Pancreatic cancer is the leading cause of cancer-related fatalities. When the disease is localized, the five-year survival rate is 44%, but once it has spread, the rate drops to around 3%. The symptoms of pancreatic cancer, including stomach pain, unexplained weight loss, new-onset diabetes, and jaundice, are non-specific and often resemble those of other conditions. By the time these symptoms appear, the cancer is typically already advanced and inoperable. Approximately 95% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC), with many originating from a precursor lesion called pancreatic intraepithelial neoplasia (PanIN). Detecting pre-malignant lesions, particularly PanINs, is essential for diagnosing PDAC early and understanding PanIN biology. However, unlike colorectal cancer, where polyps can be easily seen and removed during a colonoscopy, pancreatic cancer lacks non-invasive diagnostic tools for the early detection of PanINs. This limitation also hinders research on PanIN biology and the development of pancreatic tumors in humans. Additionally, PanINs are not identifiable with current imaging techniques, as precursor lesions in the pancreas are difficult to detect using magnetic resonance imaging (MRI). Therefore, there is a pressing need for advanced imaging methods to detect and characterize PanINs, enabling early diagnosis before PDAC develops.

A new study by researchers at the Champalimaud Foundation (Lisboa, Portugal) has demonstrated, for the first time, that Diffusion Tensor Imaging (DTI), a particular form of MRI, can effectively detect pre-malignant lesions in the pancreas. Published in the journal Investigative Radiology, the study could pave the way for early clinical diagnosis and treatment assessment in individuals at risk for pancreatic cancer. DTI is based on the diffusion of water molecules in tissues, which interact with cell walls and other microscopic structures, making them useful as endogenous tracers of tissue microstructure. While DTI is commonly used for brain imaging, its application for detecting pancreatic cancer precursor lesions has never been explored.

The team of scientists and clinicians embarked on this collaborative study keeping translation to the clinics in mind, considering that the most efficient strategy would be to test a method that already exists, instead of developing something completely new – and unproven. They began by imaging transgenic mouse pancreatic tissue samples using one of the world’s most advanced MRI scanners, a 16.4 Tesla ultrahigh-field MRI machine, compared to the 1.5T or 3T scanners commonly used in clinical settings. They then compared the DTI images with histological analysis of the same tissue samples to confirm if the lesions detected by DTI corresponded with those seen in histology. Histology involves examining thin slices of prepared tissue under a microscope to study cell structures and tumor characteristics. The results were a perfect match.

By leveraging the capabilities of the high-field MRI equipment, the team developed a magnetic resonance microscopy technique that allowed for direct comparison between DTI images and histology slides. This technique demonstrated that advanced DTI sequences could successfully identify pre-malignant lesions of pancreatic cancer. The team further showed that these lesions could be detected in vivo in transgenic mice, specifically engineered to develop PanINs. Finally, human tissue samples were imaged, confirming that the method was also effective for detecting lesions in humans. Histology and pathology results from the human samples validated the efficacy of DTI in detecting pancreatic cancer precursor lesions.

“I believe this study represents a milestone in research into premalignant pancreatic cancer lesions,” said Carlos Bilreiro, a doctor at the Champalimaud Clinical Centre’s Radiology Department and first author of the study. “We are now able to detect these lesions in animals and better understand how pancreatic cancer develops. We also know that DTI is just as effective in the human pancreas. As for its clinical application, further studies will be needed to adapt the technique to the clinical context and to explore interventional or surveillance possibilities for pre-malignant lesions. This study thus represents a first step towards the early detection of pancreatic cancer with magnetic resonance imaging, even before the cancer develops.”

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