OPTICAL TOMOGRAPHY FOR THE DIAGNOSIS OF JOINT DISEASES

Summary

Principal Investigator: ANDREAS HIELSCHER
Abstract: This is a competitive renewal application that builds on the achievements of a previously NIH funded project. The longterm goal of that study was and is to develop an optical tomographic imaging modality to assist in the diagnosis, chracterization, and monitoring of joint diseases. Towards that goal we have successfully implemented and tested image reconstruction schemes and instrumentation for optical tomographic imaging of finger joints. Using theses codes and instrumentation we have performed clinical pilot studies with 30 patients to explore the feasibility of diagnosing rheumatoid arthritis (RA). We showed that optically derived classifiers can be found that can distinguish between affected and non-affected joints and that correlate well with ultrasound findings and clinical examination. The initial hypothesis that changes in the synovial fluid provide optical contrast appeared to be true, however, the clinical results suggest a more complex scenario as initially expected. Based on our studies we now believe that three main processes (effusion, erosion, and hypertrophy of the synovial membrane (synovitis)) that accompany RA can be distinguished by optical tomography (OT). Doing so without contrast agents, OT promises to provide a convenient, non-invasive, and economical imaging adjunct to existing modalities. However, to be able to better distinguish between these different symptoms and detect smallest changes in optical properties as early as possible, one needs to improve the spatial resolution and enhance differentiation between optical absorption and scattering effects. The main hypothesis of this renewal application is that this can be achieved by moving from a steady-state imaging system to a frequency-domain imaging device. In detail, we propose the following three specific aims: (1) Develop a model-based iterative image reconstruction code that uses the three-dimensional frequency-domain equation of radiative transfer as an accurate model of light propagation in tissue. Such a code does currently not exist but is essential for accurate imaging in small geometries that include void-like spaces with low scattering and absorption coefficients. (2) Assemble and optimize a frequency-domain charge-coupled-device (CCD) camera system that allows for the acquisition of a larger number of data points in a shorter period of time. By being ergonometrically designed the system will be patient friendly and together with faster data acquisition minimizes movement artifacts. (3) Perform clinical studies that will allow quantifying the sensitivity and specificity of optical tomographic imaging with respect to detecting the three major aspects (effusion, erosion, and synovitis) of RA. Besides gaining fundamental knowledge on contrast mechanisms in OT joint imaging, we will specifically focus on detection of symptoms characteristic for early RA. The performance of the new code and improved instrumentation will be compared with the currently existing system. The ultimate goal of this proposal is to lay the groundwork for a clinical viable joint imager that can be used in a phase II clinical trial in i subsequent studies.
Funding Period: 1999-09-15 - 2010-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Comparison of two and three-dimensional optical tomographic image reconstructions of human finger joints
    Rong Song
    Depts of Biomedical Engineering and Radiology at Columbia University, New York, NY 10027 USA
    Conf Proc IEEE Eng Med Biol Soc . 2006
  2. pmc Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2: image classification
    Ludguier D Montejo
    Department of Biomedical Engineering, Columbia University, New York, New York 10025, USA
    J Biomed Opt 18:076002. 2013
  3. pmc Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 1: feature extraction
    Ludguier D Montejo
    Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA
    J Biomed Opt 18:076001. 2013
  4. pmc Computer-aided interpretation approach for optical tomographic images
    Christian D Klose
    Columbia University, Department of Biomedical Engineering, New York, NY 10027, USA
    J Biomed Opt 15:066020. 2010
  5. ncbi Frequency-domain optical tomographic imaging of arthritic finger joints
    Andreas H Hielscher
    Department of Biomedical Engineering, Columbia University, New York 10027, USA
    IEEE Trans Med Imaging 30:1725-36. 2011
  6. pmc Parametric image reconstruction using the discrete cosine transform for optical tomography
    Xuejun Gu
    Columbia University, Department of Biomedical Engineering, 351 Engineering Terrace, MC8904, 1210 Amsterdam Avenue, New York, New York 10027, USA
    J Biomed Opt 14:064003. 2009
  7. ncbi Multiparameter classifications of optical tomographic images
    Christian D Klose
    Columbia University, Department of Biomedical Engineering, New York, New York 10027, USA
    J Biomed Opt 13:050503. 2008
  8. ncbi Optimal source-modulation frequencies for transport-theory-based optical tomography of small-tissue volumes
    Hyun Keol Kim
    Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
    Opt Express 16:18082-101. 2008
  9. ncbi Multipixel system for gigahertz frequency-domain optical imaging of finger joints
    Uwe J Netz
    Institut für Medizinische Physik und Lasermedizin, Charite Universitatsmedizin Berlin, 14195 Berlin, Germany
    Rev Sci Instrum 79:034301. 2008
  10. ncbi Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints
    Joseph M Lasker
    Columbia University, Department of Biomedical Engineering, 500 West 120th Street, ET351 Mudd Building, MC8904, New York, New York 10027, USA
    J Biomed Opt 12:052001. 2007

