Fake “Frank” Lu, an assistant professor of biomedical engineering, uses stimulated Raman scattering (SRS), a molecule identification technique, to develop a multicolor imaging technology for brain cancer pathology during surgery.

A three-year, $750,000 R00 grant from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) supports his research at Binghamton.

There are two steps to get rid of a brain tumor: removing the literal mass and then removing the lingering cancer cells at the edges. Removing the lingering cells can be tough, requiring evaluation to avoid destroying functioning brain structures.

Cancer cells are denser than normal cells, which helps them to be identified. Modern procedures involve a pathologist standing by for intraoperative consultation, using neuronavigation systems (such as an MRI scan) or fluorescence imaging to detect lingering cancer cells. Each of these techniques has drawbacks:

• With intraoperative staining-based histopathology, tissue samples are taken and evaluated in a nearby laboratory. Although accurate, this is ultimately a slow process, only allowing three samples to be evaluated during surgery.
• Neuronavigation systems can also be flawed as a result of the brain moving during the surgery, which is called “brain shift.”
• Fluorescence imaging uses fluorescent dyes to label and locate the cancer cells. Unfortunately, this is a messy process and isn’t accurate at distinguishing the margins of the tumor.

Lu’s technology is label-free, rapid and detailed. He expects that in the future, SRS can be used to evaluate 20-30 tissue samples during surgery to help delineate the tumor margin.

SRS detects “molecular fingerprints” by exciting the chemical bonds in molecules and reading the frequencies emitted by the vibrational states of the bond. This information is then used to assign different colors to the molecules, allowing for a detailed image.

Lu has also improved SRS so that it can create images of lipids, fatty acids that he says are important markers for the presence of cancer cells. Axons, the long, thread-like sections of nerve cells, are wrapped in lipid layers called myelin sheath. In areas affected by cancer, they break down, leaving lipid droplets that can be easily detected by Lu’s technology.

Lu envisions the technology being incorporated into a machine for operating rooms, and he is debating two options: a handheld probe to create images of the internal cavity, or a device that creates images of tissue samples from multiple locations. “We are providing a tool that is complementary to the current neuronavigation system,” he says.

The next step is to collect more data to solidify the efficiency of the technology. Lu is collaborating with SUNY Upstate Medical University and Brigham and Women’s Hospital to get larger data sets.

Eventually, Lu would like to implement machine learning into the technology for faster and more efficient diagnosis. He also hopes to apply this technology to other types of cancer diagnosis and even other neurological diseases, including Alzheimer’s, and do more work in live cell imaging.

Before joining Binghamton’s faculty in 2017, Lu completed a post-doctoral fellowship at Brigham and Women’s Hospital and Harvard Medical School, where he collaborated with cancer pathologists, surgeons and researchers to transform this technology. He also secured a prestigious NIH K99 Pathway to Independence Award, which is designed to facilitate researchers’ transitions from post-doctoral work to independent tenure-track jobs.

“Everyone contributes to the technical development of this technology, [but] Frank’s definitely the driving force behind the work,” says Sandro Santagata, a neuropathologist and assistant professor at Harvard Medical School and Lu’s post-doc collaborator. “He’s a team player, which is very important in scientific research.”

Lu, who was born in Shandong, China, received an undergraduate degree in optoelectronics from Zhejiang University in China and a graduate degree in bioengineering from the National University of Singapore.

He eventually realized he wanted to move toward healthcare applications of photonics rather than pure engineering and technology, which led him to Raman bioimaging. “For me, pure engineering work was not that exciting,” Lu says. “Later in my career I started thinking about practical applications of biophotonics in life science.”

As a kid, Lu was always tinkering, even attempting to develop a FM radio and an electric generator. Ever since, he has been on course to create innovations that would benefit society.

“To be successful in science requires a pretty remarkable drive,” Santagata says, “and he’s got it.”

The 21- member panel is the advisory committee to the NIH director on issues important to the public. The Office of the Director is responsible for setting policy for NIH, which includes 27 institutes and centers.

Wilton is an associate professor of human development and Africana studies. He specializes in health disparities related to HIV and AIDS in black communities, community-based research and evaluation and black psychological development and mental health. As a regional trainer for the American Psychological Association’s HIV Office for Psychology Education, Wilton provides outreach to diverse communities about HIV prevention. He has extensive experience as a psychologist in providing mental health care related to HIV prevention in black communities.

Wilton, who spent most of last week in Bethesda, Md., attending his first meeting as a member of the council, said he is delighted to serve the country in this way. “This is really important in terms of public health,” he said.

Wilton said he already played a role in a recent request for consumer health information released by the NIH. He and a number of Binghamton students will lead the data analysis of the results, which will look at the public’s health information needs and information-seeking behaviors.

“It’s good to know you’re having an impact on public health in the nation,” he said. “It’s interesting to get to participate on that level.”

“Malaria is responsible for 1-3 million deaths a year, most of whom are children under 5 in sub-Saharan Africa,” said J. Koji Lum, associate professor of anthropology and biological sciences, principal investigator for the grant. “This is equivalent to the death toll from the attacks of 9/11 every eight to 24 hours.”

Lum and Ralph Garruto, professor of biomedical anthropology and a co-investigator on the grant, together have about 11,000 archived human blood samples from malarious regions of the Pacific collected from the 1950s to the present. The samples will be analyzed and researchers will document the accumulation of genetic changes that resulted in chloroquine’s treatment failure in the Pacific.

Malaria is relatively easy to eliminate in places that have a good health-care infrastructure. In the developing world, particularly in the tropics, the disease is treated primarily through chemotherapy, Lum said.

The problem is that parasites develop resistance to the drugs over time. This study will help scientists understand how malaria parasites evolved resistance to chloroquine. They also hope to learn lessons that may be relevant to current treatments and their interactions with the disease. Ultimately, a better understanding of past episodes of drug resistance evolution will help doctors get the maximum possible impact from newer drugs.

Other studies have had to rely on theoretical modeling of resistant parasites to infer how they evolved. Lum and Garruto expect to be able to directly observe the accumulation of the nine mutations in the transporter gene that confer resistance to chloroquine. They’ll study parasites collected during the past 50 years and stored in the freezers of the NIH-BU Biomedical Anthropology archive.

“This funding will allow us to do a little bit of time traveling,” Lum said.

Lum considers malaria the most important infectious disease in human history. It continues to exact a devastating toll, in part because the resulting loss of education, work and young lives creates a cycle that makes it nearly impossible for nations to rise from poverty.

To eliminate malaria, countries must treat their entire populations, even asymptomatic adults. But there’s rarely enough money and medicine for developing nations to do that, Lum explained. Doctors focus their energies on the young, people who are clearly ill. Adults who have developed some level of immunity to malaria end up as reservoirs for parasites, continuing to spread the illness without ever feeling sick.