A grant from the National Institutes of Health will support a biomedical engineering professor's pursuit of technologies that can identify treatment-resistant tumors early in the treatment process.
Narasimhan Rajaram, assistant professor of biomedical engineering, has received a five-year, $2.03 million R01 grant from the National Cancer Institute to develop optical imaging technologies that can determine response to radiation and chemotherapy therapy during treatment of head and neck cancer.
The goal is to help patients and physicians by monitoring treatment response during therapy and allowing changes to the treatment plan to more effectively treat patients.
The current standard of care is to treat these tumors with a seven-week regimen of radiation and chemotherapy. Follow-up clinical imaging using MRI and X-ray CT is used eight weeks after treatment to determine whether a tumor has responded.
The problem, Rajaram said, is the treatment plan lacks a way to identify how well the treatment is working during the process.
"Unfortunately, there are currently no methods that can identify treatment response in the clinic during therapy, which causes patients - both responsive and resistant - to lose critical time when alternative approaches could be considered," he said.
Rajaram's team has partnered with researchers from Johns Hopkins University and the University of Arkansas for Medical Sciences (UAMS) to conduct the research. Technology development and pre-clinical studies will be conducted at the University of Arkansas in Fayetteville and at Johns Hopkins, and clinical trials in patients will be conducted at UAMS. Rajaram's initial work in this area, to demonstrate the feasibility of the approach, was supported by startup funds from the University of Arkansas and the Arkansas Biosciences Institute.
The team includes Professor Robert Griffin and Assistant Professor Ruud Dings from UAMS Radiation Biology, Dr. Mauricio Moreno, director of head and neck otolaryngology at UAMS, and Ishan Barman, associate professor of mechanical engineering at Johns Hopkins University.
The research will lead to the development of an endoscope-compatible fiberoptic probe that combines diffuse reflectance and Raman spectroscopy. Diffuse reflectance spectroscopy uses optical fibers to deliver low-power, non-ionizing visible light on tissue and collect the diffusely reflected light. The Rajaram lab has developed models of light-tissue interaction to extract meaningful quantitative information from this reflected light, such as tissue oxygenation. Raman spectroscopy is an optical fiber-based technique that uses a near-infrared laser to provide a highly specific fingerprint of molecules in tissue. Since every molecule has unique Raman features, mathematical models can be used to separately identify and quantify the contributions of individual molecules.
"These complementary tools can provide information about tumor oxygenation levels, which is critical for radiation therapy to work, as well as the contributions of key biomolecules in the tumor microenvironment that contribute to the development of radiation resistance," Rajaram said.
Rajaram said radiation is an important method for treating cancer, with most cancer patients receiving some form of radiation therapy to treat their cancers. Monitoring the effectiveness of that treatment can help doctors and patients make more informed decisions.
"For head and neck cancer specifically, the long treatment duration of seven weeks makes it imperative to find out right away if changes are required to the treatment regimen for non-responding tumors," he said. "Exceptional responders could also benefit by allowing potential de-escalation of the radiation dose."
The research is conducted by three teams with complementary expertise in optical imaging and radiation biology to develop a tool that can reveal key metabolic, functional and molecular changes in cancer cells, Rajaram said. The combination of diffuse reflectance spectroscopy and Raman spectroscopy is designed to allow real-time monitoring of oxygen levels and metabolism in tumors, which can provide key indicators of treatment response.
The possibilities extend beyond just chemotherapy and radiation therapy that forms the crux of this grant, Rajaram said.
"There are new drugs constantly being developed to treat different cancers and such optical technologies could also be utilized to evaluate treatment outcomes sooner than currently possible."
Raj Rao, head of the Department of Biological Engineering, said the grant represents a major achievement.
"Receipt of this R01 grant demonstrates the significance of the multi-disciplinary research program that Dr. Rajaram has developed and highlights the usefulness of specific biomedical imaging modalities to contribute to improved clinical outcomes," he said.