Researchers have made a breakthrough in the visualization of human brain tissue at the microscopic level. The study was published in Nature Communications. For understanding the brain function, scientists need to map the nerve cells (neurons) are wired to form circuitries in both healthy and disease states. Traditionally, this was accomplished by thinly slicing brain tissue and tracing the cut nerve fibers over many sections.

New techniques for visualization of human brain tissue

However, this approach is difficult and labor-intensive, as the neuronal circuitries span great distances in three dimensions and are tightly entangled microscopically. To avoid the sectioning of tissues, tissue clearing techniques that turn opaque tissue transparent have been developed, enabling deep, high-resolution imaging of neuronal circuitries. Although such techniques have been very effective on rodent brain tissue, only limited studies have found success with human brain tissue.

The difficulties and challenges may be attributed to fundamental differences between the human and the mice brain. To overcome these barriers, the team developed a new tissue clearing solution, OPTIClear. OPTIClear selectively adjusts the optical properties of tissue without damaging or changing their structural components. Combined with fluorescent staining and other tissue processing methods, the team created a simple, yet versatile tool for the study of microscopic structures in the human brain.

Nerve cells, glial cells, and blood vessels were visualized in exquisite detail, with their 3-D relationship determined. The team performed 3-D morphological analysis on human brainstem dopaminergic neurons in the millimeter scale, and imaged more than 3,000 large neurons in the human basal forebrain in just five days, normally, such procedures take at least three weeks.

These neurons have been implicated in neurological and psychiatric diseases such as dementia and depression; the promising results suggest that this novel method applies to future research on these conditions.

The team hopes that this simple method can catalyze further scientific development. By allowing scientists to study human tissue quicker and better, OPTIClear could potentially speed up the elucidation of circuitry mechanisms in a multitude of brain diseases.

The author hopes that a better understanding of the connections and circuitries of the brain will help uncover the pathologies that underlie the common degenerative diseases of the brain, such as Alzheimer's and Parkinson's disease. Regarding future developments, a principle, this method is also applicable to other human organs and clinical specimens. They hope that this technique can also be used in studying other diseases, and eventually, help us to unravel the mysteries of the human body.