Blueprint for a Semi-automated Image Processing Tool to Characterize Stent Features: Application to a Pediatric Growth-Adaptive Stent.

The goal of this work was to develop a general blueprint for a semi-automated image processing tool (SIPT) to measure small, complex features of stent prototypes that can replace the current gold standard of manual measurements. The stents were designed using CAD software and manufactured via laser cutting. Stent prototypes were imaged using a Keyence microscope in top and side view orientations. The SIPT algorithm was developed in MATLAB to extract and measure 4 dimensions of the stent (inner and outer diameter, spring bend outer radius, spring bend width). The same dimensions were also manually measured by an experienced metrology technician as a gold standard comparison. We successfully made over 5000 unique measurements across the 4 key dimensions of 15 stents using the SIPT algorithm. Compared to the gold standard manual method, SIPT reduced measurement time by nearly 90% and increased the total number of measurements captured by over 2300%. The two one-sided test and Bland-Altman analysis demonstrated that SIPT achieved equivalency against the manual method of measurement for all 4 dimensions. In summary, we found that our SIPT software could be used to replace manual measurements and provided substantial time savings with consistent accuracy. Overall, this paper presents a generalizable workflow to isolate and measure critical features of stent prototypes that we believe will provide a valuable, cost-effective tool to other medical device designers seeking to rapidly iterate on unique stent designs or other manufactured parts with small and complex structures.

Detection and mapping of specular surfaces using multibounce LiDAR returns.

We propose methods that use specular, multibounce LiDAR returns to detect and map specular surfaces that might be invisible to conventional LiDAR systems that rely on direct, single-scatter returns. We derive expressions that relate the time- and angle-of-arrival of these multibounce returns to scattering points on the specular surface, and then use these expressions to formulate techniques for retrieving specular surface geometry when the scene is scanned by a single beam or illuminated with a multi-beam flash. We also consider the special case of transparent specular surfaces, for which surface reflections can be mixed together with light that scatters off of objects lying behind the surface.

Field-Portable Microplastic Sensing in Aqueous Environments: A Perspective on Emerging Techniques.

Microplastics (MPs) have been found in aqueous environments ranging from rural ponds and lakes to the deep ocean. Despite the ubiquity of MPs, our ability to characterize MPs in the environment is limited by the lack of technologies for rapidly and accurately identifying and quantifying MPs. Although standards exist for MP sample collection and preparation, methods of MP analysis vary considerably and produce data with a broad range of data content and quality. The need for extensive analysis-specific sample preparation in current technology approaches has hindered the emergence of a single technique which can operate on aqueous samples in the field, rather than on dried laboratory preparations. In this perspective, we consider MP measurement technologies with a focus on both their eventual field-deployability and their respective data products (e.g., MP particle count, size, and/or polymer type). We present preliminary demonstrations of several prospective MP measurement techniques, with an eye towards developing a solution or solutions that can transition from the laboratory to the field. Specifically, experimental results are presented from multiple prototype systems that measure various physical properties of MPs: pyrolysis-differential mobility spectroscopy, short-wave infrared imaging, aqueous Nile Red labeling and counting, acoustophoresis, ultrasound, impedance spectroscopy, and dielectrophoresis.

High-density speckle contrast optical tomography of cerebral blood flow response to functional stimuli in the rodent brain.

Noninvasive, three-dimensional, and longitudinal imaging of cerebral blood flow (CBF) in small animal models and ultimately in humans has implications for fundamental research and clinical applications. It enables the study of phenomena such as brain development and learning and the effects of pathologies, with a clear vision for translation to humans. Speckle contrast optical tomography (SCOT) is an emerging optical method that aims to achieve this goal by directly measuring three-dimensional blood flow maps in deep tissue with a relatively inexpensive and simple system. High-density SCOT is developed to follow CBF changes in response to somatosensory cortex stimulation. Measurements are carried out through the intact skull on the rat brain. SCOT is able to follow individual trials in each brain hemisphere, where signal averaging resulted in comparable, cortical images to those of functional magnetic resonance images in spatial extent, location, and depth. Sham stimuli are utilized to demonstrate that the observed response is indeed due to local changes in the brain induced by forepaw stimulation. In developing and demonstrating the method, algorithms and analysis methods are developed. The results pave the way for longitudinal, nondestructive imaging in preclinical rodent models that can readily be translated to the human brain.

