Fluorescence tomography technique optimized for noninvasive imaging of the mouse brain.

In vivo molecular fluorescence tomography of brain disease mouse models has two very specific demands on the optical setup: the use of pigmented furry mice does not allow for a purely noncontact setup, and a high spatial accuracy is required on the dorsal side of the animal due to the location of the brain. We present an optimized setup and tomographic scheme that meet these criteria through a combined CW reflectance-transmittance fiber illumination approach and a charge-coupled device contactless detection scheme. To consider the anatomy of the mouse head and take short source detector separations into account, the forward problem was evaluated by a Monte Carlo simulation input with a magnetic resonance image of the animal. We present an evaluation of reconstruction performance of the setup under three different condition. (i) Using a simulated dataset, with well-defined optical properties and low noise, the reconstructed position accuracy is below 0.5 mm. (ii) Using experimental data on a cylindrical tissue-simulating phantom with well-defined optical properties, a spatial accuracy of about 1 mm was found. (iii) Finally, on an animal model with a fluorescent inclusion in the brain, the target position was reconstructed with an accuracy of 1.6 mm.

[1]  M. Cristy Applying the reciprocal dose principle to heterogeneous phantoms: practical experience from Monte Carlo studies. , 1983, Physics in medicine and biology.

[2]  Vasilis Ntziachristos,et al.  In vivo tomographic imaging of near-infrared fluorescent probes. , 2002, Molecular imaging.

[3]  D. Delpy,et al.  Use of the water absorption spectrum to quantify tissue chromophore concentration changes in near-infrared spectroscopy. , 1994, Physics in medicine and biology.

[4]  A. Welch,et al.  A review of the optical properties of biological tissues , 1990 .

[5]  D. Boas,et al.  Three dimensional Monte Carlo code for photon migration through complex heterogeneous media including the adult human head. , 2002, Optics express.

[6]  M. Glas,et al.  Principles of Computerized Tomographic Imaging , 2000 .

[7]  M J Eppstein,et al.  Fluorescence-enhanced optical imaging of large phantoms using single and simultaneous dual point illumination geometries. , 2004, Medical physics.

[8]  R. Weissleder,et al.  Optical-based molecular imaging: contrast agents and potential medical applications , 2003, European Radiology.

[9]  Vasilis Ntziachristos,et al.  The inverse source problem based on the radiative transfer equation in optical molecular imaging , 2005 .

[10]  E. Loli Piccolomini,et al.  The conjugate gradient regularization method in Computed Tomography problems , 1999, Appl. Math. Comput..

[11]  Vasilis Ntziachristos,et al.  A submillimeter resolution fluorescence molecular imaging system for small animal imaging. , 2003, Medical physics.

[12]  Alexander D Klose,et al.  Fluorescence tomography with simulated data based on the equation of radiative transfer. , 2003, Optics letters.

[13]  Yong Xu,et al.  Improved accuracy of reconstructed diffuse optical tomographic images by means of spatial deconvolution: two-dimensional quantitative characterization. , 2005, Applied optics.

[14]  Bernd J Pichler,et al.  A hyperspectral fluorescence system for 3D in vivo optical imaging , 2006, Physics in medicine and biology.

[15]  Vasilis Ntziachristos,et al.  Noncontact optical tomography of turbid media. , 2003, Optics letters.

[16]  Hamid Dehghani,et al.  Contrast-detail analysis characterizing diffuse optical fluorescence tomography image reconstruction. , 2005, Journal of biomedical optics.

[17]  Vasilis Ntziachristos,et al.  Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy. , 2003, Neoplasia.

[18]  R. Weissleder,et al.  Tomographic fluorescence mapping of tumor targets. , 2005, Cancer research.

[19]  R. Alcouffe,et al.  Comparison of finite-difference transport and diffusion calculations for photon migration in homogeneous and heterogeneous tissues. , 1998, Physics in medicine and biology.

[20]  R. Weissleder,et al.  Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media. , 2002, Medical physics.

[21]  A. Chatziioannou,et al.  Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study , 2005, Physics in medicine and biology.

[22]  E. Aydin,et al.  A comparison between transport and diffusion calculations using a finite element-spherical harmonics radiation transport method. , 2002, Medical physics.

[23]  Roy,et al.  Active constrained truncated Newton method for simple-bound optical tomography , 2000, Journal of the Optical Society of America. A, Optics, image science, and vision.

[24]  P. Marquet,et al.  In vivo local determination of tissue optical properties: applications to human brain. , 1999, Applied optics.

[25]  Ulrich Dirnagl,et al.  Noninvasive Near-infrared Imaging of Fluorochromes within the Brains of Live Mice: An In Vivo Phantom Study , 2006, Molecular imaging.