Fluid-attenuated Inversion Recovery Changes Research Articles

Reversible Edema in the Penumbra Correlates With Severity of Hypoperfusion.

We aimed to investigate fluid-attenuated inversion recovery changes in the penumbra. We determined core and perfusion lesions in subjects from the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) and AXIS 2 trial (Granulocyte Colony-Stimulating Factor in Patients With Acute Ischemic Stroke) with perfusion- and diffusion-weighted imaging at baseline. Only subjects with a mismatch volume >15 mL and ratio >1.2 were included. We created voxel-based relative fluid-attenuated inversion recovery signal intensity (rFLAIR SI) maps at baseline and follow-up. We studied rFLAIR SI in 2 regions of interest: baseline penumbra (baseline perfusion lesion−[core lesion+voxels with apparent diffusion coefficient <620 10−6 mm2/s]) and noninfarcted penumbra (baseline perfusion lesion−follow-up fluid-attenuated inversion recovery lesion) at 24 hours (WAKE-UP) or 30 days (AXIS 2). We analyzed the association between rFLAIR SI and severity of hypoperfusion, defined as time to maximum of the residue function. In the baseline penumbra, rFLAIR SI was elevated (ratio, 1.04; P=1.7×10−13; n=126) and correlated with severity of hypoperfusion (Pearson r, 0.03; P<1.0×10−4; n=126). In WAKE-UP, imaging at 24 hours revealed a further increase of rFLAIR SI in the noninfarcted penumbra (ratio, 1.05 at 24 hours versus 1.03 at baseline; P=7.1×10−3; n=43). In AXIS 2, imaging at 30 days identified reversibility of the rFLAIR SI (ratio, 1.02 at 30 days versus 1.04 at baseline; P=1.5×10−3; n=26) since it was no longer different from 1 (ratio, 1.01 at 30 days; P=0.099; n=26). Penumbral rFLAIR SI increases appear early after stroke onset, correlate with severity of hypoperfusion, further increase at 24 hours, and are reversible by 30 days. URL: https://clinicaltrials.gov; Unique identifier: NCT01525290. URL: https://clinicaltrials.gov; Unique identifier: NCT00927836.

Abstract P352: Reversible Relative FLAIR Signal Intensity Changes in the Penumbra Correlate With Severity of Hypoperfusion

In ischemic stroke, the study of edema, measurable as fluid attenuated inversion recovery (FLAIR) signal increase, has mainly focused on the ischemic core and less on the surrounding penumbra. To the naked eye, no FLAIR changes are present in the penumbra. However, changes in perfusion status could induce physiological changes resulting in subtle penumbral FLAIR signal alterations. To investigate penumbral FLAIR changes, we included subjects from the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) and Granulocyte Colony-Stimulating Factor in Patients With Acute Ischemic Stroke (AXIS 2) trial with perfusion- and diffusion-weighted imaging (PWI, DWI) and FLAIR at baseline. We used RAPID software to calculate the core and perfusion lesion on DWI and PWI and selected subjects with a minimal mismatch volume (15 ml) and ratio (1.2). We created voxel-based relative FLAIR signal intensity (rFLAIR SI) maps at baseline and follow up (FU) by calculating the ratio of the FLAIR intensity in one voxel and the median FLAIR intensity in a sphere with 15 mm radius around a contralateral homologues voxel. We studied rFLAIR SI in two regions of interest: the baseline penumbra (baseline perfusion lesion - [core lesion + voxels with apparent diffusion coefficient &lt;620 10 -6 mm 2 /s]) and the non-infarcted penumbra (baseline perfusion lesion - FU FLAIR lesion) at 24 hours (WAKE-UP) or 30 days (AXIS 2). Severity of hypoperfusion was defined as the time to maximum of the residue function. In the baseline penumbra, rFLAIR SI was elevated (ratio=1.04, p=1.7*10 -13 , n=126) and correlated with severity of hypoperfusion (Pearson’s r 0.03, p&lt;1.0*10 -4 , n=126). At 24 hours in a subgroup from WAKE-UP, rFLAIR SI in the non-infarcted penumbra further increased (ratio=1.05 at 24h vs 1.03 at baseline, p=7.1*10 -3 , n=43). In a different subgroup from AXIS 2, this increase in rFLAIR SI was reversible (ratio=1.02 at 30d vs 1.04 at baseline, p=1.5*10 -3 n=26) since it was no longer different from 1 at 30 days (ratio=1.01 at 30 days, p=0.099, n=26). Increases in rFLAIR SI, likely representing edema, are not restricted to the ischemic core and correlate with severity of hypoperfusion in the penumbra. They appear early after stroke onset, further increase at 24 hours and are reversible by 30 days.

