Changhuei Yang

Summary

Affiliation: California Institute of Technology
Country: USA

Publications

  1. ncbi request reprint Protein-based molecular contrast optical coherence tomography with phytochrome as the contrast agent
    Changhuei Yang
    Department of Biomedical Engineering, 136 Hudson Hall, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:1396-8. 2004
  2. pmc Molecular contrast optical coherence tomography: a review
    Changhuei Yang
    Electrical Engineering Department, Engineering and Applied Sciences Division, California Institute of Technology, Pasadena, CA 91125, USA
    Photochem Photobiol 81:215-37. 2005
  3. pmc Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent
    Changhuei Yang
    Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:2016-8. 2004
  4. ncbi request reprint Amplification of optical delay by use of matched linearly chirped fiber Bragg gratings
    Changhuei Yang
    Department of Biomedical Engineering, 136 Hudson Hall, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:685-7. 2004
  5. ncbi request reprint Molecular contrast optical coherence tomography: A pump-probe scheme using indocyanine green as a contrast agent
    Zahid Yaqoob
    California Institute of Technology, Department of Electrical Engineering, Biophotonics Laboratory, 4 Moore Building, M C 136 93, 1200 E California Blvd, Pasadena, California 91125, USA
    J Biomed Opt 11:054017. 2006
  6. ncbi request reprint Homodyne en face optical coherence tomography
    Zahid Yaqoob
    Department of Electrical Engineering, MC 136 93, California Institute of Technology, Pasadena, 91125, USA
    Opt Lett 31:1815-7. 2006
  7. ncbi request reprint Harmonically matched grating-based full-field quantitative high-resolution phase microscope for observing dynamics of transparent biological samples
    Jigang Wu
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Express 15:18141-55. 2007
  8. doi request reprint Improving weak-signal identification via predetection background suppression by a pixel-level, surface-wave enabled dark-field aperture
    Guoan Zheng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Lett 35:2636-8. 2010
  9. pmc On-chip continuous monitoring of motile microorganisms on an ePetri platform
    Seung Ah Lee
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Lab Chip 12:2385-90. 2012
  10. pmc Turbidity suppression from the ballistic to the diffusive regime in biological tissues using optical phase conjugation
    Emily J McDowell
    California Institute of Technology, Department of Bioengineering, 1200 East California Boulevard, Mail Code 136 93, Pasadena, California 91125, USA
    J Biomed Opt 15:025004. 2010

Research Grants

  1. Spectral Triangulation Molecular Contrast OCT
    Changhuei Yang; Fiscal Year: 2005
  2. Optofluidic Microscope
    Changhuei Yang; Fiscal Year: 2007