Compact, multi-exposure speckle contrast optical spectroscopy (SCOS) device for measuring deep tissue blood flow.

Speckle contrast optical spectroscopy (SCOS) measures absolute blood flow in deep tissue, by taking advantage of multi-distance (previously reported in the literature) or multi-exposure (reported here) approach. This method promises to use inexpensive detectors to obtain good signal-to-noise ratio, but it has not yet been implemented in a suitable manner for a mass production. Here we present a new, compact, low power consumption, 32 by 2 single photon avalanche diode (SPAD) array that has no readout noise, low dead time and has high sensitivity in low light conditions, such as in vivo measurements. To demonstrate the capability to measure blood flow in deep tissue, healthy volunteers were measured, showing no significant differences from the diffuse correlation spectroscopy. In the future, this array can be miniaturized to a low-cost, robust, battery operated wireless device paving the way for measuring blood flow in a wide-range of applications from sport injury recovery and training to, on-field concussion detection to wearables.

Near infrared spectroscopy for measuring changes in bone hemoglobin content after exercise in individuals with spinal cord injury.

Bone blood perfusion has an essential role in maintaining a healthy bone. However, current methods for measuring bone blood perfusion are expensive and highly invasive. This study presents a custom built near-infrared spectroscopy (NIRS) instrument to measure changes in bone blood perfusion. We demonstrated the efficacy of this device by monitoring oxygenated and deoxygenated hemoglobin changes in the human tibia during and after exercise in able-bodied and in individuals with spinal cord injury (SCI), a population with known impaired peripheral blood perfusion. Nine able-bodied individuals and six volunteers with SCI performed a 10 min rowing exercise (functional electrical stimulation rowing for those with SCI). With exercise, during rowing, able-bodied showed an increase in deoxygenated hemoglobin in the tibia. Post rowing, able-bodied showed an increase in total blood content, characterized by an increase in total hemoglobin content due primarily to an increase in deoxygenated hemoglobin. During rowing and post-rowing, those with SCI showed no change in total blood content in the tibia. The current study demonstrates that NIRS can non-invasively detect changes in hemoglobin concentration in the tibia. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:183-191, 2018.

Enhanced tagging of light utilizing acoustic radiation force with speckle pattern analysis.

In optical imaging, the depth and resolution are limited due to scattering. Unlike light, scattering of ultrasound (US) waves in tissue is negligible. Hybrid imaging methods such as US-modulated optical tomography (UOT) use the advantages of both modalities. UOT tags light by inducing phase change caused by modulating the local index of refraction of the medium. The challenge in UOT is detecting the small signal. The displacement induced by the acoustic radiation force (ARF) is another US effect that can be utilized to tag the light. It induces greater phase change, resulting in a stronger signal. Moreover, the absorbed acoustic energy generates heat, resulting in change in the index of refraction and a strong phase change. The speckle pattern is governed by the phase of the interfering scattered waves; hence, speckle pattern analysis can obtain information about displacement and temperature changes. We have presented a model to simulate the insonation processes. Simulation results based on fixed-particle Monte Carlo and experimental results show that the signal acquired by utilizing ARF is stronger compared to UOT. The introduced mean irradiance change (MIC) signal reveals both thermal and mechanical effects of the focused US beam in different timescales. Simulation results suggest that variation in the MIC signal can be used to generate a displacement image of the medium.

High-density speckle contrast optical tomography (SCOT) for three dimensional tomographic imaging of the small animal brain.

High-density speckle contrast optical tomography (SCOT) utilizing tens of thousands of source-detector pairs, was developed for in vivo imaging of blood flow in small animals. The reduction in cerebral blood flow (CBF) due to local ischemic stroke in a mouse brain was transcanially imaged and reconstructed in three dimensions. The reconstructed volume was then compared with corresponding magnetic resonance images demonstrating that the volume of reduced CBF agrees with the infarct zone at twenty-four hours.

