Fransisca Indraswari, MD

Aoki J, Sakamoto Y, Suzuki K, Nishi Y, Kutsuna A, Takei Y, et al. Fluid-Attenuated Inversion Recovery May Serve As a Tissue Clock in Patients Treated With Endovascular Thrombectomy. Stroke. 2021;52:2232–2240.

This retrospective study by Aoki et al. investigated the role of fluid-attenuated inversion recovery (FLAIR) sequence in the magnetic resonance imaging (MRI) of the brain as a tool to predict outcome after an endovascular thrombectomy (EVT), regardless of the time of symptom onset. The notion of imaging-based prognostication of clinical outcome has been elucidated in previous trials, e.g., THAWS1 and WAKE UP.2 Similarly, the concept of extending therapeutic window of thrombectomy up to 24 hours based on imaging selection criteria in DAWN3 and DEFUSE3.4 They hypothesized that if the signal change on FLAIR was associated with the clinical outcome after EVT, FLAIR may be able to serve not only as a time clock, but also as a tissue clock.

Patients with acute ischemic stroke treated with EVT were recruited between September 2014 and December 2018. They were divided between FLAIR-positive and FLAIR-negative groups based on the parenchymal change on FLAIR sequence in their MRI brain. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. Clinical outcome at 3 months was defined as modified Rankin Scale Score (mRS) with 0-1 being good outcome.

The result of this study showed that patients with FLAIR-negative imaging had a higher rate of good outcomes than those with FLAIR positive imaging (41% vs. 27%, p-value 0.047), with mRS 0-1 defined as good outcome. They have also found factors associated with good outcome, such as younger age (p=0.012), absence of hypertension (p=0.004), lower NIHSS score (p<0.001), higher DWI-ASPECT score (p<0.001), smaller ischemic core volume (p<0.001), and lower D-dimer (p<0.001). As part of EVT complications, they analyzed parenchymal hematoma using Heidelberg Bleeding Classification. Eighteen percent of patients with HBC score ³ 1c hemorrhage had good outcome, whilst 43% of patients without HBC ³ 1c hemorrhage had good outcome. FLAIR negative status was associated with good outcome (41% vs. 27%, p = 0.047), more so without HBC ³ 1c hemorrhage (47% vs. 21%, p=0.009). As for patients with FLAIR-positive images, HBC ³ 1c hemorrhage status is associated with worse outcome (14% vs. 37%, p=0.028).

These findings implicate our further interpretation of FLAIR images, especially with respect to patient prognostication after EVT. The absence of FLAIR signal changes on the MRI brain during acute ischemic stroke is independently associated with good outcome at 3 months regardless of the time of symptom onset, though the characteristics of the FLAIR-negative group tend to have shorter time of symptom presentation to imaging, and also smaller ischemic core volume, which means ischemia has not caused enough irreversible damage to cause bad clinical outcome. In acute stroke intervention, time is brain. Loss of time means loss of neurons, which means identifying optimal time for acute stroke intervention is essential in optimizing patients’ clinical outcome. This can be really challenging, given the chaos that clinicians are facing during stroke code and inaccurate history given by patients or witnesses. A patient-specific approach, given by FLAIR signal change on the imaging studies, has shed light into providing the extent of tissue damage, hence objective measures in our decision-making to proceed with thrombolysis or EVT. This “time-flexible” approach in acute stroke intervention using FLAIR signal changes is greatly influenced by interrater reliability, which includes occlusive site, cerebral pre-conditioning, collateral flow status, systemic blood pressure, which then affects the volume of penumbra, i.e., area of the brain with perfusion-diffusion mismatch. Implementing a tissue-based timing in our acute stroke protocol can be really challenging as it requires prompt hyperacute MRI in the first few hours of patients’ arrival, instead of the widely available CT scan, which we normally base our decision on. The clock-based timing is more convenient for non-neurologist physicians or non-physicians to follow. However, having MRI-based FLAIR-negative imaging could also be used to select patients for endovascular therapy (EVT) when reliable history is not available or for centers where perfusion studies are not available but MRI is available. Despite its described limitations, this study further supported the new paradigm of tissue-based timing, or tissue clock, which could only be implemented at the vascular neurologist’s discretion and interpreted on a case-by-case basis to decide on acute stroke intervention.


  1. Koga M, Yamamoto H, Inoue M, Asakura K, Aoki J, Hamasaki T, Kanzawa T, Kondo R, Ohtaki M, Itabashi R, et al. Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial. Stroke. 2020;51:1530-1538.
  2. Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, Cheripelli B, Cho TH, Fazekas F, Fiehler J, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018;379:611-622.
  3. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378:11-21.
  4. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018;378:708-718.