Clinical significance of intracranial hemorrhage after thrombectomy detected solely by magnetic resonance imaging and not by computed tomography

Background and objective: Whether intracranial hemorrhage (ICH) detected using magnetic resonance imaging (MRI) affects the clinical outcomes of patients with large-vessel occlusion (LVO) treated with mechanical thrombectomy (MT) remains unclear. This study investigated the clinical features of ICH after MT detected solely by MRI. Methods: This was a retrospective analysis of patients with acute ischemic stroke and occlusion of the internal carotid artery or middle cerebral artery treated with MT between April 2011 and March 2021. Among 632 patients, patients diagnosed with no ICH using CT, with a pre-morbid modified Rankin Scale (mRS) score ≤ 2, and those who underwent MRI including T2* and computed tomography (CT) within 72 h from MT were enrolled. The main outcomes were the association between ICH detected solely by MRI and clinical outcomes at 90 days. Poor clinical outcomes were defined as mRS score > 2 at 90 days after onset. Results: Of the 246 patients, 29 (12%) had ICH on MRI (MRI-ICH( + )), and 217 (88%) were MRI-ICH( (cid:0) ). There was no significant difference between number of patients with MRI-ICH( + ) experiencing poor (10 [12%]) and favorable (19 [12%]) outcomes. The mRS score at 90 days between patients with MRI-ICH ( + ) and MRI-ICH( (cid:0) ) was not significantly different (2 [1 – 4] vs. 2 [1 – 4], respectively). Higher age and lower ASPECTS were independent risk factors for poor outcomes, as shown by multivariate regression analysis. MRI-ICH( + ) status was not associated with poor outcomes. Conclusions: ICH detected by MRI alone did not influence clinical outcomes in patients with LVO treated with MT.


Introduction
Mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) has become the gold standard treatment, and there has been a notable increase in the number of MT performed after its efficacy was confirmed in several clinical trials [1].
Intracranial hemorrhage (ICH), whether symptomatic or asymptomatic, is a common complication occurring in approximately 40% of patients with LVO treated with MT. [2,3] Symptomatic ICH is associated with worse clinical outcomes 1 [3][4][5].,Asymptomatic ICH is a more common event than symptomatic ICH, occurring in 30%-40% of AIS patients after MT [2][3][4] and there is an association between asymptomatic ICH and unfavorable outcomes [6][7][8].In General, T2* on MRI can detect ICH with higher sensitivity than CT [9,10].Although ICH is not detected by computed tomography (CT) in more than half of patients, there have been a few cases of ICH detected by magnetic resonance imaging (MRI) alone (Fig. 1).However, the clinical features of ICH detected by MRI alone are unclear.
This retrospective analysis aimed to investigate the clinical impact of ICH detected by MRI alone.

Patients
A total of 632 consecutive patients with AIS admitted to a single center and treated with MT were registered in our prospective MT registry.Written informed consent was obtained from the patients or their relatives.This study was approved by the local Institutional Review Board.From this prospective MT registry, patients with LVO in the anterior circulation, a pre-morbid modified Rankin Scale (mRS) score ≤ 2, no diagnosis of ICH on CT, and those who underwent T2* on MRI and CT within 72 h of MT between April 2011 and March 2021 were retrospectively enrolled in this study.Patients with contraindications to MRI (e.g., implanted cardiac pacemakers) were excluded.The following clinical information was obtained: age, sex, medical history of hypertension, dyslipidemia, diabetes mellitus, presence of atrial fibrillation, smoking, stroke etiology as defined by the TOAST classification [11], initial neurological deficit, occluded artery, DWI-ASPECTS score [12], use of intravenous thrombolysis, onset-to-door time, and clinical outcomes.Upon admission, neurological deficits were scored using the National Institutes of Health Stroke Scale (NIHSS) score.

Design and assessment of MRI detected ICH
First, patients were divided into two groups based on T2* on MRI: MRI-detected ICH (MRI-ICH(+)) and no ICH (MRI-ICH(− )).MRI-ICH(+) was defined as a hemorrhagic change on T2* and no change on CT.MRI-ICH(− ) was defined as the absence of hemorrhagic changes on either T2* or CT.The two groups were evaluated by two vascular neurologists (A.K. and N.M.).

Clinical outcomes
The patients were followed up for 90 days after onset.A poor and favorable outcome was defined as mRS score > 2 and ≤ 2 at 90 days after onset, respectively.The mRS score was assessed by physical examination or telephone interviews with the patients or their relatives 90 days after onset by site personnel who were blinded to the clinical information.

