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Small “Molecular Flashlight” Could Change Brain Disease Detection
Posted by Okachinepa on 01/01/2025 @ 
SynEVOL Source

Brain Cancer Laser Treatment
Courtesy of SynEvol
Credit: Centro Nacional De Investigaciones Oncologicas



In biomedical research, it has long been difficult to examine molecular alterations in the brain brought on by neurological illnesses and cancer without intrusive treatments. Now, researchers have created a novel method that allows for in-depth molecular analysis by shining light into mice's brains using an incredibly thin probe. International researchers, including teams from the Spanish National Cancer Research Centre (CNIO) and the Spanish National Research Council (CSIC), collaborated to produce the findings, which were published today (December 31) in the journal Nature Methods.

Because it illuminates nerve tissue and reveals its chemical makeup, the researchers refer to this invention as a "molecular flashlight." With this method, researchers can identify genetic alterations linked to primary and metastatic brain cancers as well as traumas like traumatic brain injury.

Invisible to the human sight, the molecular flashlight is a probe that is less than 1 mm thick and has a tip that is only one micron wide, or around one thousandth of a millimeter. Since a human hair is between 30 and 50 microns in diameter, it can be put deeply into the brain without harming it.

The flashlight-probe is mainly a "promising" research tool in animal models that enables "monitoring molecular changes caused by traumatic brain injury, as well as detecting diagnostic markers of brain metastasis with high accuracy," according to the paper's authors. It is not yet ready for patient testing.

The experiment was conducted by the European NanoBright consortium, which comprises two Spanish groups: the Neuronal Circuits Laboratory of the Cajal Institute at the CSIC, led by Liset Menéndez de la Prida, and the group headed by Manuel Valiente, who leads the CNIO's Brain Metastasis Group. The instrumentation was built by teams from French and Italian institutions, while both teams have been in charge of the biomedical research at NanoBright.


Vibrational Spectroscopy Instrument
Courtesy of SynEvol
Credit:CNIO



Although it is a fantastic accomplishment, the use of light to record or stimulate brain function is not a novel technology. For instance, individual neurons' activity can be controlled by light using so-called optogenetic techniques. To make the neurons light-sensitive, these techniques include introducing a gene into the neurons. A paradigm change in biomedical research has been brought about by NanoBright's revolutionary technology, which allows the brain to be investigated without any prior alterations.

The new molecular lamp is based on a technique known as vibrational spectroscopy. It operates by taking use of a characteristic of light called the Raman effect, which states that the way light interacts with molecules depends on their structure and chemical makeup. This makes it possible to identify a distinct spectrum, or signal, for every molecule. After then, the spectrum serves as a molecular signature that reveals details about the makeup of the tissue that is illuminated.

"This technology enables us to study the brain in its natural state without the need for prior alteration," says Manuel Valiente. Furthermore, unlike other technologies, it allows us to examine any kind of brain structure, not simply those that have been genetically marked or altered. When a pathology is present, vibrational spectroscopy allows us to observe any chemical changes in the brain.

Neurosurgery already makes use of Raman spectroscopy, albeit in a less accurate and invasive way. According to Valiente, "studies have been conducted on its use during brain tumor surgery in patients." After the majority of the tumor has been surgically removed, a Raman spectroscopy probe can be placed in the operating room to determine whether any cancer cells are still present. the region. But only when the cavity is sufficiently big and the brain is already open is this done. These comparatively big "molecular flashlights" cannot be used in live animal models in a minimally invasive manner.

The NanoBright consortium's probe is referred regarded as "minimally invasive" since it is so thin that any harm it might do when inserted into brain tissue is deemed insignificant.

In Nature Methods, the authors offer particular applications. In experimental models of brain metastases, Valiente's team at CNI has employed the molecular flashlight: "As happens with patients, we have observed tumor fronts releasing cells that would escape surgery," says Valiente. "The difference with current technology is that, regardless of the depth of the tumor, we can now perform this analysis in a minimally invasive manner."

Determining if the data from the probe can "differentiate various oncological entities, such as types of metastases, based on their mutational profiles, by their primary origin, or from different types of brain tumors" is one of the CNIO team's current objectives.

The Cajal Institute team has applied the method to investigate the epileptogenic regions around traumatic brain injury. Depending on whether they were linked to a tumor or a trauma, we were able to distinguish distinct vibrational signatures in the same brain areas that are susceptible to epileptic convulsions. This suggests that the molecular signatures of these areas are affected differently and could be used to distinguish between different pathological entities using automatic classification algorithms, including artificial intelligence,” explains Liset Menéndez de la Prida.

The CSIC researcher says, "We will be able to find new high-precision diagnostic markers by combining vibrational spectroscopy with other modalities for recording brain activity and advanced computational analysis using artificial intelligence." "This will make it easier to create cutting-edge neurotechnology for novel biomedical uses."