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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046255-07
Application #
7263183
Study Section
Diagnostic Imaging Study Section (DMG)
Program Officer
Witter, James
Project Start
1999-09-15
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2010-05-31
Support Year
7
Fiscal Year
2007
Total Cost
$342,679
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Montejo, Ludguier D; Jia, Jingfei; Kim, Hyun K et al. (2013) Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2: image classification. J Biomed Opt 18:076002
Montejo, Ludguier D; Jia, Jingfei; Kim, Hyun K et al. (2013) Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 1: feature extraction. J Biomed Opt 18:076001
Hielscher, Andreas H; Kim, Hyun Keol; Montejo, Ludguier D et al. (2011) Frequency-domain optical tomographic imaging of arthritic finger joints. IEEE Trans Med Imaging 30:1725-36
Klose, Christian D; Klose, Alexander D; Netz, Uwe J et al. (2010) Computer-aided interpretation approach for optical tomographic images. J Biomed Opt 15:066020
Montejo, Ludguier D; Klose, Alexander D; Hielscher, Andreas H (2010) Implementation of the equation of radiative transfer on block-structured grids for modeling light propagation in tissue. Biomed Opt Express 1:861-878
Gu, Xuejun; Ren, Kui; Masciotti, James et al. (2009) Parametric image reconstruction using the discrete cosine transform for optical tomography. J Biomed Opt 14:064003
Klose, Christian D; Klose, Alexander D; Netz, Uwe et al. (2008) Multiparameter classifications of optical tomographic images. J Biomed Opt 13:050503
Kim, Hyun Keol; Netz, Uwe J; Beuthan, Jurgen et al. (2008) Optimal source-modulation frequencies for transport-theory-based optical tomography of small-tissue volumes. Opt Express 16:18082-101
Netz, Uwe J; Beuthan, Jurgen; Hielscher, Andreas H (2008) Multipixel system for gigahertz frequency-domain optical imaging of finger joints. Rev Sci Instrum 79:034301
Lasker, Joseph M; Fong, Christopher J; Ginat, Daniel T et al. (2007) Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints. J Biomed Opt 12:052001

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