The overall goal of this proposal is the development of a three-dimensional optical tomographic (OT) near-infrared imaging system for oximetry in small animals. The system will be designed to allow for co-registration of OT data and magnetic resonance (MR) imaging data, but may also be used as a stand-alone optical imaging unit. While commercial systems that perform optical blood-oxygenation monitoring exist, these instruments have not been optimized for small animal studies and have not been combined with MR imaging systems. Furthermore, the available devices often operate with a limited number of sources and detectors, do not generate three-dimensional volumetric images, and the image reconstruction is performed with diffusion-theory-based algorithms. It is well known, however, that diffusion theory does not fully account for the effects of light propagation in small biological media (diameter 1-2 cm), because at these dimensions the diffusion approximation to the more generally applicable theory of radiative transfer is not sufficiently accurate. The proposed work attempts to overcome the current shortfalls and develop a near-infrared optical imaging system that can be used in combination with standard small animal MR scanners. The main hypothesis of this project is that current limitations of optical tomographic imaging can be addressed by implementing a three-dimensional frequency-domain reconstruction scheme that is based on the equation of radiative transfer (ERT). This algorithm will be implemented and used in conjunction with a commercially available frequency-domain measurement system (IAMGENT from ISS, Urban-Champaign, IL), which will be adapted to collect data inside an MR small animal imager. By co-registering optical and MR data one can combine the benefits of MR's high-spatial-resolution, with OT's high temporal resolution and its capability of separating oxyhemoglobin, deoxyhemoglobin, and blood volume effects. For this project we will pursue the following three specific aims: (1) Develop and numerically validate of a three-dimensional, transport-theory-based, frequency-domain image reconstruction code for diffuse optical tomography; (2) Validate and evaluate the optical tomographic imaging system (code and instrument) in a small animal magnetic resonance imager; and (3) Compare frequency-domain and steady-state, transport-theory based optical tomography with diffusion-theory-based optical tomography. This comparison will quantify the advantages and disadvantages of these different optical imaging modalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB001900-02
Application #
6801990
Study Section
Special Emphasis Panel (ZRG1-EB (52))
Program Officer
Zhang, Yantian
Project Start
2003-09-15
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$477,903
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
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Gu, Xuejun; Ren, Kui; Hielscher, Andreas H (2007) Frequency-domain sensitivity analysis for small imaging domains using the equation of radiative transfer. Appl Opt 46:1624-32
Ren, Kui; Bal, Guillaume; Hielscher, Andreas H (2007) Transport- and diffusion-based optical tomography in small domains: a comparative study. Appl Opt 46:6669-79
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Masciotti, James M; Lasker, J M; Hielscher, A H (2006) Digital lock-in algorithm for biomedical spectroscopy and imaging instruments with multiple modulated sources. Conf Proc IEEE Eng Med Biol Soc 1:3198-201
Hielscher, Andreas H (2005) Optical tomographic imaging of small animals. Curr Opin Biotechnol 16:79-88