Author: Pierre Gardair, Johnathan E Leeman, Claire Keun Sun Park, Atchar Sudhyadhom ๐จโ๐ฌ
Affiliation: Brigham and Womenโs Hospital, Dana Farber Cancer Institute, Harvard Medical School, Brigham and Womenโs Hospital and Dana Farber Cancer Institute, Harvard Medical School,, Brigham and Womenโs Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Medical School ๐
Purpose: Dose is a poor surrogate for radiobiological damage but no in vivo technology exists to directly measure damage such as DNA strand breaks and free radical generation (FRG). Recent advances in MR-Linacs now allow imaging of FRG. This study presents a novel ultrafast MRI method on a clinical MR-Linac to detect and quantify radiation-produced FRG with synchronization to the temporal scales of linac pulses.
Methods: We developed a prototype Sub-Millisecond Periodic Event Encoded Dynamic Imaging (SPEEDI) pulse sequence on a ViewRay MR-Linac to achieve real-time FRG synchronized with linac radiation pulses at a temporal resolution of 1 ฮผs. This configuration enables capture of multiple MR images during the ~5 ฮผs linac pulse duration. In a preliminary study, an ex vivo meat phantom was irradiated under two conditions: Multi-Leaf Collimator (MLC) open (tissue exposed to radiation) and MLC closed. MR phase changes were analyzed to detect individual Linac pulse events, with signal processing incorporating wavelet-based denoising and linac pulse detection using synchronized event markers.
Results: The synchronized SPEEDI sequence successfully detected FRG at individual linac pulse intervals in the ex vivo meat phantom, as indicated by distinct phase changes observed in the MR signal under irradiation conditions with MLC open. The FRG signal was observed to coincide with each linac pulse at the PRF of 135 Hz, corresponding to a ~7.41 ms pulse interval. Linear regression (R2 = 1.0) confirmed alignment with the expected pulse timing. No equivalent signal changes were detected with the MLC closed, confirming the methodโs specificity for Linac pulse radiation-induced FRG.
Conclusion: We have, for the first time, demonstrated feasibility of SPEEDI on an MR-Linac to capture radiation-produced FRG in real-time at individual linac pulse intervals. This advancement paves the way for precision dosing protocols that respond dynamically to biological responses, moving toward personalized cancer treatments.