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By Laser Beam into the Window to the Brain

2 Jul | By Biophotonics.World
By Laser Beam into the Window to the Brain
Demonstrator at the Medical University of Vienna.
Image source: Med. Uni Wien
By: Ewald Unger

A team from Leibniz IPHT shows for the first time how Raman measurements in the eye are possible. Research partners in Vienna are now building a device that will be able to detect Alzheimer's disease

The "laser" sign above Clara Stiebing's lab is lit up red. Only to be entered with protective goggles, it means. It doesn't mean a laser beam will hit your eye. Meanwhile, inside, Clara Stiebing is experimenting with exactly that: What happens if she aims a laser at a human eye? To be more precise, what must this beam be like so that it does not harm the eye, but helps to make visible signs of diseases that cannot be detected otherwise? 

"We use the laser light to obtain comprehensive information about the biochemical composition of the retina," explains Clara Stiebing, who has been working as a postdoctoral fellow at the Leibniz IPHT for three years. „These are important, for example, for the early detection of age-related macular degeneration." The disease, which shows hardly any symptoms in its initial stage, is the most common cause of severe visual impairment or even blindness. In most cases this could be avoided if the changes in the macula were detected as early as possible. 

Clara Stiebing is part of a team from Leibniz IPHT and the Friedrich Schiller University Jena, working together with the Medical University of Vienna, the Netherlands Organisation for Applied Scientific Research in Leiden and Radborg University in Nijmegen to research the technology that this improved diagnostics will be able to provide in the future. The researchers combine two optical methods to deliver high-resolution, non-invasive images from the eye: Raman spectroscopy and optical coherence tomography. 

The idea with which the researchers from Jena started the joint project is to obtain a molecular fingerprint of the retina using Raman spectroscopy. To do this, the back of the eye is irradiated with laser light, which stimulates the molecules of the retina to oscillate. The scattered light shows characteristic patterns which decipher the chemical structure of the retina – without touching the eye or using special markers. From the content of lipids, proteins, carotenoids, and nucleic ac- ids, physicians can then derive important health information. Measuring at the eye with a laser is a great challenge: Eyes are sensitive, aiming a laser at this organ can be dangerous. "A laser with too much power could cause burns on the retina and, in the worst case, lead to blindness or clouding of the lens," explains Clara Stiebing. Moreover, the conditions in the eye are not ideal for optical measurements. Using international safety standards, the researchers calculated how strong their laser beam should be at a wavelength of 785 nm. The result: one milliwatt - twenty times weaker than lasers that they normally use for their spectroscopic measurements. "We were skeptical whether this would work," admits Clara Stiebing. 

It worked very well: Raman measurements on human retinal sam- ples provided significant spectra that allow precise conclusions about the condition of the retina. "This was a great pleasure for us," reports Rainer Leitgeb from the Medical University
of Vienna, who coordinates the European research project MOON (Multimodal Optical Diagnostics for Age-related Diseases of the Eye and Central Nervous System). According to Leitgeb, these promising results have decisively advanced the project. 

To prove for the first time that Raman measurements in the human eye with a wavelength of 785 nm are theoretically possible, the researchers constructed a setup in the Jena laboratory that simulates the optical conditions of the eye. It simulates the conditions under which light is excited and collected in the eye. 

Based on these results, the team of scientists at the Medical University in Vienna is developing a device that will enable fast and contact-free diagnosis via eye scan in the future: "We scan the eye with light and measure the light that comes back from the eye. And this returning light contains all the information I need for diagnostics," explains Rainer Leitgeb. "Optical coherence tomography very quickly maps the morphology of the fundus of the eye. This enables us to identify suspicious areas, which can then be analysed more precisely on a molecular level, i. e. chemically, using Raman spectroscopy. 

The researchers hope to use the device to carry out initial measurements on humans. Rainer Leitgeb is convinced that this will enable doctors to not only identify eye dis- eases, but also signs of deterioration in the brain. "It is always said that the eye is the window to the brain. The eye itself is nerve tissue that is directly connected to the brain. This means that all changes, all diseases affecting the central nervous system can also be seen in the retina." 

So neurological diseases like Alzheimer's could leave their mark on the retina. Nowadays, the typical protein deposits in the brain of Alzheimer's patients can only be detected after their death. With the help of the Raman scan one could make them visible in the back of the eye earlier. 

Before the researchers can show this in experiments on humans, they have the planned study carefully examined by the ethics commission at the University Hospital in Vienna. For ethical reasons, only Alzheimer's patients in whom the disease does not yet limit the ability to make rational decisions may participate in clinical studies. Because the optical procedure is so sensitive, the researchers are convinced that the eye scanner could already provide meaningful results at such early stages and detect characteristic deposits in the brain.

Source: Leibniz IPHT

Related journal article: Clara Stiebing et al., Nonresonant Raman spectroscopy of isolated human retina samples complying with laser safety regulations for in vivo measurements, Neurophotonics, 6(4), 041106 (2019), https://doi.org/10.1117/1. NPh.6.4.041106 

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