Detail Information

Publications55

  1. ncbi request reprint Protein-based molecular contrast optical coherence tomography with phytochrome as the contrast agent
    Changhuei Yang
    Department of Biomedical Engineering, 136 Hudson Hall, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:1396-8. 2004
    ..We demonstrate molecular imaging with this new MCOCT modality in a target sample containing a mixture of 0.2% Intralipid and 83 microM of phyA...
  2. pmc Molecular contrast optical coherence tomography: a review
    Changhuei Yang
    Electrical Engineering Department, Engineering and Applied Sciences Division, California Institute of Technology, Pasadena, CA 91125, USA
    Photochem Photobiol 81:215-37. 2005
    ..We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development...
  3. pmc Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent
    Changhuei Yang
    Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:2016-8. 2004
    ..We demonstrate molecular imaging with this new MCOCT modality by mapping the distribution of indocyanine green, a FDA-approved infrared red dye, within a stage 54 Xenopus laevis...
  4. ncbi request reprint Amplification of optical delay by use of matched linearly chirped fiber Bragg gratings
    Changhuei Yang
    Department of Biomedical Engineering, 136 Hudson Hall, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:685-7. 2004
    ..We demonstrate operation of such an optical delay line over a delay range of 3.5 mm using a pair of matched 1300-nm chirped FBGs with a bandwidth of 20 nm each...
  5. ncbi request reprint Molecular contrast optical coherence tomography: A pump-probe scheme using indocyanine green as a contrast agent
    Zahid Yaqoob
    California Institute of Technology, Department of Electrical Engineering, Biophotonics Laboratory, 4 Moore Building, M C 136 93, 1200 E California Blvd, Pasadena, California 91125, USA
    J Biomed Opt 11:054017. 2006
    ..The paper also demonstrates ICG-based MCOCT imaging in tissue phantoms as well as within stage 54 Xenopus laevis...
  6. ncbi request reprint Homodyne en face optical coherence tomography
    Zahid Yaqoob
    Department of Electrical Engineering, MC 136 93, California Institute of Technology, Pasadena, 91125, USA
    Opt Lett 31:1815-7. 2006
    ..4 microm laterally with a 90 dB signal-to-noise ratio at 10 micros integration time. En face OCT imaging of a stage 52 Xenopus laevis was successfully demonstrated at a depth of 600 microm within the sample...
  7. ncbi request reprint Harmonically matched grating-based full-field quantitative high-resolution phase microscope for observing dynamics of transparent biological samples
    Jigang Wu
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Express 15:18141-55. 2007
    ..The system has a lateral resolution of 1.6 mum and a phase sensitivity of 62 mrad. We employed the system to acquire high resolution phase images of onion skin cells and a phase movie of amoeba proteus in motion...
  8. doi request reprint Improving weak-signal identification via predetection background suppression by a pixel-level, surface-wave enabled dark-field aperture
    Guoan Zheng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Lett 35:2636-8. 2010
    ..96W/m(2), integration time=5ms), we further demonstrate that a SWEDA pixel can detect a weak localized signal buried in a high background, while conventional postdetection background subtraction cannot (improved SNR=2.2 versus SNR=0.26)...
  9. pmc On-chip continuous monitoring of motile microorganisms on an ePetri platform
    Seung Ah Lee
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Lab Chip 12:2385-90. 2012
    ..As a miniaturized and automated culture monitoring platform, this ePetri technology can greatly improve studies and experiments with motile microorganisms...
  10. pmc Turbidity suppression from the ballistic to the diffusive regime in biological tissues using optical phase conjugation
    Emily J McDowell
    California Institute of Technology, Department of Bioengineering, 1200 East California Boulevard, Mail Code 136 93, Pasadena, California 91125, USA
    J Biomed Opt 15:025004. 2010
    ..Our results describe the highest level of scattering that has been phase conjugated in biological tissues to date...
  11. pmc The application of Fresnel zone plate based projection in optofluidic microscopy
    Jigang Wu
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Express 16:15595-602. 2008
    ..We demonstrate the capability of the integrated system by flowing the protist Euglena gracilis across the aperture array microfluidically and performing OFM imaging of the samples...
  12. ncbi request reprint Methods and application areas of endoscopic optical coherence tomography
    Zahid Yaqoob
    Engineering and Applied Sciences Division, Electrical Engineering Department, California Institute of Technology, Pasadena, California 91125, USA
    J Biomed Opt 11:063001. 2006
    ..We highlight two additional applications--biopsy procedures and neurosurgery--where sufficiently compact OCT-based endoscopes can have significant clinical impacts...
  13. pmc Color capable sub-pixel resolving optofluidic microscope and its application to blood cell imaging for malaria diagnosis