Scientific Experts

  • ANDREAS HIELSCHER
  • Alexander K Scheel
  • Uwe J Netz
  • Xuejun Gu
  • Kui Ren
  • Ludguier D Montejo
  • Christian D Klose
  • Joseph M Lasker
  • Alexander D Klose
  • Jurgen Beuthan
  • Gerhard A Müller
  • Hyun K Kim
  • Jingfei Jia
  • Sabine Blaschke
  • Hyun Keol Kim
  • Rong Song
  • Juergen Beuthan
  • Matthew Schoenecker
  • Edward Dwyer
  • James M Masciotti
  • Daniel T Ginat
  • Christoph H Schmitz
  • Christopher J Fong

Detail Information

Publications17

  1. ncbi Comparison of two and three-dimensional optical tomographic image reconstructions of human finger joints
    Rong Song
    Depts of Biomedical Engineering and Radiology at Columbia University, New York, NY 10027 USA
    Conf Proc IEEE Eng Med Biol Soc . 2006
    ..In particular we examined how these different approaches affect the discrimination between healthy and RA joints...
  2. pmc Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2: image classification
    Ludguier D Montejo
    Department of Biomedical Engineering, Columbia University, New York, New York 10025, USA
    J Biomed Opt 18:076002. 2013
    ..These results underscore the high potential for DOT to become a clinically useful diagnostic tool and warrant larger prospective clinical trials to conclusively demonstrate the ultimate clinical utility of this approach...
  3. pmc Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 1: feature extraction
    Ludguier D Montejo
    Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA
    J Biomed Opt 18:076001. 2013
    ..8. These findings suggest that DOT may be capable of distinguishing between PIP joints that are healthy and those affected by RA with or without effusion, erosion, or synovitis...
  4. pmc Computer-aided interpretation approach for optical tomographic images
    Christian D Klose
    Columbia University, Department of Biomedical Engineering, New York, NY 10027, USA
    J Biomed Opt 15:066020. 2010
    ..9 can be achieved. These values are much higher than values obtained when only single parameter classifications were used, where sensitivities and specificities remained well below 0.8...
  5. ncbi Frequency-domain optical tomographic imaging of arthritic finger joints
    Andreas H Hielscher
    Department of Biomedical Engineering, Columbia University, New York 10027, USA
    IEEE Trans Med Imaging 30:1725-36. 2011
    ..Parameters derived from the scattering coefficient perform slightly better than absorption derived parameters. Furthermore we found that data obtained at 600 MHz leads to better classification results than data obtained at 0 or 300 MHz...
  6. pmc Parametric image reconstruction using the discrete cosine transform for optical tomography
    Xuejun Gu
    Columbia University, Department of Biomedical Engineering, 351 Engineering Terrace, MC8904, 1210 Amsterdam Avenue, New York, New York 10027, USA
    J Biomed Opt 14:064003. 2009
    ..We especially focus on the influence of initial guesses and noise levels on the reconstruction results...
  7. ncbi Multiparameter classifications of optical tomographic images
    Christian D Klose
    Columbia University, Department of Biomedical Engineering, New York, New York 10027, USA
    J Biomed Opt 13:050503. 2008
    ..54, and an area under the curve (AUC) of 0.72. These values are higher than for previously reported single parameter classifications with a best sensitivity and specificity of 0.71, a Youden index of 0.41, and an AUC of 0.66...
  8. ncbi Optimal source-modulation frequencies for transport-theory-based optical tomography of small-tissue volumes
    Hyun Keol Kim
    Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
    Opt Express 16:18082-101. 2008
