Hyperintense Acute Reperfusion Marker Research Articles

An MRI Hyperintense Acute Reperfusion Marker Is Related to Elevated Peripheral Monocyte Count in Acute Ischemic Stroke.

Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke. We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan. Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011). Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke.

Temporal evolution of the signal intensity of hyper-acute ischemic lesions in a canine stroke model: influence of hyperintense acute reperfusion marker.

To assess the influence of the hyperintense acute reperfusion marker (HARM) on the relative signal intensity (rSI) and apparent diffusion coefficient (ADC) of hyper-acute ischemic lesions in a canine stroke model. Middle cerebral artery occlusion models were established using autologous clot embolization. Diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) imaging was performed at 1, 2, 3, 4.5 and 6h after embolization. HARM was defined as the delayed enhancement of cerebrospinal fluid on the subsequent FLAIR images after contrast media used. Twenty-four stroke models were successfully established and divided into the HARM (n=16) and No-HARM group (n=8). No significant differences were found in the rSI on DWI (b0 and b1000 map) and relative ADC between the two groups at each time point after embolization (all P>0.05). There were no significant differences in the rSI on FLAIR at 1 and 2h after embolization between the two groups (P>0.05), while the HARM group showed significantly higher rSI on FLAIR than the No-HARM group at 3, 4.5 and 6h after embolization (P=0.044, 0.036 and 0.001, respectively). HARM should be noted during the quantitative analysis of FLAIR images in future clinical practice.

Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery

BackgroundMechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though...

Hyperintense Acute Reperfusion Marker on FLAIR in Posterior Circulation Infarction.

PurposeIn the present study, we aimed to investigate the frequency of blood brain barrier injury in posterior circulation infarction as demonstrated by the hyperintense acute reperfusion marker (HARM) on fluid attenuated inversion recovery images (FLAIR).MethodsFrom a MRI report database we identified patients with posterior circulation infarction who underwent MRI, including perfusion-weighted images (PWI), within 12 hours after onset and follow-up MRI within 24 hours and analyzed diffusion-weighted images (DWI), PWI, FLAIR, and MR angiography (MRA). On FLAIR images, the presence of HARM was noted by using pre-specified criteria (focal enhancement in the subarachnoid space and/or the ventricles).ResultsOverall 16 patients (median age of patients 68.5 (IQR 55.5–82.75) years) with posterior circulation infarction were included. Of these, 13 (81.3%) demonstrated PCA occlusion, and 3 (18.7%) patients BA occlusion on MRA. Initial DWI demonstrated ischemic lesions in the thalamus (68.8%), splenium (18.8%), hippocampus (75%), occipital lobe (81.3%), mesencephalon (18.8%), pons (18.8%), and cerebellum (50%). On follow-up MRA recanalization was noted in 10 (62.5%) patients. On follow-up FLAIR images, HARM was observed in 8 (50%) patients. In all of these, HARM was detected remote from the acute ischemic lesion. HARM was more frequently observed in patients with vessel recanalization (p = 0.04), minor infarction growth (p = 0.01), and smaller ischemic lesions on follow-up DWI (p = 0.05).ConclusionsHARM is a frequent finding in posterior circulation infarction and associated with vessel recanalization, minor infarction growth as well as smaller infarction volumes in the course. Neuroradiologists should be cognizant of the fact that HARM may be present on short interval follow-up FLAIR images in patients with acute ischemic infarction who initially underwent MRI and received intravenous gadolinium-based contrast agents.

Early Stage of Hyperintense Acute Reperfusion Marker on Contrast-Enhanced FLAIR Images in Patients With Acute Stroke.

Hyperintense acute reperfusion marker (HARM) is defined as delayed CSF enhancement on FLAIR images in patients with acute stroke and was observed in follow-up FLAIR images after initial MRI with contrast material administration. We hypothesized that different imaging findings of HARM could be present depending on the timing of FLAIR imaging after contrast material administration. Of 218 consecutive patients with acute stroke or transient ischemic attack over 3 months, 12 with linear contrast enhancement on the cortical surface in initial FLAIR images underwent serial FLAIR imaging. Initial FLAIR images were obtained 5 minutes after contrast material administration, and follow-up unenhanced FLAIR images were obtained 2.5-29 hours (mean, 13.2 hours) after initial FLAIR imaging. The enhancement patterns between initial and follow-up FLAIR images were compared. In all 12 patients, initial contrast-enhanced FLAIR images showed focal or multifocal linear contrast enhancement along the cortical surface near acute infarctions. On follow-up unenhanced FLAIR images, initial cortical enhancement spread diffusely and filled the subarachnoid space. HARM in acute stroke can be detected earlier than previously reported on initial contrast-enhanced FLAIR images. Different imaging findings of HARM depend on the timing of FLAIR imaging after contrast material administration.

