Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom.

We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom. A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm <sup>3</sup> ) and polylactic acid (∼1.24 g/cm <sup>3</sup> ) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm <sup>3</sup> ). Hounsfield units (HU), densities and print-to-print stability of the phantoms were assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. Compared to the reference CT scan, CT scans of the phantom demonstrated mass density differences of 0.10 g/cm <sup>3</sup> for bone, 0.12 g/cm <sup>3</sup> for lung, and 0.03 g/cm <sup>3</sup> for soft tissue regions. Differences in HU between phantoms were <10 HU for soft tissue and bone, with lung showing the most variation (54 HU), but with minimal impact on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3% to 1.2%), while differences from the prescribed dose decreased for both CONV (3.6% to 2.5%) and FLASH (6.4% to 2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, though these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance. This study marks the first dosimetric audit for FLASH using a non-homogeneous phantom, challenging conventional calibration practices reliant on homogeneous phantoms. The comparison protocol offers a framework for credentialing multi-institutional studies in FLASH preclinical research to enhance reproducibility of biological findings

Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies.

We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100-1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates. The need to establish optimal beam parameters capable of achieving the in vivo FLASH effect has become paramount. It is therefore necessary to validate and replicate dosimetry across multiple sites conducting UHDR studies with distinct beam configurations and experimental set-ups. Using a custom cuboid phantom with a cylindrical cavity (5 mm diameter by 10.4 mm length) designed to contain three type of dosimeters (thermoluminescent dosimeters (TLDs), alanine pellets, and Gafchromic films), irradiations were conducted at expected doses of 7.5 to 16 Gy delivered at UHDR or conventional dose rates using various electron beams at the Radiation Oncology Departments of the CHUV in Lausanne, Switzerland and Stanford University, CA. Data obtained between replicate experiments for all dosimeters were in excellent agreement (+/- 3 %). In general, films and TLDs were in closer agreement with each other, while alanine provided the closest match between the expected and measured dose, with certain caveats related to absolute reference dose. In conclusion, successful cross-validation of different electron beams operating under different energies and configurations lays the foundation for establishing dosimetric consensus for UHDR irradiation studies, and, if widely implemented, decrease uncertainty between different sites investigating the mechanistic basis of the FLASH effect