Distinguished Medical Engineering Seminar

Magnetic resonance guided focused ultrasound (MRgFUS) is one of a set of focal techniques in the treatment of musculoskeletal conditions, cancer and neurological disease. In cancer applications, pre-clinical results suggest that focal techniques such as MRgFUS or radiation therapy can cause immunogenic cell death, leading to an anti-tumor response and facilitating synergies with drugs, genes or immunotherapy. With a high duty cycle and intensity, MRgFUS can selectively ablate tissue deep in the body; alternatively, MRgFUS can provide a low-intensity mechanical tissue stimulation. Local ablation results in a short-lived presentation of specific T cell receptors and tumor antigens on macrophages and dendritic cells. We are developing strategies to combine MRgFUS with immunotherapy using protocols optimized to create a complete response in disseminated cancers. For the ablation-immunotherapy protocols, an innate immune response is triggered in the region exposed to ultrasound, and in distant lesions a dense infiltration of activated T cells results in tumor cell apoptosis. We have identified ~10,000 genes that are altered by the combination treatment as compared with a no-treatment control tumor (~6000 more than are altered by immunotherapy only). We find the ablation-immunotherapy therapy combination is more effective than immunotherapy alone, particularly in the presence of a high tumor burden. Many of these gene subsets provide interesting opportunities to selectively enhance response. Other aspects of our ongoing work include image-guided transfection and drug delivery. When coupled with injected microbubbles, MRgFUS can enhance localized drug delivery or transfection. Our current research combines many aspects of such protocols: transducer array design, nanoparticle design, biological characterization using RNA and T cell receptor sequencing, and the development of methods to characterize response and toxicity with MR imaging and positron emission tomography. We will summarize several examples of how novel imaging and methods for biological characterization can enhance outcomes in protocols that combine focal and systemic therapies. Biography: As of July 1, Dr. Ferrara will be Professor of Radiology at Stanford University. She is currently a Distinguished Professor of Biomedical Engineering at UC Davis and the Director of the Center for Content Rich Evaluation of Therapeutic Efficacy (cCRETE). Dr. Ferrara is a member of the National Academy of Engineering and a fellow of the IEEE, American Association for the Advancement of Science, the Biomedical Engineering Society, the Acoustical Society of America and the American Institute of Medical and Biological Engineering. Prior to her PhD, Dr. Ferrara was a project engineer for General Electric Medical Systems, involved in the development of early magnetic resonance imaging and ultrasound systems. Following an appointment as an Associate Professor in the Department of Biomedical Engineering at the University of Virginia, Charlottesville, Dr. Ferrara served as the founding chair of the Department of Biomedical Engineering at UC Davis. ferraralab.bme.ucdavis.edu