Abstract 157: Hyperintense Acute Reperfusion Marker is an Important Risk Factor of Stroke Recurrence in Patients With Transient Ischemic Attack

Objectives: Diffusion weighted MRI image (DWI) improves the prediction of the early risk of stroke after transient ischemic attack (TIA). Hyperintense acute reperfusion marker (HARM) is occasionally observed in patients with TIA. The predictive value of HARM in TIA is not well known. Methods: This is a retrospective study of patients who were diagnosed as TIA. From June 2008 to June 2014, 759 consecutive patients with TIA underwent DWI and axial postcontrast fluid attenuated inversion recovery images (FLAIR) within 24 hours after onset of symptoms. Presence of positive DWI findings, HARM on postcontrast FLAIR image, atrial fibrillation (AF), other risk factor of cardioembolic stroke, and recurrence of stroke were assessed. Results: DWI and HARM was positive in 276 (36.4%) and 28 (3.7%) patients. 45 (5.9%) patients had AF and 123 (16.2%) patients were diagnosed cardioembolic TIA. Recurrence of stroke was higher in patients with HARM (25.0%) than patients with DWI (6.5%) and lesion negative TIA (5.1%). Cardioembolic TIA (26.1% vs 10.3%) and AF (11.6% vs 2.6%) were common in patients with DWI than lesion negative TIA significantly. There were no statistically significant difference of cardioembolic TIA (14.3% vs 26.1%) and AF (3.6% vs 11.6%) between HARM and DWI group. Conclusion: TIA with HARM is associated with the high risk of stroke recurrence. Taking postcontrast FLAIR image improves the prediction of the risk of stroke after TIA.

Hyperintense Acute Reperfusion Marker on FLAIR in a Patient with Transient Ischemic Attack.

The hyperintense acute reperfusion marker (HARM) has initially been described in acute ischemic stroke. The phenomenon is caused by blood-brain barrier disruption following acute reperfusion and consecutive delayed gadolinium enhancement in the subarachnoid space on fluid attenuated inversion recovery (FLAIR) images. Here we report the case of an 80-year-old man who presented with transient paresis and sensory loss in the right arm. Initial routine stroke MRI including diffusion- and perfusion-weighted imaging demonstrated no acute pathology. Follow-up MRI after three hours demonstrated subarachnoid gadolinium enhancement in the left middle cerebral artery territory consistent with HARM that completely resolved on follow-up MRI three days later. This case illustrates that even in transient ischemic attack patients disturbances of the blood-brain barrier may be present which significantly exceed the extent of acute ischemic lesions on diffusion-weighted imaging. Inclusion of FLAIR images with delayed acquisition after intravenous contrast agent application in MRI stroke protocols might facilitate the diagnosis of a recent acute ischemic stroke.

Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke.

The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3%). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. • Hyperintense acute reperfusion marker on MRI indicates blood-brain barrier disruption. • This observational study on stroke patients characterizes HARM. • Incidence depends on contrast agent dosage on the previous day. • HARM is also associated with older age and poor kidney function. • Interpretation of HARM must take dosage into consideration.

Clinical Implications of Sulcal Enhancement on Postcontrast Fluid Attenuated Inversion Recovery Images in Patients with Acute Stroke Symptoms.

ObjectiveHyperintense acute reperfusion marker (HARM) without diffusion abnormalities is occasionally found in patients with an acute stroke. This study was to determine the prevalence and clinical implications of HARM without diffusion abnormalities.Materials and MethodsThere was a retrospective review of magnetic resonance images 578 patients with acute strokes and identified those who did not have acute infarction lesions, as mapped by diffusion-weighted imaging (DWI). These patients were classified into an imaging-negative stroke and HARM without diffusion abnormalities groups, based on the DWI findings and postcontrast fluid attenuated inversion recovery images. The National Institutes of Health Stroke Scale (NIHSS) scores at admission, 1 day, and 7 days after the event, as well as clinical data and risk factors, were compared between the imaging-negative stroke and HARM without diffusion abnormalities groups.ResultsSeventy-seven acute stroke patients without any DWI abnormalities were found. There were 63 patients with an imaging-negative stroke (accounting for 10.9% of 578) and 13 patients with HARM without diffusion abnormalities (accounting for 2.4% of 578). The NIHSS scores at admission were higher in HARM without diffusion abnormalities group than in the imaging-negative stroke group (median, 4.5 vs. 1.0; p < 0.001), but the scores at 7 days after the event were not significantly different between the two groups (median, 0 vs. 0; p = 1). The patients with HARM without diffusion abnormalities were significantly older, compared with patients with an imaging-negative stroke (mean, 73.1 years vs. 55.9 years; p < 0.001).ConclusionPatients with HARM without diffusion abnormalities are older and have similarly favorable short-term neurological outcomes, compared with the patients with imaging-negative stroke.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Early Time Course of FLAIR Signal Intensity Differs between Acute Ischemic Stroke Patients with and without Hyperintense Acute Reperfusion Marker

