Corey P Neu

Purdue University, ウェストラファイエット, Indiana, United States

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Publications (72)163.61 Total impact

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    ABSTRACT: PurposeThis work evaluates the ability of MRIcontrasts to discriminate between normal and pathological human osteochondral plugscharacterized by the OARSI histological system.Methods Normal and osteoarthritic human osteochondralplugswere scored using the OARSI histological system and imaged at 3T using MRI sequences measuring T1, T2, and T2* relaxation times, magnetization transfer, anddiffusion. The classification accuracies of quantitative MRI parameters and corresponding weighted image contrasts were evaluated.Classification models based on the Mahalanobis distance metric for each MRI measurement were trained and validated using leave-one-out cross-validation with plugsgrouped according to OARSI histological grade and score. MRI measurements used for classification were performed using a region-of-interest analysis which included superficial, deep, and full-thickness cartilage.ResultsThe best classifiers based on OARSI grade and score were T1- and T2-weighted image contrast, which yielded accuracies of 0.68 and 0.75, respectively. Classification accuracies using OARSI score-based group membership were generally higher compared with grade-based group membership.ConclusionsMRI-based classification—either using quantitative MRI parameters or weighted image contrast—is able to detect early osteoarthritic tissue changes as classified by the OARSI histological system.These findings suggest the benefit of incorporating quantitative MRI acquisitions in a comprehensive clinical evaluation of OA. This article is protected by copyright. All rights reserved
    Journal of Orthopaedic Research 01/2015; 33(5):640-50. DOI:10.1002/jor.22810 · 2.97 Impact Factor
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    ABSTRACT: Visualizing the three-dimensional morphology and spatial patterning of cells embedded deep within dense connective tissues of the musculoskeletal system has been possible only by utilizing destructive techniques. Here we utilize fructose-based clearing solutions to image cell connectivity and deep tissue-scale patterning in situ by standard confocal microscopy. Optical clearing takes advantage of refractive index matching of tissue and the embedding medium to visualize light transmission through a broad range of bovine and whole mount murine tissues, including cartilage, bone, and ligament, of the head and hindlimb. Using non-destructive methods, we show for the first time intercellular chondrocyte connections throughout the bulk of cartilage, and we reveal in situ patterns of osteocyte processes and the lacunar-canalicular system deep within mineralized cortical bone. Optical clearing of connective tissues is expected to find broad application for the study of cell responses in normal physiology and disease pathology.
    PLoS ONE 01/2015; 10(1):e0116662. DOI:10.1371/journal.pone.0116662 · 3.53 Impact Factor
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    ABSTRACT: Collagen fibrils form the structural basis for a broad range of complex biological tissues and materials. Collagen serves as an ideal natural polymer, formed as gels or matrices, for engineering solutions aimed at the regeneration of tissues following damage or disease. Recapitulation of native tissue hierarchical structure involves the careful consideration of the fibril-microstructure of the target tissue extracellular matrix and the choice of fibrillogenesis conditions that favor spatially-dependent fibril alignment. While magnetic fields non-destructively influence collagen fibrillogenesis and alignment, previous methods have demonstrated only limited control, especially when preparing large volume tissue constructs suitable for implantation. In this study, we investigate the use of temperature-controlled fibrillogenesis over a range of applicable collagen concentrations for improved magnetic alignment of polymerizable collagen-fibril gels. Magnetically aligned collagen gels show that bulk and microscale fibril alignment depend on both polymerization temperature and collagen concentration. The degree of fibril alignment at the microscale increased with decreasing polymerization temperature and collagen concentration. Further, computational simulations suggest that lower polymerization temperatures affect the internal gel temperature distribution and convective fluid velocity, potentially facilitating greater fibril alignment. This work demonstrates improvements in observed fibril anisotropy compared to previous work using similar magnetic field strengths, suggesting that temperature and collagen concentration may be utilized to achieve desired fibril alignment and structural properties. Improved control of collagen-based gel structure may better emulate native tissue structural (alignment) and physical properties, with enhanced potential for repair success in vivo.