    Seung Ah Lee
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California, United States of America
    PLoS ONE 6:e26127. 2011
    ..We applied the prototypes to perform color imaging of red blood cells (RBCs) infected with Plasmodium falciparum, a particularly harmful type of malaria parasites and one of the major causes of death in the developing world...
  14. ncbi request reprint Characterization of light collection through a subwavelength aperture from a point source
    Xin Heng
    Department of Electrical Engineering MC136 93, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 14:10410-25. 2006
    ..5 is achievable with subwavelength aperture based devices when the aperture size is smaller than 225 nm...
  15. doi request reprint Handheld forward-imaging needle endoscope for ophthalmic optical coherence tomography inspection
    Shuo Han
    California Institute of Technology, Department of Electrical Engineering, Pasadena, California 91125, USA
    J Biomed Opt 13:020505. 2008
    ..g., vitrectomy)...
  16. pmc Implementation of a digital optical phase conjugation system and its application to study the robustness of turbidity suppression by phase conjugation
    Meng Cui
    Department of Electrical Engineering, California Institute of Technology, 1200 E California Blvd, MC 136 93, CA, 91125, USA
    Opt Express 18:3444-55. 2010
    ....
  17. pmc Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging
    Xiquan Cui
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 105:10670-5. 2008
    ..We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications...
  18. doi request reprint Characterization of acceptance angles of small circular apertures
    Ying Min Wang
    Department of Bioengineering MC138 78, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 17:23903-13. 2009
    ..This work in understanding of the behavior of light transmission through subwavelength apertures will guide the design of better aperture based imaging devices where apertures are used as light collection units...
  19. doi request reprint Manual-scanning optical coherence tomography probe based on position tracking
    Jian Ren
    Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
    Opt Lett 34:3400-2. 2009
    ..A phantom target was used to validate the method. In addition, we report OCT images of a 54-stage Xenopus laevis tadpole acquired by manual scanning...
  20. doi request reprint Wide field-of-view microscope based on holographic focus grid illumination
    Jigang Wu
    Department of Electrical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA
    Opt Lett 35:2188-90. 2010
    ..74 microm. We demonstrate the prototype by imaging a U.S. Air Force target and a lily anther. This technology is scalable and represents a cost-effective way to implement wide FOV microscopy systems...
  21. doi request reprint Quantitative surface normal measurement by a wavefront camera
    Jian Ren
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Lett 37:199-201. 2012
    ..The results agree well with their expected values. To demonstrate the application of the camera, we applied this method to measure the deformation of a microfluidic channel under pressure...
  22. pmc The application of on-chip optofluidic microscopy for imaging Giardia lamblia trophozoites and cysts
    Lap Man Lee
    Department of Bioengineering MC138 78, California Institute of Technology, Pasadena, CA 91125, USA
    Biomed Microdevices 11:951-8. 2009
    ..Finally, we report the successful microscopy imaging of both Giardia trophozoites and cysts with an OFM that has a focal plane resolution of 0.8 microns...
  23. pmc The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM)
    Guoan Zheng
    Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 108:16889-94. 2011
    ..Smart Petri dish based on this technology can significantly streamline and improve cell culture experiments by cutting down on human labor and contamination risks...
  24. doi request reprint Implementation of a color-capable optofluidic microscope on a RGB CMOS color sensor chip substrate
    Shuo Pang
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Lab Chip 10:411-4. 2010
    ....
  25. pmc Pixel level optical-transfer-function design based on the surface-wave-interferometry aperture
    Guoan Zheng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 18:16499-506. 2010
    ..Pixel level OTF design provides a low-cost, ultra robust, highly compact method for numerous applications such as optofluidic microscopy, wavefront detection, darkfield imaging, and computational photography...
  26. doi request reprint Focal plane tuning in wide-field-of-view microscope with Talbot pattern illumination
    Jigang Wu
    Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
    Opt Lett 36:2179-81. 2011
    ..By tuning the wavelength of the laser, we can tune the focal plane of the WFM and acquire images of different depth into the sample. Images of a green algae microscope slide were acquired at different focal planes for demonstration...
  27. doi request reprint Sub-pixel resolving optofluidic microscope for on-chip cell imaging