Abstract P579: Fluid Attenuated Inversion Recovery Correlates With Time of Onset of Arterial Ischemic Stroke in Childhood

Background: In adults, time since stroke onset correlates with efficacy and risk of recanalization therapies; beyond this temporal window there is increased risk of adverse events in particular hemorrhage with thrombolysis and decreased benefit of recanalization due to irreversible tissue injury. In adults the appearance of fluid attenuated inversion recovery (FLAIR) signal is a proxy for time, and is typically present by 6 hours. The time to FLAIR signal hyperintensity in childhood stroke is unknown but is of interest with potential utility due to the often greater uncertainty as to timing symptom onset. Methods: Time to FLAIR signal hyperintensity on brain MRI performed on children within 24 hours of stroke onset was studied with logistic regression. Results: A total of 68 MRIs with FLAIR imaging were available from 54 children (27 female), age 0.8 to 17.9 years, median 12.0 years. Seventy-four percent (40/54) of children and 72% (49/68) of scans had anterior circulation stroke. Interquartile range for time to FLAIR presence was 7.8 to 19.1 hours. The 90% probability of FLAIR change was reached at 11.2 hours for all strokes (Figure, dotted line; 80% highest density interval (HDI): 1.2-11.2 hours), and 9.3 hours for anterior circulation only strokes (Figure, solid line; 80% HDI: 3.3-9.3 hours), though nearly all had FLAIR change by 6 hours. FLAIR change was absent in 4 children after 6 hours, two with anterior circulation stroke (16 year-old at 6.1 hours, 10 year-old at 7.0 hours) and 2 with posterior circulation stroke (15 year-old at 7.3 hours, 9 month-old at 18.2 hours). Conclusion: Similar to adults, FLAIR hyperintensity can be used to estimate time since stroke ictus in childhood stroke. Children may have somewhat delayed time to FLAIR signal change compared with adults, suggesting that they may have a longer window for effective recanalization therapies.

Long-term effectiveness of natalizumab on MRI outcomes and no evidence of disease activity in relapsing-remitting multiple sclerosis patients treated in a Czech Republic real-world setting: A longitudinal, retrospective study

BackgroundMagnetic resonance imaging (MRI) data from multiple sclerosis (MS) patients treated in real-world settings are important for understanding disease-modifying therapy effects, including no evidence of disease activity (NEDA) assessment. This longitudinal, retrospective, single-cohort analysis assessed MRI and clinical disease outcomes in patients with relapsing-remitting MS treated with natalizumab for up to 5 years in Prague, the Czech Republic. MethodsThe primary study endpoint was the proportion of patients free of new or enlarging fluid-attenuated inversion recovery (FLAIR) lesions after at least 2 years of natalizumab treatment. Secondary endpoints included percentage brain volume change over time, the number of new T1-hypointense lesions that persisted for ≥6 months, FLAIR and T1-hypointense lesion volume change over time, and the proportion of patients with NEDA-3 (defined as no relapses, no confirmed disability worsening, and no new or enlarging FLAIR lesions). ResultsA total of 193 patients were included in the study. During year 1 of natalizumab treatment, 78.9% of patients had no new or enlarging FLAIR lesions and 79.5% had no new T1 lesions. These proportions increased in years 2–5, with ≥98.0% of patients free of new or enlarging FLAIR lesions and ≥98.8% free of new T1 lesions. During year 1 on natalizumab, 52.2% of patients achieved NEDA-3; this proportion increased to ≥69.2% in years 2–5. ConclusionThis study provides additional evidence that long-term MS disease activity, as measured by both MRI activity and NEDA-3, is well-controlled in patients treated with natalizumab in real-world settings.

MRI-EEG correlation for outcome prediction in postanoxic myoclonus: A multicenter study.