    RSC Advances 12/2014; 5(3). DOI:10.1039/C4RA11480A · 3.71 Impact Factor
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    ABSTRACT: Functional imaging refers broadly to the visualization of organ or tissue physiology using medical image modalities. In load-bearing tissues of the body, including articular cartilage lining the bony ends of joints, changes in strain, stress, and material properties occur in osteoarthritis (OA), providing an opportunity to probe tissue function through the progression of the disease. Here, biomechanical measures in cartilage and related joint tissues are discussed as key imaging biomarkers in the evaluation of OA. Emphasis will be placed on the (1) potential of radiography, ultrasound, and magnetic resonance imaging to assess early tissue pathomechanics in OA, (2) relative utility of kinematic, structural, morphological, and biomechanical measures as functional imaging biomarkers, and (3) improved diagnostic specificity through the combination of multiple imaging biomarkers with unique contrasts, including elastography and quantitative assessments of tissue biochemistry. In comparison to other modalities, magnetic resonance imaging provides an extensive range of functional measures at the tissue level, with conventional and emerging techniques available to potentially to assess the spectrum of preclinical to advance OA.
    Osteoarthritis and Cartilage 10/2014; 22(10):1349-1359. DOI:10.1016/j.joca.2014.05.016 · 4.66 Impact Factor
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    ABSTRACT: Engineered tissue microenvironments impart specialized cues that drive distinct cellular phenotypes and function. Microenvironments with defined properties, such as mechanical properties and fibril alignment, can elicit specific cellular responses that emulate those observed in vivo. Collagen- and glycosaminoglycan(GAG)- based tissue matrix have been popularized due to their biological ubiquity in a broad range of tissues and the ability to tune structure and mechanical properties through a variety of processes. Here, we investigate the combined effects of static magnetic fields, and GAG and cell encapsulation, on the structure (e.g. collagen fibril orientation) and material properties of collagen matrices. We found that magnetic fields align the collagen-GAG matrix, alter equilibrium mechanical properties, and provide a method for encapsulating cells within a 3D aligned matrix. Cells are encapsulated prior to polymerization, allowing for controlled cell density and eliminating the need for cell seeding. Increased relative GAG concentrations reduced the ability to magnetically align collagen fibrils, in part through a mechanism involving increased viscosity and polymerization time of the collagan-GAG solution. This work provides a functional design space for the development of pure collagen and hybrid collagen-GAG matrices in the presence of magnetic fields. Additionally, this work shows that magnetic fields are effective for the fabrication of collagen constructs with controlled fibril orientation, and can be coupled with GAG incorporation to modulate mechanical properties and the response of embedded cells.
    Acta Biomaterialia 09/2014; 11. DOI:10.1016/j.actbio.2014.09.031 · 5.68 Impact Factor
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    ABSTRACT: The purpose of this study was to compare displacement behavior of cyclically loaded cadaveric human intervertebral discs as measured noninvasively on a clinical 3.0 T and a research 9.4 T MRI system. Intervertebral discs were cyclically compressed at physiologically relevant levels with the same MRI-compatible loading device in the clinical and research systems. Displacement-encoded imaging was synchronized to cyclic loading to measure displacements under applied loading with MRI (dualMRI). Displacements from the two systems were compared individually using linear regression and, across all specimens, using Bland–Altman analysis. In-plane displacement patterns measured at 3.0 T and 9.4 T were qualitatively comparable and well correlated. Bland–Altman analyses showed that over 90% of displacement values within the intervertebral disc regions of interest lay within the limits of agreement. Measurement of displacement using dualMRI using a 3.0 T clinical system is comparable to that of a 9.4 T research system. Additional refinements of software, technique implementation, and image processing have potential to improve agreement between different MRI systems. Despite differences in MRI systems in this initial implementation, this work demonstrates that dualMRI can be reliably implemented at multiple magnetic field strengths, permitting translation of dualMRI for a variety of applications in the study of tissue and biomaterial biomechanics.
