  Early assessment of tumor therapeutic response is an important topic in
precision medicine to optimize personalized treatment regimens and reduce
unnecessary toxicity, cost, and delay. Although diffusion MRI (dMRI) has shown
potential to address this need, its predictive accuracy is limited, likely due
to its unspecific sensitivity to overall pathological changes. In this work, we
propose a new quantitative dMRI-based method dubbed EXCHANGE (MRI of water
Exchange, Confined and Hindered diffusion under Arbitrary Gradient waveform
Encodings) for simultaneous mapping of cell size, cell density, and
transcytolemmal water exchange. Such rich microstructural information
comprehensively evaluates tumor pathologies at the cellular level. Validations
using numerical simulations and in vitro cell experiments confirmed that the
EXCHANGE method can accurately estimate mean cell size, density, and water
exchange rate constants. The results from in vivo animal experiments show the
potential of EXCHANGE for monitoring tumor treatment response. Finally, the
EXCHANGE method was implemented in breast cancer patients with neoadjuvant
chemotherapy, demonstrating its feasibility in assessing tumor therapeutic
response in clinics. In summary, a new, quantitative dMRI-based EXCHANGE method
was proposed to comprehensively characterize tumor microstructural properties
at the cellular level, suggesting a unique means to monitor tumor treatment
response in clinical practice.
