Yanmei Tie

A chance look at an online job posting in 2005 led Yanmei Tie, PhD, to a career in brain imaging. At the time, Tie was in the final stage of completing her doctoral studies in Biomedical Engineering at Louisiana Tech University and was contemplating a return to her native China. When a lab mate showed her the advertisement for a postdoctoral position under Alexandra Golby, MD, at the Brigham, Tie ended up applying — and got the job.

Now, 18 years later, Tie is an assistant professor in the Department of Neurosurgery, focusing on functional magnetic resonance imaging (fMRI) studies. Tie credits her mentor Golby for understanding her potential, even though she did not have directly relevant experience at the time.

“My graduate research focused on biomedical signal and image processing and neural engineering towards the development of a spinal cord-computer interface. I had no experience with functional MRI brain mapping,” she said. “But Dr. Golby realized that the image processing technique that I was working on then could be applied to analyze fMRI data. So, I joined her lab, and the Brigham has been my research home ever since.”

Mitigating Language Loss Through Presurgical Mapping

Tie’s research centers around the use of neuroimaging techniques for presurgical mapping of critical brain areas for surgery planning and guidance.

“Patients can have brain tumors located very close to language areas. Surgeons want to know where these functional tissues are, so that they don’t damage them when they go in and remove the tumor,” Tie said. “Some of these tumors can result in patients having low rates of survival. It would be really devastating if, even though the tumor is gone, the patient now can’t talk.”

The importance of presurgical planning has even pervaded popular culture. Tie recalls watching an episode of “Grey’s Anatomy” in which two neurosurgeons resect a tumor from a patient’s brain. However, in doing so, the TV surgeons damaged a language-processing region, leaving the patient mute.

In order to prevent such incidents in real life, scientists like Tie use neuroimaging to locate functional language areas in the brain before surgery.

“We ask patients to complete language tasks like antonym generation or sentence completion, while they are inside the MRI scanner,” she said. “We want to activate their language regions so that we can map them.”

Innovating to Adapt to Patient Needs

Nearly half of patients already suffer from language deficits due to lesions prior to surgery. Others find it hard to respond in a timely manner, which is essential for task-based fMRI mapping. Since many patients are unable to perform the standard tasks adequately for presurgical mapping, Tie and her team have developed new methods to address their needs.

“We call it task-free fMRI. We ask the patients to just lie inside the scanner, trying not to think of anything in particular,” Tie said. “We can extract language network activity even in the absence of a specific task.”

Tie’s use of resting-state brain activity for presurgical language mapping was one of the first applications of its kind. Now, she is pursuing the next phase of her research by developing a new technique for patients with pre-existing neurologic impairments. This spring, she received an R01 grant from the National Institutes of Health for her project utilizing naturalistic stimuli such as movie clips to engage neural networks supporting language.

This method allows researchers to stimulate the desired brain regions in patients without requiring them to speak. In comparison to the resting-state paradigm, the movie fMRI paradigm offers added benefits — patients’ mental activity can be directed and their attention to the movie content results in reduced head motion and thus decreases artifacts in the imaging data.

“In our pilot study, we showed patients a seven-minute clip of ‘The Parent Trap,’” Tie said. “Watching a short sequence with people talking is a more natural stimulus, like an everyday life conversation situation. We can then extract the language network using that.”

According to Tie, these new paradigms are less demanding for patients to perform and technologists to administer, but developing the paradigm and deciphering meaningful information from the data is not straightforward. This is where Tie’s computational background comes in handy. She hopes to continue to improve presurgical mapping techniques by developing advanced methods to analyze recorded signals.

Finding Meaningful Solutions to Real World Problems

“The environment at the Brigham is perfect for what I’m trying to do,” Tie said. “I’m developing new techniques, but I also really care about how to apply them to solve real world problems. By working in a research hospital, I have more opportunities to collaborate with clinicians on projects that apply these techniques.”

For one such project, Tie is working with Samuel Patz, PhD, from the Department of Radiology, to develop a novel imaging method called functional magnetic resonance elastography (fMRE) for presurgical mapping. fMRE may be able to detect fast neural activity more directly and thus better than fMRI, which relies on blood oxygen levels as an indirect readout of brain activity.

Tie is also interested in studying brain network connectivity to understand pathophysiology and develop imaging biomarkers for neurologic diseases. She is currently partnering with Rohit Bakshi, MD, and Ellen Bubrick, MD, of the Department of Neurology, to study resting-state connectivity in patients with multiple sclerosis and epilepsy.

In the competitive world of academia, Tie highlights the importance of support. In 2014, she received the Harvard Medical School Eleanor and Miles Shore Fellowship, which awards junior faculty funds to support their career as they try to balance personal and work life responsibilities. Later, Tie was awarded a couple of R21 grants. Grateful for the support from the department and her mentor and collaborator Golby, Tie perseveres through challenges, actively working to secure funding for her research.

“I applied for the Shore Fellowship three times before I got it,” she said. “And it took four rounds of new applications before we received the R01 grant. Perseverance really pays off.”

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