Q & A with Vanderbilt University’s Will Grissom and Charles Caskey

Charles Caskey, PhD, and Will Grissom, PhD, at Vanderbilt University’s Institute of Imaging Science address questions about their site and its important focused ultrasound work. In May 2016, the team at Vanderbilt debuted DIY hardware blueprints and open-source software so that other researchers can build their own systems to conduct pre-clinical MR-guided FUS studies.

John GoreQ. Tell us about the founding of your Institute.
Vanderbilt University Institute of Imaging Science (VUIIS) began as a University-level initiative between the School of Medicine and the central University in 2003 when they recruited internationally renowned expert Professor John Gore from Yale University to direct the effort. The university made a large initial capital investment for a dedicated building, and a wide range of imaging technology. Under Dr. Gore’s leadership, the Institute has grown to 42 faculty and more than 80 support staff and students.

Q. What is your vision and mission?
As stated on our website, “At Vanderbilt we believe the grea successes for imaging in the future will come from environments where the complementary natures of different imaging approaches are exploited, where experts in basic sciences and technical aspects of image formation and analysis collaborate closely with biomedical scientists who ask appropriate questions, and where the basic underlying science of imaging is fostered.”

caskeygrissom captionQ. What types of facilities, space, and equipment do you have?
With 42,000 square feet of space dedicated entirely to research, VUIIS houses 11 MRIs that accommodate studies ranging from small animals to human clinical trials. We have two 3T scanners and one ultrahigh field 7T scanner that is used only for research. We do not compete with clinical staff for magnet time. Preclinical hardware includes Sonic Concepts transducers. We are currently in the process of purchasing a 128-channel neuromodulation system from Image Guided Therapy, a French company. The transducers built by Image Guided Therapy also interface with Imasonic transducers.

Q. Which FUS applications and biomechanisms are you investigating?
Brain: Neuromodulation, neurostimulation with fMRI, temperature mapping, autofocusing through the skull, and whole brain temperature mapping. Neurostimulation with fMRI allows us to indirectly visualize and correlate blood flow with electrophysical activity. The tool box for temperature mapping of the whole brain in real time is a project that has been funded by the Focused Ultrasound Foundation.

Breast: Immunomodulation/FUS immune stimulation for breast cancer that initially began with applying mild hyperthermia but grew to become mechanical stimulation to train the immune system to attack the cancer. The study will help researchers understand which parts of the immune system are being activated by various types of stimulation. Results from this project were recently presented at the International Society of Therapeutic Ultrasound (ISTU). Another project with Megan Poorman, a graduate student in biomedical engineering, is assessing water/fat and multi-contrast temperature mapping.

Pancreatic Cancer: FUS to increase the delivery of drugs and diagnostic agents to pancreatic cancer cells.

Uterine Fibroids: We participated in the Philips SOFIA clinical trial. Dr. Arora has continued interest in using FUS to ablate the blood supply to uterine fibroids, a project that he studied prior to his arrival at Vanderbilt.

Technical: Bench top research transducers.

Future projects: Desmoplasia, bone metastases, and new clinical and technical projects in collaboration with Philips.

Q. Who are your internal and external collaborators?
We have internal projects in collaboration with departments of neuroscience, biomedical engineering, interventional radiology, radiology, urology, and gynecology.

Neuroscientist Limin Chen, MD, PhD, an expert in motor systems and somatosensory systems, is collaborating on the neuromodulation project along with Neuroscience and Psychology Professor Jeffrey D. Schall, PhD, the Director of the Center for Integrative Cognition & Cognitive Neuroscience. He is an expert in the visual system of nonhuman primates.

Todd Giorgio, PhD, the Chair of Biomedical Engineering, is currently studying immunotherapy for breast cancer.

Sandeep Arora, MBBS, is an interventional radiologist who recently came to Vanderbilt from UCSF, where he was working on their FUS uterine fibroid vascular ablation project. Besides continuing his basic research on vascular ablation, Dr. Arora will pursue FUS research on other broad applications. Additionally, he and David Penson, MD, MPH, the Chair of Urology, have recently been named a co-Principle Investigators for Profound Medical’s prostate clinical trial.

Reed A. Omary, MD, the Chair of Radiology, received an internal grant to look at increasing delivery of drugs to pancreatic xenograft models, connecting the dots for our radiochemistry research program. He used FUS to quantitatively measure drug intake of targeted positron emission tomography (PET) agents into a pancreatic tumor in the hind quarter of a mouse after treatment. He is an integral force in pushing FUS forward.

