An international research team develops a new method to extract the "molecular fingerprint" of deep brain areas. A new experimental method that allows the identification of a molecular fingerprint of brain tissue in remote areas of the brain opens new avenues for studying the central nervous system. A group of research institutes and universities, including the Italian Institute of Technology (IIT) in Lecce and Genoa Centers, the Department of Physics and Astronomy at the University of Padua, the University of Salento, the 'Magna Graecia' University of Catanzaro, and the Polytechnic University of Bari, has identified an innovative approach to analyze the molecular composition of neural tissue, extracting a digital fingerprint that allows for the evaluation of both physiological and pathological characteristics. The study was published in the international scientific journal Nature Methods and was also conducted in collaboration with the National Center for Oncological Research and the Spanish National Research Council - Cajal Institute in Madrid.
The researchers have developed a technique to detect brain tissue components without the aid of contrast agents or markers of any kind, paving the way for a broader use of photonics in neuroscience and, in the long term, neurosurgery. "The technique we used exploits a particular, albeit elusive, characteristic of light-matter interaction. When a beam of light, of a very well-defined color, hits a molecule, a minimal part of the light's energy triggers vibrations in the molecule. Immediately after, a small portion of the beam is scattered with a slight alteration of the initial color. Measuring this color nuance provides valuable information about the chemical structure of the hit molecule, without the need to use external markers," explains Filippo Pisano, Associate Professor at the Department of Physics and Astronomy of the University of Padua.
"This phenomenon, known as Raman scattering, has already been used in the study of biological tissues, with some recent applications in the clinical field," says Ferruccio Pisanello, Coordinator of the Center for Biomolecular Nanotechnologies at the Italian Institute of Technology in Lecce. "For the first time, we have managed to make recordings in deep brain areas, minimizing tissue damage. This was possible thanks to an unconventional combination of near-infrared light, implantable optical fibers, specially designed microscopes, and advanced data analysis techniques, including artificial intelligence algorithms."
"Although still far from medical applications, this methodology opens up new possibilities for a deeper understanding of brain physiology that hypothesizes promising applications in the study of pathological neurological conditions, such as brain tumors and head traumas," states Massimo De Vittorio, Professor at the University of Salento and researcher at IIT in Lecce.
The research stems from projects funded by European funds, such as the DEEPER and NanoBright projects, which aim to develop new technologies for investigating deep brain regions to identify molecular and cellular dysfunctions underlying brain disorders and diseases.
The study involved contributions from: Three research units of the Italian Institute of Technology - with key contributions from researchers Maria Samuela Andriani, Mohammadrahim Kazemzadeh, Liam Collard, Marco Bianco, Francesco Tantussi coordinated by Ferruccio Pisanello, Massimo De Vittorio, and Francesco de Angelis - the Department of Physics and Astronomy of the University of Padua with Filippo Pisano, the University of Salento, the company Optogenix with Marco Pisanello and Leonardo Sileo, the Polytechnic University of Bari, and the 'Magna Graecia' University of Catanzaro with Francesco Gentile. Additionally, as part of European consortia, contributions were also made by the Brain Metastasis group of the National Center for Oncological Research with Mariam Masmudi-Martín, Patricia Baena, Manual Valiente, and the Cajal Institute of the Spanish National Research Council with Elena Cid, Teresa Jurado Parras, and Liset Menendez de La Prida, and the Sorbonne University - Kastler Brossel Laboratory with Antonio Balena.
Funding: The work was funded by the European Union's Horizon 2020 research and innovation programs with the NanoBright project, the DEEPER project, the ProID project, the Marie Sklodowska-Curie SPEEDBUMPS action, by the AIRC Foundation, by the PARD 2024 of the University of Padua, by the Scientific Foundation of the Spanish Association Against Cancer, and by the 'RAISE' Project.
Link to the publication: https://doi.org/10.1038/s41592-024-02557-3
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 & Ferruccio Pisanello "Vibrational fiber photometry: label-free and reporter-free minimally invasive Raman spectroscopy deep in the mouse brain" Nat Methods 22, 371–379 (2025)