Background: In animal models of stroke, the time course of blood-brain barrier (BBB) disruptions has been elaborately studied. In human patients, leakage of gadolinium into cerebrospinal fluid (CSF) space, visualized on MRI fluid attenuated inversion recovery (FLAIR) images, is considered a sign of BBB disruptions. It was termed ‘hyperintense acute reperfusion marker' (HARM) and was associated with hemorrhages. However, the time course of the leakage is unknown and difficult to study in human patients. Also, the association of HARM with signal intensities and enhancement in the parenchyma on FLAIR images has not been thoroughly researched. Methods: We analyzed imaging data of acute ischemic stroke patients who underwent repetitive MRI examinations within the first 36 h after the time of symptom onset. HARM was evaluated on FLAIR images. Regions of interest (ROI) of the hyperintensities on diffusion-weighted imaging (DWI) were determined for each time point and mirrored to the contralateral side. The ROI were furthermore corrected for CSF-filled space, using apparent diffusion coefficient (ADC) images. The corrected ROI were used to determine mean signal intensities of the lesions relative to the contralateral side on FLAIR, ADC and B₀ images for each time point. Results: The 18 included patients (5 females; median age: 69 years; median NIHSS score: 5) received 3-5 MRI examinations on the first day and 1-2 examinations on day 2 after stroke. Eight of the patients (44.4%) showed HARM on at least 1 examination. In 6 of these patients, HARM was already seen at the second examination, at the earliest 3.5 h after symptom onset. The HARM-positive patients had higher relative signal intensities (rSI) on FLAIR images in the parenchyma corresponding to the DWI-positive tissue compared with the HARM-negative patients. This difference between groups was statistically significant for the 2nd and 3rd examination (medians of 4.31 and 6.37 h from symptom onset, p < 0.001 and p = 0.005, respectively). No significant difference in rSI between groups was seen for ADC or B₀ images. Conclusion: HARM does not only represent a contrast medium leakage from the pial system into the CSF space. It is accompanied by a markedly increased rSI in the early ischemic lesion on FLAIR images, which is likely due to parenchymal enhancement. The lack of differences on B₀ images excludes a pure T2 effect.

Reperfusion Injury on Magnetic Resonance Imaging After Carotid Revascularization

Reperfusion injury can be revealed as delayed gadolinium enhancement in the subarachnoid space on a fluid-attenuated inversion recovery image, which is designated as a hyperintense acute reperfusion marker (HARM). We sought to investigate the occurrence and predictors of HARM and its association with new ischemic infarcts after carotid revascularization. Forty-five patients who underwent carotid endarterectomy or stenting were prospectively enrolled. Diffusion-weighted imaging and fluid-attenuated inversion recovery were performed before and 24 hours after the procedures. Postprocedural fluid-attenuated inversion recovery was done after intravenous gadolinium injection. HARM was observed in 8 (17.8%) patients. Of these, 4 patients showed neurological deterioration associated with HARM. These symptomatic HARMs disappeared on follow-up magnetic resonance imaging. Patients with symptomatic HARM were older (P=0.010) and had more frequent leukoaraiosis (P=0.012) and higher postprocedural systolic blood pressure (P=0.025) than those without. New brain infarcts on postprocedural diffusion-weighted imaging were identified in 13 (28.9%) patients. HARM was not associated with new infarcts. HARM after carotid revascularization is not uncommon. Symptomatic HARM was associated with old age, underlying leukoaraiosis, and postprocedural high blood pressure.

