Abstract Oncolytic virotherapy is a promising treatment for high mortality cancers 1 . Non-invasive imaging of the underlying molecular processes is an essential tool for therapy optimization and assessment of viral spread, innate immunity, and therapeutic response 2, 3 . However, previous methods for imaging oncolytic viruses did not correlate with late viral activity 4 or had poor sensitivity and specificity 5 . Similarly, methods developed to image treatment response, such as apoptosis, proved to be slow, nonspecific, or require the use of radioactive or metal-based contrast agents 6–8 . To date, no method has been widely adopted for clinical use. We describe here a new method for fast magnetic resonance molecular imaging with quantitative proton chemical-exchange specificity to monitor oncolytic virotherapy treatment response. A deep neural network enabled the computation of quantitative biomarker maps of protein and lipid/macromolecule concentrations as well as intracellular pH in a glioblastoma multiforme mouse brain tumor model. Early detection of apoptotic response to oncolytic virotherapy, characterized by decreased cytosolic pH and protein synthesis, was observed in agreement with histology. Clinical translation was demonstrated in a normal human subject, yielding molecular parameters in good agreement with literature values 9 . The developed method is directly applicable to a wide range of pathologies, including stroke 10 , cancer 11–13 , and neurological disorders 14, 15 .

AI boosted molecular MRI for apoptosis detection in oncolytic virotherapy