Functional imaging of cancer typically involves the use of fluorodeoxyglucose-positron emission tomography (FDG-PET) in combination with computerized tomography (CT) for anatomical mapping. Standard clinical imaging for central nervous system (CNS) malignancies is magnetic resonance imaging (MRI), due to its superior soft tissue resolution compared to CT. We developed a novel functional MRI technique that uses oral deuterated water labeling followed by deuterium MRI (dMRI) for the initial diagnosis of brain tumors and treatment response assessment, including detection of pseudo-progression. Deuterated water (d-water) is NOT radioactive and safe to imbibe. Deuterium-enriched tissues/cells can be differentially detected by MRI. Standard MRI uses magnetic waves to image protons abundant within normal human tissues and provides anatomical mapping. Deuterium MRI detects deuterium-labeled tissues, i.e., providing functional or molecular imaging. Deuterium labeling can be achieved by drinking deuterated water, which looks and tastes like regular water. Deuterated water preferentially labels highly proliferating cells including tumors, which then have an increased dMRI signal compared no healthy tissues as a result of their rapid growth. Additionally, using our d-water-dMRI approach we have been able to detect pseudo-progression, a recognized pattern of tumor response to therapy. Pseudo-progression is a challenge and an impactful barrier for drug development because it’s a false signal of tumor progression that can lead to patients discontinuing effective therapies prematurely. Pseudo-progression is seen by anatomical imaging (including MRI) as an initial increase in tumor size/volume, which is eventually followed by tumor shrinking. Pseudo-progression is more commonly seen in the setting of immunotherapy compared to chemotherapy and radiation and can lead to effective treatments being halted and patients undergoing additional unnecessary biopsies to identify the next therapy for their “progressing” tumor. We have been able to differentiate pseudo-progression from true tumor progression by d-water labeling (oral) followed by d-MRI. In August 2025 we opened an investigator initiated clinical trial at the Roswell Park Comprehensive Cancer Center (PI Buxbaum) using dMRI in patients with primary CNS lymphoma. 

Learning Objectives:

1. Describe how deuterium magnetic resonance imaging (dMRI) works and how it differs from standard MRI and FDG-PET.

2. Explain how deuterated water labeling highlights proliferating tumor cells for functional imaging.

3. Assess the potential of dMRI to distinguish pseudo-progression from true tumor progression in cancer patients, particularly in the context of immunotherapy.