Automatically Determining the Confocal Parameters From OCT B-Scans for Quantification of the Attenuation Coefficients.

The attenuation coefficient is a relevant biomarker for many diagnostic medical applications. Recently, the Depth-Resolved Confocal (DRC) technique was developed to automatically estimate the attenuation coefficients from Optical Coherence Tomography (OCT) data with pixel-level resolution. However, DRC requires that the confocal function parameters (i.e., focal plane location and apparent Rayleigh range) be known a priori. In this paper, we present the autoConfocal algorithm: a simple, automatic method for estimating those parameters directly from OCT imagery when the focal plane is within the sample. We present autoConfocal+DRC results on phantom data, ex-vivo biological tissue data, and in-vivo clinical data.

Low-power, low-cost urinalysis system with integrated dipstick evaluation and microscopic analysis.

We introduce a coupled dipstick and microscopy device for analyzing urine samples. The device is capable of accurately assessing urine dipstick results while simultaneously imaging the microscopic contents within the sample. We introduce a long working distance, cellphone-based microscope in combination with an oblique illumination scheme to accurately visualize and quantify particles within the urine sample. To facilitate accurate quantification, we couple the imaging set-up with a power-free filtration system. The proposed device is reusable, low-cost, and requires very little power. We show that results obtained with the proposed device and custom-built app are consistent with those obtained with the standard clinical protocol, suggesting the potential clinical utility of the device.

Robust dipstick urinalysis using a low-cost, micro-volume slipping manifold and mobile phone platform.

We introduce a novel manifold and companion software for dipstick urinalysis that eliminate many of the aspects that are traditionally plagued by user error: precise sample delivery, accurate readout timing, and controlled lighting conditions. The proposed all-acrylic slipping manifold is reusable, reliable, and low in cost. A simple timing mechanism ensures results are read out at the appropriate time. Results are obtained by capturing videos using a mobile phone and by analyzing them using custom-designed software. We show that the results obtained with the proposed device are as accurate and consistent as a properly executed dip-and-wipe method, the industry gold-standard, suggesting the potential for this strategy to enable confident urinalysis testing in home environments.

Multimodal 3D cancer-mimicking optical phantom.

Three-dimensional (3D) organ-mimicking phantoms provide realistic imaging environments for testing various aspects of optical systems, including for evaluating new probe designs, characterizing the diagnostic potential of new technologies, and assessing novel image processing algorithms prior to validation in real tissue. We introduce and characterize the use of a new material, Dragon Skin (Smooth-On Inc.), and fabrication technique, air-brushing, for fabrication of a 3D phantom that mimics the appearance of a real organ under multiple imaging modalities. We demonstrate the utility of the material and technique by fabricating the first 3D, hollow bladder phantom with realistic normal and multi-stage pathology features suitable for endoscopic detection using the gold standard imaging technique, white light cystoscopy (WLC), as well as the complementary imaging modalities of optical coherence tomography and blue light cystoscopy, which are aimed at improving the sensitivity and specificity of WLC to bladder cancer detection. The flexibility of the material and technique used for phantom construction allowed for the representation of a wide range of diseased tissue states, ranging from inflammation (benign) to high-grade cancerous lesions. Such phantoms can serve as important tools for trainee education and evaluation of new endoscopic instrumentation.

Fabrication of healthy and disease-mimicking retinal phantoms with tapered foveal pits for optical coherence tomography.

Optical coherence tomography (OCT) has become a standard tool in ophthalmology clinics for diagnosing many retinal diseases. Nonetheless, the technical and clinical communities still lack a standardized phantom that could aid in evaluating and normalizing the many protocols and systems used for diagnosis. Existing retinal phantoms are able to mimic the thickness and scattering properties of the retinal layers but are unable to model the morphology of the foveal pit, particularly the tapering of the retinal layers. This work demonstrates a new fabrication procedure that is capable of reliably and consistently replicating the shape and tapered appearance of the retinal layers near the foveal pit using a combination of spin-coating and replica molding. We characterize the effects of using different mold sizes which enable us to achieve a range of pit dimensions. We also present a modified procedure to replicate two diseased states of the retinal tissue, such as retinal detachment and dry aged-related macular degeneration. The ability to create an anatomically correct foveal pit for healthy and disease-mimicking phantoms will allow for a new standard better suited for intra- and inter-system evaluation and for improved comparison of retinal segmentation algorithms

Automated, Depth-Resolved Estimation of the Attenuation Coefficient From Optical Coherence Tomography Data.

