Dynamics of Ionic and Cytotoxic Edema During Acute and Subacute Stages of Patients With Ischemic Stroke: Complementarity of 23Na MRI and Diffusion MRI

Abstract

Cerebral imaging is crucial in the diagnosis and treatment algorithm of acute stroke to determine salvageable brain tissue. While diffusion MRI is commonly used to define the ischemic core, it cannot reliably distinguish irreversibly damaged from salvageable tissue. We investigated the added value of ²³Na MRI to define irreversible necrotic tissue after a stroke. Fifteen patients with acute stroke involving medial cerebral artery occlusion were longitudinally explored with conventional and ²³Na MRI within 24 h, 70 h following stroke and at 3 months to characterize the necrotic area. Time-courses of sodium accumulations were observed within regions presenting with or spared by cytotoxic/ionic edema and converting or not to necrosis. Dynamics of sodium accumulations were very different across subjects. At the group level, time-courses of sodium signal in cytotoxic edema showed a non-linear increase with an upper asymptote of 59 ± 6%% relative to the contralateral hemisphere. Regions with a larger early increase in ²³Na signal (ionic edema) showed a non-linear accumulation during the first 70 h and were associated with subsequent necrosis at month 3. Some of the regions with no ionic edema during the first 70 h became necrotic at month 3, showing that pejorative pathophysiological processes could worsen after 70 h following attack. Final necrotic volume was well predicted by the cytotoxic volume (ADC decrease) during the first 24 h, and by the volume of ionic edema during the subacute period (25-70 h) following attack. The regions showing ionic edema showed a non-linear increase of ²³Na signal during the first 70 h, with larger sodium accumulations in regions converting to necrosis at month 3. It may be of interest to consider the role of ionic edema imaging in the 70 h after stroke and reperfusion, with a view to better understand stroke pathophysiology. Sodium MRI could add complementary information about the fate of cell necrosis within low ADC signal regions.

Keywords: 23Na MRI; MRI; edema; sodium; stroke.

FIGURE 1

Representative MRI images from the 15 patients with ischemic stroke explored during the acute and subacute phases and at 3 months. The arrows indicate the stroke lesion. The subjects were ranked in descending order of the volume necrosis at 3 months.

FIGURE 2

Dynamics of (A) ²³Na and (B) ADC signals during the first 70 h following ischemic stroke. (A) Relative sodium intensity increases non‐linearly over time during the first 70 h after stroke onset (n = 28; RMSE = 15.8; α = 91 + 108, δ = 0.71 + 0.9, γ = 2.3 + 0.8), while (B) a plateau of low ADC is reached during the first hours following attack.

FIGURE 3

Dynamics of ²³Na accumulations and low ADC in acute and subacute stages of ischemic stroke. (A) This figure depicts the regions of interest (ROIs) identified on the hyperintense ²³Na (red circle) and hyperintense FLAIR (black circle) sequences. The intersections between these ROIs (overlapping areas) and the regions exclusive to each ROI are highlighted to facilitate visualization of the data presented in (A). (B) This figure depicts the regions of interest (ROIs) identified on the hypointense ADC (light blue circle) and hyperintense FLAIR (black circle) sequences. The intersections between these ROIs (overlapping areas) and the regions exclusive to each ROI are highlighted to facilitate visualization of the data presented in (A). (C) Curves represent the relative variations of ²³Na and ADC in lesions compared to homologous contralateral regions. The dynamics of regions showing different long‐term prognosis (necrosis or recovery), and different early pathophysiological processes (ionic edema, cytotoxic edema, no edema) are compared. @M3, at 3 months.

FIGURE 4

volumes of cytotoxic and ionic edema during the acute and subacute phases. (A) Subject‐wise volume dynamics of cytotoxic (red) and ionic (blue) edema compared to final volume of necrosis at 3 months (green). (B) The better prediction of final necrotic volume by cytotoxic edema during the first 24‐h period (left) while ionic edema predicts better necrosis at 3 months during the subacute period (right).

FIGURE 5

Inter‐individual heterogeneity in the dynamics of ²³Na accumulations and ADC decreases in stroke patients.