A preclinical radiotherapy dosimetry audit using a realistic 3D printed murine phantom.

Preclinical radiation research lacks standardized dosimetry procedures that provide traceability to a primary standard. Consequently, ensuring accuracy and reproducibility between studies is challenging. Using 3D printed murine phantoms we undertook a dosimetry audit of Xstrahl Small Animal Radiation Research Platforms (SARRPs) installed at 7 UK centres. The geometrically realistic phantom accommodated alanine pellets and Gafchromic EBT3 film for simultaneous measurement of the dose delivered and the dose distribution within a 2D plane, respectively. Two irradiation scenarios were developed: (1) a 10 × 10 mm2 static field targeting the pelvis, and (2) a 5 × 5 mm2 90° arc targeting the brain. For static fields, the absolute difference between the planned dose and alanine measurement across all centres was 4.1 ± 4.3% (mean ± standard deviation), with an overall range of - 2.3 to 10.5%. For arc fields, the difference was - 1.2% ± 6.1%, with a range of - 13.1 to 7.7%. EBT3 dose measurements were greater than alanine by 2.0 ± 2.5% and 3.5 ± 6.0% (mean ± standard deviation) for the static and arc fields, respectively. 2D dose distributions showed discrepancies to the planned dose at the field edges. The audit demonstrates that further work on preclinical radiotherapy quality assurance processes is merited.

An open source heterogeneous 3D printed mouse phantom utilising a novel bone representative thermoplastic.

The lack of rigorous quality standards in pre-clinical radiation dosimetry has renewed interest in the development of anthropomorphic phantoms. Using 3D printing customisable phantoms can be created to assess all parts of pre-clinical radiation research: planning, image guidance and treatment delivery. We present the full methodology, including material development and printing designs, for the production of a high spatial resolution, anatomically realistic heterogeneous small animal phantom. A methodology for creating and validating tissue equivalent materials is presented. The technique is demonstrated through the development of a bone-equivalent material. This material is used together with a soft-tissue mimicking ABS plastic filament to reproduce the corresponding structure geometries captured from a CT scan of a nude mouse. Air gaps are used to represent the lungs. Phantom validation was performed through comparison of the geometry and x-ray attenuation of CT images of the phantom and animal images. A 6.6% difference in the attenuation of the bone-equivalent material compared to the reference standard in softer beams (0.5 mm Cu HVL) rapidly decreases as the beam is hardened. CT imaging shows accurate (sub-millimetre) reproduction of the skeleton (Distance-To-Agreement 0.5 mm ± 0.4 mm) and body surface (0.7 mm ± 0.5 mm). Histograms of the voxel intensity profile of the phantom demonstrate suitable similarity to those of both the original mouse image and that of a different animal. We present an approach for the efficient production of an anthropomorphic phantom suitable for the quality assurance of pre-clinical radiotherapy. Our design and full methodology are provided as open source to encourage the pre-clinical radiobiology community to adopt a common QA standard.

Preclinical dosimetry: exploring the use of small animal phantoms.

Preclinical radiotherapy studies using small animals are an indispensable step in the pathway from in vitro experiments to clinical implementation. As radiotherapy techniques advance in the clinic, it is important that preclinical models evolve to keep in line with these developments. The use of orthotopic tumour sites, the development of tissue-equivalent mice phantoms and the recent introduction of image-guided small animal radiation research platforms has enabled similar precision treatments to be delivered in the laboratory.These technological developments, however, are hindered by a lack of corresponding dosimetry standards and poor reporting of methodologies. Without robust and well documented preclinical radiotherapy quality assurance processes, it is not possible to ensure the accuracy and repeatability of dose measurements between laboratories. As a consequence current RT-based preclinical models are at risk of becoming irrelevant.In this review we explore current standardization initiatives, focusing in particular on recent developments in small animal irradiation equipment, 3D printing technology to create customisable tissue-equivalent dosimetry phantoms and combining these phantoms with commonly used detectors.