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The distinction between intracellular (ICE) and extracellular edema (ECE) has a crucial prognostic and therapeutic importance in patients with severe traumatic brain injury (STBI). Indeed, ICE usually leads to cellular death, and maintenance of a cerebral perfusion pressure (CPP) above 70 mmHg is still under debate since this practice may increase ECE. The purpose of this study was to describe the ECE and ICE kinetics associated with STBI using quantitative diffusion MRI. Twelve patients were prospectively studied. The initial ADC in ICE measured on day 1.3±0.7 is significantly reduced compared to normal-appearing parenchyma (0.51±0.12 * 10-3 mm2/s vs. 0.76±0.03 * 10-3 mm2/s, n=12, P<0.0001) and reaches normality on MRI 3 performed on day 14.2±3.3. In patients presenting an extension of ICE on MRI 2 performed on day 6.7±1.4 (ADCMRI2=0.40±0.11 * 10-3 mm2/s), ADC values in the extension area at the first MRI were slightly, but not significantly reduced compared to normal parenchyma (0.69±0.05 * 10-3 mm2/s, P=0.29). Normalization occurred equally by day 14. ADC in ECE (1.34±0.22 * 10-3 mm2/s) was elevated and stable with time under CPP therapy. Therefore, ECE is not worsened by CCP therapy, and ICE appears more relevant than ECE in STBI.