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    ABSTRACT: Recent developments in optical clearing and microscopy technology have enabled the imaging of intact tissues at the millimeter scale to characterize cells via fluorescence labeling. While these techniques have facilitated the three-dimensional cellular characterization within brain and heart, study of dense connective tissues of the musculoskeletal system have been largely unexplored. Here, we quantify how optical clearing impacted the cell and tissue morphology of collagen-, proteoglycan-, and mineral-rich cartilage and bone from the articulating knee joint. Water-based fructose solutions were used for optical clearing of bovine osteochondral tissues, followed by imaging with transmission and confocal microscopy. To confirm preservation of tissue structure during the clearing process, samples were mechanically tested in unconfined compression and visualized by cryoSEM. Optical clearing enhanced light transmission through cartilage, but not subchondral bone regions. Fluorescent staining and immunolabeling was preserved through sample preparations, enabling imaging to cartilage depths 5 times deeper than previously reported, limited only by the working distance of the microscope objective. Chondrocyte volume remained unchanged in response to, and upon the reversal, of clearing. Equilibrium modulus increased in cleared samples, and was attributed to exchange of interstitial fluid with the more viscous fructose solution, but returned to control levels upon unclearing. In addition, cryoSEM-based analysis of cartilage showed no ultrastructural changes. We anticipate large-scale microscopy of diverse connective tissues will enable the study of intact, three-dimensional interfaces (e.g. osteochondral) and cellular connectivity as a function of development, disease, and regeneration, which have been previously hindered by specimen opacity. Copyright © 2014. Published by Elsevier Ltd.
    World Congress of Biomechanics, Boston, MA USA; 07/2014
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    World Congress of Biomechanics; 07/2014
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    Tissue Engineering and Regenerative Medicine International Society European Conference, Genoa, Italy; 06/2014
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    Tissue Engineering and Regenerative Medicine International Society European Conference, Genoa, Italy; 06/2014
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    ABSTRACT: The purpose of this study was to compare displacement behavior of cyclically loaded cadaveric human intervertebral discs as measured noninvasively on a clinical 3.0T and a research 9.4T MRI system. Intervertebral discs were cyclically compressed at physiologically relevant levels with the same MRI-compatible loading device in the clinical and research systems. Displacement-encoded imaging was synchronized to cyclic loading to measure displacements under applied loading with MRI (dualMRI). Displacements from the two systems were compared individually using linear regression and, across all specimens, using Bland-Altman analysis. In-plane displacement patterns measured at 3.0T and 9.4T were qualitatively comparable and well correlated. Bland-Altman analyses showed that over 90% of displacement values within the intervertebral disc regions of interest lay within the limits of agreement. Measurement of displacement using dualMRI using a 3.0T clinical system is comparable to that of a 9.4T research system. Additional refinements of software, technique implementation, and image processing have potential to improve agreement between different MRI systems. Despite differences in MRI systems in this initial implementation, this work demonstrates that dualMRI can be reliably implemented at multiple magnetic field strengths, permitting translation of dualMRI for a variety of applications in the study of tissue and biomaterial biomechanics.
