Early Detection of Cell Death Using Transmembrane Water Exchange Magnetic Resonance Imaging.

Area of Science:

• Biophysics
• Medical Imaging
• Oncology

Background:

• Cell death is crucial in cancer progression and therapy.
• Compromised cell membrane integrity is a hallmark of cell death.
• Early detection of cell death is vital for effective cancer treatment.

Purpose of the Study:

• To establish transmembrane water exchange rate as an early biomarker of cell death.
• To evaluate the efficacy of apparent exchange rate (AXR) measurements in detecting cell death onset.
• To compare AXR with existing methods like diffusion-weighted MRI (DWI) and flow cytometry.

Main Methods:

• Utilized magnetic resonance filter-exchange spectroscopy (FEXSY) and imaging (FEXI) to measure transmembrane water exchange.
• Quantified the apparent exchange rate (AXR) as a biomarker.
• Employed 13C magnetic resonance imaging (MRI) to measure the malate/fumarate ratio (MFR) in tumors.
• Validated findings in cell cultures, animal models, and human subjects.

Main Results:

• AXR detected cell death onset earlier than DWI in vivo.
• AXR demonstrated comparable sensitivity to flow cytometry in vitro.
• AXR correlated with MFR in tumors with diffuse necrosis.
• AXR identified early treatment response in colorectal and lymphoma models, while DWI did not.
• AXR showed sensitivity to post-embolization changes in human uterine fibroids.

Conclusions:

• AXR is a sensitive and early biomarker for cell death.
• AXR offers advantages over DWI for detecting early treatment response.
• AXR shows significant clinical translatability for various medical applications.