Multi-modality bedding platform for combined imaging and irradiation of mice

Abstract

Preclinical imaging and irradiation yields valuable insights into clinically relevant research topics. While complementary imaging methods such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) can be combined within single devices, this is technically demanding and cost-intensive. Similarly, bedding and setup solutions are often specific to certain devices and research questions. We present a bedding platform for mice that is compatible with various preclinical imaging modalities (combined PET/MRI, cone beam CT) and irradiation with photons and protons. It consists of a 3D-printed bedding unit (acrylonitrile butadiene styrene, ABS) holding the animal and features an inhalation anesthesia mask, jaw fixation, ear pins, and immobilization for the hind leg. It can be embedded on mounting adaptors for multi-modal imaging and into a transport box (polymethyl methacrylate, PMMA) for experiments outside dedicated animal facilities while maintaining the animal’s hygiene status. A vital support unit provides heating, inhalation anesthesia, and a respiration monitor. We dosimetrically evaluated used materials in order to assess their interaction with incident irradiation. Proof-of-concept multi-modal imaging protocols were used on phantoms and mice. The measured attenuation of the bedding unit for 40/60/80/200 kV X-rays was less than 3%. The measured stopping-power-ratio of ABS was 0.951, the combined water-equivalent thickness of bedding unit and transport box was 4.2 mm for proton energies of 150 MeV and 200 MeV. Proof-of-concept imaging showed no loss of image quality. Imaging data of individual mice from different imaging modalities could be aligned rigidly. The presented bed aims to provide a platform for experiments related to both multi-modal imaging and irradiation, thus offering the possibility for image-guided irradiation which relies on precise imaging and positioning. The usage as a self-contained, stand-alone unit outside dedicated animal facilities represents an advantage over setups designed for specific devices.

Late Side Effects in Normal Mouse Brain Tissue After Proton Irradiation

“…At an age of 11–13 weeks, the right hippocampal area of the mice was irradiated with protons at the experimental beam line of the UPTD as described in ( 31 ). A designated mouse bedding unit ( 29 ) maintained mouse hygiene status and body temperature.…”

“…We recently established a workflow for high-precision proton irradiation of mouse brains ( 29 , 30 ) and showed immediate DNA damage induction in a defined subvolume ( 31 ). Being able to reproduce clinical fields including a dose gradient and tissue sparing, investigating underlying tissue damaging mechanisms or alternative treatment options is now possible.…”

Combined proton radiography and irradiation for high-precision preclinical studies in small animals

“…The position of all axes can be changed remotely by the in-house developed interfaces ScattERR (https://github.com/ schneidorlein/ScattERR) and RadiAiDD (https://github.com/jomueller/RadiAiDD, Version 0.1.0). The mouse was placed within a multi-modality bedding platform; the components and features as previously described by Müller et al (19).…”

Applying Tissue Slice Culture in Cancer Research—Insights from Preclinical Proton Radiotherapy

“…Patient-derived and cell line-derived HNSCC models were shown to recapitulate the parental tumor characteristics, and are suitable for chemotherapy and radiotherapy testing [ 11 , 12 , 13 , 14 ]. However, the immunocompromised mice hosting the tumor have high demands, and request individual solutions for radiation exposure [ 15 ]. In addition, animal experiments are time-extensive, and experimental beamtime is usually limited at proton facilities.…”