Improving MR cell size imaging by inclusion of transcytolemmal water exchange.

The goal of the current study is to include transcytolemmal water exchange in MR cell size imaging using the IMPULSED model for more accurate characterization of tissue cellular properties (e.g., apparent volume fraction of intracellular space <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>v</mml:mi> <mml:mtext>in</mml:mtext></mml:msub> </mml:math> ) and quantification of indicators of transcytolemmal water exchange. We propose a heuristic model that incorporates transcytolemmal water exchange into a multicompartment diffusion-based method (IMPULSED) that was developed previously to extract microstructural parameters (e.g., mean cell size <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>d</mml:mi></mml:math> and apparent volume fraction of intracellular space <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>v</mml:mi> <mml:mtext>in</mml:mtext></mml:msub> </mml:math> ) assuming no water exchange. For <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>t</mml:mi> <mml:mtext>diff</mml:mtext></mml:msub> </mml:math> ≤ 5 ms, the water exchange can be ignored, and the signal model is the same as the IMPULSED model. For <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>t</mml:mi> <mml:mtext>diff</mml:mtext></mml:msub> </mml:math> ≥ 30 ms, we incorporated the modified Kärger model that includes both restricted diffusion and exchange between compartments. Using simulations and previously published in vitro cell data, we evaluated the accuracy and precision of model-derived parameters and determined how they are dependent on SNR and imaging parameters. The joint model provides more accurate <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>d</mml:mi></mml:math> values for cell sizes ranging from 10 to 12 microns when water exchange is fast (e.g., intracellular water pre-exchange lifetime <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>τ</mml:mi> <mml:mtext>in</mml:mtext></mml:msub> <mml:mspace/></mml:math> ≤ 100 ms) than IMPULSED, and reduces the bias of IMPULSED-derived estimates of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>v</mml:mi> <mml:mtext>in</mml:mtext></mml:msub> </mml:math> , especially when water exchange is relatively slow (e.g., <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>τ</mml:mi> <mml:mtext>in</mml:mtext></mml:msub> <mml:mspace/></mml:math> &gt; 200 ms). Indicators of transcytolemmal water exchange derived from the proposed joint model are linearly correlated with ground truth <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>τ</mml:mi> <mml:mtext>in</mml:mtext></mml:msub> </mml:math> values and can detect changes in cell membrane permeability induced by saponin treatment in murine erythroleukemia cancer cells. Our results suggest this joint model not only improves the accuracy of IMPULSED-derived microstructural parameters, but also provides indicators of water exchange that are usually ignored in diffusion models of tissues.