Research Site Profile: Washington University in St. Louis

The Chen Ultrasound Laboratory at Washington University in St. Louis, Missouri (WUSTL) is the epicenter of focused ultrasound research that is conducted across at least eight different academic departments within the University. Hong Chen, PhD, Assistant Professor of Biomedical Engineering and Radiation Oncology, launched her laboratory in 2015 but within three short years, this incredible leader has established powerful collaboration with Washington University’s neurosurgeons, pediatricians, radiation oncologists, oncologists, chemists, and nanoparticle and MRI imaging experts. Besides the collaborative work, Chen’s research laboratory combines biology, engineering, and medicine to develop ultrasound techniques for noninvasive, targeted, and personalized cancer treatment.

We interviewed Dr. Chen to learn more about the projects and people at this dynamic center.


Hong Chen 2What is the vision and mission of your laboratory?
The mission of the Chen Ultrasound Laboratory is to translate basic research advances in ultrasound imaging and therapy into image-guided therapy devices that can impact cancer patient care.

What types of facilities, space, and equipment do you have and use?
The lab at the Danforth Campus has about 600 square feet of wet lab space and student office space. The lab at the Medical Campus has about 400 square feet of bench-space that is located in an open space laboratory. We have access to the Sonalleve focused ultrasound system from Profound Medical and own research systems from Image Guided Therapy and Alpinion (the VIFU 2000).

Where does your funding originate, and what is your annual budget?
We have received funding from NIH, ONR, and NSF, as well as departmental and institute funding from WUSTL. The annual budget for my laboratory is currently $500,000.

Investigators

WU in St. Louis team sm

How many total staff work in your laboratory and in what positions?
Besides myself, I have one technician and four graduate students.

How did you become interested in focused ultrasound?
I began working with focused ultrasound in 2002 at Xi’an Jiaotong University in China. I was moved by a visit to a hospital where patients were lined up for high-intensity focused ultrasound treatment. That image was burned in my mind and it convinced me to center my undergraduate and master’s research on understanding focused ultrasound as a treatment modality. My advisor was Prof. Mingxi Wan from Xi'an Jiaotong University. My specific area of interest was in understanding cavitation-caused tissue damage. Because of this work, I received the 2005 RWB Stephens Prize Stephens Prize at the World Congress in Ultrasonics/Ultrasonics International and became the first Chinese student ever to win this international award. At that meeting, I met Dr. Lawrence Crum from the University of Washington, and he invited me to apply to the PhD program there. (I’m so happy that I applied, because it changed my whole career.)

While pursuing my PhD at the University of Washington under the mentoring of Drs. Lawrence Crum and Thomas Matula, I investigated and revealed the physical mechanisms of vascular disruption by ultrasound in combination with microbubbles. This work led to a publication in one of the prestigious journal for physics research (Chen et al., Physical Review Letters, 2011). After graduation, I worked with Dr. Joo Ha Hwang in the University of Washington’s School of Medicine for one year. That work focused on developing passive cavitation detection techniques for monitoring ultrasound-induced cavitation used for drug delivery for pancreatic cancer.

In 2012, I moved to Columbia University. There, I worked with Dr. Elisa Konofagou on developing ultrasound techniques for drug delivery to the brain, including FUSIN. I also worked on developing an ultrasound elasticity imaging technique, called harmonic motion imaging, to estimate pancreatic tumor stiffness. This work was featured on the cover of the IEEE Trans Ultrason Ferroelectr Freq Control [2015; 62(9)].

In 2014, I received a Young Investigator Award at the Focused Ultrasound Foundation’s International Symposium in recognition of my “outstanding research in the field of focused ultrasound.” The next year I opened my laboratory at WUSTL.

Who are your internal collaborators?
WUSTL prides itself on its faculty collaborations. This type of work is highly promoted, and I am grateful to have worked with many experts across a variety of specialties. I truly believe that collaboration is the key to helping us all move forward, and without it we are so limited.