We present a method for automated, depth-resolved extraction of the attenuation coefficient from Optical Coherence Tomography (OCT) data. In contrast to previous automated, depth-resolved methods, the Depth-Resolved Confocal (DRC) technique derives an invertible mapping between the measured OCT intensity data and the attenuation coefficient while considering the confocal function and sensitivity fall-off, which are critical to ensure accurate measurements of the attenuation coefficient in practical settings (e.g., clinical endoscopy). We also show that further improvement of the estimated attenuation coefficient is possible by formulating image denoising as a convex optimization problem that we term Intensity Weighted Horizontal Total Variation (iwhTV). The performance and accuracy of DRC alone and DRC+iwhTV are validated with simulated data, optical phantoms, and ex-vivo porcine tissue. Our results suggest that implementation of DRC+iwhTV represents a novel way to improve OCT contrast for better tissue characterization through quantitative imaging.

Label-free and non-contact optical biosensing of glucose with quantum dots.

We present a label-free, optical sensor for biomedical applications based on changes in the visible photoluminescence (PL) of quantum dots in a thin polymer film. Using glucose as the target molecule, the screening of UV excitation due to pre-absorption by the product of an enzymatic assay leads to quenching of the PL of quantum dots (QDs) in a non-contact scheme. The irradiance changes in QD PL indicate quantitatively the level of glucose present. The non-contact nature of the assay prevents surface degradation of the QDs, which yields an efficient, waste-free, cost-effective, portable, and sustainable biosensor with attractive market features. The limit of detection of the demonstrated biosensor is ~3.5 µm, which is competitive with existing contact-based bioassays. In addition, the biosensor operates over the entire clinically relevant range of glucose concentrations of biological fluids including urine and whole blood. The comparable results achieved across a range of cost-affordable detectors, including a spectrophotometer, portable spectrometer, and iPhone camera, suggest that label-free and visible quantification of glucose with QD films can be applied to low-cost, point-of-care biomedical sensing as well as scientific applications in the laboratory for characterizing glucose or other analytes.

Single-shot speckle noise reduction by interleaved optical coherence tomography.

Speckle noise is one of the dominant factors that degrade image quality in optical coherence tomography (OCT). Here, we propose a new strategy, interleaved OCT (iOCT), for spatial compounding and angular compounding. We demonstrate the efficiency of compounding with iOCT to restrain speckle noise without compromising imaging speed in phantoms and tissue samples.

Quantitative measurements of strain and birefringence with common-path polarization-sensitive optical coherence tomography.

We demonstrate the first system for optical coherence tomography (OCT) that enables simultaneous measurement of quantitative birefringence and strain in biological samples using a common-path configuration. Owing to its superior phase stability, common-path polarization sensitive optical coherence tomography (CoPPSe-OCT) achieves a sub-nanometer displacement sensitivity of 0.52 nm at an SNR of 48 dB. We utilize CoPPSe-OCT to measure reflectance, birefringence, and strain for distinguishing burnt regions in a birefringent biological sample (chicken breast muscle).

Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy.

We describe a combination of fabrication techniques and a general process to construct a three-dimensional (3-D) phantom that mimics the size, macroscale structure, microscale surface topology, subsurface microstructure, optical properties, and functional characteristics of a cancerous bladder. The phantom also includes features that are recognizable in white light (i.e., the visual appearance of blood vessels), making it suitable to emulate the bladder for emerging white light+optical coherence tomography (OCT) cystoscopies and other endoscopic procedures of large, irregularly shaped organs. The fabrication process has broad applicability and can be generalized to OCT phantoms for other tissue types or phantoms for other imaging modalities. To this end, we also enumerate the nuances of applying known fabrication techniques (e.g., spin coating) to contexts (e.g., nonplanar, 3-D shapes) that are essential to establish their generalizability and limitations. We anticipate that this phantom will be immediately useful to evaluate innovative OCT systems and software being developed for longitudinal bladder surveillance and early cancer detection.