To examine the prognostic ability of the combination of EEG and MRI in identifying patients with good outcome in postanoxic myoclonus (PAM) after cardiac arrest (CA). Adults with PAM who had an MRI within 20 days after CA were identified in 4 prospective CA registries. The primary outcome measure was coma recovery to command following by hospital discharge. Clinical examination included brainstem reflexes and motor activity. EEG was assessed for best background continuity, reactivity, presence of epileptiform activity, and burst suppression with identical bursts (BSIB). MRI was examined for presence of diffusion restriction or fluid-attenuated inversion recovery changes consistent with anoxic brain injury. A prediction model was developed using optimal combination of variables. Among 78 patients, 11 (14.1%) recovered at discharge and 6 (7.7%) had good outcome (Cerebral Performance Category < 3) at 3 months. Patients who followed commands were more likely to have pupillary and corneal reflexes, flexion or better motor response, EEG continuity and reactivity, no BSIB, and no anoxic injury on MRI. The combined EEG/MRI variable of continuous background and no anoxic changes on MRI was associated with coma recovery at hospital discharge with sensitivity 91% (95% confidence interval [CI], 0.59-1.00), specificity 99% (95% CI, 0.92-1.00), positive predictive value 91% (95% CI, 0.59-1.00), and negative predictive value 99% (95% CI, 0.92-1.00). EEG and MRI are complementary and identify both good and poor outcome in patients with PAM with high accuracy. An MRI should be considered in patients with myoclonus showing continuous or reactive EEGs.

Abstract WP483: Grouped Cortical Micro Bleeds a Unique Radiological Marker in Inflammatory Cerebral Amyloid Angiopathy

Background: Inflammatory Cerebral Amyloid Angiopathy (iCAA) is a rare cause of rapidly progressive cognitive decline. Prior studies have proposed radiological diagnostic criteria and demonstrated evidence of inflammation related to Aβ. Though lacking any therapeutic trials, various authors have suggested a single pulse IV Methyl Prednisolone (MPS) therapy as curative in most patients. Methods: We studied clinical, radiological and neuropathological features of 2 of biopsy proven iCAA cases over the past 5 years correlating their neuropathological and radiological features. We also reviewed published literature for radiological findings of proven cases of ICAA Clinical features Case 1: 75/female presented with visual hallucinations, her neurological examination was un-remarkable &gt;Case 2: 84/female presented with language and memory difficulties her neurological examination was remarkable for word finding and object naming difficulties Radiological Features: Gadolinium enhanced brain MRI with fluid attenuated inversion recovery (FLAIR) and susceptibility weighted imaging (SWI) were obtained Patient 1: SWI artifact s in bilateral cerebral hemispheres basal ganglia and cerebellum suggestive of cortical micro-bleeds (CMBs ) there was a cluster of CMBs in the right parietal region associated with FLAIR changes and gadolinium enhancement Patient 2 numerous scattered cortical micro-bleeds (CMBs). There was a large cluster of CMBs in left temporal lobe along with FLAIR changes and gadolinium enhancement Biopsy: B oth patient underwent lesional biopsy corresponding to the area of clustered CMBs Neuropathology: demonstrated histopathological and electron microscopic evidence of perivascular inflammation and amyloid deposition consistent with iCAA Review of literature : In a total of 7 brain MRI s in 3 recently published case series 4 had reported CMBs of which 3 patients were identified representing MRI findings consistent with Grouped CMBs associated with FLAIR changes Conclusion: iCAA is a rare and treatable cause of subacute cognitive decline. We suggest grouped cortical micro bleeds (GCMBs) associated with FLAIR changes as a unique radiological feature of this disorder.

Biologic Dose and Imaging Changes in Pediatric Brain Tumor Patients Receiving Spot Scanning Proton Therapy

