Supplemental data for "Bridging the translational gap: Implementation of multimodal small animal imaging strategies for tumor burden assessment in a co-clinical trial" PLOS ONE, 2019

Abstract: In designing co-clinical cancer studies, preclinical imaging brings unique challenges that emphasize the gap between man and mouse. Our group is developing quantitative imaging methods for the preclinical arm of a co-clinical trial studying immunotherapy and radiotherapy in a soft tissue sarcoma model. In line with treatment for patients enrolled in the clinical trial SU2C-SARC032, primary mouse sarcomas are imaged with multi-contrast micro-MRI (T1 weighted, T2 weighted, and T1 with contrast) before and after immune checkpoint inhibition and pre-operative radiation therapy. Similar to the patients, after surgery the mice will be screened for lung metastases with micro-CT using respiratory gating. A systems evaluation was undertaken to establish a quantitative baseline for both the MR and micro-CT systems against which others systems might be compared. We have constructed imaging protocols which provide clinically-relevant resolution and contrast in a genetically engineered mouse model of sarcoma. We have employed tools in 3D Slicer for semi-automated segmentation of both MR and micro-CT images to measure tumor volumes efficiently and reliably in a large number of animals. Assessment of tumor burden in the resulting images was precise, repeatable, and reproducible. Furthermore, we have implemented a publicly accessible platform for sharing imaging data collected during the study, as well as protocols, supporting information, and data analyses. In doing so, we aim to improve the clinical relevance of small animal imaging and begin establishing stan The mouse imaging zip data files (MRI and micro-CT in Dicom format) were used in tn the paper to assess repeatability (user precision) and reproducibility (consistency with shifting position). MRI data in a soft tissue sarcoma mouse modelPrimary sarcomas 113 (p53/MCA model) are generated by intramuscular delivery into the gastrocnemius of adenovirus expressing Cre recombinase (Adeno-Cre) into p53 fl/fl mice followed by intramuscular injection of 0.3 mg 3- 116 methylcholanthrene (MCA) at the same site. MR imaging with a surface coil was performed on a heated bed, with animals lying on their side. The leg was not restrained or restricted when under the coil. The T1 weighted, T2 weighted, and T1 with contrasts sets were acquired multiple times. The zip files contain all data for each mouse as dicom images and are named animal1.zip, animal2.zip....animal6.zip. For animals 1-3, the mice were scanned 3 times in succession, adjusting the mouse position between each scan set. These image sets included a T1 without contrast agent, and a T2 image. The last of the 3 images also included a T1 scan with contrast at the end, with the exception of animal 1, where a T1, T2, and T1 plus contrast set was acquired the following day (folder labeled "day 2"). These images appear as sets (set 1, set 2, and set 3). Animals 4-6 contain a single set of T1, T2, and t1 plus contrast. Included with each image is a document called a "Generic Report". This is a scanner-generated description of all of the acquisition parameters entered into the software to acquire the image, as well as all identifiers of the image. Micro-CT data in a primary lung cancer mouse model. To assess the performance of our respiratory gated lung tumor imaging, we used mice with primary lung cancer. Lung tumors were generated by intranasal injection of Adeno-Cre into LSLKrasG12D; p53 258 fl/fl mice.Each mouse was scanned three times in vivo with and without respiratory gating. A post-mortem scan was also performed for each mouse and deemed the gold standard for lesion sizes. The Micro-CT sets for two mice (IDs 180315-5 and 180615-5 ) are: 180315-5-Position1-Gating.zip - With Resp Gating180315-5-Position1-nonGating.zip - No Resp Gating180315-5-Position2-Gating.zip - With Resp Gating180315-5-Position2-nonGating.zip - No Resp Gating180315-5-Position3-Gating.zip - With Resp Gating180315-5-Position3-nonGating.zip - No Resp Gating180315-5-PostMortem.zip 180615-5-Position1-Gating.zip - With Resp Gating180615-5-Position1-nonGating.zip - No Resp Gating180615-5-Position2-Gating.zip - With Resp Gating180615-5-Position2-nonGating.zip - No Resp Gating180615-5-Position3-Gating.zip - With Resp Gating180615-5-Position3-nonGating.zip - No Resp Gating180615-5-PostMortemScan1.zip180615-5-PostMortemScan2.zip 180615-5-PostMortemScan3.zip We also provide the scanning protocol: Generalized Scanning Protocol (U24) SOP.pdf for MRI imaging. The protocol includes a generalized stepwise discussion of animal imaging with a surface coil on a preclinical scanner, as well as a more detailed section which describes the scanner-specific steps by which the included MR images were acquired.