How MRI scans can help in the diagnosis and treatment of brain tumors
Brain tumors – gliomas – are difficult to treat, which is why they still constitute a death sentence for most of those affected. To diagnose them and plan treatment, Elke Hattingen uses a method that visualizes the tumor’s metabolic activity: metabolic imaging. This allows her to look not only at the tumor itself but also its immediate environment, which the tumor manipulates and needs to survive and grow.
Although comparatively rare, they are among the most dreaded types of cancer: Glioblastomas are still fatal in most cases due to their rapid and aggressive growth. They are tumors that grow out of the brain tissue itself. More accurately, they develop out of degenerated glial cells, whose main purpose, in a healthy state, is to support and nourish the nervous system. Gliomas are classified in four grades depending on their malignancy. Grade 1 tumors, at best, may still be curable. But as soon as the cancer begins to spread into healthy brain tissue, known therapies can only buy time for the person affected. This is because not all cancer cells can generally be eradicated, and it is not possible with conventional diagnostic procedures to recognize the remaining cancer foci with absolute certainty.
Radiologist Elke Hattingen wants to change this. She is a senior consultant at University Hospital Frankfurt, where she is also the director of the Institute of Neuroradiology. One of her team’s central tasks is to diagnose cancer or other brain diseases and monitor treatment by means of imaging techniques, especially magnetic resonance imaging (MRI), on which Hattingen has been focusing for many years. MRI is particularly suitable for visualizing soft tissue such as the brain and can produce high-resolution cross-sectional images. As imaging is done with strong magnetic fields, patients are not subjected to potentially harmful X-rays. Neuroradiology has fascinated Hattingen since early on because you must use your “detective skills”, she says, to make a diagnosis. “An MRI scan alone is usually not enough. We have to assemble all the pieces of the puzzle – clinical picture, lab results, medical history, pathology and histology. I still find that very exciting even after 25 years!”
Whole brain in view
If a glioma is suspected, radiologists conduct an MRI brain scan. In most cases, the disease is already at a relatively advanced stage by then because gliomas often do not affect brain function for a very long time. This makes them particularly insidious. Once the first symptoms appear, the patient often has little time left despite treatment. “Patients with grade 4 gliomas, which are particularly aggressive, often die within a year,” says Hattingen. They can strike at any age, although the more aggressive forms are more prevalent in older people.
To buy time for the patient, doctors exhaust all therapeutic options. The first step is surgery to remove as much of the diseased brain tissue as possible. Extensive radiation of the affected area then follows, accompanied by chemotherapy. However, depending on where they are located, for example in areas of the brain responsible for important functions such as language or breathing, even benign grade 1 gliomas are not always operable.
And even if the operation is successful, it is highly probable that undetected cancer cells will grow into new tumors after treatment has ended. “MRI only ever shows us the tip of the iceberg,” says Hattingen, who is still contributing her decades of experience to diagnostics and patient care despite her increasing organizational duties as head of the institute. “We meanwhile know that a brain tumor in fact affects more or less the whole brain. We want to use new methods to visualize the pathological changes that we cannot see with conventional MRI.”
Visualization of the tumor’s molecular fingerprint
This should then improve both diagnosis and the monitoring of treatment. Although it is possible to assess the tumor’s location and morphology and perhaps already diagnose glioma with conventional MRI and many years’ experience, “for the standard treatment common today, which is tailored to the individual patient, we need to know the molecular profile of the cancer cells,” says Hattingen, adding, “but we cannot get any further with conventional imaging.” The tumor’s molecular fingerprint, that is, the genetic mutations that transform glial cells into cancerous ones, determines which therapies are promising and to which drugs the cancer cells are most likely resistant. To identify this fingerprint, doctors analyze the DNA of cancer cells obtained via a biopsy.