Ted Anderson, MD, the Division Director for Gynecology, worked on the Philips SOFIA uterine fibroid clinical trial.

Externally, we have worked with Charles Mougenot at SickKids (auto focusing through the skull); Ari Partanen at Philips Healthcare (software development and temperature mapping); Samuel Picardo at Thunder Bay (software development, image reconstruction, clinical interface engineering); and Craig Meyer at the University of Virginia (whole brain temperature mapping algorithms and sequences).

Additionally, Dr. Grissom has worked within a Philips research consortium to develop open source temperature mapping software that is now accessible to all Philips sites worldwide.

Q. Where does your funding come from?
Our major grants for FUS research include:

  • National Institutes of Health Brain Initiative R24 Grant (2015): To modulate the brain with ultrasound and visualize the effects using functional magnetic resonance imaging (fMRI). 3 year grant.
  • American Cancer Society (2015): 1-year pilot grant on the use of FUS plus microbubbles to enhance a radiotherapy sensitizer in a focal application for head and neck cancers. (Presented at the October 2015 Biomedical Engineering Society annual meeting and in process for publication and follow-on funding.)
  • Focused Ultrasound Foundation (3rd Quarter 2014): Noninvasive Targeted Neuromodulation and Functional Imaging in Behaving Macaques. Precursor work that led to the NIH R24 grant.
  • Focused Ultrasound Foundation (1st Quarter 2014): MR Temperature Imaging Toolbox for Focused Ultrasound Neurosurgery.
  • Vanderbilt Initiative in Surgery and Injury (April 2012): An adenomyosis ablation pilot project with gynecology Division Director Ted Anderson, MD, PhD.
  • Vanderbilt University Central Discovery Grant (May 2014): A preclinical pancreatic study investigated by Will Grissom, Charles Caskey, Charles Manning, and Reed Omary.
  • The US Department of Defense (DoD) (2013): A breast cancer immunotherapy project by Will Grissom and Todd Giorgio.

Q. What is your wish list to increase your impact (funding, people, technology)?
It’s difficult to get clinical applications off the ground. The main barrier is that every new idea needs an investigational device exemption (IDE). We do not have the staff, the expertise, or the time needed to write and submit IDE applications. We would love to know how other sites handle this. Surprisingly, it’s not the lack of clinical interest. We have people that want to try it for various things, they show up, and it takes the wind out of the sails to find out that we can’t try things or even get the FDA’s thoughts on it. For example, we have a clinician who would like to use FUS for desmoplasia. So, our wish list is to have the bandwidth to submit IDEs and further increase the translational aspect of our work. We want to push forward to clinical applications and grow our pilot projects to the next stages.

Q. What is your role in education?
We have participated in the Focused Ultrasound Foundation’s Global Internship Program in 2014 (Mike Kremer) and 2015 (Patricia Twilley). This year, 2016, Jad al Harake will do aberration correction work for transcranial ultrasound, and Tianyi (Mason) Chen will work on his mouse holder and MR-ARFI. Graduate and undergraduate students assist in our laboratories.

We both teach biomedical engineering courses (imaging and imaging instrumentation). In Dr. Grissom’s instrumentation course, students must each build three tabletop scanners: a CT scanner based on infrared light, a B-mode ultrasound unit, and an MRI scanner. VUIIS also provides STEM outreach education to area high school students, including offering classes for college credit.

Q. What’s next?
Vanderbilt has been chosen as the host location for the International Society of Therapeutic Ultrasound’s 2018 Annual meeting. We are looking forward to creating an educational component for the meeting that can showcase the VUIIS capabilities. Nashville will be a fun city for the event, and we will hold the Gala dinner at the Country Music Hall of Fame.

Q. What is the role of the Foundation in your work?
The Foundation has provided grants that have allowed us to develop our ideas into projects that garner larger funding opportunities. We have participated in Foundation workshops where we met academic and industry collaborators like Craig Meyer at UVA. We read and use many of the resources (papers and technical developments) that the Foundation produces and shares freely online.

Past Coverage

December 2014: 2014 4th Quarter Research Awards

April 2014: Vanderbilt’s Grissom Receives External Research Award to Improve Brain Temperature Imaging