Role of Hyperintense Acute Reperfusion Marker for Classifying the Stroke Etiology

Abstract

Purpose: The hyperintense acute reperfusion marker (HARM) is a delayed enhancement of the subarachnoid or subpial space observed on post-contrast fluid-attenuated inversion recovery (FLAIR) images and is associated with permeability changes to the blood-brain barrier in acute stroke. We investigated the relationship between HARM and stroke etiology based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. In addition, we evaluated the relationship between HARM and stroke locations with respect to vascular territories and anatomic compartments.

Materials and methods: We recruited 264 consecutive patients (109 women; mean age 68.63 years) who were diagnosed with acute ischemic stroke and underwent brain magnetic resonance imaging (MRI) including post-contrast FLAIR and DWI within 7 days of symptom onset from May 2015 to March 2016 for this retrospective study. Post-contrast FLAIR images were obtained 5 min after gadolinium administration. The mean time interval between the onset of stroke symptoms and MRI acquisition in total included patients was 18 h and 7 min (median 12 h and 57 min, range 2-127 h). We analyzed the overall incidence and distribution patterns of HARM in acute ischemic stroke cases and compared the relative incidence and distribution patterns of HARM between the subgroups of stroke etiology based on conventional TOAST classification. We obtained odds ratio (OR) of HARM in different stroke locations based on vascular territories and anatomical compartments. This study was approved by our institutional review board.

Results: Among the 264 patients, 67 (25.38%) patients were HARM positive and 197 (74.62%) patients were HARM negative. There was significant difference in HARM incidence among the stroke subgroups (p < 0.001). Small vessel occlusion (SVO) was associated with the HARM-negative group (p < 0.001), while large artery atherosclerosis (LAA) and cardioembolism (CE) were associated with the HARM-positive group (p = 0.001). Also, regional pattern of HARM on the same vascular territory as the acute infarction was dominantly demonstrated regardless of stroke etiology. The OR for HARM from middle cerebral artery (MCA) infarction was 1.868 [95% confidence interval (CI): 1.025-3.401]. The OR for HARM from cortical infarction was 9.475 (95% CI: 4.754-18.883) compared to other anatomic compartments.

Conclusion: The presence of the HARM was significantly associated with embolic infarctions including LAA and CE. Conversely, SVO was exclusively associated with the absence of the HARM. Second, MCA and cortical infarction showed a more pronounced HARM compared to infarctions at other vascular territories and anatomic compartments. According to the results in the current study, we speculate that the presence of HARM on post-contrast FLAIR images was associated with specific stroke causes especially in embolic causes.

Keywords: Trial of ORG 10172 in Acute Stroke Treatment classification; acute stroke; hyperintense acute reperfusion marker; magnetic resonance imaging; post-contrast fluid-attenuated inversion recovery.

Figure 1

A 72-year-old male with a complaint of acute onset left arm weakness. Stroke due to large artery to artery atherosclerosis. (A) DWI shows acute border zone infarctions on the right cerebral hemisphere. (B) Three-dimensional time-of-flight MRA of extracranial arteries shows moderate-to-severe stenosis with plaque at right proximal internal carotid artery and ECA (arrows). Compared with non-contrast fluid-attenuated inversion recovery (FLAIR) (C), the post-contrast FLAIR (D) image shows diffuse sulcal enhancement (hyperintense acute reperfusion marker sign) along the right cerebral sulci (arrows).

Figure 2

A 53-year-old female with a complaint of acute onset aphasia. Stroke due to cardioembolic. (A) DWI shows large diffusion restricted lesion on the left frontoparietotemporal lobes. (B) Post-contrast fluid-attenuated inversion recovery image shows sulcal enhancement along the left frontoparietal sulci (arrows) compatible with hyperintense acute reperfusion marker. (C) Gradient-echo imaging image shows blooming artifact at the left proximal MCA (arrowhead) indicating intravascular thrombus. Note, hemorrhagic foci of stroke area at the left temporal lobe. (D) Three-dimensional time-of-flight MRA shows occlusion of proximal M1 segment of left MCA (arrowhead). There is no stenoocclusive lesion in the cervical arteries (not shown).

Figure 3

Multiple comparisons of the relative hyperintense acute reperfusion marker (HARM) incidence according to stroke subtypes.

Figure 4

A 59-year-old male with a complaint of acute onset left side visual field defect in both eyes. Regional pattern of hyperintense acute reperfusion marker. (A) DWI shows acute infarction at the right occipital lobe involving the visual cortex. (B) Post-contrast fluid-attenuated inversion recovery image shows sulcal enhancement along the right occipital lobe (arrows). Compared with outside CTA (C), three-dimensional time-of-flight MRA (D) shows the recanalization state of right distal posterior cerebral artery (dashed arrows).

Figure 5

A 82-year-old female with a complaint of acute onset dizziness. Randomized pattern of hyperintense acute reperfusion marker. (A,B) Post-contrast fluid-attenuated inversion recovery images show a diffuse, multifocal sulcal enhancement along both cerebral hemispheres (red arrows). (C) Three-dimensional time-of-flight MRA of cervical arteries does not show a stenoocclusive lesion. Furthermore, there was no stenoocclusive lesion in the intracranial arteries (not shown). (D) Contrast-enhanced T1WI shows multiple nodular or dot-like enhancing lesions (white arrows) on both cerebral hemispheres (not fully shown in this image) indicating acute to subacute stage infarctions.