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TOMOGRAPHY, June 2016, Volume 2, Issue 2: 158-165
DOI: 10.18383/j.tom.2016.00160

Co-Registration of Bioluminescence Tomography, Computed Tomography, and Magnetic Resonance Imaging for Multimodal in Vivo Stem Cell Tracking

Moussa Chehade1,2,3, Amit K. Srivastava1,2, and Jeff W. M. Bulte1,2,3,4,5

1Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland; 2Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland; 3Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland; 4Department of Chemical & Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and 5Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Abstract

We present a practical approach for coregistration of bioluminescence tomography (BLT), computed tomography (CT), and magnetic resonance (MR) images. For this, we developed a customized animal shuttle composed of nonfluorescent, MR-compatible Delrin plastic that fits a commercially available MR surface coil. Mouse embryonic stem cells were transfected with the luciferase gene and labeled with superparamagnetic iron oxide nanoparticles. Cells were stereotaxically implanted in the mouse brain and imaged weekly for 4 weeks with bioluminescent imaging (IVIS Spectrum CT scanner) and magnetic resonance imaging (MRI; 11.7 T horizontal bore scanner). Without the use of software coregistration, in vitro phantom studies yielded rootmean- square errors of 7.6 x 10-3, 0.93 mm, and 0.78 mm along the medial–lateral (ML), dorsal–ventral (DV), and anterior–posterior (AP) axes, respectively. Rotation errors were negligible. Software coregistration by translation along the DV and AP axes resulted in consistent agreement between the CT and MR images, without the need for rotation or warping. In vivo coregistered BLT/MRI mouse brain data sets showed a single diffuse region of bioluminescent imaging photon signal and MRI hypointensity. Over time, the transplanted cells formed tumors as histopathologically validated. Disagreement between BLT and MRI tumor location was greatest along the DV axis (1.4 ± 0.2 mm) than along the ML (0.5 ± 0.3 mm) and the AP axes (0.6 mm) because of the uncertainty of the depth of origin of the BLT signal. Combining the high spatial anatomical information of MRI with the cell viability/proliferation data from BLT should facilitate preclinical evaluation of novel therapeutic candidate stem cells.

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