Bridging the translational gap: Implementation of multimodal small animal imaging strategies for tumor burden assessment in a co-clinical trial

• Published in: PloS one 2019-04, Vol.14 (4), p.e0207555-e0207555
• Main Authors: Blocker, S J, Mowery, Y M, Holbrook, M D, Qi, Y, Kirsch, D G, Johnson, G A, Badea, C T
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Cancer; Cancer metastasis; Cancer research; Cancer therapies; Care and treatment; CAT scans; Clinical trials; Computed tomography; Data processing; Diagnosis; Diagnostic imaging; Gating; Genetic engineering; Genetically modified organisms; Humans; Image processing; Image segmentation; Immune checkpoint; Immune checkpoint inhibitors; Immunotherapy; Information management; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lungs; Magnetic resonance imaging; Medical imaging; Medical imaging equipment; Medical research; Medicine and Health Sciences; Metastases; Mice; Microscopy; Multimodal Imaging; Neoplasm Metastasis; NMR; Nuclear magnetic resonance; Oncology; Patients; Radiation; Radiation (Physics); Radiation therapy; Radiotherapy; Research and Analysis Methods; Sarcoma; Sarcoma - diagnostic imaging; Sarcoma - pathology; Scanners; Soft tissue sarcoma; Soft tissues; Studies; Surgery; Systems analysis; Tumor Burden; Tumors; X-Ray Microtomography
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0207555

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 standards for preclinical imaging of tumors from the perspective of a co-clinical trial.