To evaluate the incidence of imaging changes in our pediatric brain tumor population treated with spot-scanning proton therapy and analyze the spatial correlation of imaging changes with a novel biologic dose model. All pediatric patients treated during the first year of our institution's experience who received a minimum treatment planning dose (TPD) of 5040 cGyE with available follow-up magnetic resonance imaging scans were selected for analysis. Posttreatment magnetic resonance imaging scans were fused with the treatment planning computed tomography. All T1 post-gadolinium enhancement, T2 fluid attenuated inversion recovery changes, TPD, and biologic dose (BD) volumes outside of the original gross tumor volume were contoured for analysis. Thirty patients were included in the analysis, 7 of whom developed posttreatment radiologic changes. The volumetric overlap of the T2 fluid attenuated inversion recovery changes and BD volumes was significantly greater than the overlap with the TPD volumes. Median volumetric overlaps of 85%, 18%, and 0% were observed with the BD105%, BD110%, and TPD105%, respectively. A nonsignificant increase in the volumetric overlap of the T1C+ changes and BD volumes was also observed. No correlation was observed between the total volume of BD110%, BD105%, or physical dose 105% and the development of imaging changes. Within our pediatric brain tumor population treated with spot-scanning proton therapy, our BD model demonstrated superior volumetric overlap with posttreatment T2 changes compared with the TPD model. Using a BD model in treatment planning for spot-scanning proton therapy may help avoid delivery of excessive BD to critical structures and may help minimize the risk of radiation-related late effects.

Cochlear FLAIR Signal Changes in Hearing Preservation Vestibular Schwannoma Surgery.

Cochlear fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) signal intensity has been shown to be elevated in patients with vestibular schwannomas (VS). This study evaluated the preoperative and postoperative cochlear signal on FLAIR sequences in patients undergoing hearing preservation surgery. Retrospective chart review. Tertiary referral center. All patients undergoing middle cranial fossa or retrosigmoid craniotomy for VS at a single institution from September 2013 to January 2017 were screened.Hearing was graded according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification. Inclusion criteria included preoperative AAO-HNS class A or B hearing and available preoperative and postoperative FLAIR sequences. Signal intensity of cochlear FLAIR signal was measured in the affected cochlea and normalized to the contralateral cochlea. Hearing preservation was defined as AAO-HNS class A or B postoperatively. Eighteen patients met all inclusion criteria, and 12/18 experienced hearing preservation. There was no difference in preoperative FLAIR ratio between hearing preserved and nonpreserved groups (2.02 vs 2.32, p = 0.52). Postoperatively, FLAIR ratio was lower in the hearing preserved group compared to the nonpreserved group (1.19 vs 1.87, p = 0.033). The current study is the first to examine postoperative cochlear FLAIR changes in VS patients undergoing hearing preservation surgery. In our study population, abnormal hyperintense FLAIR signal normalized in patients experiencing successful hearing preservation, while those who lost hearing maintained abnormal signal. Future studies may investigate the role of FLAIR in guiding optimal timing of operative intervention in VS patients.

Topographic principles of cortical fluid-attenuated inversion recovery signal in temporal lobe epilepsy.

In drug-resistant temporal lobe epilepsy (TLE), relative to the large number of whole-brain morphological studies, neocortical T2 changes have not been systematically investigated. The aim of this study was to assess the anatomical principles that govern the distribution of neocortical T2-weighted fluid-attenuated inversion recovery (FLAIR) signal intensity and uncover its topographic principles. Using a surface-based sampling scheme, we mapped neocortical FLAIR intensity of 61 TLE patients relative to 38 healthy controls imaged at 3 T. To address topographic principles of the susceptibility to FLAIR signal changes in TLE, we assessed associations with normative data on tissue composition using 2 complementary approaches. First, we evaluated whether the degree of TLE-related FLAIR intensity changes differed across cytoarchitectonic classes as defined by Von Economo-Koskinas taxonomy. Second, as a proxy to map regions with similar intracortical composition, we carried out a FLAIR intensity covariance paradigm in controls by seeding systematically from all cortical regions, and identified those networks that were the best spatial predictors of the between-group FLAIR changes. Increased intensities were observed in bilateral limbic and paralimbic cortices (hippocampus, parahippocampus, cingulate, temporopolar, insular, orbitofrontal). Effect sizes were highest in periallocortical limbic and insular classes as defined by the Von Economo-Koskinas cytoarchitectonic taxonomy. Furthermore, systematic FLAIR intensity covariance analysis in healthy controls revealed that similarity patterns characteristic of limbic cortices, most notably the hippocampus, served as sensitive predictors for the topography of FLAIR hypersignal in patients. FLAIR intensity findings were robust against correction for morphological confounds. Patients with a history of febrile convulsions showed more marked signal changes in parahippocampal and retrosplenial cortices, known to be strongly connected to the hippocampus. FLAIR intensity mapping and covariance analysis provide a model of TLE gray matter pathology based on shared vulnerability of periallocortical and limbic cortices.

