'Molecular Lantern' Discerns Brain Changes at Molecular Level

A vibrational spectroscopy technique that uses what its developers are calling a "molecular lantern" aims to enable monitoring of the changes in the brain, at the molecular level, that are caused by cancer and other neurological pathologies in a noninvasive way. The technique, still in experimental stages, uses a probe that is <1 mm thick, with a tip of just 1 µm. Tests on animal models have enabled researchers to analyze any brain structure beyond those that have been already genetically marked or altered and see any molecular change in the brain when there is a pathology.

The work has been carried out by the European consortium NanoBright. Collaborators include a group at the Neuronal Circuits Laboratory of the Cajal Institute of the CSIC led by Liset Menéndez de la Prida, and the Brain Metastasis Group of the CNIO directed by Manuel Valiente. Both Spain-based groups have been involved in the biomedical research with NanoBright. Groups from Italian Institute of Technology and French institutions such as the Laboratoire Kastler Brossel have developed the instrumentation.

Activating and/or recording brain function using light is not new; optogenetics, for example, requires introducing a gene into the neurons that makes them sensitive to light. Raman spectroscopy is also already being used in neurosurgery, though in an invasive and less precise way. “There have been studies of its use when operating on brain tumors in patients," Valiente said. "In the operating room, once the bulk of the tumor has been surgically removed, it is possible to introduce a Raman spectroscopy probe to assess whether cancer cells remain in the area. That is, it is only used when the brain is already open and the hole is large enough. But these relatively large ‘molecular lanterns’ are incompatible with minimally invasive use in live animal models.”

With the technology under development, it is possible to study the brain without altering it beforehand

According to the researchers, the probe is not yet ready for use in patients. The researchers said that they are in the process of discovering whether the molecular lantern’s gathered information can help differentiate oncological entities, such as the types of metastases according to their mutational profiles.

Additionally, the Cajal Institute group has used the technique to investigate the epileptogenic zones surrounding traumatic brain injuries. “We were able to identify different vibrational profiles in the same brain regions susceptible to epileptic seizures, depending on their association with a tumor or trauma," de la Prida said. "This suggests that the molecular shadows of these areas are affected differently, and can be used to separate different pathological entities by automatic classification algorithms including artificial intelligence."

"The integration of vibrational spectroscopy with other modalities for recording brain activity and advanced computational analysis with artificial intelligence will allow us to identify new high-precision diagnostic markers, which will facilitate the development of advanced neurotechnologies for new biomedical applications," de la Prida said.

Research pertaining to the initiative has been published in Nature Methods (www.doi.org/10.1038/s41592-024-02557-3).