To investigate the relationship of HIF1α signaling to oxidative stress, tissue hypoxia, angiogenesis and inflammation, female Fischer 344 rats were irradiated to the right hemithorax with a fractionated dose of 40 Gy (8 Gy × 5 days). The lung tissues were harvested before and at 4, 6, 10, 14, 18, 22 and 26 weeks after irradiation for serial studies of biological markers, including markers for hypoxia (HIF1α, pimonidazole and CA IX), oxidative stress (8-OHdG), and angiogenesis/capillary proliferation (VEGF/CD 105), as well as macrophage activation (ED-1) and cell signaling/fibrosis (NFκB, TGFβ1), using immunohistochemistry and Western blot analysis. HIF1α staining could be observed as early as 4 weeks postirradiation and was significantly increased with time after irradiation. Importantly, HIF1α levels paralleled oxidative stress (8-OHdG), tissue hypoxia (pimonidazole and CA IX), and macrophage accumulation consistent with inflammatory response. Moreover, changes in HIF1α expression identified by immunohistochemistry assay parallel the changes in TGFβ1, VEGF, NFκB and CD 105 levels in irradiated lungs. These results support the notion that oxidative stress and tissue hypoxia might serve as triggering signals for HIF1α activity in irradiated lungs, relating to radiation-induced inflammation, angiogenesis and fibrosis.
Chronic inflammation and hypoxia in the microenvironment of diabetic foot ulcers (DFUs) can result in sustained vascular impairment, hindering tissue regeneration. While both nitric oxide and oxygen have been shown to promote wound healing in DFUs through anti-inflammatory and neovascularization, there is currently no available therapy that delivers both. We present a novel hydrogel consisting of Weissella and Chlorella, which alternates between nitric oxide and oxygen production to reduce chronic inflammation and hypoxia. Further experiments indicate that the hydrogel accelerates wound closure, re-epithelialization, and angiogenesis in diabetic mice and improves the survival of skin grafts. This dual-gas therapy holds promise as a potential treatment option for the management of diabetic wounds.
Purpose/Objective(s): Recently we developed a VC MRI technique to generate quasi-real-time (3 frames/s) 3D MRI based on motion modeling and 2D cine MRI for target localization. In this study, we hypothesize that the frame rate of VC MRI can be substantially accelerated using sparsely sampled 2D cine MRI. This Ultrafast VC MRI (UVC MRI) can minimize the motion artifacts for irregular breathing and provide truly real-time 3D guidance for gating/target tracking. The purpose of this study is to validate the feasibility of UVC MRI and evaluate the effects of different scanning parameters on UVC MRI. Materials/Methods: The 4D MRI acquired during patient simulation are used as prior images. Principal component analysis is used to extract 3 major respiratory deformation patterns from the deformation field maps (DFM) registered between end expiration phase and all other phases of the 4D MRI. Onboard UVC MRI at any instant is considered as a deformation of the prior MRI at the end expiration phase. The DFM for UVC MRI is represented by a linear combination of the 3 major deformation patterns. Coefficients of the deformation patterns are solved by matching the corresponding 2D slice of UVC MRI with the acquired onboard 2D cine MRI. The ultrafast onboard 2D cine MRI are acquired at 30 frames/s by sampling only 10% of the k-space on Cartesian grid, with 85% of that taken at the central k-space and the other 15% randomly sampled elsewhere. UVC MRI was evaluated using both XCAT (computerized patient model) simulation of lung cancer patients and MRI data from liver cancer patients. Three scenarios were simulated from prior to onboard volume in XCAT, including phase shift, synchronous and asynchronous motion amplitude change between tumor and body motion. The accuracy of UVC MRI was evaluated using volume percent difference (VPD) and center of mass shift (COMS) of the estimated tumor volume. Effects of region of interest (ROI) selection, 2D cine slice orientation, slice location, and slice number on the estimation accuracy were evaluated. Results: In XCAT study, the UVC MRI estimated using a single sparsely sampled sagittal 2D cine MRI with a ROI around tumor achieved VPD/ COMS of 8.54AE2.27%/0.24AE0.05 mm among all scenarios. Using the entire cine image instead of ROI reduced the accuracy to 37.37AE43.45%/ 4.03AE6.02 mm. Changing the 2D cine orientation to axial or coronal view reduced the accuracy to 9.26AE1.30%/0.76AE0.72 mm and 15.56AE2.91%/1.80AE0.56 mm, respectively. Estimation using the sagittal cine was the most robust against slice location change among all views. Using multiple parallel or orthogonal cine images did not further improve UVC MRI estimation as single cine was sufficient to fit the motion model. In patient study, profiles in the estimated and ground truth UVC MRI agreed within 5% error. Conclusion: Preliminary studies showed it is feasible to generate UVC MRI up to 30 frames/s to provide truly real-time 3D target verification. UVC MRI can potentially minimize/eliminate treatment errors in liver or lung SBRT...
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