Utilization of MRI for Cerebral White Matter Injury in a Hypobaric Swine Model-Validation of Technique.

Repetitive hypobaric exposure in humans induces subcortical white matter change, observable on magnetic resonance imaging (MRI) and associated with cognitive impairment. Similar findings occur in traumatic brain injury (TBI). We are developing a swine MRI-driven model to understand the pathophysiology and to develop treatment interventions. Five miniature pigs (Sus scrofa domestica) were repetitively exposed to nonhypoxic hypobaria (30,000 feet/FIO2 100%/transcutaneous PO2 >90%) while under general anesthesia. Three pigs served as controls. Pre-exposure and postexposure MRIs were obtained that included structural sequences, dynamic contrast perfusion, and diffusion tensor quantification. Statistical comparison of individual subject and group change was performed utilizing a two-tailed t test. No structural imaging change was noted on T2-weighted or three-dimensional fluid-attenuated inversion recovery imaging between MRI 1 and MRI 2. No absolute difference in dynamic contrast perfusion was observed. A trend (p = 0.084) toward increase in interstitial extra-axonal fluid was noted. When individual subjects were examined, this trend toward increased extra-axonal fluid paralleled a decrease in contrast perfusion rate. This study demonstrates high reproducibility of quantitative noninvasive MRI, suggesting MRI is an appropriate assessment tool for TBI and hypobaric-induced injury research in swine. The lack of fluid-attenuated inversion recovery change may be multifactorial and requires further investigation. A trend toward increased extra-axonal water content that negatively correlates with dynamic contrast perfusion implies generalized axonal injury was induced. This study suggests this is a potential model for hypobaric-induced injury as well as potentially other axonal injuries such as TBI in which similar subcortical white matter change occurs. Further development of this model is necessary.

Fluid-Attenuated Inversion Recovery Hyperintensity Is Associated with Hemorrhagic Transformation following Reperfusion Therapy

It is still controversial whether early fluid-attenuated inversion recovery (FLAIR) hyperintensity within acute ischemic lesions carries the risk of hemorrhagic transformation (HT) after reperfusion therapy. Furthermore, the association between the location of FLAIR hyperintensity and HT has not been investigated. We retrospectively reviewed patients who underwent reperfusion therapy within 6 hours of stroke onset and magnetic resonance imaging including a FLAIR sequence before completing reperfusion therapy. FLAIR hyperintensity within the diffusion-weighted imaging (DWI) lesion was rated qualitatively, and HT was assessed on follow-up gradient echo imaging. The location of the FLAIR change and HT was classified as subcortical, cortical, or cortico-subcortical. Of 134 patients with acute ischemic stroke included in this study, early FLAIR changes within DWI lesions were identified in 56 (41.8%) patients, and HT was noted in 51 (38.1%) patients. FLAIR change was independently associated with HT (odds ratio: 4.37, 95% confidence interval: 1.72-11.12). Geographically, 48.2% of the patients with a FLAIR change developed a matched HT (restricted to the region with the FLAIR change), and the risk of HT was further increased in patients with a FLAIR change in the cortico-subcortical region (68.8%). In patients in the acute stage of stroke, an early FLAIR change is associated with the risk of HT following reperfusion therapy with a highly matched geographic relationship and common risk factors. Thus, identification of FLAIR change may be a useful surrogate marker to assess the likelihood of subsequent HT in patients treated with reperfusion therapy.

