Glioblastoma—the most aggressive form of brain cancer—remains one of medicine's biggest challenges. Despite surgery, radiotherapy, and chemotherapy, most patients survive only about a year after diagnosis. However, a new discovery might change how doctors understand and monitor this deadly disease. Specifically, the study focused on isocitrate dehydrogenase (IDH) wild-type glioblastoma, the most common and rapidly growing form of the tumor, known for its poor prognosis and limited treatment options.
In a study published online on October 11, 2025, in Neuro-Oncology , researchers found that brain regions far away from the tumor—known as the contralateral hemisphere (the side opposite to tumor)—can reveal vital clues about a patient's survival in IDH wild-type glioblastoma. The team was led by Associate Professor Akifumi Hagiwara, in collaboration with Mr. Takuya Ozawa, Prof. Koji Kamagata from the Faculty of Medicine, Juntendo University, and Dr. Wataru Uchida, along with Prof. Shigeki Aoki from the Faculty of Health Data Science, Juntendo University. Using advanced magnetic resonance imaging (MRI) techniques, the team showed that disturbances in the brain's internal "fluid flow" system predict how long patients will live, independent of tumor size or location.
Dr. Hagiwara explains, "We found that even brain regions far from the tumor show signs of disrupted fluid circulation. This dysfunction was strongly linked to shorter survival, suggesting that glioblastoma is not just a local disease but affects the entire brain environment."
This fluid flow, known as the glymphatic system, acts as the brain's cleaning and drainage network. It helps remove waste, proteins, and other unwanted materials by circulating fluid along blood vessels and through brain tissue. When this system falters, toxic substances may build up, causing inflammation and further damage.
The study analyzed MRI data from a total of 546 patients across two large clinical datasets. The researchers used two non-invasive imaging markers—Diffusion Tensor Imaging (DTI) analysis along the Perivascular Space (ALPS) and Free Water (FW) imaging—to measure the movement and accumulation of fluid in brain tissue.
In simple terms, DTI-ALPS measures how easily water molecules move along the tiny channels that run beside blood vessels, while FW imaging estimates how much free fluid is trapped between brain cells. A lower ALPS index (indicating slower water movement) and higher FW levels (indicating fluid buildup) both pointed to poorer survival outcomes.
Patients with healthier fluid circulation—higher ALPS values and lower FW levels—lived significantly longer than those with impaired flow. Remarkably, these patterns were seen in the contralateral hemisphere, the side of the brain opposite the tumor, highlighting that even areas appearing normal on scans may be affected.
The implications are far-reaching. If confirmed in clinical settings, MRI-based assessments of neurofluid dynamics could become a new tool for personalized treatment planning. Patients with poor glymphatic function might benefit from more intensive or targeted therapies, such as immunotherapy or drugs that restore brain fluid balance.
Dr. Hagiwara adds, "In the future, we hope these imaging markers can help identify high-risk patients early and guide treatments that improve fluid circulation. Beyond glioblastoma, this approach may also advance our understanding of other brain disorders linked to impaired waste clearance, such as Alzheimer's disease."
The study also opens new avenues for therapeutic innovation. Treatments aimed at improving glymphatic function—such as optimizing sleep, reducing inflammation, or modulating specific water channels (aquaporins) in the brain—could potentially improve outcomes. These strategies may one day complement standard cancer therapies by restoring the brain's natural ability to flush out harmful substances.
By uncovering this hidden dimension of glioblastoma, the research underscores the importance of looking beyond the visible tumor. The brain's own plumbing system—once thought to be passive—appears to play an active role in determining how patients fare.
As Dr. Hagiwara concludes, "Glioblastoma has long been viewed as a disease of uncontrolled cell growth, but our study shows that it also involves a breakdown in how the brain maintains its internal environment. Understanding and restoring this balance could be key to improving survival and quality of life for patients."
Reference
Authors |
Akifumi Hagiwara1,2*, Wataru Uchida1,3, Takuya Ozawa1, Kaito Takabayashi1, Rui Zou1, Benjamin M. Ellingson4, Christina Andica1,3, Junko Kikuta1, Toshiaki Akashi1, Akihiko Wada1, Kanako Kunishima Kumamaru1,3, Koji Kamagata1, Osamu Akiyama5, Akihide Kondo5, and Shigeki Aoki1,3 |
Title of original paper |
Contralateral Neurofluid Dynamics Predict Survival in IDH Wild-Type Glioblastoma: A DTI-ALPS and Free Water Imaging Study |
Journal |
Neuro-Oncology |
DOI |
|
Affiliations |
1Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan 2Department of Radiology, The University of Tokyo, Tokyo, Japan 3Faculty of Health Data Science, Juntendo University, Chiba, Japan 4UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA 5Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan |
About Associate Professor Akifumi Hagiwara from Juntendo University, Faculty of Medicine
Akifumi Hagiwara, MD, PhD, is an Associate Professor in the Department of Radiology at Juntendo University Graduate School of Medicine in Tokyo, Japan. With over 15 years of experience, he has published more than 200 peer-reviewed articles in the fields of brain MRI, neurofluid (glymphatic) imaging, and neuro-oncology. His research focuses on advanced MRI biomarkers for dysfunction of brain clearance in disorders ranging from glioblastoma and multiple sclerosis to dementia. Dr. Hagiwara's notable achievements include leading international multicentre MRI studies and contributing key insights into brain "plumbing" systems.
