Browsing by Author "Wax, Adam"

Now showing 1 - 11 of 11
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    Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells.
    (PloS one, 2016-01) Park, Han Sang; Rinehart, Matthew T; Walzer, Katelyn A; Chi, Jen-Tsan Ashley; Wax, Adam
    Malaria detection through microscopic examination of stained blood smears is a diagnostic challenge that heavily relies on the expertise of trained microscopists. This paper presents an automated analysis method for detection and staging of red blood cells infected by the malaria parasite Plasmodium falciparum at trophozoite or schizont stage. Unlike previous efforts in this area, this study uses quantitative phase images of unstained cells. Erythrocytes are automatically segmented using thresholds of optical phase and refocused to enable quantitative comparison of phase images. Refocused images are analyzed to extract 23 morphological descriptors based on the phase information. While all individual descriptors are highly statistically different between infected and uninfected cells, each descriptor does not enable separation of populations at a level satisfactory for clinical utility. To improve the diagnostic capacity, we applied various machine learning techniques, including linear discriminant classification (LDC), logistic regression (LR), and k-nearest neighbor classification (NNC), to formulate algorithms that combine all of the calculated physical parameters to distinguish cells more effectively. Results show that LDC provides the highest accuracy of up to 99.7% in detecting schizont stage infected cells compared to uninfected RBCs. NNC showed slightly better accuracy (99.5%) than either LDC (99.0%) or LR (99.1%) for discriminating late trophozoites from uninfected RBCs. However, for early trophozoites, LDC produced the best accuracy of 98%. Discrimination of infection stage was less accurate, producing high specificity (99.8%) but only 45.0%-66.8% sensitivity with early trophozoites most often mistaken for late trophozoite or schizont stage and late trophozoite and schizont stage most often confused for each other. Overall, this methodology points to a significant clinical potential of using quantitative phase imaging to detect and stage malaria infection without staining or expert analysis.
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    Deformation of stem cell nuclei by nanotopographical cues.
    (Soft Matter, 2010-04-21) Chalut, Kevin J; Kulangara, Karina; Giacomelli, Michael G; Wax, Adam; Leong, Kam W
    Cells sense cues in their surrounding microenvironment. These cues are converted into intracellular signals and transduced to the nucleus in order for the cell to respond and adapt its function. Within the nucleus, structural changes occur that ultimately lead to changes in the gene expression. In this study, we explore the structural changes of the nucleus of human mesenchymal stem cells as an effect of topographical cues. We use a controlled nanotopography to drive shape changes to the cell nucleus, and measure the changes with both fluorescence microscopy and a novel light scattering technique. The nucleus changes shape dramatically in response to the nanotopography, and in a manner dependent on the mechanical properties of the substrate. The kinetics of the nuclear deformation follows an unexpected trajectory. As opposed to a gradual shape change in response to the topography, once the cytoskeleton attains an aligned and elongation morphology on the time scale of several hours, the nucleus changes shape rapidly and intensely.
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    Fiber-optic interferometric two-dimensional scattering-measurement system.
    (Opt Lett, 2010-05-15) Zhu, Yizheng; Giacomelli, Michael G; Wax, Adam
    We present a fiber-optic interferometric system for measuring depth-resolved scattering in two angular dimensions using Fourier-domain low-coherence interferometry. The system is a unique hybrid of the Michelson and Sagnac interferometer topologies. The collection arm of the interferometer is scanned in two dimensions to detect angular scattering from the sample, which can then be analyzed to determine the structure of the scatterers. A key feature of the system is the full control of polarization of both the illumination and the collection fields, allowing for polarization-sensitive detection, which is essential for two-dimensional angular measurements. System performance is demonstrated using a double-layer microsphere phantom. Experimental data from samples with different sizes and acquired with different polarizations show excellent agreement with Mie theory, producing structural measurements with subwavelength accuracy.
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    Light scattering methods for tissue diagnosis.
    (Optica, 2019-04) Steelman, Zachary A; Ho, Derek S; Chu, Kengyeh K; Wax, Adam
    Light scattering has become a common biomedical research tool, enabling diagnostic sensitivity to myriad tissue alterations associated with disease. Light-tissue interactions are particularly attractive for diagnostics due to the variety of contrast mechanisms that can be used, including spectral, angle-resolved, and Fourier-domain detection. Photonic diagnostic tools offer further benefit in that they are non-ionizing, non-invasive, and give real-time feedback. In this review, we summarize recent innovations in light scattering technologies, with a focus on clinical achievements over the previous ten years.
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    Measuring morphological features using light-scattering spectroscopy and Fourier-domain low-coherence interferometry.