Imaging
Philip Bayly, PhD, is a Professor of Mechanical Engineering with expertise in the mechanics of cells and soft tissues, nonlinear dynamics, and waves and oscillations. He uses MRI to investigate the mechanics of brain injury and brain development and studies the nonlinear dynamic phenomena that underlie the oscillatory movements of cells and microorganisms.

Joel R. Garbow, PhD, is a Professor of Radiology with expertise in magnetic resonance imaging and spectroscopy. He is the Associate Laboratory Director of the Biomedical Magnetic Resonance Laboratory (BMRL). His research interests include the development and application of novel MR methodologies for the study of cancer and radiation-induced brain injury in pre-clinical, small-animal models.

Yuan-chuan Tai, PhD, Associate Professor of Radiology and Biomedical Engineering and Lab Chief (Interim) of the Radiological Chemistry and Imaging Laboratory, develops novel molecular imaging systems and technologies for clinical, preclinical, and plant imaging applications. He has expertise in virtual-pinhole PET (VP-PET) technology for high-resolution human imaging applications, sub-millimeter resolution PET for preclinical imaging applications, and hgh resolution Cherenkov imaging.

Nanoparticles
Yongjian Liu, PhD, is an Associate Professor of Radiology who develops novel molecular probes for preclinical and translational imaging and therapy. He is an expert in nanoparticle-based agents, small molecules, peptide agents and Cherenkov imaging for biomedical applications.

Pratim Biswas, PhD, is the Assistant Vice Chancellor of International Programs, the Chair of the Department of Energy, Environmental, and Chemical Engineering, and the Director of the McDonnell Academy Global Energy and Environmental Partnership. Among his many scientific intererests and world-class accomplishments, he is an expert in nanoparticle and aerosol technology.

Neurosurgery
Gavin Dunn, MD, PhD, is an Assistant Professor of Neurological Surgery, Neurology, and Pathology/Immunology. As a member of the newly established interdisciplinary Center for Human Immunology and Immunotherapy Programs, he oversees the research program focused on the immunobiology of malignant glioma. His goal in this program is to translate basic science into clinical trials.

Eric Leuthardt, MD is a a neurosurgeon who is currently a professor with the Department of Neurological Surgery and the Department of Biomedical Engineering. He is the Director of the Center for Innovation in Neuroscience and Technology and the Brain Laser Center. One of his areas of research is advanced brain mapping for neurosurgery. Leuthardt is pioneering the use of electrical brain implants to help restore motor function to the paralysed limbs of stroke victims.

Genome Institute
Allegra Petti, PhD, is an Assistant Professor in the Department of Medicine’s Division of Oncology and the McDonnell Genome Institute. Among other research interests, she specializes in the integration of multiple types of genomic data and biomarkers to understand tumor heterogeneity and the microenvironment of solid tumors.

Pediatrics
Josh Rubin, MD, PhD, Professor of Pediatrics, Neurology, and Neuroscience, studies the biology and treatment of pediatric brain tumors. His work with diffuse intrinsic pons glioma (DIPG),the most deadly pediatric cancer, is an incredible match for focused ultrasound because of its location in the pons.

Radiation Oncology
Dennis Hallahan, MD, Elizabeth H. and James S. McDonnell III Distinguished Professor of Medicine and Chair of Department of Radiation Oncology. He has developed several drugs that have entered Phase I through Phase III clinical trials. These drugs have been developed through biotechnology start-ups and through collaborations with pharmaceutical industry.

Imran Zoberi, MD, Professor of Radiation Oncology, is chief of the breast cancer service and chief of hyperthermia service in radiation oncology. He also serves as the Clinical Director for radiation oncology at Barnes-Jewish West County Hospital.

Michael Altman, PhD, Assitant Professor of Radiation Oncology, is the lead clinical physicist for the MR/HIFU focused ultrasound program at WUSTL. His focused ultrasound research interests include quality clinical implementation of hyperthermia for MR/HIFU systems and quality assurance of MR/HIFU systems. He is leading the project on hyperthermia for radiosensitation and is seeking IRB approval and an IDE to use the Sonnalleve system for this work.

