Next Generation is a Brigham Clinical & Research News column penned by students, residents, fellows and postdocs. If you are a Brigham trainee interested in contributing a column, email us. This month’s column is written by Stecia-Marie P. Fletcher, PhD, a postdoctoral research fellow in the Focused Ultrasound Laboratory in the Department of Radiology.
When many people think of neurosurgery, they think of highly invasive procedures performed in operating rooms where a skilled neurosurgeon with steady hands is carefully maneuvering surgical tools under the glare of LED lights. At the Brigham, I have been exposed to a different type of neurosurgery — one that uses sound waves.
Focused Ultrasound (FUS) is routinely used for treating patients with essential tremor, a nervous system disorder that causes involuntary and rhythmic shaking. With no scalpels or forceps in sight, FUS doesn’t look like a typical surgical procedure. While the patient is in the magnetic resonance imaging (MRI) suite with their head in a helmet-shaped ultrasound transmitter filled with water, the neurosurgeon and an ultrasound physicist are stationed behind monitors displaying the images used for treatment guidance.
Over the last decade, I have been enthralled by this emerging technology. My passion for understanding the underlying physical mechanisms and finding applications in the central nervous system started at a young age and has taken me on a journey spanning scientific disciplines and continents.
A ‘Unique Perspective’
As a little girl from Trinidad and Tobago, I dreamt of becoming a doctor. This dream was bolstered by my mom’s successful battle with breast cancer when I was 13. However, much to the dismay of my parents and teachers, I hated learning about plants and I dropped biology in the last two years of high school. I much preferred math and physics, and I ended up going to University College London to study medical physics. There, I was introduced to the field of biomedical ultrasound. As I neared the end of my college experience, I began to think more about how I could use my degree and passion for physics to make a difference — and how I could circle back to my childhood dreams by working in a medically adjacent field.
That’s when I found out about Kullervo Hynynen, PhD, a scientist at the University of Toronto (U of T), who discovered that by using transcranial FUS to cavitate intravenously administered, micron-sized gas bubbles, he could temporarily open the blood-brain barrier to enhance drug delivery in patients with brain tumors and neurodegenerative diseases. After rotating through different labs at U of T, I signed on to work with Meaghan O’Reilly, PhD, a former trainee of Dr. Hynynen’s, who had just started her own lab. There, my thesis involved developing methods for clinical translation for FUS-induced blood-spinal cord barrier opening. Initially, my work was extremely technical, involving acoustic pulse design and field characterization in the vertebral canals of excised human vertebrae. However, as my research progressed, I became more involved with preclinical investigations. By the end of my PhD, I was enamored with preclinical research and I was eager to complete a postdoc to diversify my skills.
In April 2021, I moved to Boston for a postdoctoral research position in the FUS laboratory at the Brigham with Nathan McDannold, PhD. I knew joining this lab would provide me with the best opportunity to take my career in the direction I wanted. At the Brigham, I have primarily focused on preclinical applications of FUS, particularly in rodent models of glioblastoma multiforme (GBM).
GBM is an aggressive high-grade astrocytoma that accounts for more than 50 percent of primary brain tumors. Even with standard-of-care therapeutic intervention, GBM frequently recurs and remains one of the most devastating human cancers, with a five-year survival rate of four to five percent. Despite extensive efforts to develop new treatments, there are currently no curative treatment options for GBM and alternatives are desperately needed. I research several mechanisms for using FUS in neuro-oncology, including blood-brain barrier disruption to enhance drug delivery, thermal/mechanical ablation of brain tumors, radio-sensitization and immunomodulation.
From Childhood Ambitions to Clinical Applications
For the first time in my academic career, the potential impact of my research has been tangible. My postdoctoral work has made me more excited about the role of FUS in medicine and has shaped how I envision myself as a scientist. There is something fulfilling about this line of research, especially considering my childhood ambitions and familial medical history.
Transitioning from my background in physics to research that incorporates many aspects of biology, and even chemistry, has not been without its challenges. There was a very steep learning curve for me to learn about cell culture, tumor implantation, immunohistochemistry and more. The most unexpected part of my postdoc has been the extraordinary opportunity to get involved with clinical applications of FUS. Seeing the impact of FUS in a clinical setting is one of the most rewarding parts of my work week. Moreover, this clinical experience provides a unique perspective to inform the research I do in the lab. Being aware of the bottlenecks and challenges encountered in the clinical setting has helped me understand how to think about my research in a way that is beneficial to a wide swath of society, including patients, clinicians and device development companies.
When I complete my postdoctoral training at the Brigham, I will be a much more well-rounded and interdisciplinary scientist than when I started. My understanding of the importance of research has evolved, as I have made connections between benchtop research, preclinical research and eventual clinical applications. In the long term, I hope to stay in academia and form my own research lab. I believe all I have learned during my postdoc will positively impact my future career.