Quantitative Analysis Of Optical Molecular Tomography And Its Applications

In recent years, Optical Molecular Tomography technologies and the applicationsin serious diseases have brought into focus owing to good performances and effects.Due to optical molecular tomography possesses their several advantages such as highsenstivity, cost-effectiveness and potential absolute quantification characteristics. Untilnowadays, optical molecular tomography has been widely used in tumors,cardiovascular diseases, neuroscience etc. As one of the optical tomography,Bioluminescence Tomography also has the advantages of high-senstivity,high-sepcificity, and high-resolution for anatomical structure etc. It has abroad potentialfor biomedical applications, realization of absolute quantification analysis. The gastriccancer and stem cell transplantation for the therapy of ischemic diseases have beensystematic researched. The author’s major researches are outlined as follows:1. Hybrid system of high-resilution micro-CT and Bioluminescence Tomography(BLT) was developed for application research such as tumor and hindlimb ischemiadeseases. Quantitative calibrations were performed for BLT system, the calibrationsinclude non-uniformity calibration for the pixel response and absolute intensitycalibration for quantitative imaging. Moreover, a view-field function was constructedfor consideration of the spatial location of the tomographic optical imaging system, thus,the luminous flux could be quantified by passing through the optical lens. All aboveworks would promote the research for quantitative angiogenesis of hindlimb ischemia.2. Quantitative reconstruction method was studied for BioluminescenceTomography. A total power reconstruction strategy was provided based on finiteelement mesh generation method. We constructed the relationship between thebiological parameters and optical reporter gene characteristics and confirmed thefeasibility of total power reconstruction through transplanting a given source into mousebody. Cell number level quantification analysis was set up for tumor cell line and stemcell through PC-3M-luc-C6prostate cancer line, A549-luc-C8non-small cell lungcancer line and adipose-derived mesenchymal stem cells (AD-MSCs).3. We concentrated on the analysis of quantitative reconstruction deviation anddeviation contribution rate from peak wavelength shift of luminescent source and theanatomical structure deviation of animal models. Firstly, reconstruction deviations inlocalization and quantification were studied based on the hypothesis of the accurateoptical parameters of the emission peak wavelength. Secondly, reconstruction deviationwith peak wavelength shift was investigated based on the hppothesis of the accurate anatomical structure of animal model. Experimantal data suggested both the emissionpeak wavelength shift of luminescent light and deviation of anatomical structure modellead to errors in localization and quantification for BLT reconstruction. We find thatsub-millimeter accuracy for anntomical structure animal model and less than±10nmpeak wavelength shift are expected to be used in BLT reconstruction. Futhermore, theexperiments suggested that the deviation of the annotimcal structure model has muchmore influence on the reconstruction precision than the emission peak wavelength shiftdoes.4. Noninvasive monitoring and quantitative imaging research have been studied forthe multistep process of gastric cancer. Bioluminescence Tomography techniques wereused for longitudinal observation of orthotopic gastric cancer model and some signaldevelopments during tumor progression in the first time. We also evaluated thefeasibility of the detection for micro-metastasis of gastric carcinoma by high-resolutionmicro-CT system with omnipaque accumulative contrast enhancement method in theorgans. Moreover, this method not only privides high-quality anatomical information ofthe metastasis in vivo, but also reveals the accurate solid tumors volume of the etastasis.Hybrid imaging system of high-resolution micro-CT and Bioluminescence Tomographybecomes a useful tool for preclinical gastric cancer research.5. Quantitative assessment of angiogenesis has been studied through SpatialVascular Volume Fraction (SVVF) accompanying tracking AD-MSCs using hybridimaging system in vivo. Firstly, Noninvasive imaging of the AD-MSCs distribution andsurvival cells allows three-dimensional spatial visualization of the angiogenic perfusionand stem cells in vivo quantitative tracking in mice. In addition, angiogenesisassessment and quantification of stem cells with interactive imaging were performedusing hybrid system. Secondly, we reported a novel serial imaging of SVVF to exploreangiogenesis and this method could be used for quantitative assessment theangiogenesis in hindlimb mouse model. Thirdly, we discussed the strong active radii ofAD-MSCs through serial SVVF imaging analysis in spatiotemporal distribution.Fourthly, cross-validation was performed by several traditional methods to comfirm theangiogenesis after AD-MSCs transportation. a) Vascular corrosion casting validated thevascular density enhancement after AD-MSCs treatments. b) Scanning electronmicroscopic imaging performed visualization of the remarkably detailed narrativesabout some vascular sprouting. c) Confocal photomicrographs revealed the vasculardensity at the ischemic region and AD-MSCs presence in the ischemic tissue. d) Laser Doppler perfusion imaging (LDPI) was performed to assess tissue perfusion in theischemic hindlimb. Experimental data suggested significant enhancements of vasculardensity comparing between the treatment and control groups. In a word, this studyprovides an interactive SVVF quantification method for angiogenesis in3D space,which combined with BLT imaging analysis of the survival numbers and spatialdistribution of stem cells as a feedback. This combination of hybrid imagingmethodology and functional evaluation is suitable for the longitudinal mechanisticinvestigations of cellular therapy in vivo in3D space.Animal protocols were approved by the Institutional Administrative Panel onLaboratory Animal Care.