title: Time-Dependent Influence of Cell Membrane Permeability on MR Diffusion Measurements.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Jingping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.|Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: J Oliver
authors.initials: JO
authors.lastname: McIntyre
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.|Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.|Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D038524:Diffusion Magnetic Resonance Imaging; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D020014:K562 Cells; D016014:Linear Models; D009991:Oscillometry; D010539:Permeability; D012503:Saponins / Q000737:chemistry; D012815:Signal Processing, Computer-Assisted; D014867:Water / Q000737:chemistry
chemical_list: D012503:Saponins; D014867:Water
keywords: ADC; diffusion; diffusion time; intracellular exchange lifetime; oscillating gradient; permeability; pulsed gradient