NIMG-22MORPHOLOGICAL RECONSTRUCTION BASED AUTOMATED SEGMENTATION OF GLIOBLASTOMA TUMOR VOLUME ON MULTI-MODAL MRI IMAGES

BACKGROUND: Glioblastoma is the most aggressive brain tumor and, magnetic resonance imaging (MRI) is the most common imaging tool for brain tumor diagnosis and disease status monitoring post any intervention including craniotomy, irradiation and various chemotherapies. Tumor volume estimation using MRI is routinely used to determine responses, such as Macdonald's or RANO's criteria. Current techniques used for tumor volume measurements are manual measurements of the largest two-dimensional tumor area and they are inaccurate and operator-dependent. Automated techniques for estimating volumetric measurements are needed for minimizing human bias and to follow disease status objectively. We developed and implement automated segmentation of tumors by fusing information from multi-modal MRI. METHODS: High resolution three-dimensional (1 mm3 isotropic voxel) T2-weighted (T2), fluid attenuated inversion recovery (FLAIR), and T1-weighted (T1) pre- and post-contrast images were acquired on nine glioblastoma patients. The images were pre-processed for co-registration, skull-stripping, intensity non-uniformities correction, noise reduction, and intensity standardization. Regional maxima were obtained on T2/FLAIR images using grayscale morphological reconstruction followed by adaptive thresholding, and regional multi-modal density distribution, connectivity, and growing techniques. Enhanced region of the tumor was obtained from the T1 pre-/post-contrast images followed by the minimization of false classifications arising from enhancing vasculature. Classified regions from T2/FLAIR, and T1 pre-/post-contrast images were combined to obtain enhancing tumor component and the surrounding FLAIR changes representing vasogenic edema/tumor infiltration as the final segmentation for volumetric measurements. RESULTS: The automatic program is able to capture and calculate tumor volumes from T1 post contrast or T2/FLAIR images accurately, as judged by neuroradiologists, neurosurgeons and neuro-oncologists. Additionally, our technique performed consistently well across all the patients that we scanned without any human intervention. CONCLUSION: We developed and implemented automated technique that identifies tumor volumes precisely, improves the accuracy and efficiency of tumor status measurements significantly with minimal human bias.

Comparison of endoscopic endonasal and bifrontal craniotomy approaches for olfactory groove meningiomas: A matched pair analysis of outcomes and frontal lobe changes on MRI

We compare the outcomes and postoperative MRI changes of endoscopic endonasal (EEA) and bifrontal craniotomy (BFC) approaches for olfactory groove meningiomas (OGM). All patients who underwent either BFC or EEA for OGM were eligible. Matched pairs were created by matching tumor volumes of an EEA patient with a BFC patient, and matching the timing of the postoperative scans. The tumor dimensions, peritumoral edema, resectability issues, and frontal lobe changes were recorded based on preoperative and postoperative MRI. Postoperative fluid-attenuated inversion recovery (FLAIR) hyperintensity and residual cystic cavity (porencephalic cave) volume were compared using univariable and multivariable analyses. From a total of 70 patients (46 EEA, 24 BFC), 10 matched pairs (20 patients) were created. Three patients (30%) in the EEA group and two (20%) in the BFC had postoperative cerebrospinal fluid leaks (p=0.61). Gross total resections were achieved in seven (70%) of the EEA group and nine (90%) of the BFC group (p=0.26), and one patient from each group developed a recurrence. On postoperative MRI, there was no significant difference in FLAIR signal volumes between EEA and BFC approaches (6.9 versus 13.3cm3; p=0.17) or in porencephalic cave volumes (1.7 versus 5.0cm3; p=0.11) in univariable analysis. However, in a multivariable analysis, EEA was associated with less postoperative FLAIR change (p=0.02) after adjusting for the volume of preoperative edema. This study provides preliminary evidence that EEA is associated with quantifiable improvements in postoperative frontal lobe imaging.

Magnetic resonance imaging fluid-attenuated inversion recovery sequence signal reduction after endoscopic endonasal transcribiform total resection of olfactory groove meningiomas.

Background:Olfactory groove meningiomas grow insidiously and compress adjacent cerebral structures. Achieving complete removal without further damage to frontal lobes can be difficult. Microsurgical removal of large lesions is a challenging procedure and usually involves some brain retraction. The endoscopic endonasal approaches (EEAs) for tumors arising from the anterior fossa have been well described; however, their effect on the adjacent brain tissue has not. Herein, the authors utilized the magnetic resonance imaging fluid attenuated inversion recovery (FLAIR) sequence signal as a marker for edema and gliosis on pre- and post-operative images of olfactory groove meningiomas, thus presenting an objective parameter for brain injury after surgical manipulation.Methods:Imaging of 18 olfactory groove meningiomas removed through EEAs was reviewed. Tumor and pre/postoperative FLAIR signal volumes were assessed utilizing the DICOM image viewer OsiriX®. Inclusion criteria were: (1) No previous treatment; (2) EEA gross total removal; (3) no further treatment.Results:There were 14 females and 4 males; the average age was 53.8 years (±8.85 years). Average tumor volume was 24.75 cm3 (±23.26 cm3, range 2.8–75.7 cm3), average preoperative FLAIR volume 31.17 cm3 (±39.38 cm3, range 0–127.5 cm3) and average postoperative change volume, 4.16 cm3 (±6.18 cm3, range 0–22.2 cm3). Average time of postoperative scanning was 6 months (range 0.14–20 months). In all cases (100%) gross total tumor removal was achieved. Nine patients (50%) had no postoperative FLAIR changes. In 2 patients (9%) there was minimal increase of changes postoperatively (2.2 cm3 and 6 cm3 respectively); all others demonstrated image improvement. The most common complication was postoperative cerebrospinal fluid leakage (27.8%); 1 patient (5.5%) died due to systemic complications and pulmonary sepsis.Conclusions:FLAIR signal changes tend to resolve after endonasal tumor resection and do not seem to worsen with this operative technique.

