optical coherence tomography (OCT) system, finding good agreement. The characteristic integration time is measured to be approximately 2 ms for our system. Additionally, we find that the 1/f noise characteristics, including the exponent, alpha, as well as the characteristic integration time, are system and photodetector dependent.