An innovative technique, termed the ‘molecular lantern’, enables non-invasive monitoring of molecular changes in the brain, providing new insights into neurological pathologies and cancer.
Developed by an international team, this method uses light to analyze brain tissue without the need for genetic modification, marking a significant advancement in the field.
Non-Invasive Brain Monitoring: A New Frontier
Understanding how cancer and other neurological disorders affect the brain at the molecular level — without invasive procedures — remains a major challenge in biomedical research. A groundbreaking experimental technique now offers a solution by using a hair-thin probe to introduce light into the brains of mice. This innovation, published in Nature Methods, is the result of a collaboration led by international teams from the Spanish National Research Council (CSIC) and the Spanish National Cancer Research Centre (CNIO).
The ‘Molecular Lantern’: Shedding Light on the Brain
Dubbed the “molecular lantern,” this technique uses light to reveal the chemical composition of brain tissue. It enables the analysis of molecular changes caused by tumors, whether primary or metastatic, as well as injuries like head trauma, providing a new way to study these complex conditions.
The molecular lantern is a probe less than 1 mm thick, with a tip just a thousandth of a millimeter (a micron), invisible to the naked eye. It can be inserted deep into the brain without causing damage (as an example, a human hair measures between 30 and 50 microns in diameter).
The probe is not yet ready for use in patients; for now it is primarily a ‘promising’ research tool in animal models that allows “monitoring molecular alterations caused by traumatic brain injury, as well as detecting diagnostic markers of brain metastasis with high accuracy,” explain the authors of the paper.
Pioneering Work by European Research Teams
The work has been carried out by the European consortium NanoBright, in which two Spanish groups participate, the one led by Liset Menéndez de la Prida at the Neuronal Circuits Laboratory of the Cajal Institute of the CSIC, and the Brain Metastasis Group of the CNIO directed by Manuel Valiente. Both have been involved in the biomedical research on NanoBright, while groups from the Italian Institute of Technology and French institutions such as the Laboratoire Kastler Brossel, have developed the instrumentation.
Advancing Neuroscience Without Genetic Alteration
Activating or recording brain function using light is not new. For example, the so-called optogenetic technique make it possible to monitor the activity of individual neurons with light. However, this requires introducing a gene into the neurons that makes them sensitive to light. With the new technology now presented by NanoBright, it is possible to study the brain without altering it beforehand, which represents a paradigm shift in biomedical research.
The Science Behind the Lantern: Raman Spectroscopy
The new molecular lantern is based on a technique called vibrational spectroscopy, which leverages the Raman effect—a unique property of light. “When light interacts with molecules, it scatters in a way that depends on their composition and chemical structure. This scattering produces a distinct signal, or spectrum, that acts as a molecular fingerprint, providing detailed information about the composition of the illuminated tissue,” explains Liset M. de la Prida from CSIC.
Real-Time Insights into Brain Pathologies
“This technology allows us to study the brain in its natural state; it is not necessary to alter it beforehand. 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,” explains Manuel Valiente, from the CNIO.
Raman spectroscopy is already used in neurosurgery, although in an invasive and less precise way: “There have been studies of its use when operating on brain tumors in patients,” says Valiente. 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.”
For the CNIO group, one goal now is to find out whether the information provided by the probe allows “differentiating different oncological entities, for example, the types of metastases according to their mutational profiles, by their primary origin or from different types of brain tumors.”
Artificial Intelligence Meets Molecular Diagnostics
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. 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,” explains Liset M. de la Prida.
The Future of Neurotechnologies and Biomedical Applications
“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,” summarizes the CSIC researcher, Liset M. de la Prida.
For more on this breakthrough, see This Tiny “Molecular Flashlight” Could Transform Brain Disease Detection.
Reference: “Vibrational fiber photometry: label-free and reporter-free minimally invasive Raman spectroscopy deep in the mouse brain” by Filippo Pisano, Mariam Masmudi-Martín, Maria Samuela Andriani, Elena Cid, Mohammadrahim Kazemzadeh, Marco Pisanello, Antonio Balena, Liam Collard, Teresa Jurado Parras, Marco Bianco, Patricia Baena, Francesco Tantussi, Marco Grande, Leonardo Sileo, Francesco Gentile, Francesco De Angelis, Massimo De Vittorio, Liset Menendez de la Prida, Manuel Valiente and Ferruccio Pisanello, 31 December 2024, Nature Methods.
DOI: 10.1038/s41592-024-02557-3
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.