    (Opt Lett, 2010-02-01) Robles, Francisco E; Wax, Adam
    We present measurements of morphological features in a thick turbid sample using light-scattering spectroscopy (LSS) and Fourier-domain low-coherence interferometry (fLCI) by processing with the dual-window (DW) method. A parallel frequency domain optical coherence tomography (OCT) system with a white-light source is used to image a two-layer phantom containing polystyrene beads of diameters 4.00 and 6.98 mum on the top and bottom layers, respectively. The DW method decomposes each OCT A-scan into a time-frequency distribution with simultaneously high spectral and spatial resolution. The spectral information from localized regions in the sample is used to determine scatterer structure. The results show that the two scatterer populations can be differentiated using LSS and fLCI.
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    Parallel on-axis holographic phase microscopy of biological cells and unicellular microorganism dynamics
    (APPLIED OPTICS, 2010-05-20) Shaked, Natan T; Newpher, Thomas M; Ehlers, Michael D; Wax, Adam
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    Quantitative phase imaging of erythrocytes under microfluidic constriction in a high refractive index medium reveals water content changes.
    (Microsystems & nanoengineering, 2019-01) Park, Han Sang; Eldridge, Will J; Yang, Wen-Hsuan; Crose, Michael; Ceballos, Silvia; Roback, John D; Chi, Jen-Tsan Ashley; Wax, Adam
    Changes in the deformability of red blood cells can reveal a range of pathologies. For example, cells which have been stored for transfusion are known to exhibit progressively impaired deformability. Thus, this aspect of red blood cells has been characterized previously using a range of techniques. In this paper, we show a novel approach for examining the biophysical response of the cells with quantitative phase imaging. Specifically, optical volume changes are observed as the cells transit restrictive channels of a microfluidic chip in a high refractive index medium. The optical volume changes indicate an increase of cell's internal density, ostensibly due to water displacement. Here, we characterize these changes over time for red blood cells from two subjects. By storage day 29, a significant decrease in the magnitude of optical volume change in response to mechanical stress was witnessed. The exchange of water with the environment due to mechanical stress is seen to modulate with storage time, suggesting a potential means for studying cell storage.
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    Separating the scattering and absorption coefficients using the real and imaginary parts of the refractive index with low-coherence interferometry.
    (Opt Lett, 2010-09-01) Robles, Francisco E; Wax, Adam
    We present an analytical method that yields the real and imaginary parts of the refractive index (RI) from low-coherence interferometry measurements, leading to the separation of the scattering and absorption coefficients of turbid samples. The imaginary RI is measured using time-frequency analysis, with the real part obtained by analyzing the nonlinear phase induced by a sample. A derivation relating the real part of the RI to the nonlinear phase term of the signal is presented, along with measurements from scattering and nonscattering samples that exhibit absorption due to hemoglobin.
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    Simultaneous two-wavelength transmission quantitative phase microscopy with a color camera.
    (Opt Lett, 2010-08-01) Rinehart, Matthew T; Shaked, Natan T; Jenness, Nathan J; Clark, Robert L; Wax, Adam
    We present a quantitative phase microscopy method that uses a Bayer mosaic color camera to simultaneously acquire off-axis interferograms in transmission mode at two distinct wavelengths. Wrapped phase information is processed using a two-wavelength algorithm to extend the range of the optical path delay measurements that can be detected using a single temporal acquisition. We experimentally demonstrate this technique by acquiring the phase profiles of optically clear microstructures without 2pi ambiguities. In addition, the phase noise contribution arising from spectral channel crosstalk on the color camera is quantified.
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    Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering
    (Optics Express, 2010) Giacomelli, Michael; Zhu, Yizheng; Lee, John; Wax, Adam
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    Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy.
    (Biomed Opt Express, 2010-08-23) Shaked, Natan T; Satterwhite, Lisa L; Bursac, Nenad; Wax, Adam
    We apply wide-field interferometric microscopy techniques to acquire quantitative phase profiles of ventricular cardiomyocytes in vitro during their rapid contraction with high temporal and spatial resolution. The whole-cell phase profiles are analyzed to yield valuable quantitative parameters characterizing the cell dynamics, without the need to decouple thickness from refractive index differences. Our experimental results verify that these new parameters can be used with wide field interferometric microscopy to discriminate the modulation of cardiomyocyte contraction dynamics due to temperature variation. To demonstrate the necessity of the proposed numerical analysis for cardiomyocytes, we present confocal dual-fluorescence-channel microscopy results which show that the rapid motion of the cell organelles during contraction preclude assuming a homogenous refractive index over the entire cell contents, or using multiple-exposure or scanning microscopy.