These 3D images of neurons in the brain of a schizophrenia patient show wavy, distorted neurites, which indicate that the condition may be linked to the shape of the neurons. X-ray images were taken at the Advanced Photon Source.

Cutting edge imaging technology provides new insights into schizophrenia

March 01, 2021
by Robin Lasky, Contributing Reporter
Use of synchrotron radiation nanotomography has allowed researchers to produce uncorrupted 3D images of neurons and blood vessels for the purposes of studying schizophrenia’s effect on brain tissue.

Schizophrenia is a chronic mental disorder which can cause a range of debilitating cognitive and psychiatric symptoms, such as paranoid delusions, depression, disordered thinking, and auditory and visual hallucinations. Despite it long being the subject of medical research, which has produced various psychiatric treatment options, Schizophrenia continues to frustrate scientific discovery into precise underlying causes. However, various genetic, environmental, and other physical factors have been identified as correlating with an increased likelihood of developing the disorder.

A new study from the University of Tokai, in Japan, in conjunction with other institutions, published in Translational Psychiatry on January 13th, seeks to shed more light on the physical differences of brain tissue in people afflicted with this disorder, in the hopes of eventually contributing to a better understanding of its causes and impact on the brain.

"The current treatment for schizophrenia is based on many hypotheses we don't know how to confirm," Ryuto Mizutani, professor at Tokai University, said in a statement. "The first step is to analyze the brain and see how it is constituted differently."

For the study, four brains of deceased patients with schizophrenia were obtained, along with four healthy brains to serve as the control group. Researchers focused on an area of the brain associated with having a role in processing spoken language and other auditory stimuli.

Through the use of an advanced 3D imaging technique, they were able to discern marked differences between the structure of the neurons in the brains of patients with schizophrenia compared with the control samples that may indicate association with the disorder.

Various brain imaging systems have been used to contrast the differences between healthy brains and the brains of patients with schizophrenia in order to better understand its effects on the brain. For instance, MR scans have been used to contrast the neuro-electrical responses to certain stimuli with that of healthy control groups. MR scans have also been used to identify and target specific areas of the brains for studies of proposed novel treatments for schizophrenia.

Until recently, technological limitations have prevented a more in-depth analysis of the microscopic differences of the brain’s actual physical tissue. Prior studies that have attempted to construct 3D mapping of brain tissue such as neurons and blood vessels, which measure in nanometers, have been performed by imaging a series of sections taken of the cellular structure of tissue using electron microscopy, and then digitally reconstructing a comprehensive 3D map of the inside of the tissue. However, since soft tissue is deformed by the sectioning process, such mapping relies on technicians being able to artificially account for and correct for this damage in the digital reconstruction.

The new approach utilized by Mizutani’s team uses synchrotron radiation nanotomography to obtain more accurate imaging of the inside of cellular material with a method that does not require sectioning. A synchrotron is a type of particle accelerator that moves electrons at a speed sufficient to produce the energy wavelength to produce X-rays, and then with the use of magnetic fields, can manipulate the direction of the X-ray beams around the interior of an object.

With the cooperation of Advanced Photon Source and the U.S. Department of Energy, the researchers were able to perform nanotomography using Fresnel zone plate optics to produce 3D Cartesian coordinate models of the microscopic cellular structures.

"There are only a few places in the world where you can do this research,” explained Mizutani. “Without 3D analysis of brain tissues this work would not be possible."