NanoBRIGHT project detects early signs of brain cancer

07 Jan 2025

Vibrational photometry technique images biomarkers of metastasis as route to diagnosis.

A new technique to detect brain metastases in mice could assist preclinical investigations of the brain and other organs in human patients.

Developed by the NanoBRIGHT project consortium, the new platform employs vibrational fiber photometry as a method to "image the cytoarchitecture of the mouse brain, monitor molecular alterations caused by traumatic brain injury, as well as detect markers of brain metastasis with high accuracy," said the project.

Initial results published in Nature Methods indicate that NanoBRIGHT's "molecular flashlight" research tool reaches deep into the brain without causing appreciable damage.

"Optical approaches to monitoring neural activity are transforming neuroscience, owing to a fast-evolving palette of genetically encoded molecular reporters," commented the project in its published paper.

"However, the field still requires robust and label-free technologies to monitor the multifaceted biomolecular changes accompanying brain development, aging or disease."

The NanoBRIGHT consortium includes two Spanish partners, the National Cancer Research Center (CNIO) and neurobiology research lab the Cajal Institute, which have been responsible for the project's biomedical research. Partners at the Kastler-Brossel Laboratory in Paris and the Italian Institute of technology (IIT) have developed the NanoBRIGHT instrumentation.

Minimally invasive analysis

NanoBRIGHT employs vibrational fiber photometry as a low-invasive method for label-free monitoring of the biomolecular content of arbitrarily deep regions of the mouse brain, viewed in vivo through spontaneous Raman spectroscopy. The project's initial platform employs a tapered fiber probe said to be 1-micron thin at its tip.

"This technology allows us to study the brain in its natural state without the need for prior alteration," commented Manuel Valiente, head of the CNIO Brain Metastasis Group.

"Moreover, it enables us to analyze any type of brain structure, not just those that have been genetically marked or altered, as was necessary with previous technologies. With vibrational spectroscopy we can see any molecular change in the brain when a pathology is present."

Although Raman spectroscopy already has a place in neurosurgery, current implementations are more invasive and less precise, according to NanoBRIGHT.

It has been used during brain tumor surgery to assess whether any cancer cells remain in the area after tumor removal, but this is only done when the brain is already open and the cavity is large enough. These relatively bulky instruments are incompatible with minimally invasive use in live animal models, said the project.

Trials using NanoBRIGHT on experimental models of brain metastases suggest that it can observe tumour fronts releasing cells that would escape surgery.

"The difference with existing technology is that we can now perform this analysis in a minimally invasive way, regardless of whether the tumor is superficial or deep," commented Valiente.