Fluid-Attenuated Inversion Recovery Hyperintensity Correlates With Matrix Metalloproteinase-9 Level and Hemorrhagic Transformation in Acute Ischemic Stroke

Matrix metalloproteinase-9 (MMP-9) is elevated in patients with acute stroke who later develop hemorrhagic transformation (HT). It is controversial whether early fluid-attenuated inversion recovery (FLAIR) hyperintensity on brain MRI predicts hemorrhagic transformation (HT). We assessed whether FLAIR hyperintensity was associated with MMP-9 and HT. We analyzed a prospectively collected cohort of acute stroke subjects with acute brain MRI images and MMP-9 values within the first 12 hours after stroke onset. FLAIR hyperintensity was measured using a signal intensity ratio between the stroke lesion and corresponding normal contralateral hemisphere. MMP-9 was measured using enzyme-linked immunosorbent assay. The relationships between FLAIR ratio (FR), MMP-9, and HT were evaluated. A total of 180 subjects were available for analysis. Patients were imaged with brain MRI at 5.6±4.3 hours from last seen well time. MMP-9 blood samples were drawn within 7.7±4.0 hours from last seen well time. The time to MRI (r=0.17, P=0.027) and MMP-9 level (r=0.29, P<0.001) were each associated with FR. The association between MMP-9 and FR remained significant after multivariable adjustment (P<0.001). FR was also associated with HT and symptomatic hemorrhage (P=0.012). FR correlates with both MMP-9 level and risk of hemorrhage. FLAIR changes in the acute phase of stroke may predict hemorrhagic transformation, possibly as a reflection of altered blood-brain barrier integrity.

Validation of FLAIR Hyperintense Lesions as Imaging Biomarkers to Predict the Outcome of Acute Stroke after Intra-Arterial Thrombolysis following Intravenous Tissue Plasminogen Activator

Background: Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis. Methods: With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions. Results: Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores. Conclusions: This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.

Reperfusion Therapy in Unclear-Onset Stroke Based on MRI Evaluation (RESTORE)

Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke. This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch>20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries. Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5±10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14-4.49). In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.

Prevalence of MRI-defined recent silent ischemia and associated bleeding risk with thrombolysis

Uncertainties about the frequency and the associated bleeding risk of recent silent ischemia (RSI), incidentally found on pretreatment MRI, in candidates for thrombolysis require clarification because exclusion from therapy is a serious consequence for patients with such MRI findings.We retrospectively analyzed the fluid-attenuated inversion recovery (FLAIR)/diffusion-weighted imaging (DWI) obtained before IV thrombolysis in 115 patients to search for MRI-defined RSI; these corresponded to well-developed FLAIR/DWI brain hyperintensities (RSI+), as distinct from the acute index ischemia, which typically lacked FLAIR changes. Patients without such findings were assigned to the RSI- group. Groups were compared for baseline characteristics and for rates of symptomatic and asymptomatic hemorrhagic transformation (HT) using odds ratios (OR) and their 95%confidence intervals (CI).We observed RSI in 21 patients (18.3%). The mean (SD) volume of RSI was 6.5 (12) mL (interquartile range 0.6-9). None of the baseline parameters differed between groups. There was no significant difference in rates of any type of HT between groups. Parenchymal hemorrhage type 1 or type 2 according to European Cooperative Acute Stroke Study criteria occurred in 2 (10%) RSI+ patients and in 10 (11%) RSI- patients (OR 0.88; 95% CI 0.18-4.37). Symptomatic HT, defined according to National Institute of Neurological Disorders and Stroke criteria, occurred in 1 (5%) RSI+ patient and in 10 (11%) RSI- patients (OR 0.42; 95% CI 0.05-3.47).We found that 18.3% of patients with acute stroke treated by IV thrombolysis in a stroke unit had RSI on pretreatment MRI. However, the presence of RSI was not associated with an increased risk of asymptomatic or symptomatic HT.

