[Paper Review] Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom

M. Ramish Ashraf, Stavros Melemenidis+23 more|arXiv (Cornell University)|Sep 28, 2023

Nuclear Physics and ApplicationsPhysics and Astronomy3 citations

TL;DR

This multi-institutional study evaluates dosimetric variability in FLASH and conventional electron irradiation using a 3D-printed, anatomically realistic mouse phantom. The phantom, fabricated with dual-nozzle 3D printing using materials matching tissue, bone, and lung densities, demonstrated high reproducibility and minimal dose differences (<0.5%) between phantoms, with dose variability decreasing from 4.3% to 1.2% between replicates, supporting its use in credentialing preclinical FLASH research.

ABSTRACT

We conducted a multi-institutional audit of dosimetric variability 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 ($~1.02 g/cm^3$) and polylactic acid ($~1.24 g/cm^3$) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid ($~0.64 g/cm^3$). Hounsfield units (HU) and densities were compared with the reference CT scan of the live mouse. Print-to-print reproducibility of the phantom was assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected mouse 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 $0.10 g/cm^3$ for bone, $0.12 g/cm^3$ for lung, and $0.03 g/cm^3$ for soft tissue regions. Between phantoms, the difference in HU for soft tissue and bone was &lt;10 HU from print to print. Lung exhibited the most variation (54 HU) but minimally affected dose distribution (&lt;0.5% dose differences between phantoms). The mean difference between FLASH and CONV from the first replicate to the second decreased from 4.3% to 1.2%, and the mean difference from the prescribed dose decreased from 3.6% to 2.5% for CONV and 6.4% to 2.7% for FLASH. The framework presented here is promising for credentialing of multi-institutional studies of FLASH preclinical research to maximize the reproducibility of biological findings.

Motivation & Objective

• To assess dosimetric variability across institutions in FLASH and conventional electron irradiation using a standardized phantom.
• To develop a 3D-printed, anatomically realistic mouse phantom with tissue-equivalent densities for preclinical dosimetry.
• To evaluate print-to-print reproducibility and dose distribution consistency across multiple institutions.
• To establish a framework for credentialing multi-institutional FLASH preclinical studies.

Proposed method

• A CT scan of a live mouse was used to create a 3D model of bony structures, lungs, and soft tissues.
• A dual-nozzle 3D printer fabricated the phantom using acrylonitrile butadiene styrene (1.02 g/cm³) for soft tissue and polylactic acid (1.24 g/cm³) for bone.
• Lungs were printed separately using lightweight polylactic acid (0.64 g/cm³) to match low-density lung tissue.
• Hounsfield units (HU) and mass densities were validated against the reference CT scan of the live mouse.
• Radiochromic film was used to measure dose differences between FLASH and conventional dose rates at selected anatomic regions.
• Three institutions each performed two irradiation replicates, and dose distributions were compared across sites and conditions.

Experimental results

Research questions

• RQ1 How accurately does the 3D-printed mouse phantom replicate the Hounsfield units and mass densities of real mouse anatomy?
• RQ2 What is the inter-institutional variability in dose delivery between FLASH and conventional electron beams using the same phantom?
• RQ3 How reproducible are the phantom prints across multiple institutions in terms of HU and dose distribution?
• RQ4 To what extent does phantom variability affect dose differences in FLASH and conventional irradiation?
• RQ5 Can this phantom serve as a standardized credentialing tool for multi-institutional FLASH preclinical studies?

Key findings

• The phantom's mass density differed by 0.10 g/cm³ for bone, 0.12 g/cm³ for lung, and 0.03 g/cm³ for soft tissue compared to the reference CT scan.
• Print-to-print reproducibility showed <10 HU difference in Hounsfield units for soft tissue and bone, with lung showing 54 HU variation but minimal impact on dose (<0.5% difference).
• The mean dose difference between FLASH and conventional dose distributions decreased from 4.3% to 1.2% across replicates.
• Deviation from prescribed dose decreased from 3.6% to 2.5% for conventional and from 6.4% to 2.7% for FLASH across replicates.
• The framework demonstrated high reproducibility and low inter-institutional variability, supporting its use in credentialing multi-institutional FLASH research.
• The study establishes a standardized, anatomically realistic phantom as a viable tool for improving consistency in preclinical FLASH dosimetry.