Improvements in image-guided-radiotherapy (IGRT) enable accurate and precise radiotherapy treatments of moving tumors in the abdomen while simultaneously sparing healthy tissue. However, the lack of validation tools for newly developed IGRT hybrid devices such as MR-Linac is an open issue. This study presents an abdominal phantom with respiratory organ motion and multimodal imaging contrast to perform end-to-end tests in IGRT. The abdominal phantom contains anatomically shaped liver and kidney models made of Ni-DTPA and KCl-doped agarose mixtures that can be reproducibly positioned within the phantom. Organ models are wrapped in foil to avoid ion exchange with the surrounding agarose-based fatty tissue and to allow stable imaging contrast. Breathing motion is realized by a diaphragm connected to an actuator that is hydraulically controlled via a programmable logic controller (PLC). With this system, artificial and patient-specific breathing patterns can be carried out. In 1.5 and 3 T magnetic resonance imaging (MRI) and computed tomography (CT) series, diaphragm, liver and kidney motion was measured and compared to the breathing motion of a healthy male volunteer for different breathing amplitudes including shallow, normal and deep breathing. The constructed abdominal phantom demonstrated tissue-equivalent contrast in CT as well as in MRI. T1-weighted (T1w) and T2-weighted (T2w) relaxation times and CT-numbers were 552.9 ms, 48.2 ms and 48.8 HU (liver) and 950.42 ms, 79 ms and 28.2 HU (kidney), respectively. These values were stable for more than one month. Extracted breathing motion from a healthy volunteer revealed a liver to diaphragm motion ratio (LDMR) of 64.4 % and a kidney to diaphragm motion ratio (KDMR) of 30.7 %. Well-comparable values were obtained for the phantom (LDMR: 65.5 %, KDMR: 27.5 %). The abdominal phantom demonstrated anthropomorphic imaging contrast and physiological motion pattern in MRI and CT. This allows for wide use in the validation of IGRT.

Over recent decades, stereotactic body radiotherapy has garnered increasing popularity. Unfortunately, conventional preclinical 2D in vitro models are often insufficient for studying radiotherapy effects. Therefore, in this study, we developed a novel anthropomorphic in vitro liver phantom, which simulates the relevant hepatocellular carcinoma (HCC) tumor microenvironment and spatial organization. The liver phantom was 3D printed, filled with tissue-mimicking agarose mixture, and designed to fit ten microfluidic chips (MCs), in which HepG2 cells were seeded. Airtight MCs induced hypoxic conditions, as verified by Hif1α staining. Irradiation was conducted with 20 Gy in one fraction using a CyberKnife, in either a 2D setup, or by irradiating MCs arranged in the 3D-printed liver model using an individually calculated treatment plan. Post-irradiation cellular damage was determined via γH2AX staining. Here, we demonstrate a new physiologically relevant approach to model HCC pathology following radiotherapy. Comparing γH2AX staining in normoxic conditions to cells grown in MCs (hypoxic conditions) revealed a reduction in cellular damage of 30.24% (p = 0.0001) in the hypoxic environment. Moreover, we compared the scattering effect of radiation on a conventional 2D in vitro model to our new 3D anthropomorphic liver phantom and observed a significant γH2AX intensity reduction of 9.6% (p = 0.0294) in HepG2 cells irradiated in the phantom. Our approach of utilizing a liver phantom takes into account the hypoxic tumor microenvironment and 3D scattering effects of tissue irradiation, thereby modeling both physical and biological parameters of HCC tumors. The use of tissue phantoms lays the groundwork for future examination of other hypoxic tumors and offers a more comprehensive approach for screening and analysis of novel cancer therapeutics.