Ultra-Thin Endo-Microscope Provides Unprecedented Visualization of Sensitive Brain Areas

Human understanding of neuronal diseases such as autism, epilepsy, Alzheimer's, and Parkinson's disease remains poor due to their complexity. Consequently, prevention, treatment, or alleviation of these diseases presents significant challenges. A crucial part of understanding these diseases involves studying affected nerve cells, often nestled deep within the brain, within the natural complexity of the whole organism. To examine the activity of neuronal structures as well as the interaction of nerve cells, there is a need for minimally invasive technologies that can generate images from sensitive deep-brain tissues. Now, scientists have created an ultra-thin endo-microscope that offers gentle in-depth observations, enabling detailed investigation of the brain. This innovation could potentially help in studying the onset and progression of severe neuronal diseases, providing new insight for neuroscientists to formulate strategies against these debilitating conditions.

The endoscope developed by an international research team with the participation of Leibniz IPHT (Jena, Germany) has a diameter of only 110 micrometers, making it about as thin as human hair. This slim structure allows the device to capture images deep within tissues and at a subcellular level. This advancement enables research into previously inaccessible deep-brain structures and accurate study of individual neurons' connectivity and signaling activity. Traditional endoscopic tools employed in in-vivo neuroscience research often use specialized rod lenses (GRIN) that transmit images from one end to the other, which can pose a risk of tissue damage and compromise the validity of studies due to their size. The newly-developed holographic endoscope avoids this issue by using a single multimode optical fiber as the imaging probe, making it minimally invasive for observing sensitive brain regions.

The research team also utilized a novel fiber probe, known as a side-view probe, which allows for perpendicular observations of the tissue relative to the fiber axis. This approach lessens tissue stress and damage caused by the endoscope's insertion compared to conventional bare-terminated probes. As the probe can penetrate deeper, the side-view probe can stitch together individual frames into a panorama-like image, providing a comprehensive view of the brain's depth. The new endoscopic solution allows direct observation of structural connectivity between neurons, especially dendritic spines (microstructures emanating from dendrites), and intracellular processes. Researchers can study dynamics of subcellular structures, alterations in intra-cellular calcium concentration (which is linked to nerve cell signaling activity), and individual vessel blood flow speeds. These observations could offer neuroscientists valuable insights into pathological changes in the brain.

“In neuronal diseases, the cognitive and motor performance of the affected organism may be irreversibly limited by changes or loss of nerve cells,” said Prof. Dr. Tomáš Čižmár, head of the Fiber Research and Technology Research Department at Leibniz IPHT, who has led the development of the instrument. “We are developing technologies to monitor signs of a disease, for example, through altered neuronal communication, at an early stage. With these new and powerful light-based instruments, we can help to provide unprecedented insights into the control center of vital functions with high image quality and thus expand the understanding of neuronal diseases.”

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