    Guoan Zheng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Lab Chip 10:3125-9. 2010
    ....
  28. ncbi request reprint Paired-angle-rotation scanning optical coherence tomography forward-imaging probe
    Jigang Wu
    Department of Electrical Engineering, California Institute of Technology, California 91125, USA
    Opt Lett 31:1265-7. 2006
    ..The system sensitivity was measured to be 93 dB by using the prototype probe with an illumination power of 450 microW on the sample. Moreover, the axial and the lateral resolutions of the probe are 9.3 and 10.3-12.5 microm, respectively...
  29. ncbi request reprint Instantaneous quadrature low-coherence interferometry with 3 x 3 fiber-optic couplers
    Michael A Choma
    Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 28:2162-4. 2003
    ....
  30. ncbi request reprint Spectral-domain phase microscopy
    Michael A Choma
    Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 30:1162-4. 2005
    ..A shot-noise limit to the displacement sensitivity of this technique is derived. Measurement of cellular dynamics was performed on spontaneously beating cardiomyocytes isolated from chick embryos...
  31. pmc Chip-scale fluorescence microscope based on a silo-filter complementary metal-oxide semiconductor image sensor
    Seung Ah Lee
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Lett 38:1817-9. 2013
    ..Our prototype device achieves 13 μm resolution over a wide field of view (4.8 mm × 4.4 mm). We demonstrate bright-field and fluorescence longitudinal imaging of living cells in a compact, low-cost configuration...
  32. pmc Optical phase conjugation (OPC)-assisted isotropic focusing
    Mooseok Jang
    Electrical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA
    Opt Express 21:8781-92. 2013
    ..This method can potentially improve 4Pi microscopy and 3D microstructure patterning...
  33. pmc Wide field-of-view on-chip Talbot fluorescence microscopy for longitudinal cell culture monitoring from within the incubator
    Chao Han
    Electrical Engineering, California Institute of Technology, Pasadena, California 91125, United States
    Anal Chem 85:2356-60. 2013
    ..We also employed the system to analyze the cells' dynamic response to an anticancer drug, camptothecin (CPT). This method can provide a compact and simple solution for automated fluorescence imaging of cell cultures in incubators...
  34. doi request reprint Markov speckle for efficient random bit generation
    Roarke Horstmeyer
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 20:26394-410. 2012
    ....
  35. pmc Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light
    Ying Min Wang
    Bioengineering and Electrical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA
    Nat Commun 3:928. 2012
    ..5 mm in biological tissues at a lateral resolution of 36 μm×52 μm and an axial resolution of 657 μm. Our results set the stage for a range of deep-tissue imaging applications in biomedical research and medical diagnostics...
  36. pmc Fluorescence microscopy imaging with a Fresnel zone plate array based optofluidic microscope
    Shuo Pang
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Lab Chip 11:3698-702. 2011
    ..0 μm due to Nyquist criterion consideration. As a demonstration, we show that such a system can be used to image the cell nuclei stained by Acridine Orange and cytoplasm labeled by Qtracker(®)...
  37. ncbi request reprint Fundamental sensitivity limit imposed by dark 1/f noise in the low optical signal detection regime
    Emily J McDowell
    Department of Bioengineering, Mail Code 136 93, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 16:6822-32. 2008
    ....
  38. ncbi request reprint Polarization-resolved second-harmonic-generation optical coherence tomography in collagen
    Brian E Applegate
    Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 29:2252-4. 2004
    ..We demonstrate this new technique on a skin sample from the belly of Icelandic salmon, acquiring polarization-resolved SHOCT and OCT images simultaneously...
  39. doi request reprint Ex vivo optical coherence tomography imaging of collector channels with a scanning endoscopic probe
    Jian Ren
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Invest Ophthalmol Vis Sci 52:3921-5. 2011
    ..To achieve high-fidelity optical coherence tomography (OCT) imaging of ex vivo collector channels (CCs) exiting Schlemm's canal (SC) using a paired-angle rotating scanning endoscopic probe...
  40. ncbi request reprint Optofluidic microscopy--a method for implementing a high resolution optical microscope on a chip
    Xin Heng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Lab Chip 6:1274-6. 2006
    ....
  41. pmc An in vivo study of turbidity suppression by optical phase conjugation (TSOPC) on rabbit ear
    Meng Cui
    California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 18:25-30. 2010
    ..The experimental findings address the minimum speed limit of a broad range of optical time reversal experiments for in vivo applications on tissues...
  42. pmc Surface-wave-enabled darkfield aperture for background suppression during weak signal detection
