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Hajjarian, Zeinab

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Hajjarian

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Zeinab

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Hajjarian, Zeinab

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    Optical sensing of anticoagulation status: Towards point-of-care coagulation testing
    (Public Library of Science, 2017) Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth; Nadkarni, Seemantini
    Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57–0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61–0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing.
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    Laser Speckle Rheology for evaluating the viscoelastic properties of hydrogel scaffolds
    (Nature Publishing Group, 2016) Hajjarian, Zeinab; Nia, Hadi; Ahn, Shawn; Grodzinsky, Alan J.; Jain, Rakesh; Nadkarni, Seemantini
    Natural and synthetic hydrogel scaffolds exhibit distinct viscoelastic properties at various length scales and deformation rates. Laser Speckle Rheology (LSR) offers a novel, non-contact optical approach for evaluating the frequency-dependent viscoelastic properties of hydrogels. In LSR, a coherent laser beam illuminates the specimen and a high-speed camera acquires the time-varying speckle images. Cross-correlation analysis of frames returns the speckle intensity autocorrelation function, g2(t), from which the frequency-dependent viscoelastic modulus, G*(ω), is deduced. Here, we establish the capability of LSR for evaluating the viscoelastic properties of hydrogels over a large range of moduli, using conventional mechanical rheometry and atomic force microscopy (AFM)-based indentation as reference-standards. Results demonstrate a strong correlation between |G*(ω)| values measured by LSR and mechanical rheometry (r = 0.95, p < 10−9), and z-test analysis reports that moduli values measured by the two methods are identical (p > 0.08) over a large range (47 Pa – 36 kPa). In addition, |G*(ω)| values measured by LSR correlate well with indentation moduli, E, reported by AFM (r = 0.92, p < 10−7). Further, spatially-resolved moduli measurements in micro-patterned substrates demonstrate that LSR combines the strengths of conventional rheology and micro-indentation in assessing hydrogel viscoelastic properties at multiple frequencies and small length-scales.
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    Evaluating the Viscoelastic Properties of Tissue from Laser Speckle Fluctuations
    (Nature Publishing Group, 2012) Hajjarian, Zeinab; Nadkarni, Seemantini
    Most pathological conditions such as atherosclerosis, cancer, neurodegenerative, and orthopedic disorders are accompanied with alterations in tissue viscoelasticity. Laser Speckle Rheology (LSR) is a novel optical technology that provides the invaluable potential for mechanical assessment of tissue in situ. In LSR, the specimen is illuminated with coherent light and the time constant of speckle fluctuations, τ, is measured using a high speed camera. Prior work indicates that τ is closely correlated with tissue microstructure and composition. Here, we investigate the relationship between LSR measurements of τ and sample mechanical properties defined by the viscoelastic modulus, G*. Phantoms and tissue samples over a broad range of viscoelastic properties are evaluated using LSR and conventional mechanical testing. Results demonstrate a strong correlation between τ and |G*| for both phantom (r = 0.79, p <0.0001) and tissue (r = 0.88, p<0.0001) specimens, establishing the unique capability of LSR in characterizing tissue viscoelasticity.
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    Evaluation and Correction for Optical Scattering Variations in Laser Speckle Rheology of Biological Fluids
    (Public Library of Science, 2013) Hajjarian, Zeinab; Nadkarni, Seemantini
    Biological fluids fulfill key functionalities such as hydrating, protecting, and nourishing cells and tissues in various organ systems. They are capable of these versatile tasks owing to their distinct structural and viscoelastic properties. Characterizing the viscoelastic properties of bio-fluids is of pivotal importance for monitoring the development of certain pathologies as well as engineering synthetic replacements. Laser Speckle Rheology (LSR) is a novel optical technology that enables mechanical evaluation of tissue. In LSR, a coherent laser beam illuminates the tissue and temporal speckle intensity fluctuations are analyzed to evaluate mechanical properties. The rate of temporal speckle fluctuations is, however, influenced by both optical and mechanical properties of tissue. Therefore, in this paper, we develop and validate an approach to estimate and compensate for the contributions of light scattering to speckle dynamics and demonstrate the capability of LSR for the accurate extraction of viscoelastic moduli in phantom samples and biological fluids of varying optical and mechanical properties.