202 - Assessing Tissue Oxygen Response to Radiation Therapy Using Spatially-Resolved Oxygen-Enhanced MRI
Presenter(s)
P. S. Lara Mejia1, C. Ubert2,3, R. C. O'Connell2, M. M. Kmiec2, S. V. Petryakov2, A. Kheirollah4, P. E. Schaner1, and P. Kuppusamy1,2; 1Department of Radiation Oncology and Applied Sciences, Geisel School of Medicine and Dartmouth-Hitchcock Medical Center, Lebanon, NH, 2Department of Radiology, Geisel School of Medicine and Dartmouth-Hitchcock Medical Center, Lebanon, NH, 3Thayer School of Engineering, Dartmouth College, Hanover, NH, 4Department of Surgery, Geisel School of Medicine and Dartmouth-Hitchcock Medical Center, Lebanon, NH
Purpose/Objective(s): Hypoxia is a common feature of solid malignancies and is strongly associated with poor oncologic outcomes. Oxygen-Enhanced MRI (OE-MRI) is a promising 1H-MRI method for quantifying tumor oxygen delivery in vivo. Due to molecular oxygen’s paramagnetic properties, the longitudinal relaxation rate (R1= 1/T1) is sensitive to changes in the quantity of O2 dissolved in tissue, and functions as a surrogate marker for tissue oxygenation. In this study, we assessed oxygenation during radiotherapy via OE-MRI in mouse SCC7 tumor models, and quantified tumor oxygen responses to radiotherapy. An exploratory spatial analysis was conducted to evaluate whether OE-MRI can be used for spatially-resolved sub-region assessments of treatment response.
Materials/Methods: Six male C3H mice (n=6) with SCC7 tumors on the right hind leg underwent a radiotherapy protocol consisting of daily fractionated treatment (2 Gy daily, 320 kV, 3 Gy/min) for 7 days followed by a single large dose of 60 Gy (TCD95). Longitudinal OE-MRI was performed at baseline and every other day (12 days) using a custom MRI-compatible 3D-printed housing. OE-MRI sequences were acquired on a 3T Siemens MAGNETOM scanner under 21% and 100% O2 breathing conditions. R1 maps were generated from variable flip angle (VFA) T1 maps, correcting for B1 field inhomogeneities, and tumor oxygenation was quantified by calculating ?R1 = R1(100% O2) - R1(21% O2). A novel exploratory spatial analysis was conducted by dividing tumors into an equal proportion matrix to assess oxygen response in tumor subregions during radiation treatment.
Results: During fractionated treatment, whole tumor ?R1 remained relatively constant with increasing tumor volumes, indicating insufficient tumor control and progressive hypoxia. Following the 60 Gy single dose, ?R1 increased during the subsequent two scans and tumor volume decrease was observed with the last scan, indicating reoxygenation response after effective treatment. In the spatial analysis, tumor subregions showed varying oxygen responses to effective radiotherapy. Tumor subregions most proximal to normoxic, non-tumor tissue showed the largest oxygen response (see table), suggesting OE-MRI can detect spatial gradients of oxygen response consistent with known tumor biology.
Abstract 202 – Table 1Conclusion: Our findings support the utility of OE-MRI as a non-invasive tool for spatially-resolved tumor oxygenation assessment during radiotherapy. ?R1 imaging, in combination with tumor volume measurements, has the potential to guide treatment modifications to improve the efficacy of radiotherapy. This methodology leverages extant technology already present in the clinical setting, and offers advantages over other hypoxia visualization strategies with respect to clinical feasibility.
| Tumor Subregion | Day 1 ?R1 (s-1) | Day 8 ?R1 (s-1) | Day 12 ?R1 (s-1) |
| Nearest to Normoxic Tissue | 0.022 ± 0.009 | 0.025 ± 0.008 | 0.045 ± 0.009 |
| Remaining Volume | 0.013 ± 0.006 | 0.010 ± 0.008 | 0.038 ± 0.006 |