Early detection of cell death using transmembrane water exchange MRI

Motivation: Early detection of cell death with FEXI. Goal(s): Investigate the sensitivity of AXR measurements to tumor cell death after therapy. Approach: Evaluate FEXI, DWI, hyperpolarized malate/fumarate CSI, H&E histology, and fluorescence imaging in preclinical tumors. Compare FEXI and DWI for clinical uterine fibroids therapy response assessment. Results: AXRs and malate/fumarate ratios correlate, but not with ADC, in solid-growing EL4 lymphoma in mice. FEXI and DWI of EL4 lymphoma treated with etoposide or Colo205 colorectal carcinoma treated with a TRAILR2 agonist had increased AXR. Clinical FEXI shows sensitivity to embolization after 24 hours. Impact: Transmembrane water permeability measured by AXR is a sensitive marker for cell death during cancer progression or therapy. FEXI is a contrast agent-free technique that can be easily included in clinical MR protocols.