Imaging
MRI studies, including T2* and time-of-flight magnetic resonance angiography, were performed on admission using a commercially available echo planar instrument operating at 1.5 T (Echelon Oval, Hitachi Medical Systems, Tokyo, Japan).T2* was obtained using the following parameters: TR/TE, 647.4/18.0ms; field of view, 24 cm; acquisition matrix 256 × 204; and a slice thickness of 4.5 mm, with a 1.0 mm intersection gap.The site of arterial occlusion was determined using initial magnetic resonance angiography of the internal carotid artery, middle cerebral artery horizontal segment, and middle cerebral artery insular segment.

Statistical analysis
First, we performed a descriptive analysis of baseline variables, treatments, and outcomes for patients with MRI-ICH(+) and MRI-ICH (− ) using Welch's test, a two-tailed Fisher's exact test, and Pearson's test for non-normally distributed continuous and categorical variables and the three groups for categorical variables.Second, we compared the patients according to their clinical outcomes.Subsequently, to investigate independent factors associated with poor clinical outcomes, we performed multivariate logistic regression analysis to calculate the odds ratios (ORs) and 95% confidence intervals (CIs).Age and other significant parameters (p < 0.1) were included in multivariate analysis.Finally, we compared clinical outcomes between patients with MRI-ICH (+) and MRI-ICH(− ).

Discussion
This study has three major findings.First, 12% of patients with no ICH on CT were identified as having an ICH on MRI.Second, ICH detected solely by MRI was not associated with clinical outcomes.
Numerous reports have shown that MRI may be as accurate as CT in detecting acute hemorrhage in patients with acute focal stroke symptoms [13].Current AHA guidelines recognize up to 89% sensitivity for unenhanced brain CT and 81% for brain MRI [14].Hyperacute ICH produces a characteristic imaging pattern on stroke MRI and can be detected with excellent accuracy [15].CS Kindwell et al. compared 200 patients to determine the accuracy of MRI compared to CT for the detection of hyperacute intracerebral hemorrhage.For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% agreement).Acute hemorrhage was diagnosed using both MRI and CT in 25 patients.
In four other patients, acute hemorrhage was present on MRI but not on the corresponding CT.Each of these four cases was interpreted as a hemorrhagic transformation of an ischemic infarct [16].The detection of hemorrhagic changes in an ischemic infarct, including ICH, after MT may be superior on MRI rather than on CT.
Recently, patients with asymptomatic ICH after MT have been reported to have poorer clinical outcomes than those without ICH [8,17].In this study, we investigated the clinical significance of ICH detected solely by MRI and not by CT for the first time.However, ICH being detected solely by MRI did not influence the clinical outcomes.Past reports have shown that MRI, including T2*-weighted gradient echo and susceptibility-weighted imaging sequences, is more sensitive for the detection of ICH than non-contrast CT [16,18].We speculate that the detection of ICH using MRI alone has little clinical significance.
As for risk factors of ICH after MT, the use of stent retrievers [19], infarct size, serum glucose levels, thrombectomy pass count [20],  intravenous rt-PA [21], race, and intraprocedural complications [22] have been reported from recent studies.In addition, previous studies have suggested that blood-brain barrier impairment caused by infarction, mechanical stimulation, and direct damage to the blood vessel wall after MT is the main cause of ICH [23,24].

Limitations
This study had several limitations.First, this was a single-center retrospective analysis of a small population.The small sample size may have caused a bias or affected the statistical validity of the results.Second, the presence of ICH depends on the impressions of the person reading the results.Although two vascular neurologists evaluated ICH using both MRI and CT, automated software may be required.Third, alteplase is approved for administration at 0.6 mg/kg in Japan, which may influence the rate and degree of ICH [25].Further studies are required including a larger amount of multicenter data assessed using automated software.

Conclusions
Among patients with acute large-vessel occlusion stroke treated with MT, detection of ICH by MRI alone did not influence the clinical outcomes at 90 days.

Sources of funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Research ethics and patient consent
This study was approved by the ethics committee of Nippon Medical School Hospital (26-10-398), and written informed consent was obtained from the patients or their relatives.

Fig. 1 .
Fig. 1.We show the case 24 h after mechanical thrombectomy which ICH was not detected by CT (A) and detected by MRI (B).

Table 1
Characteristics of the patients at baseline.

Table 2
Characteristics of patients according to clinical outcomes at 90 days from onset.Poor and favorable outcomes were defined as a modified Rankin scale (mRS) score of >2 and ≤ 2 at 90 days after onset, respectively.