In vivo bioluminescence tomography with a blocking-off finite-difference SP3 method and MRI/CT coregistration.

PURPOSE: Bioluminescence imaging is a research tool for studying gene expression levels in small animal models of human disease. Bioluminescence light, however, is strongly scattered in biological tissue and no direct image of the light-emitting reporter probe's location can be obtained. Therefore, the authors have developed a linear image reconstruction method for bioluminescence tomography (BLT) that recovers the three-dimensional spatial bioluminescent source distribution in small animals. METHODS: The proposed reconstruction method uses third-order simplified spherical harmonics (SP3) solutions to the equation of radiative transfer for modeling the bioluminescence light propagation in optically nonuniform tissue. The SP3 equations and boundary conditions are solved with a finite-difference (FD) technique on a regular grid. The curved geometry of the animal surface was taken into account with a blocking-off region method for regular grids. Coregistered computed tomography (CT) and magnetic resonance (MR) images provide information regarding the geometry of the skin surface and internal organs. The inverse source problem is defined as an algebraic system of linear equations for the unknown source distribution and is iteratively solved given multiview and multispectral boundary measurements. The average tissue absorption parameters, which are used for the image reconstruction process, were calculated with an evolution strategy (ES) from in vivo measurements using an implanted pointlike source of known location and spectrum. Moreover, anatomical information regarding the location of the internal organs and other tissue structures within the animal's body are provided by coregistered MR images. RESULTS: First, the authors recovered the wavelength-dependent absorption coefficients (average error of 14%) with the ES under ideal conditions by using a numerical mouse model. Next, they reconstructed the average absorption coefficient of a small animal by using an artificial implanted light source and the validated ES. Last, they conducted two in vivo animal experiments and recovered the spatial location of the implanted light source and the spatial distribution of a bioluminescent reporter system located in the kidneys. The source reconstruction results were coregistered to CT and MR images. They further found that accurate bioluminescence image reconstructions could be obtained when segmenting a voidlike cyst with low-scattering and absorption parameters, whereas inaccurate image reconstructions were obtained when assuming a uniform optical parameter distribution instead. The image reconstructions were completed within 23 min on a 3 GHz Intel processor. CONCLUSIONS: The authors demonstrated on in vivo examples that the combination of anatomical coregistration, accurate optical tissue properties, multispectral acquisition, and a blocking-off FD-SP3 solution of the radiative transfer model significantly improves the accuracy of the BLT reconstructions.

Effects of endurance training on tissue glutathione homeostasis and lipid peroxidation in streptozotocin-induced diabetic rats.

The aims of our study were to assess whether endurance training strengthens glutathione-dependent antioxidant defenses and decreases oxidative stress in experimental diabetes. Streptozotocin-induced diabetic rats were divided into trained and untrained groups, which were further divided into resting and acute exercise groups. Endurance training consisted of treadmill running for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted until exhaustion. Eight weeks' treadmill training increased the endurance, favorably decreased lipid peroxidation as measured by thiobarbituric acid reactive substances but not conjugated dienes levels in kidney and vastus lateralis muscle and upregulated glutathione peroxidase in red gastrocnemius muscle. However, it adversely decreased total glutathione level and glutathione peroxidase activity in kidney. Acute exhaustive exercise up-regulated glutathione peroxidase activity in liver. Endurance training did not prevent the increase in thiobarbituric acid reactive substances level in liver due to acute exhaustive exercise. Activities of glutathione disulfide reductase and glutathione S-transferase were not affected. Even though endurance training appeared to upregulate glutathione dependent antioxidant defense in skeletal muscle and to decrease lipid peroxidation in kidney and vastus lateralis muscle as measured by TBARS, our results suggests that beneficial effects of 8 weeks of endurance training are limited in this rat model of uncontrolled diabetes mellitus.