Semiautomatic landmark-based two-dimensional-three-dimensional image fusion in living mice: correlation of near-infrared fluorescence imaging of Cy5.5-labeled antibodies with flat-panel volume computed tomography.

Connecting fluorescence signals with anatomic structures enhances our ability to monitor biologic processes in mice. Here, we present a semiautomated approach to correlate two-dimensional (2D) noninvasive near-infrared fluorescence (NIRF) imaging with three-dimensional (3D), high-resolution, flat-panel volume computed tomography (fpVCT). We developed an algorithm to colocalize fluorescence signals of NIRF-labeled antibodies directed against matriptase and urokinase plasminogen activator receptor (uPAR) to orthotopic carcinomas in mice visualized by fpVCT. For this purpose, mice were anesthetized and fixed on a multimodality animal bed containing fiducial markers filled with iodine-containing contrast agent and fluorescent dye. After intravenous administration of contrast agent and Cy5.5-labeled antibodies, NIRF and fpVCT images were obtained, without repositioning the mice. Binding of Cy5.5-labeled matriptase-specific antibody to pancreatic tumors and Cy5.5-labeled uPAR-specific antibody to mammary carcinomas was assessed by time-domain NIRF imaging measuring the location of fluorescence intensity and its lifetime. In summary, we developed a novel 2D-3D registration technique for image fusion with NIRF imaging and fpVCT to provide complementary information in tumor models on the in vivo association of functional information with anatomic structures. The combination of fpVCT with NIRF imaging will now allow targeted and effective monitoring of preclinical tumor therapies.

The use of flat panel volumetric computed tomography (fpVCT) in osteoporosis research.

RATIONALE AND OBJECTIVES: Improvements in imaging technology have led to the increased use of computed tomography (CT). For example, micro-CT and quantitative CT (QCT) are now often used in osteoporosis research, in which micro-CT is able to analyze small bones or bone samples with high spatial resolution. In contrast, QCT is able to investigate large samples with low spatial resolution. The aim of this study was to test the usefulness of flat-panel volumetric CT (fpVCT) in a rat model of osteopenia. MATERIAL AND METHODS: Twenty-two 3-month-old rats underwent ovariectomy and were either left untreated or supplemented with estradiol for 15 weeks. After sacrificing, the rats' second lumbar vertebral body bone mineral density (BMD) was analyzed using fpVCT and ashing. The results were compared to those of a microstructural analysis of the first lumbar vertebrae and a biomechanical evaluation of the fourth lumbar vertebrae. RESULTS: BMD measurements using both fpVCT (0.39 vs 0.35 mg/cm(3)) and ashing (0.52 vs 0.48 mg/cm(3)) demonstrated a significant improvement after estradiol supplementation. The correlation coefficient of the two methods was 0.858. After estradiol supplementation, the bone microstructural and bone biomechanical parameters were improved, compared to no treatment. The correlations of both the microstructural and the biomechanical evaluations were closer for BMD measured using fpVCT (r = 0.482-0.769) than on the basis of ashing (r = 0.345-0.573). FpVCT was not able to display the trabecular microstructure of the rat lumbar vertebrae. CONCLUSION: The use of fpVCT demonstrated a close relationship between morphologic and biomechanical evaluations in a rat model of osteopenia. Because of its different proportions, fpVCT might be able to bridge the gap between micro-CT and QCT in analyzing larger animals.