Radiologists are now able, however, to visualize a tumor’s molecular fingerprint indirectly in the body and without invasive procedures, Hattingen explains. “The molecular profile affects the tumor’s metabolism in a very specific manner. Our metabolic MRI enables us to visualize these metabolic changes and in this way distinguish diseased from healthy tissue.” In addition to the tumor’s metabolic profile, MRI is useful for examining many other biological characteristics: Especially changes in blood flow in pathologically altered regions of the brain, the brain’s microstructure and texture as well as changes in its functionality are very revealing, she says. “Our innovative MRI gives us a deeper insight into tumor pathology, but it also helps us diagnose brain diseases that otherwise do not show up on MRI scans, such as schizophrenia or inflammatory diseases,” she adds.
Planning certainty
Prior to surgery, MRI can show how far the tumor has already spread into healthy tissue and whether it is located in an important region of the brain such as the language center. This information makes it easier to plan and perform the operation. After radiotherapy and chemotherapy, metabolic and conventional MRI are used in tandem and cerebral blood flow is measured to check whether treatment has been successful. According to Hattingen, judging whether the tumor is growing again is extremely difficult: “The brain reacts to the aggressive therapy by swelling or through a disruption of the blood-brain barrier. In many cases, it is not possible to distinguish these changes from tumor growth on a normal MRI scan.” Increased blood flow and the presence of cell markers that indicate growth, on the other hand, are clear signs that the tumor has returned.
This is where metabolic MRI helps to evaluate whether treatment has worked or should be terminated. Hattingen emphasizes the tangible consequences for patients: “Treatment planning optimized in this way can certainly give some patients another three to five years with a good quality of life.” The new techniques can, however, also be used for purposes other than cancer: It is now even possible, for example, to determine neurotransmitters in the brain directly in the patient’s head. An imbalance of these neurotransmitters plays a role in epilepsy and presumably also in neurodegenerative diseases. The measuring procedure is gentle on the patient, and a whole metabolic profile can be detected at once.
Help from AI
However, all these examinations generate vast amounts of data that can meanwhile only be mastered with the help of artificial intelligence. “We radiologists with our scans are just one element,” says Hattingen. “Also relevant are the results of other examinations and information about the patient’s medical history, previous illnesses and risk factors as well as genetic profiles. Comprehending all this with normal statistics is no longer possible.” Diagnosis today is still largely based on the doctor’s experience, she says, “but if we want to make it better and more reliable, we need artificial intelligence that can recognize patterns and take additional information into account.” It is important to Hattingen that humans remain the final authority and check the plausibility of all diagnoses made with AI. If this is the case, then AI can save time when making a diagnosis and spare the patient unnecessary examinations. “Precisely in times like these where there is a growing shortage of qualified staff, I hope that AI will be a big help for us doctors,” she says.
Neuroradiologists do not have to worry that computer-assisted methods will put them out of work. “What’s completely new for us is that we now also operate,” Hattingen is pleased to say. “Since about 2014, neuroradiologists can remove blood clots from cerebral arteries in the event of a stroke if the arteries blocked by the clot are large enough to be reached via a catheter.” This often leads to a significant improvement or even a cure, she says. “Imagine if a patient comes to us who is paralyzed down one side and goes home cured. That’s simply fantastic, isn’t it?” says Hattingen. “It makes our discipline even more exciting and also very attractive for the next generation of doctors.”
About / Elke Hattingen is the director of the Institute of Neuroradiology at University Hospital Frankfurt. After studying medicine and earning her doctoral degree at the University of Freiburg, she worked in the Neurosurgery Department at Karlsruhe Municipal Hospital before joining the Radiology Department at University Hospital Bonn. After completing her specialist training in radiology, Hattingen earned her postdoctoral degree (Habilitation) in Frankfurt. In 2014, she was made Head of Neuroradiology at University Hospital Bonn, and in 2018 she was appointed to her current position.
hattingen@med.uni-frankfurt.de
The author / Larissa Tetsch studied biology and earned her doctoral degree in microbiology. She then worked in basic research and later in medical training. She has been working as a freelance science and medical journalist since 2015 and is also the managing editor of the science magazine “Biologie in unserer Zeit”.
www.larissa-tetsch.de
