SIEMENS

What’s your name?” — “Auguste.” — “Your last name?” — “Auguste.” — “What’s your husband’s name?” — “Auguste, I think.” This conversation between the psychiatrist Alois Alzheimer and his patient, 51-year-old Auguste Deter, made medical history. Deter was the world’s first Alzheimer’s patient. After her death, Alzheimer dissected her brain and found that the parts of the cerebral cortex that are responsible for memory, orientation, and feelings had changed significantly. Among other things, Alzheimer discovered protein plaques, “matted fibers, and dead nerve cells.” Only a few nerve cells had survived the disease. The study Alzheimer published in 1906 was the first to describe this “peculiar disease of the cerebral cortex.” His analyses marked the beginning of research into Alzheimer’s.

Alzheimer’s disease (AD) gradually kills brain cells. Nonetheless, scientists still do not fully understand how this process occurs. Medical researchers agree, however, that Alzheimer’s probably results from a great variety of factors.

The changes it produces in the brain include the buildup of a protein known as beta amyloid in areas outside the brain’s nerve cells (neurons) and a chemical alteration of the tau protein inside the neurons. Both processes are considered to be among the most likely causes of the obstruction of information transmission through the brain’s synapses that occurs in Alzheimer’s patients.

Back in 2009, “Alzheimer Disease International” (ADI) estimated that 35.6 million people around the world were afflicted with dementia — a number that is expected to double every 20 years and reach 115 million by 2050. These figures include all forms of dementia; it’s estimated that over half of the victims have Alzheimer’s. Alzheimer’s cannot be diagnosed in a living patient. Statistically speaking, one out of every five people considered to have Alzheimer’s is actually not afflicted with the disease but instead with another type of neurodegenerative illness. Only an autopsy can prove the diagnosis wrong.

But if a reliable evaluation could be made at an earlier stage, it would enable patients and their relatives to prepare for the changes to come and make arrangements for home care, etc. Furthermore, a reliable evaluation tool might make it possible to determine when a patient is unlikely to have Alzheimer’s, and therefore likely to be suffering from a different neurodegenerative disease.

Biomarkers in the Brain. Siemens is now supplying an amyloid imaging solution for Alzheimer’s evaluation. The solution begins with the positron emission imaging (PET) biomarker manufacturing and distribution expertise of Siemens’ PETNET Solutions, which has the largest network of PET radiopharamaceutical manufacturing facilities in the U.S.A. Additionally, Siemens’ PETNET Solutions employs appropriately qualified staff and the necessary infrastructure for the production of amyloid imaging biomarkers. As a result, it can offer imaging centers and hospitals a high level of delivery reliability. After a PET imaging biomarker is administered to a patient, he or she is scanned in a PET-computed tomography device (PET/CT), such as the new Biograph mCT scanner from Siemens.

The radioactive substance travels through the bloodstream and concentrates in the part of the body being imaged either because of metabolic activity or because it seeks out biomarkers in tissues specific to a disease. Tracer signals from white brain matter are considered normal, whereas amyloid plaque in gray matter indicates potential neurodegeneration. Thanks to the industry’s finest volumetric resolution of up to 87 cubic millimeters and a 400 percent improvement in contrast over previous models, the Biograph mCT helps physicians distinguish between white and gray matter. With automatic daily calibrations and proven PET and CT alignment accuracy, the Biograph mCT supports accurate quantification in dementia imaging. In addition, quantifying software recently introduced by Siemens for amyloid imaging automatically compares the amyloid PET image with amyloid PET reference images, identifying target regions of interest. Quantification software, although it does not replace visual assessment by a physician, assists physicians in making an interpretation of the PET image. The new software’s algorithm correlates with the reference model (now known as the Fleisher method) developed by Dr. Adam Fleisher and his research team at the Banner Alzheimer’s Institute in Phoenix, Arizona. Fleisher identified six regions of amyloid plaque buildup and defined a threshold value to distinguish between healthy and AD brains. Fleisher also collected data about healthy and diseased patients in comparative research conducted over many years.

Thanks to Fleisher’s research, the new Siemens software offers an intelligent solution — ranging from radiopharmaceutical to PET-CT, as well as quantification software. In this manner, the company contributes to making it possible to depict the presence and buildup of beta amyloid in the brain accurately, while providing additional information to support physicians with their evaluation of Alzheimer’s and other forms of cognitive decline.

Britta Fünfstück, Chief Executive Officer of Molecular Imaging at Siemens Healthcare, believes Siemens offers a major advantage to users with its comprehensive amyloid imaging solution. “PETNET Solutions’ PET imaging biomarker manufacturing and distribution expertise, Siemens’ new Biograph mCT PET-CT, and our syngo.PET Amyloid Plaque neurology quantification software will give physicians in the United States additional tools for the evaluation of Alzheimer’s disease and other neurological conditions,” she says.

The Road Ahead. Siemens is going a step further in its Alzheimer’s research. Because the alterations observed in the tau protein are also suspected of causing Alzheimer’s (along with the buildup of amyloid), Dr. Hartmuth Kolb, Vice President of Molecular Imaging Biomarker Research at Siemens Healthcare, and his research team in the Los Angeles area — are now developing new imaging biomarkers that will make the affected nerve strands (axons) visible. Until now there have been no such imaging biomarkers on the market. “Approximately 30 percent of all normal elderly people have amyloid plaques in their brains, even though they don’t suffer from dementia,” says Kolb. “The advantage of focusing on tau is that the amount and distribution of that protein in the brain most probably has more to do with dementia symptoms than is the case with amyloid.”

Kolb and his colleagues have developed two imaging biomarkers that dock with tau strands and make it possible for PET technology to visually depict them. Siemens is currently conducting clinical studies with these biomarkers and associated investigational radiopharmaceuticals in the Los Angeles area, where Kolb and his team produce the imaging agents and can immediately make them available for clinical tests. Researchers want to use these tests to determine whether the tau imaging biomarker triggers a stronger PET signal in the brain of an Alzheimer’s patient than it does in the brain of a healthy individual. Kolb also wants to find out if the tau protein buildup occurs in the regions of the brain where researchers currently suspect it does, or whether other brain regions might also be affected.