‘Molecular Flashlight’ Detects Brain Metastasis Using Ultra-Thin Probe

One of the major challenges in biomedical research is the non-invasive monitoring of molecular changes in the brain caused by cancer and other neurological conditions. Now, a new experimental technique addresses this challenge by introducing light into the brains of mice through a very thin probe.

This method, developed by an international team that includes researchers from the Spanish National Research Council (CSIC, Madrid, Spain) and the Spanish National Cancer Research Centre (CNIO, Madrid, Spain), has been dubbed the "molecular lantern." The technique provides detailed information about the chemical composition of brain tissue in response to light, allowing for the analysis of molecular changes caused by both primary and metastatic tumors, as well as brain injuries such as traumatic head trauma. The molecular lantern is a probe less than 1 mm in diameter, with a tip only a micron thick—about a thousandth of a millimeter—making it virtually invisible to the naked eye. It can be safely inserted deep into the brain without causing damage, as the tip is smaller than a human hair (which measures between 30 and 50 microns in diameter). Although the probe is not yet ready for clinical use, it is a promising tool for research, enabling the monitoring of molecular alterations due to traumatic brain injuries and providing highly accurate detection of diagnostic markers for brain metastasis. These findings were detailed in a paper published in Nature Methods.

Image: Vibrational spectroscopy instrument (Photo courtesy of Mariam Al-Masmudi/CNIO)

While using light to activate or monitor brain function is not new—such as with optogenetics, which allows for the observation of individual neurons' activity through light—this new technique is different. It does not require altering the brain beforehand, marking a significant shift in biomedical research. The molecular lantern relies on vibrational spectroscopy, which utilizes the Raman effect—a property of light where light scattering depends on the molecular composition and chemical structure of the tissue. This scattering creates a unique spectrum, or "molecular fingerprint," that reveals detailed information about the illuminated tissue's composition. This allows researchers to observe molecular changes in the brain caused by pathological conditions or injuries.

The research team’s next goal is to determine whether the probe’s data can distinguish between different types of cancers, such as identifying metastases based on their mutational profiles, origin, or type of brain tumor. They also used the technique to examine areas surrounding traumatic brain injuries that are prone to epilepsy and found distinct vibrational profiles in brain regions that were more susceptible to seizures depending on their association with tumors or trauma. This suggests that the molecular changes in these areas vary depending on their underlying pathology, and these differences could be used to classify various pathologies using automated algorithms, potentially enhanced by artificial intelligence.

“This technology allows us to study the brain in its natural state; it is not necessary to alter it beforehand,” said CNIO’s Manuel Valiente. “But it also makes it possible to analyze any type of brain structure, not only those that have been genetically marked or altered, as was the case with the technologies used until now. With vibrational spectroscopy we can see any molecular change in the brain when there is a pathology.”

“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,” added CSIC researcher, Liset M. de la Prida.