  Purpose: Cell size is a fundamental characteristic of all tissues, and
changes in cell size in cancer reflect tumor status and response to treatments,
such as apoptosis and cell cycle arrest. Unfortunately, cell size can only be
obtained by pathologic evaluation of the tumor in the current standard of care.
Previous imaging approaches can be implemented on only animal MRI scanners or
require relatively long acquisition times that are undesirable for clinical
imaging. There is a need to develop cell size imaging for clinics. Experimental
Design: We propose a new method, IMPULSED (Imaging Microstructural Parameters
Using Limited Spectrally Edited Diffusion) that can characterize mean cell
sizes in solid tumors. We report the use of combined sequences with different
gradient waveforms on human MRI and analytical equations that link DWI signals
of real gradient waveforms and specific microstructural parameters such as cell
size. We also describe comprehensive validations using computer simulations,
cell experiments in vitro, and animal experiments in vivo and finally
demonstrate applications in pre-operative breast cancer patients. Results: With
fast acquisitions (~ 7 mins), IMPULSED can provide high-resolution (1.3 mm
in-plane) mapping of mean cell size of human tumors in vivo on
currently-available 3T MRI scanners. All validations suggest IMPULSED provide
accurate and reliable measurements of mean cell size. Conclusion: The proposed
IMPULSED method can assess cell size variations in the tumor of breast cancer
patients, which may have the potential to assess early response to neoadjuvant
therapy.