Human Corneal Fibroblast Pattern Evolution and Matrix Synthesis on Mechanically Biased Substrates.

In a fibroblast colony model of corneal stromal development, we asked how physiological tension influences the patterning dynamics of fibroblasts and the orientation of deposited extracellular matrix (ECM). Using long-term live-cell microscopy, enabled by an optically accessible mechanobioreactor, a primary human corneal fibroblast colony was cultured on three types of substrates: a mechanically biased, loaded, dense, disorganized collagen substrate (LDDCS), a glass coverslip, and an unloaded, dense, disorganized collagen substrate (UDDCS). On LDDCS, fibroblast orientation and migration along a preferred angle developed early, cell orientation was correlated over long distances, and the colony pattern was stable. On glass, fibroblast orientation was poorly correlated, developed more slowly, and colony patterns were metastable. On UDDCS, cell orientation was correlated over shorter distances compared with LDDCS specimens. On all substrates, the ECM pattern reflected the cell pattern. In summary, mechanically biasing the collagen substrate altered the early migration behavior of individual cells, leading to stable emergent cell patterning, which set the template for newly synthesized ECM.

Diffusion model for ultrasound-modulated light.

Researchers use ultrasound (US) to modulate diffusive light in a highly scattering medium like tissue. This paper analyzes the US-optical interaction in the scattering medium and derives an expression for the US-modulated optical radiance. The diffusion approximation to the radiative transport equation is employed to develop a Green's function for US-modulated light. The predicted modulated fluence and flux are verified using finite-difference time-domain simulations. The Green's function is then utilized to illustrate the modulated reflectance as the US-optical interaction increases in depth. The intent of this paper is to focus on high US frequencies necessary for high-resolution imaging because they are of interest for applications such as phase conjugation.

Analysis and modeling of an ultrasound-modulated guide star to increase the depth of focusing in a turbid medium.

The effects of strong scattering in tissue limit the depth to which light may be focused. However, it has been shown that scattering may be reduced utilizing adaptive optics with a focused ultrasound (US) beam guidestar. The optical signal traveling through the US beam waist is frequency shifted and may be isolated with demodulation. This paper utilizes a multiphysics simulation to model the optical and US interactions in both synthetic tissue and random scattering media. The results illustrate that optical energy may be focused within a turbid medium utilizing a US guidestar. The results also suggest that optical energy travels preferentially along optical channels within a turbid medium.

Error analysis of finite-spectral-linewidth illumination in optical oximetry systems.

Multi-spectral systems consisting of a small number of wavelengths are increasingly using light emitting diodes (LEDs) to reduce the overall costs of the system. However, LEDs typically have broad spectral bandwidths and cannot be modeled as having a single discrete wavelength. This paper puts forth a simple model to analyze the effects of using LEDs to illuminate a single layer of homogenous tissue. Monte Carlo simulations are used to approximate photon propagation through a semi-infinite turbid medium oximetry system using two light emitting diodes with broad spectra for varying oxygen saturations. The results are then compared against diffusion solutions for narrow-band illumination at the same two center wavelengths.

Multiple-source optical diffusion approximation for a multilayer scattering medium.

A method for improving the accuracy of the optical diffusion theory for a multilayer scattering medium is presented. An infinitesimally narrow incident light beam is replaced by multiple isotropic point sources of different strengths that are placed in the scattering medium along the incident beam. The multiple sources are then used to develop a multilayer diffusion theory. Diffuse reflectance is then computed using the multilayer diffusion theory and compared with accurate data computed by the Monte Carlo method. This multisource method is found to be significantly more accurate than the previous single-source method.

Computational microscopy in embryo imaging.

The growth of computing power has greatly improved our ability to extract quantitative information about complicated three-dimensional structures from microscope images. New hardware techniques are also being developed to provide suitable images for these tasks. However, a need exists for synthetic data to test these new developments. The work reported here was motivated by studies of embryo health, but similar needs exist across the field of microscopy. We report a rigorous computer model, based on Maxwell's equations, that can produce the required synthetic images for bright-field, differential interference contrast, interferometric imaging, and polarimetric imaging. After a description of the algorithm, sample results are presented, followed by a discussion of future plans and applications.