The use of MR-detectable reporter molecules and ions to evaluate diffusion in normal and ischemic brain

Abstract

As a result of the technical challenges associated with distinguishing the MR signals arising from intracellular and extracellular water, a variety of endogenous and exogenous MR-detectable molecules and ions have been employed as compartment-specific reporters of water motion. Although these reporter molecules and ions do not have the same apparent diffusion coefficients (ADCs) as water, their ADCs are assumed to be directly related to the ADC of the water in which they are solvated. This approach has been used to probe motion in the intra- and extracellular space of cultured cells and intact tissue. Despite potential interpretative challenges with the use of reporter molecules or ions and the wide variety used, the following conclusions are consistent considering all studies: (i) the apparent free diffusive motion in the intracellular space is approximately one-half of that in dilute aqueous solution; (ii) ADCs for intracellular and extracellular water are similar; (iii) the intracellular ADC decreases in association with brain injury. These findings provide support for the hypothesis that the overall brain water ADC decrease that accompanies brain injury is driven primarily by a decrease in the ADC of intracellular water. We review the studies supporting these conclusions, and interpret them in the context of explaining the decrease in overall brain water ADC that accompanies brain injury.

Figure 1

Plot of intracellular apparent diffusion coefficient (ADC) vs. free ADC in dilute aqueous solution for several reporter molecules at a diffusion time of 8.6 ms. The water ADC representative of the entire cell was calculated from imaging experiments. All other ADCs were calculated from MRS data. The data were well modeled (R² = 0.983) by a least-squares fit to a straight line with a slope of 0.45 ± 0.02 and y-intercept of 2 ± 2 μm²/ms. FDG-6-P, 2-fluorodeoxyglucose-6-phosphate; PEG, polyethylene glycol; TMA, tetramethylammonium ion. [Reproduced with permission from (29).]