    Journal of Biomechanics 06/2014; 47(11). DOI:10.1016/j.jbiomech.2014.05.026 · 2.50 Impact Factor
  • Deva D Chan, Corey P Neu
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    ABSTRACT: PURPOSE: Noninvasive assessment of tissue mechanical behavior could enable insights into tissue function in healthy and diseased conditions and permit the development of effective tissue repair treatments. Measurement of displacements under applied loading with MRI (dualMRI) has the potential for such biomechanical characterization on a clinical MRI system. METHODS: dualMRI was translated from high-field research systems to a 3T clinical system. Precision was calculated using repeated tests of a silicone phantom. dualMRI was demonstrated by visualizing displacements and strains in an intervertebral disc and compared to T2 measured during cyclic loading. RESULTS: The displacement and strain precisions were 24 µm and 0.3% strain, respectively, under the imaging parameters used in this study. Displacements and strains were measured within the intervertebral disc, but no correlations were found with the T2 values. CONCLUSION: The translation of dualMRI to a 3T system unveils the potential for in vivo studies in a myriad of tissue and organ systems. Because of the importance of mechanical behavior to the function of a variety of tissues, it's expected that dualMRI implemented on a clinical system will be a powerful tool in assessing the interlinked roles of structure, mechanics, and function in both healthy and diseased tissues. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 03/2014; 71(3). DOI:10.1002/mrm.24757 · 3.40 Impact Factor
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    ABSTRACT: PURPOSE: Medical imaging has the potential to noninvasively diagnose early disease onset and monitor the success of repair therapies. Unfortunately, few reliable imaging biomarkers exist to detect cartilage diseases before advanced degeneration in the tissue. METHOD: In this study, we quantified the ability to detect osteoarthritis (OA) severity in human cartilage explants using a multicontrast magnetic resonance imaging (MRI) approach, inclusive of novel displacements under applied loading by MRI, relaxivity measures, and standard MRI. RESULTS: Displacements under applied loading by MRI measures, which characterized the spatial micromechanical environment by 2D finite and Von Mises strains, were strong predictors of histologically assessed OA severity, both before and after controlling for factors, e.g., patient, joint region, and morphology. Relaxivity measures, sensitive to local macromolecular weight and composition, including T1ρ , but not T1 or T2 , were predictors of OA severity. A combined multicontrast approach that exploited spatial variations in tissue biomechanics and extracellular matrix structure yielded the strongest relationships to OA severity. CONCLUSION: Our results indicate that combining multiple MRI-based biomarkers has high potential for the noninvasive measurement of OA severity and the evaluation of potential therapeutic agents used in the treatment of early OA in animal and human trials. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 02/2014; 71(2). DOI:10.1002/mrm.24725 · 3.40 Impact Factor
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    ABSTRACT: Nuclear structure and mechanics play a critical role in diverse cellular functions, such as organizing direct access of chromatin to transcriptional regulators. Here, we use a new, to our knowledge, hybrid method, based on microscopy and hyperelastic warping, to determine three-dimensional strain distributions inside the nuclei of single living cells embedded within their native extracellular matrix. During physiologically relevant mechanical loading to tissue samples, strain was transferred to individual nuclei, resulting in submicron distributions of displacements, with compressive and tensile strain patterns approaching a fivefold magnitude increase in some locations compared to tissue-scale stimuli. Moreover, nascent RNA synthesis was observed in the interchromatin regions of the cells studied and spatially corresponded to strain patterns. Our ability to measure large strains in the interchromatin space, which reveals that movement of chromatin in the nucleus may not be due to random or biochemical mechanisms alone, but may result from the transfer of mechanical force applied at a distant tissue surface.
    Biophysical Journal 11/2013; 105(10):2252-2261. DOI:10.1016/j.bpj.2013.09.054 · 3.83 Impact Factor
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    ABSTRACT: Biomechanical factors play an important role in the growth, regulation, and maintenance of engineered biomaterials and tissues. While physical factors (e.g. applied mechanical strain) can accelerate regeneration, and knowledge of tissue properties often guide the design of custom materials with tailored functionality, the distribution of mechanical quantities (e.g. strain) throughout native and repair tissues is largely unknown. Here, we directly quantify distributions of strain using noninvasive magnetic resonance imaging (MRI) throughout layered agarose constructs, a model system for articular cartilage regeneration. Bulk mechanical testing, giving both instantaneous and equilibrium moduli, was incapable of differentiating between the layered constructs with defined amounts of 2% and 4% agarose. In contrast, MRI revealed complex distributions of strain, with strain transfer to softer (2%) agarose regions, resulting in amplified magnitudes. Comparative studies using finite element simulations and mixture (biphasic) theory confirmed strain distributions in the layered agarose. The results indicate that strain transfer to soft regions is possible in vivo as the biomaterial and tissue changes during regeneration and maturity. It is also possible to modulate locally the strain field that is applied to construct-embedded cells (e.g. chondrocytes) using stratified agarose constructs.