    Guoan Zheng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 107:9043-8. 2010
    ....
  43. pmc Characterization of spatially varying aberrations for wide field-of-view microscopy
    Guoan Zheng
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 21:15131-43. 2013
    ..We believe that this easy-to-use spatially-varying pupil characterization method may facilitate new optical imaging strategies for a variety of wide field-of-view imaging platforms. ..
  44. pmc Physical key-protected one-time pad
    Roarke Horstmeyer
    Departments of Electrical Engineering and Bioengineering, California Institute of Technology, Pasadena, CA 91125
    Sci Rep 3:3543. 2013
    ....
  45. pmc Wide field-of-view Talbot grid-based microscopy for multicolor fluorescence imaging
    Shuo Pang
    Department of Electrical Engineering, California Institute of Technology, 1200 E California Blvd Pasadena, CA 91125, USA
    Opt Express 21:14555-65. 2013
    ..This imaging method is scalable and simple for implementation of high-speed wide FOV fluorescence microscopy...
  46. pmc Wide and scalable field-of-view Talbot-grid-based fluorescence microscopy
    Shuo Pang
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Lett 37:5018-20. 2012
    ..2 μm and an FOV of 3.9 mm × 3.5 mm. We demonstrate the imaging capability of FTM on fluorescently labeled breast cancer cells (SK-BR-3) and human embryonic kidney 293 (HEK) cells expressing green fluorescent protein...
  47. doi request reprint Microscopy refocusing and dark-field imaging by using a simple LED array
    Guoan Zheng
    Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Opt Lett 36:3987-9. 2011
    ..Images of a starfish embryo were acquired by using such an approach for demonstration...
  48. ncbi request reprint Fourier-domain low-coherence interferometry for light-scattering spectroscopy
    Adam Wax
    Department of Biomedical Engineering and the Fitzpatrick Center for Photonics, Duke University, Durham, North Carolina 27708, USA
    Opt Lett 28:1230-2. 2003
    ..Application of the technique to probing the size of cell nuclei in living epithelial tissues is discussed...
  49. pmc Wavefront image sensor chip
    Xiquan Cui
    Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Opt Express 18:16685-701. 2010
    ..Besides phase microscopy, WIS can benefit machine recognition, object ranging, and texture assessment for a variety of applications...
  50. ncbi request reprint Developing optofluidic technology through the fusion of microfluidics and optics
    Demetri Psaltis
    Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Nature 442:381-6. 2006
    ..We categorize optofluidics according to three broad categories of interactions: fluid-solid interfaces, purely fluidic interfaces and colloidal suspensions. We describe examples of optofluidic devices in each category...
  51. ncbi request reprint In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry
    Adam Wax
    Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA
    Cancer Res 63:3556-9. 2003
    ..This technique also may provide a new screening tool for intraepithelial neoplasia...
  52. pmc Cellular organization and substructure measured using angle-resolved low-coherence interferometry
    Adam Wax
    G R Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge Massachusetts 02139, USA
    Biophys J 82:2256-64. 2002
    ..We also identify spatial correlations on a scale large compared with the size of a cell, indicating an overlying order within the monolayer...
  53. ncbi request reprint Determination of particle size by using the angular distribution of backscattered light as measured with low-coherence interferometry
    Adam Wax
    G R Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge 02139, USA
    J Opt Soc Am A Opt Image Sci Vis 19:737-44. 2002
    ..We also present various considerations for extending this technique to determining structural information in biological tissues, such as the effects of a distribution of particle sizes and the need to average out speckle contributions...
  54. ncbi request reprint Images of spinal nerves and adjacent structures with optical coherence tomography: preliminary animal studies
    David T Raphael
    Keck School of Medicine, University of Southern California, Department of Anesthesiology, Los Angeles, California 90033, USA
    J Pain 8:767-73. 2007
    ..Further studies are needed to determine whether such OCT technology has a potential niche in the performance of spine pain procedures...
  55. ncbi request reprint Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer
    Andrew Ahn
    G R Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Appl Opt 44:1188-90. 2005
    ..We demonstrate quantitative phase-dispersion images of test structures and biological samples...

Research Grants4

  1. Spectral Triangulation Molecular Contrast OCT
    Changhuei Yang; Fiscal Year: 2005
    ..abstract_text> ..
  2. Optofluidic Microscope
    Changhuei Yang; Fiscal Year: 2007
    ..elegans phenotyping. With the completion of the proposed research, we expect the technology will be sufficiently refined to tackle a wide range of basic research and biomedicine challenges. ..