Beckman Institute Postdoctoral Fellow Fan Lam is developing and applying advanced magnetic resonance (MR)-based techniques to more accurately map the molecular information in the brain.

Beckman Institute Postdoctoral Fellow Fan Lam is developing and applying advanced magnetic resonance (MR)-based techniques to more accurately map the molecular information in the brain. The ability to map and quantify molecular fingerprints of neural tissues would have significant impact on the study of the physiological basis of brain functions and neurodegenerative diseases, early diagnosis of central nervous system disorders, as well as accurate monitoring of treatment efficacy on these diseases.  

Advancing the Technology

MRI has been established as an essential tool to probe the brain’s anatomy and function by imaging the water molecules, but Lam is working to extract additional information from the MR signals, and enable researchers to visualize detailed spatial and temporal variations of many different molecules in the brain, which are involved in various important physiological functions and are altered in specific diseases and their subtypes.

The imaging technology Fan Lam and colleagues are developing allows researchers to map biochemical profiles of the brain at an unprecedented high resolution, adding another dimension of information to the anatomical information obtained from standard MRI exams, on left.

“There are many molecules in the brain, such as metabolites and neurotransmitters, which are very important in terms of brain function, and provide abundant information in characterizing different types of diseases,” Lam said.

“My research focuses on developing imaging tools to visualize these molecules in the brain non-invasively,” Lam said. “Specifically I’m developing a set of MR spectroscopic imaging (MRSI)-based technologies which will allow us to detect and quantify these molecules without the need of injecting any contrast agents into the body.”

MRSI has been used to study metabolic changes in the brain as well as other organs. “The main challenges for achieving such label-free molecular imaging using MRSI lie in the facts that these molecules typically have three to four orders of magnitude lower concentrations than water molecules—existing imaging methods to acquire their information are very slow, preventing them from being practically useful,” Lam said.

To address these challenges, he has dedicated his research to the development of new models, data acquisition strategies, and quantitative analysis and computational tools to address the speed, resolution, and sensitivity challenges for MRSI—and its integration with other neuroimaging technologies to study brain functions at normal and diseased states.

Lam, who earned his master’s and doctoral degrees in electrical and computer engineering (ECE) at Illinois, was named a Beckman Graduate Fellow in 2012, working with Zhi-Pei Liang, a professor of ECE, and Brad Sutton, a professor of bioengineering—both members of the Bioimaging Science and Technology Group (BST). As a Beckman Institute Postdoctoral Fellow, Lam is able to continue these collaborations, but has greater autonomy.

“The Beckman Postdoctoral Fellowship provides me with a lot of flexibility in choosing the projects that I am interested in, and also opportunities to seek collaborations with colleagues from different disciplines,” Lam said. “I am really excited about brain mapping, both for its scientific importance and the technological challenges. Beckman has the Biomedical Imaging Center (BIC), an amazing facility, and a lot of people working on neuroscience and neuroimaging, so it turned out to be very easy to realize ideas and establish collaborations, by leveraging the campus’ strength in engineering and neuroimaging expertise in Beckman.”

Development of SPICE

With Liang and his students, Lam has already contributed to the development of what is considered an important advance in MRSI technology: SPICE (spectroscopic imaging by exploiting spatiospectral correlation). In development by Liang’s group for more than a decade, the new approach addresses fundamental technical challenges in MRSI using novel signal generation, encoding and decoding methods developed within a subspace imaging framework.

“Fan is an outstanding researcher; he is one of those rare talents that a professor may encounter once in every 10 years or so,” Liang said. “I was very pleased to have recruited him to my group and he has exceeded all my expectations, making important contributions to our solution of the long-standing problems associated with MRSI.”

Through his postdoc fellowship, Lam has elevated SPICE even further and established a new technological framework for achieving rapid, ultrahigh-resolution MRSI. “Now we are able to achieve whole brain mapping of a number of metabolites in just five minutes with resolution matching that of a standard functional MRI scan. This is already more than an order of magnitude improvement over any existing methods,” Lam said. “My goal is to make simultaneous metabolite and neurotransmitter mapping, and comprehensive metabolic profiling of neural tissues into reality. I believe that with our recent progress these goals are within reach. Accomplishing them would lead to early diagnosis of diseases, better and more efficient treatment, and more importantly, move us toward the goal of better understanding the molecular basis of brain function and diseases.”

Collaborative Effort

Lam also acknowledges the colleagues from Liang’s group whom he has been collaborating with, including Chao Ma, a former Beckman Postdoc Fellow who is now a faculty member at Harvard Medical School and Massachusetts General Hospital in Boston; Xi Peng, a former Beckman visiting scholar; and graduate students, Bryan Clifford, Rong Guo, Yudu Li, and Yibo Zhao. “I feel very fortunate that I was able to work closely with these motivated and talented researchers. Their valuable contributions helped make SPICE possible.”

Lam’s research also is looking at incorporating machine learning into the imaging process. He has developed an algorithm that takes advantage of known spin physics, biochemistry, and extensively available low-resolution spectroscopy data to derive prior information that can be used in quantitative metabolic imaging studies using MRSI. In addition, his collaborative research has demonstrated the feasibility of simultaneous quantitative susceptibility mapping (QSM) and metabolic imaging of the brain using SPICE-based techniques, which could offer a wide range of applications including the study of brain metabolism and neurodegenerative diseases.

His advancements may impact a range of neuroscience studies in Beckman and across campus. He is working with BST members Ryan Dilger, a professor of animal sciences, and Austin Mudd, a graduate student, on a nutritional study using neuroimaging to look at how iron deficiencies in piglets affect brain development and determine if iron supplementation later in life can improve brain function. This study has been published in the journal Nutrients.

He also has an ongoing collaboration with Aron Barbey, an associate professor of psychology, using SPICE to image patients with traumatic brain injury (TBI). “We need to have a way to measure brain function to give a more accurate diagnosis and prognosis. It has been shown that the metabolic information is very helpful in terms of accessing tissue damage and predicting how the patient recovers. We hope by integrating our joint susceptibility and metabolite mapping technique into a multimodal neuroimaging protocol, we will be able to identify new biomarkers for the diagnosis and treatment of traumatic brain injury,” Lam said.

Having access to facilities at Beckman has helped advance Lam’s research. “BIC is an amazing facility with strong technical support,” Lam said. “I work very closely with the people in BIC. And the neuroimaging expertise and exciting research from faculty members like Sutton and Barbey also attracted me to the Beckman community.”

What’s Next?

Lam is devoted to his research at Illinois and values the collaborative relationships he has developed that help further his goals and find new applications for these imaging techniques. He is excited about the continued opportunities he will have as a faculty member in the Department of Bioengineering at Illinois, beginning this fall, (pending approval by the U of I Board of Trustees).

“I’m very excited that I will be able to continue some of these collaborations, and I want to establish a new collaboration with the Carle Illinois College of Medicine to develop and translate new molecular imaging technologies to study specific neurodegenerative diseases and assess the effectiveness of treatments.” Lam said.  

“I have no doubt that he will become a key technical leader of our field. I excitedly look forward to continuing our collaboration after he assumes his faculty position with the Department of Bioengineering,” Liang said.