Hua Li1,2, Xiaoyu Jiang1,3, Jingping Xie1, J Oliver McIntyre1,3,4, John C Gore1,2,3,5,6, Junzhong Xu1,2,3. 1. Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA. 2. Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA. 3. Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA. 4. Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA. 5. Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA. 6. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
Abstract
PURPOSE: To investigate the influence of cell membrane permeability on diffusion measurements over a broad range of diffusion times. METHODS: Human myelogenous leukemia K562 cells were cultured and treated with saponin to selectively alter cell membrane permeability, resulting in a broad physiologically relevant range of 0.011-0.044 μm/ms. Apparent diffusion coefficient (ADC) values were acquired with the effective diffusion time (Δeff ) ranging from 0.42 to 3000 ms. Cosine-modulated oscillating gradient spin echo (OGSE) measurements were performed to achieve short Δeff from 0.42 to 5 ms, while stimulated echo acquisitions were used to achieve long Δeff from 11 to 2999 ms. Computer simulations were also performed to support the experimental results. RESULTS: Both computer simulations and experiments in vitro showed that the influence of membrane permeability on diffusion MR measurements is highly dependent on the choice of diffusion time, and it is negligible only when the diffusion time is at least one order of magnitude smaller than the intracellular exchange lifetime. CONCLUSION: The influence of cell membrane permeability on the measured ADCs is negligible in OGSE measurements at moderately high frequencies. By contrast, cell membrane permeability has a significant influence on ADC and quantitative diffusion measurements at low frequencies such as those sampled using conventional pulsed gradient methods.
PURPOSE: To investigate the influence of cell membrane permeability on diffusion measurements over a broad range of diffusion times. METHODS:Human myelogenous leukemiaK562 cells were cultured and treated with saponin to selectively alter cell membrane permeability, resulting in a broad physiologically relevant range of 0.011-0.044 μm/ms. Apparent diffusion coefficient (ADC) values were acquired with the effective diffusion time (Δeff ) ranging from 0.42 to 3000 ms. Cosine-modulated oscillating gradient spin echo (OGSE) measurements were performed to achieve short Δeff from 0.42 to 5 ms, while stimulated echo acquisitions were used to achieve long Δeff from 11 to 2999 ms. Computer simulations were also performed to support the experimental results. RESULTS: Both computer simulations and experiments in vitro showed that the influence of membrane permeability on diffusion MR measurements is highly dependent on the choice of diffusion time, and it is negligible only when the diffusion time is at least one order of magnitude smaller than the intracellular exchange lifetime. CONCLUSION: The influence of cell membrane permeability on the measured ADCs is negligible in OGSE measurements at moderately high frequencies. By contrast, cell membrane permeability has a significant influence on ADC and quantitative diffusion measurements at low frequencies such as those sampled using conventional pulsed gradient methods.
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