Prevalence of MRI-defined recent silent ischemia and associated bleeding risk with thrombolysis

Uncertainties about the frequency and the associated bleeding risk of recent silent ischemia (RSI), incidentally found on pretreatment MRI, in candidates for thrombolysis require clarification because exclusion from therapy is a serious consequence for patients with such MRI findings. We retrospectively analyzed the fluid-attenuated inversion recovery (FLAIR)/diffusion-weighted imaging (DWI) obtained before IV thrombolysis in 115 patients to search for MRI-defined RSI; these corresponded to well-developed FLAIR/DWI brain hyperintensities (RSI+), as distinct from the acute index ischemia, which typically lacked FLAIR changes. Patients without such findings were assigned to the RSI- group. Groups were compared for baseline characteristics and for rates of symptomatic and asymptomatic hemorrhagic transformation (HT) using odds ratios (OR) and their 95%confidence intervals (CI). We observed RSI in 21 patients (18.3%). The mean (SD) volume of RSI was 6.5 (12) mL (interquartile range 0.6-9). None of the baseline parameters differed between groups. There was no significant difference in rates of any type of HT between groups. Parenchymal hemorrhage type 1 or type 2 according to European Cooperative Acute Stroke Study criteria occurred in 2 (10%) RSI+ patients and in 10 (11%) RSI- patients (OR 0.88; 95% CI 0.18-4.37). Symptomatic HT, defined according to National Institute of Neurological Disorders and Stroke criteria, occurred in 1 (5%) RSI+ patient and in 10 (11%) RSI- patients (OR 0.42; 95% CI 0.05-3.47). We found that 18.3% of patients with acute stroke treated by IV thrombolysis in a stroke unit had RSI on pretreatment MRI. However, the presence of RSI was not associated with an increased risk of asymptomatic or symptomatic HT.

Safety and Efficacy of MRI-Based Thrombolysis in Unclear-Onset Stroke

Background: Standard selection criteria for thrombolysis typically exclude patients with acute ischemic stroke with unclear onset. Multimodal MRI screening may be able to identify those with a favorable benefit-risk ratio for thrombolysis. We aimed to evaluate the safety and efficacy of MRI-based thrombolysis in unclear-onset stroke (UnCLOS). Methods: We reviewed the thrombolysis database registries from 3 medical centers in Korea. Subjects received thrombolysis with intravenous tissue plasminogen activator (tPA) or combined intravenous tPA and intra-arterial urokinase within 3 h, or intra-arterial urokinase within 6 h from symptom detection. For patients with UnCLOS, MRI-specific eligibility criteria (i.e. positive perfusion-diffusion mismatch and absence of well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions) were applied. Rates of immediate and 5-day recanalization, early neurological improvement and symptomatic intracranial hemorrhage (ICH) within 48 h after treatment and 3-month modified Rankin Scale (mRS) scores were compared between patients with UnCLOS and those with clear-onset stroke (CLOS). Results: 32 patients with UnCLOS and 223 patients with CLOS were included. Baseline characteristics were comparable between the two groups, except that the proportion of MRI screening was higher, and detection-to-door time and door-to-needle time were longer in the UnCLOS group (p < 0.01). Rates of recanalization (immediate, 81.3 vs. 63.1%; delayed, 80.6 vs. 69.1%), early neurological improvement (on day 1, 46.9 vs. 35.9%; on day 7, 50.0 vs. 49.3%), symptomatic ICH (6.3 vs. 5.8%) and 3-month outcome (mRS 0–1, 37.5 vs. 35.0%; mRS 0–2, 50.0 vs. 49.3%) did not differ between the UnCLOS and CLOS groups. Conclusion: These preliminary results suggest that thrombolysis based on MRI criteria may safely be applied to acute stroke patients with unclear onset.