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 currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging. There is a need to develop cell‐size imaging for clinical applications.Methods: We propose a clinically feasible IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) approach that can characterize mean cell sizes in solid tumors. We report the use of a combination of pulse sequences, using different gradient waveforms implemented on clinical MRI scanners and analytical equations based on these waveforms to analyze diffusion‐weighted MRI signals and derive specific microstructural parameters such as cell size. We also describe comprehensive validations of this approach using computer simulations, cell experiments in vitro, and animal experiments in vivo and demonstrate applications in preoperative breast cancer patients.Results: With fast acquisitions (~7 minutes), IMPULSED can provide high‐resolution (1.3 mm in‐plane) mapping of mean cell size of human tumors in vivo on clinical 3T MRI scanners. All validations suggest that IMPULSED provides accurate and reliable measurements of mean cell size.Conclusion: The proposed IMPULSED method can assess cell‐size variations in tumors of breast cancer patients, which may have the potential to assess early response to neoadjuvant therapy.

We present a Monte Carlo simulation program for the propagation of polarized photons in an anisotropic scattering model consisting of poly-dispersed spherical and infinite long cylindrical scatterers. The cylinders are aligned following a Gaussian distribution. Densities and sizes of the spherical and cylindrical scatterers, as well as the orientation of the cylinders are variables for the simulation of different anisotropic media. The good agreement between the simulation and experimental results of polarization imaging confirms the validity of the polarization-dependent Monte Carlo simulation program.

Purpose To investigate the influence of transcytolemmal water exchange on estimates of tissue microstructural parameters derived from diffusion MRI using conventional PGSE and IMPULSED methods. Methods Computer simulations were performed to incorporate a broad range of intracellular water life times τ_in (50–∞ ms), cell diameters d (5–15 μm), and intrinsic diffusion coefficient D_in (0.6–2 μm²/ms) for different values of signal‐to‐noise ratio (SNR) (10 to 50). For experiments, murine erythroleukemia (MEL) cancer cells were cultured and treated with saponin to selectively change cell membrane permeability. All fitted microstructural parameters from simulations and experiments in vitro were compared with ground‐truth values. Results Simulations showed that, for both PGSE and IMPULSED methods, cell diameter d can be reliably fit with sufficient SNR (≥ 50), whereas intracellular volume fraction f_in is intrinsically underestimated due to transcytolemmal water exchange. D_in can be reliably fit only with sufficient SNR and using the IMPULSED method with short diffusion times. These results were confirmed with those obtained in the cell culture experiments in vitro. Conclusion For the sequences and models considered in this study, transcytolemmal water exchange has minor effects on the fittings of d and D_in with physiologically relevant membrane permeabilities if the SNR is sufficient (> 50), but f_in is intrinsically underestimated. Magn Reson Med 77:2239–2249, 2017. © 2016 International Society for Magnetic Resonance in Medicine