    Journal of Biomechanics 10/2013; DOI:10.1016/j.jbiomech.2013.09.025 · 2.50 Impact Factor
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    ABSTRACT: Cells remarkably are capable of large deformations during motility and when subjected to mechanical force. Measurement of mechanical deformation (i.e. displacements, strain) is critical to understand functional changes in cells and biological tissues following disease, and to elucidate basic relationships between applied force and cellular biosynthesis. Microscopy-based imaging modalities provide the ability to noninvasively visualize small cell or tissue structures and track their motion over time, often using two-dimensional (2D) digital image (texture) correlation algorithms. For the measurement of complex and nonlinear motion in cells and tissues, implementation of texture correlation algorithms with high order approximations of displacement mapping terms are needed to minimize error. Here, we extend a texture correlation algorithm with up to third-order approximation of displacement mapping terms for the measurement of cell and tissue deformation. We additionally investigate relationships between measurement error and image texture, defined by subset entropy. Displacement measurement error is significantly reduced when the order of displacement mapping terms in the texture correlation algorithm matches or exceeds the order of the deformation observed. Displacement measurement error is also inversely proportional to subset entropy, with well-defined cell and tissue structures leading to high entropy and low error. For cell and tissue studies where complex or nonlinear displacements are expected, texture correlation algorithms with high order terms are required to best characterize the observed deformation.
    Journal of Biomechanics 08/2013; 46(14). DOI:10.1016/j.jbiomech.2013.07.035 · 2.50 Impact Factor
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    ABSTRACT: The advancement of spectroscopy methods attained through increases in sensitivity, and often with the coupling of complementary techniques, has enabled real-time structure and function measurements of single cells. The purpose of this review is to illustrate, in light of advances, the strengths and the weaknesses of these methods. Included also is an assessment of the impact of the experimental setup and conditions of each method on cellular function and integrity. A particular emphasis is placed on noninvasive and nondestructive techniques for achieving single cell detection, including nuclear magnetic resonance, in addition to physical, optical, and vibrational methods.
    Methods 07/2013; 64(2). DOI:10.1016/j.ymeth.2013.07.025 · 3.22 Impact Factor
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    ABSTRACT: Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
    ASME 2013 Summer Bioengineering Conference; 06/2013
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    ABSTRACT: The nucleus is a regulation center for cellular gene expression 1. Mechanical forces transfer to the nucleus directly and indirectly through cellular cytoskeletal structures and pathways 2, 3. The transmitted strains often cause nuclear deformation which is thought to trigger mechanosensitive gene expression within the nucleus 4. Protein dynamics inside the nucleus are additionally important for maintaining the nuclear structure and in facilitating gene expression at the transcription level 5. Probing spatiotemporal relationships between mechanical forces and localized gene expression (i.e. biophysical and biochemical factors) in the nuclei of cells is important in order to clarify variability observed in large and heterogeneous cell populations within complex tissues. This requires the development of innovative methods for intranuclear strain measurements of cells in situ, and the further capability to quantify associated biochemical responses. This abstract describes a method combining the simultaneous measurement of newly synthesized RNA with spatiotemporal intranuclear strain mapping in single cells embedded in native tissue.
    ASME 2013 Summer Bioengineering Conference; 06/2013
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    ABSTRACT: Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
    ASME 2013 Summer Bioengineering Conference; 06/2013

Publication Stats

544 Citations
163.61 Total Impact Points

Institutions

  • 2009–2015
    • Purdue University
      • Weldon School of Biomedical Engineering
      ウェストラファイエット, Indiana, United States
  • 2003–2012
    • University of California, Davis
      • • Center for Tissue Regeneration and Repair
      • • Department of Orthopaedic Surgery
      Davis, California, United States
  • 2007
    • University of California, Berkeley
      Berkeley, California, United States