What are the novel findings of this work?This is the first study to compare microfocus computed tomography (micro-CT) and high-field magnetic resonance imaging (HF-MRI) in postmortem whole-body fetal imaging. We have shown that micro-CT enables higher quality imaging, with higher resolution, image contrast and signal-to-noise ratio, compared with HF-MRI. Furthermore, the ability to recognize and assess anatomical structures is greater when using micro-CT images. What are the clinical implications of this work?This work represents advancement in postmortem fetal imaging as a service for parents who have experienced early pregnancy loss. Previously, it was assumed that the performance of HF-MRI and micro-CT was similar and that the choice of the imaging modality should depend on availability. Here, we provide substantial evidence that micro-CT is superior to HF-MRI and, therefore, should be the preferred imaging modality.

Radiotherapy plus cisplatin (chemoradiation) is standard treatment for women with locoregionally advanced cervical cancer. Both radiotherapy and cisplatin induce DNA single and double-strand breaks (SSBs and DSBs). These double-strand breaks can be repaired via two major DNA repair pathways: Classical Non-Homologous End-Joining (cNHEJ) and Homologous Recombination. Besides inducing DNA breaks, cisplatin also disrupts the cNHEJ pathway. Patients contra-indicated for cisplatin are treated with radiotherapy plus hyperthermia (thermoradiation). Hyperthermia inhibits the HR pathway. The aim of our study is to enhance chemoradiation or thermoradiation by adding PARP1-inhibition, which disrupts both the SSB repair and the Alternative NHEJ DSB repair pathway. This was studied in cervical cancer cell lines (SiHa, HeLa, C33A and CaSki) treated with hyperthermia (42 °C) ± ionizing radiation (2–6 Gy) ± cisplatin (0.3–0.5 µM) ± PARP1-inhibitor (olaparib, 4.0–5.0 µM). Clonogenic assays were performed to measure cell reproductive death. DSBs were analyzed by γ-H2AX staining and cell death by live cell imaging. Both chemoradiation and thermoradiation resulted in lower survival fractions and increased unrepaired DSBs when combined with a PARP1-inhibitor. A quadruple modality, including ionizing radiation, hyperthermia, cisplatin and PARP1-i, was not more effective than either triple modality. However, both chemoradiation and thermoradiation benefit significantly from additional treatment with PARP1-i.