Quantification of cell size using temporal diffusion spectroscopy

Abstract

Purpose A new approach has been developed to quantify cell sizes and intracellular volume fractions using temporal diffusion spectroscopy with diffusion-weighted acquisitions. Theory and Methods Temporal diffusion spectra may be used to characterize tissue microstructure by measuring the effects of restrictions over a range of diffusion times. Oscillating gradients have been used previously to probe variations on cellular and subcellular scales, but their ability to accurately measure cell sizes larger than 10 μm is limited. By combining measurements made using oscillating gradient spin echo (OGSE) and a conventional pulsed gradient spin echo (PGSE) acquisition with a single, relatively long diffusion time, we can accurately quantify cell sizes and intracellular volume fractions. Results Based on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes and intracellular volume fractions were obtained in vitro for (i) different cell types with sizes ranging from 10 to 20 μm, (ii) different cell densities, and (iii) before and after anti-cancer treatment. Conclusion Hybrid OGSE-PGSE acquisitions sample a larger region of temporal diffusion spectra and can accurately quantify cell sizes over a wide range. Moreover, the maximum gradient strength used was lower than 15 G/cm, suggesting that this approach is translatable to practical MR imaging.

Time-Dependent Diffusion MRI in Cancer: Tissue Modeling and Applications

“…Additional parameters are required to describe the ECS diffusion outside the tortuosity limit (D = cste) and short-time regime (Equations 1-2), or to model additional compartments, such as vasculature with VERDICT [16]. In practice, multiple PGSE [16,45] or a combination of PGSE and OGSE [14,15] measurements are combined in order to probe diffusion in a specific or over several frequency/time domains.…”

“…The IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) model combines multiple low-frequency OGSE measurements (f OGSE < 150 Hz) and a single PGSE acquisition in the long time regime (Figure 4A) to quantify the characteristic size of restriction and ICS fraction [14,46]. This approach was shown successful in estimating cancer cell size in vitro in the range (5-10) µm using only a small subset of measurements on murine (MEL) and human leukemia cells (K562) [14].…”

“…This approach was shown successful in estimating cancer cell size in vitro in the range (5-10) µm using only a small subset of measurements on murine (MEL) and human leukemia cells (K562) [14]. In vivo, the correlation between histology and IMPULSEDbased cellularities were found superior than between histology and conventional PGSE measurements, in three different colorectal cancer xenograft tumor models (DiFi, HCT116, and SW620) [46].…”

“…Additional parameters are required for modeling timedependence in the ECS [14] and/or a vasculature compartment [16]. In practice, the narrow range of diffusion times available in most scanners ( Figure 5) prevents the completely unambiguous estimation of all model parameters.…”

“…Using these results, the main models used to characterize tumor tissue using TDD are reviewed: IMPULSED [14], POMACE [15], and VERDICT [16]. Modeling cells as impermeable spheres, additional assumptions are made to describe the ECS, and finally estimate diffusivities, cell size and volume fraction ex vivo and in vivo.…”