Xiaowei Wang, PhD, is an Associate Professor of Radiation Oncology and Biomedical Engineering. He is an expert in biomarkers, specifically in identifying prognostic biomarkers for human cancers and developing microRNA therapeutics for human cancers. The Wang Lab is currently collaborating with radiation oncologists to validate the clinical utility of prognostic biomarkers to guide treatment decisions.

Projects

Which focused ultrasound applications and biomechanisms do you investigate?
We use the mechanical applications of focused ultrasound to deliver drugs to the brain. We use thermal mechanisms in projects to target soft tissue sarcomas and tumors in the lower abdomen, such as cervical cancer. We hope to start clinical trials early next year, and Dr. Altman is taking the lead on the clinical translation of mild hyperthermia.

Tell us about your various projects and studies?
Our preclinical projects are for brain drug delivery. Clinically we are testing hyperthermia for radiosensitization of tumors.

What are your successes? Any Failures?
My passion is in promoting the focused ultrasound technique, and I’m getting closer to realizing my goal of developing innovative focused ultrasound techniques and pushing them into the clinic to have more patients benefit from this novel technique. I never consider anything a failure. Failure happens all of the time, but it is more valuable than success in teaching us new things.

Does the Foundation play a role in your work?
As a junior scientist, I appreciated the Foundation so much in the way that it united people to achieve a common goal.

What is on your wish list to increase your impact?
People: more talented students and Postdocs to join my group.

Education

What is your role in education?
I teach ultrasound imaging to undergraduate and graduate students at WUSTL.

How many students do you teach?
Each year, I teach about 15 undergraduate students and 15 graduate students in the biomedical engineering program. I also contribute lectures in courses for other professors.

Do you do any community outreach or education projects?
For the past several years, I have participated in a program called “Moving and Shaking,” which is an introduction to engineering for local students.


Key Publications

Focused Ultrasound Combined with Microbubble-mediated Intranasal Delivery of Gold Nanoclusters to the Brain
Ye D, Zhang X, Yue Y, Raliya R, Biswas P, Taylor S, Tai YC, Rubin JB, Liu Y, Chen H.
J Control Release 2018 Sept 28;286:145-153.

Focused Ultrasound-enabled Delivery of Radiolabeled Nanoclusters to the Pons
Ye D, Sultan D, Zhang X, Yue Y, Heo GS, Kothapalli SVVN, Luehmann H, Tai YC, Rubin JB, Liu Y, Chen H.
J Control Release 2018 Aug 10;283:143-150.

Focused Ultrasound-enabled Brain Tumor Liquid Biopsy
Zhu L, Cheng G, Ye D, Nazeri A, Yue Y, Liu W, Wang X, Dunn GP, Petti AA, Leuthardt EC, Chen H.
Sci Rep 2018 Apr 26;8(1):6553.

Evaluation and Selection of Anatomic Sites for Magnetic Resonance Imaging-guided Mild Hyperthermia Therapy: A Healthy Volunteer Study
V V N Kothapalli S, Altman MB, Zhu L, Partanen A, Cheng G, Gach HM, Straube W, Zoberi I, Hallahan DE, Chen H.
Int J Hyperthermia 2018 Jan 4:1-9. doi: 10.1080/02656736.2017.1418536.

Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer.
Chen H, Hou GY, Han Y, Payen T, Palermo CF, Olive KP, Konofagou EE.
IEEE Trans Ultrason Ferroelectr Freq Control 2015 Sep;62(9):1662-73.

Blood Vessel Deformations on Microsecond Time Scales by Ultrasonic Cavitation
Chen H, Kreider W, Brayman AA, Bailey MR, Matula TJ.
Phys Rev Lett 2011 Jan 21;106(3):034301.


Past Coverage

Dunn Awarded Inaugural CRI/FUSF Immunotherapy Program Grant June 2018

Focused Ultrasound-Released Brain Tumor Biomarkers Could Replace Biopsy May 2018

Washington University’s work has also mentioned in several recent meeting reports: STM 2017, AAPM 2017, and STM 2018.