    ..We present numerical and experimental studies with a focus on small tissue volumes, as encountered in small animal and human finger imaging. Best reconstruction results were achieved in the 600-800 MHz frequency range...
  9. ncbi Multipixel system for gigahertz frequency-domain optical imaging of finger joints
    Uwe J Netz
    Institut für Medizinische Physik und Lasermedizin, Charite Universitatsmedizin Berlin, 14195 Berlin, Germany
    Rev Sci Instrum 79:034301. 2008
    ....
  10. ncbi Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints
    Joseph M Lasker
    Columbia University, Department of Biomedical Engineering, 500 West 120th Street, ET351 Mudd Building, MC8904, New York, New York 10027, USA
    J Biomed Opt 12:052001. 2007
    ..Focusing on three cases studies, we illustrated our major finds. These studies support our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints...
  11. ncbi Parametric reconstruction method in optical tomography
    Xuejun Gu
    Dept of Biomed Eng, Columbia Univ, New York, NY 10027, USA
    Conf Proc IEEE Eng Med Biol Soc 1:2667-70. 2006
    ..In this way the amount of measured data is equal or larger than the number of unknowns. Using synthetic data, we show examples that demonstrate how this approach leads to improvements in imaging quality...
  12. ncbi Development of a finger joint phantom for evaluation of frequency domain measurement systems
    Uwe J Netz
    Inst fur Medizinische Phys and Lasermedizin, Charite Universitatsmedizin Berlin
    Conf Proc IEEE Eng Med Biol Soc 1:1937-40. 2006
    ..Reliability of the phantom measurement was investigated by repeated assembling. The results show clear discrimination between different stages of joints within the signal deviation due to reassembling of the phantom...
  13. ncbi Transport- and diffusion-based optical tomography in small domains: a comparative study
    Kui Ren
    Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027, USA
    Appl Opt 46:6669-79. 2007
    ..However, transport-based reconstructions are considerably slower than diffusion-based reconstructions...
  14. ncbi Digital-signal-processor-based dynamic imaging system for optical tomography
    Joseph M Lasker
    Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace MC8904, New York, NY 10027, USA
    Rev Sci Instrum 78:083706. 2007
    ..First experiments on tissue phantoms show that dynamic behavior is accurately captured and spatial location can be correctly tracked using this system...
  15. ncbi Frequency-domain sensitivity analysis for small imaging domains using the equation of radiative transfer
    Xuejun Gu
    Columbia University, New York, New York 10027, USA
    Appl Opt 46:1624-32. 2007
    ..These results will be useful in the design of experiments and optical tomographic imaging systems that probe small tissue volumes...
  16. ncbi Optical tomographic imaging of small animals
    Andreas H Hielscher
    Department of Biomedical Engineering, Columbia University, ET351 Mudd Building, 500 West 120th Street, MC8904, New York, NY 10027, USA
    Curr Opin Biotechnol 16:79-88. 2005
    ..The past three years have seen an array of novel technological developments that have led to the first optical tomographic studies of small animals in the areas of cerebral ischemia and cancer...
  17. pmc First clinical evaluation of sagittal laser optical tomography for detection of synovitis in arthritic finger joints
    A K Scheel
    Department of Medicine, Nephrology and Rheumatology, Georg August University Gottingen, Robert Koch Strasse 40, D 37075 Gottingen, Germany
    Ann Rheum Dis 64:239-45. 2005
    ..To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis...