Seamless quantitative assessments from whole body to cellular level for high dose radiation-induced mouse intestinal injury/rescue.

Purpose: For development of medical techniques to cure severe tissue injury of patients caused by rare accidental high dose irradiation, preclinical animal studies with precise quantitative assessment of the targeted tissue injury/rescue are necessary. In this study, mouse intestine is chosen as a target tissue for developing seamless quantitative assessments from whole body to cellular level. Experiments: The seamless quantitative assessments consist of 1) Localized high dose X-ray irradiation of mouse intestinal area, 2) Non-invasive, quantitative assessment of intestinal injury, 3) Three dimensional, quantitative assessment of intestinal villi integrity, 4) Quantitative histochemical assessment of intestinal cells. Briefly, for localized intestinal high dose irradiation, mice were kept anesthesized by continuous supply of isoflurane gas through a long tube with nose cone. Non-intestinal areas of mouse body were shielded from X-ray by tangsten sheets. After irradiation, occasional intravenous injection of Tc-99m-labelled human serum albumin (HSAD) and SPECT imaging represented severity of inflammatory injury in intestine. The intestines isolated at certain periods after irradiation were cut into several pieces, then the tubular pieces were incised and fixed flatly on slide glasses in paraformaldehyde solution. Three-dimensional integrity of the villi on the flattened intestinal pieces was observed by a stereoscopy. The pieces of interest were then processed for detailed quantitative histochemical analysis using predisposed BrdU as a marker for regenerative activity.\nResults and Conclusion: Medical cares, such as treatment of mesenchymal stem cells on localized intestinal injury by various doses of X-ray, are now under assessment by this system. Detailed quantitative investigation of tissues and cells would provide information to uncover mechanisms of injury/rescue, which is necessary for feedback cycles to maximize the rescuing ability.15th International Congress of Radiation Researc