Preclinical MRI Scanner Behind a BSL3 Barrier

Washington University, Saint Louis MO

Investigators

Abstract

Enabled by acquisition of the requested lightweight, small-footprint, cryogen-free, ?benchtop? MRI scanner, this proposal focuses on the establishment of a small-animal Biological Safety Level 3 (BSL3 or ABSL3) magnetic resonance imaging (MRI) program at the Washington University School of Medicine (WUSM). In vivo medical imaging modalities are powerful tools to supplement studies of highly pathogenic, infectious-disease processes using murine models. Imaging biomarkers can inform the kinetics of host-pathogen interactions and enable the development of novel diagnostic and treatment modalities. Most importantly, these approaches can allow longitudinal studies of single subjects without altering the ensuing infectious process and host responses to pathogens. The longitudinal approaches enabled by in vivo imaging can provide highly statistical results while greatly reducing the numbers of animals needed to evaluate the impact of genes or proteins of interest, or therapies that target them. Importantly, in vivo imaging studies that test anti-inflammatory or anti-infectious agents could provide evidence that the pathogenesis of infectious processes in certain animal models is similar to that observed in humans. MRI, in particular, can provide precise, high-resolution anatomic information, including characterization of areas of vascular leakage and changes in blood flow or water diffusion, that are directly impacted by host-pathogen interactions within infected organs. Thus, MRI can assess the severity of inflammation, track host responses to wild-type or mutated pathogens, determine whether targeted deletions in host genes impact on the infectious process, and evaluate post-infection or treatment outcomes throughout the life of the animal. MRI can also provide information regarding relative levels of oxygen consumption, which could be especially useful in studies of necrotizing infections with BSL3 pathogens. MRI techniques that assess and quantify vascular permeability and/or integrity of the blood?brain barrier are particularly valuable in studies of viruses that cause arthropathies, hemorrhagic fever, or encephalitis. Research in infectious diseases at WUSM stretches across numerous departments, with programs addressing every family of pathogen, including bacteria, viruses, fungi, and parasites. Many of our researchers examine BSL3 pathogens, including emerging infections and select agents, which severely hampers their ability to perform in vivo assessments of infectious processes. The establishment of a BSL3 MRI program would, therefore, provide a highly valuable approach for our infectious diseases researchers in their efforts to understand, diagnose, and treat the most severe infections threatening the public.