Ocular hyperintense acute reperfusion marker

Hyperintense signal within the subarachnoid space (SAS), visualized on delayed postcontrast fluid-attenuated inversion recovery (FLAIR) in MRI, is proposed to be caused by early blood–brain barrier (BBB) breakdown due to ischemia,1 and must be differentiated from subarachnoid hemorrhage. Reperfusion is the strongest independent predictor of early BBB disruption following ischemia and the phenomenon is described as hyperintense acute reperfusion marker (HARM).2 We present a case of hyperintense signal …

Abstract 3569: The Effect of Minocycline on the HARM MRI Marker of Blood-CSF Barrier Opening After Transient MCAO in SHR Rats

Introduction. Early blood-CSF barrier opening imaged as gadolinium enhancement of CSF on FLAIR MRI, the Hyperintense Acute Reperfusion Marker (HARM), has been associated with increased plasma MMP-9 in both clinical and experimental stroke [ 1 - 2 ]. In patients, both elevated MMP-9 and HARM have been associated with tPA treatment and hemorrhagic transformation [ 3 - 4 ]. Minocycline is an MMP-9 inhibitor under investigation as an acute stroke therapy [ 5 ]. We hypothesized that minocycline would reduce the early HARM signal in SHR rats undergoing 45 minutes of transient right middle cerebral artery occlusion (MCAO) via the intraluminal suture model. Methods. Twenty-two consecutive male SHR rats with confirmed non-hemorrhagic stroke on 7T/30cm MRI were randomly assigned to receive minocycline (3mg/kg @ 1mg/mL) or saline control intravenously, injected at the time of reperfusion. Gadolinium was injected at 60 minutes post-reperfusion. Outcome FLAIR images were acquired pre-contrast and at 10 minutes post-contrast. Image analysis, performed blinded to treatment assignment, assessed pre-post FLAIR changes for (1) signal intensity of gadolinium enhancement in the ventricles (2) appearance of HARM in the ipsilateral ventricle (3) appearance of parenchymal enhancement within the infarct. Results. Ipsilateral ventricular HARM was visible in 9 of 11 animals in each group. Parenchymal enhancement was seen in 6 of 11 in each group. Increase in gadolinium enhancement in the ventricle (either total or ipsilateral only) did not significantly differ between the two groups. Conclusions. We found no evidence that minocycline reduced blood-CSF or blood-brain barrier opening in this model of 45 minutes transient MCAO in SHR rats. Potential effects of minocycline on blood-CSF or blood-brain barrier at later times after minocycline, on MMP-9 levels or in the presence of tPA in this model requires further study.

The Hyperintense Acute Reperfusion Marker on Fluid-Attenuated Inversion Recovery Magnetic Resonance Imaging Is Caused by Gadolinium in the Cerebrospinal Fluid

The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery MRI is believed to be caused by gadolinium-based contrast agents crossing a disrupted blood-brain barrier. However, this hypothesis has never been directly verified in humans. In this study, we analyzed cerebrospinal fluid samples of patients with HARM on imaging regarding the presence and concentration of gadolinium-based contrast agents. Gadobutrol was found in concentrations of approximately 50 μmol/L. Using phantom MRI experiments, we demonstrate that the detected concentrations are consistent with the observed HARM imaging pattern. Our study yields first direct evidence in humans that the imaging phenomenon HARM is indeed caused by leakage of gadolinium-based contrast agents into the cerebrospinal fluid.

Hyperintense acute reperfusion marker on FLAIR is not associated with early haemorrhagic transformation in the elderly

The hyperintense acute reperfusion marker (HARM) has been described as a predictor for haemorrhagic transformation (HT) in acute ischaemic stroke. We hypothesised that this phenomenon is not present in the elderly. It was possible to assess 47/84 consecutive patients aged 80 and over with diagnosed ischaemic stroke or transient ischaemic attack (TIA). MRI was performed within 24 h of onset of symptoms with follow-up MRI within a further 48 h. Of 47 included patients, 19 showed HARM; it was only seen on follow-up examination. Ten of the 47 patients underwent thrombolysis with recombinant tissue plasminogen activator (rt-PA); 4 of them showed HARM, and 1 of those showed HT. HARM was found in three out of eight patients with haemorrhagic transformation on baseline and/or follow-up MRI. We did not observe an association between HARM and early HT either in the whole group or in the patients who received thrombolysis. HARM was not associated with HT in the elderly after ischaemic stroke, independent of treatment. While it may indicate dysfunction of the blood-brain barrier (BBB), it does not necessarily amount to HT.

Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption.

Loss of integrity of the blood-brain barrier (BBB) resulting from ischemia and reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and worse clinical outcome than would be expected from the beneficial effects of reperfusion. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in acute focal brain ischemia and tested associations with reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption was evident as delayed gadolinium enhancement of cerebrospinal fluid space on fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144 (33%) ischemic stroke patients. Reperfusion was found to be the strongest independent predictor of early BBB disruption (P=0.018) in multivariate analysis. HARM was associated with HT and worse clinical outcome (after adjustment for initial severity). It was also associated with more severe strokes at onset and greater age. Because the timing of the disruption was early enough (median estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by HARM may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome.