A new experimental technique developed by an international team that includes researchers from the Spanish National Research Council (CSIC) and the Spanish National Cancer Research Centre (CNIO) now offers a noninvasive way to monitor molecular changes in the brain caused by cancer and neurological disorders. It is called a “molecular lantern.”
The technique uses an ultra-thin probe—less than 1 mm thick with a micron-sized tip—to introduce light into the brain. This allows precise analysis of the chemical composition of brain tissue, identifying molecular changes caused by tumors, injuries, or trauma without damaging surrounding tissue.
This molecular lantern is a research tool that can accurately detect diagnostic markers for brain metastases and monitor molecular changes associated with traumatic brain injuries. It has great potential to help advance neuroscience and oncology in research at the present time.
Scanning the brain with light without altering it previously
While the application of light to stimulate or monitor brain activity is not novel, most approaches, including optogenetics, require genetic engineering to render neurons light-sensitive. However, the newly presented molecular lantern from NanoBright has broken this pattern and enabled the possibility of investigating the brain without previous manipulation. This is a paradigm shift in biomedical research.
The molecular lantern relies on vibrational spectroscopy based on the Raman effect.
“When light interacts with molecules, it scatters in a way that reflects their composition and chemical structure. This scattering creates a unique signal, or spectrum, that serves as a molecular fingerprint, offering detailed insights into the composition of the illuminated tissue,” explains Liset M. de la Prida from CSIC.
This innovative approach provides a noninvasive and precise tool for analyzing brain function and pathology.
“We can see any molecular change produced in the brain by a pathology or injury.”
A new approach to treat brain metastasis
Manuel Valiente, from the CNIO, said, “This technology allows us to study the brain in its natural state; it is not necessary to alter it beforehand. However, it also makes it possible to analyze any brain structure, not only those that have been genetically marked or altered, as was the case with the technologies used until now. When there is a pathology, we can see any molecular change in the brain with vibrational spectroscopy.”
Raman spectroscopy is already used in neurosurgery, although in an invasive and less precise way. Studies have shown its use when operating on brain tumors in patients. Once the bulk of the tumor has been surgically removed, a Raman spectroscopy probe can be introduced in the operating room to assess whether cancer cells remain in the area.
It is only used when the brain is open, and the hole is large enough. However, 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 various kinds of brain tumors.
Artificial intelligence to search for diagnostic markers
The Cajal Institute team applied the technique to study epileptogenic zones around traumatic brain injuries. “We discovered distinct vibrational profiles within the same brain regions prone to epileptic seizures, varying depending on whether they were associated with a tumor or trauma. This indicates that the molecular characteristics of these areas are differently impacted and can be differentiated using automatic classification algorithms, including artificial intelligence,” the researchers explained.
“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.
Journal Reference:
- Pisano, F., Masmudi-Martín, M., Andriani, M.S. et al. Vibrational fiber photometry: label-free and reporter-free minimally invasive Raman spectroscopy deep in the mouse brain. Nat Methods (2024). DOI: 10.1038/s41592-024-02557-3
