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Between 1992-2002, 285 pts were enrolled onto a prospective IRB-approved clinical study to assess RT-induced lung injury. Patients had pre- and post-RT SPECT (single photon emission computed tomography) perfusion lung scans, which provide a 3D map of regional lung perfusion. By registering the SPECT images with the planning CT scan, we were able to relate regional dose (calculated to reflect tissue density heterogeneity) to regional changes in perfusion. Most patients were treated with conventional fractionation (2 Gy/fraction), but some were treated with a BID or concurrent boost technique, thereby providing data for 0.35, 1.25, and 1.6 Gy/fraction. This provided an opportunity to assess the impact of fraction size on the degree of RT-induced reduction in regional perfusion. Software was developed to isolate lung regions that received a constant dose per fraction. Pre-and 6 month post-RT SPECT scans were compared in 19 patients (40 fields), and used to calculate a population dose-response curve for each fractionation schedule. Volumes contributing less than 1% of each field's volume were explicitly excluded to address penumbra. For each fraction size, the dose producing 50% perfusion reduction (ED50) was extrapolated. A reciprocal plot (1/ED50 vs. fraction size) was
generated to estimate the ratio.