Taner Akkin

Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging

We describe a novel microscopy technique for quantitative phase-contrast imaging of a transparent specimen. The technique is based on depth-resolved phase information provided by common path spectral-domain optical coherence tomography and can measure minute phase variations caused by changes in refractive index and thickness inside the specimen. We demonstrate subnanometer level path-length sensitivity and present images obtained on reflection from a known phase object and human epithelial cheek cells.

Detection of neural activity using phase-sensitive optical low-coherence reflectometry

We demonstrate non-contact sub-nanometer optical measurement of neural surface displacement associated with action potential propagation. Experimental results are recorded from nerve bundles dissected from crayfish walking leg using a phase-sensitive optical low coherence reflectometer. No exogenous chemicals or reflection coatings are applied. Transient neural surface displacement is less than 1 nm in amplitude, 1 ms in duration and is coincident with action potential arrival to the optical measurement site. Because the technique uses back-reflected light, noninvasive detection of various neuropathies may be possible.

Retinal nerve fiber layer thickness map determined from optical coherence tomography images

We introduce a method to determine the retinal nerve fiber layer (RNFL) thickness in OCT images based on anisotropic noise suppression and deformable splines. Spectral-Domain Optical Coherence Tomography (SDOCT) data was acquired at 29 kHz A-line rate with a depth resolution of 2.6 mum and a depth range of 1.6 mm. Areas of 9.6x6.4 mm2 and 6.4x6.4 mm2 were acquired in approximately 6 seconds. The deformable spline algorithm determined the vitreous-RNFL and RNFL-ganglion cell/inner plexiform layer boundary, respectively, based on changes in the reflectivity, resulting in a quantitative estimation of the RNFL thickness. The thickness map was combined with an integrated reflectance map of the retina and a typical OCT movie to facilitate clinical interpretation of the OCT data. Large area maps of RNFL thickness will permit better longitudinal evaluation of RNFL thinning in glaucoma.

Polarization-maintaining fiber-based optical low-coherence reflectometer for characterization and ranging of birefringence

We describe a polarization-maintaining fiber-based polarization-sensitive optical low-coherence reflectometer for measurement of depth-resolved birefringence. Unlike for other fiber-based polarization-sensitive optical low-coherence reflectometers, here the linear birefringence of a sample can be measured from data recorded in a single A scan. Simultaneous measurement of retardation and orientation of birefringent axes with mica wave plates is demonstrated. The measured retardation is insensitive to sample rotation in the plane perpendicular to ranging.

Spectral domain polarization-sensitive optical coherence tomography at 850 nm

Spectral-Domain Polarization-Sensitive Optical Coherence Tomography (SD-PS-OCT) is a technique developed to measure the thickness and birefringence of the nerve fiber layer in vivo as a tool for the early diagnosis of glaucoma. A clinical SD-PS-OCT system was developed and scans were made around the optic nerve head (ONH) using ten concentric circles of increasing diameter. One healthy volunteer was imaged. Retinal nerve fiber layer thickness and birefringence information was extracted from the data. Polarization-sensitive OCT images were acquired at video rate (29 frames per second (fps), 1000 A-lines / frame) and at 7 fps (1000 A-lines / frame). The last setting improved the signal to noise ratio by approximately 6 dB. Birefringence measurements on the healthy volunteer gave similar results as earlier reported values that were obtained with a time-domain setup. The measurement time was reduced from more than a minute to less than a second.

Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.

We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.

Significantly Improved Analytical Sensitivity of Lateral Flow Immunoassays by Using Thermal Contrast

The ability to rapidly identify diseases enables prompt treatment and improves outcomes. This has increased the development and use of rapid point-of-care diagnostic devices capable of biomolecular detection in both high-income and resource-limited settings.[1] Lateral flow assays (LFAs) are inexpensive, simple, portable, and robust,[2] making LFAs commonplace in medicine, agriculture, and over-the-counter personal use such as for pregnancy testing. Although the analytical performance of some LFAs are comparable to laboratory based methods,[1a] the sensitivity of most LFAs is in the mM to μM range,[2–3] which is many folds less sensitive than other molecular techniques such as enzyme-linked immunoassays (ELISA). As a consequence, LFAs are not particularly useful for detection early in a disease course when there is low level of antigen. Due to the increasing need for highly sensitive molecular diagnostics, researchers have focused on developing microfluidics,[1a, 1b] biobar codes,[1c, 1d] and enzyme-based immunoassay technologies[4] technologies to fulfill the need since these technologies have nM to pM detection sensitivity for protein analysis and can potentially be miniaturized as handheld point-of-care diagnostic devices.[1c] These emerging technologies are still early in development and are not yet field-ready.

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.

Phase-sensitive optical low-coherence reflectometry for the detection of analyte concentrations

Optical techniques may potentially be used for noninvasive glucose sensing. We investigated the application of phase-sensitive optical low-coherence reflectometry (PS-OLCR) to the measurement of analyte concentrations. The dependence of the PS-OLCR signal on the concentration of various analytes, including aqueous solutions of glucose, calcium chloride, magnesium chloride, sodium chloride, potassium chloride, potassium bicarbonate, urea, bovine serum albumin, and bovine globulin, were determined in clear and turbid media. Obtained results demonstrated (1) a high degree of sensitivity and accuracy of the phase measurements of analyte concentrations with PS-OLCR; (2) a concentration-dependent change in the phase-shift for glucose that is significantly greater than that of other analytes sampled over the same physiological range; and (3) a high submillimolar sensitivity of PS-OLCR for the measurement of glucose concentration. Further exploration of the application of PS-OLCR to the noninvasive, sensitive, and specific monitoring of glucose concentration seems warranted.

Blockface histology with optical coherence tomography: A comparison with Nissl staining

Spectral domain optical coherence tomography (SD-OCT) is a high resolution imaging technique that generates excellent contrast based on intrinsic optical properties of the tissue, such as neurons and fibers. The SD-OCT data acquisition is performed directly on the tissue block, diminishing the need for cutting, mounting and staining. We utilized SD-OCT to visualize the laminar structure of the isocortex and compared cortical cytoarchitecture with the gold standard Nissl staining, both qualitatively and quantitatively. In histological processing, distortions routinely affect registration to the blockface image and prevent accurate 3D reconstruction of regions of tissue. We compared blockface registration to SD-OCT and Nissl, respectively, and found that SD-OCT-blockface registration was significantly more accurate than Nissl-blockface registration. Two independent observers manually labeled cortical laminae (e.g. III, IV and V) in SD-OCT images and Nissl stained sections. Our results show that OCT images exhibit sufficient contrast in the cortex to reliably differentiate the cortical layers. Furthermore, the modalities were compared with regard to cortical laminar organization and showed good agreement. Taken together, these SD-OCT results suggest that SD-OCT contains information comparable to standard histological stains such as Nissl in terms of distinguishing cortical layers and architectonic areas. Given these data, we propose that SD-OCT can be used to reliably generate 3D reconstructions of multiple cubic centimeters of cortex that can be used to accurately and semi-automatically perform standard histological analyses.