Revealing the secrets of Alzheimer and Co.
High resolution imaging of the human brain improves our understanding of, as well as the means of diagnosing and treating, complex brain disorders.
Even ten years before the typical symptoms of Alzheimer’s occur, high resolution imaging can visualize the deposits in the brain that are typical of the disease. Building on this finding, the global Dominantly Inherited Alzheimer Network (DIAN) is now looking for study participants whose parents suffer from the disease in order to refine diagnostics and find therapeutic approaches. Participants who bear the suspect genetic mutation and ones in whom there are no indications that they will contract the disease later are wanted.
The project is one of dozens in which researchers worldwide are trying to find a cure for Alzheimer’s. Yet brain research involves more: Major research projects with funding running into the billions, such as the BRAIN Initiative in the U.S. or the EU’s Human Brain Project, are currently compiling all available knowledge about the human brain, mapping it and replicating its functions in simulations in meticulous detail. At the same time, teams are conducting research into the concomitant physiological symptoms of diseases such as Parkinson’s, epilepsy, multiple sclerosis, schizophrenia or chronic headaches. The key tool for that are imaging methods.
A look inside the living brain
Study participants in the DIAN project undergo multi-stage diagnosis with memory tests, analyses of blood and cerebrospinal fluid and up to four imaging methods. They include magnetic resonance imaging (MRI) to enable deep insights into the brain’s structures. In particular, the new 7 Tesla technology is giving a boost to brain research thanks to resolutions in the sub-millimeter range. Apart from deposits typical of Alzheimer’s or Parkinson’s, the equipment identifies tumors in their early stage, which greatly increases the chances of recovery. Initial research centers use 9.4, 10.5 or even 11.7 Tesla scanners. Thanks to functional MRI (fMRI), that means brain functions can also be observed. For example, active regions of the brain are visible, since blood that is particularly oxygen-rich flows there. Comparative analyses then enable the researchers to identify which regions of the brain process what information and how brain functions change as we age or in response to diseases. Water transport in the brain can also be tracked in vivo. If it is diffuse or restricted, that is a clear indication that there are problems in the affected region of the brain.
Other methods, including near-infrared spectroscopy (NIRS) and fluorodeoxyglucose positron emission tomography (FDG-PET), give researchers direct insights into the living brain. In the latter, a slightly radioactive market substance is injected into patients in order to track the processes in the living brain. Positron emission tomography is also used in the DIAN project to detect plaques with the aid of the Pittsburgh Compound-B (PIB-PET). That makes it possible to track whether and where injected substances bond to the plaque in the brain.
Welcome optical methods
Optionally, the brains of the study participants are analyzed further by microscope after their death. New chemical methods such as CLARITY enable the brain as a whole to be made transparent. Instead of analyzing sectioned parts, researchers can visualize intact brains right down to the level of individual cells by means of optical methods—whether using electron or fluorescence microscopes from manufacturers such as Zeiss, Leica Microsystems, Picoquant, Thorlabs or Qioptiq or the microscopic cameras with high spatial and temporal resolution from Jenoptik.
However, high resolution microscopy is also used in operations on a living brain. In conjunction with fluorescent dyes and software, neurosurgeons are now daring to undertake operations that would have been unthinkable a few years ago—such as correcting dangerous malformations of the blood vessels deep in the brain. By injecting the dyes, the surgeons can not only very clearly see the veins with the appropriate modules in the microscope, but also monitor whether there is still a sufficient flow of blood during the operation. Zeiss presents a case example to show how the technology can save life even in the most difficult of cases.
Source image: Forschungszentrum Jülich