Fluid-attenuated Inversion Recovery Lesion Volume Research Articles

A pro-inflammatory diet in people with multiple sclerosis is associated with an increased rate of relapse and increased FLAIR lesion volume on MRI in early multiple sclerosis: A prospective cohort study

Background: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. Objective: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. Methods: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. Results: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = −1.16, 4.33, p = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (β = 0.38, 95% CI = 0.04, 0.72, p = 0.03). Conclusion: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.

Morphometric evaluation of traumatic axonal injury and the correlation with post-traumatic cerebral atrophy and functional outcome.

Imaging plays a crucial role in the diagnosis, prognosis and follow-up of traumatic brain injury. Whereas computed tomography plays a pivotal role in the acute setting, magnetic resonance imaging is best suited to detect the true extent of traumatic brain injury, and more specifically diffuse axonal injury. Post-traumatic brain atrophy is a well-known complication of traumatic brain injury. This study investigated the correlation between diffuse axonal injury detected with fluid-attenuated inversion recovery and susceptibility-weighted imaging magnetic resonance imaging, post-traumatic brain atrophy and functional outcome (Glasgow outcome scale - extended). Twenty patients with a closed head injury and diffuse axonal injury detected with fluid-attenuated inversion recovery and susceptibility-weighted imaging were included. The total volumes of the diffuse axonal injury fluid-attenuated inversion recovery lesions were determined for each subject's initial (<14 days) and follow-up magnetic resonance scan (average: day 303 ± 83 standard deviation). The different brain volumes were automatically quantified using a validated and both US Food and Drug Administration-cleared and CE-marked machine learning algorithm (icobrain). The number of susceptibility-weighted imaging lesions and functional outcome scores (Glasgow outcome scale - extended) were retrieved from the Collaborative European NeuroTrauma Effectiveness Research Traumatic Brain Injury dataset. The volumetric fluid-attenuated inversion recovery diffuse axonal injury lesion load showed a significant inverse correlation with functional outcome (Glasgow outcome scale - extended) (r = -0.57; P = 0.0094) and white matter volume change (r = -0.50; P = 0.027). In addition, white matter volume change correlated significantly with the Glasgow outcome scale - extended score (P = 0.0072; r = 0.58). Moreover, there was a strong inverse correlation between longitudinal fluid-attenuated inversion recovery lesion volume change and whole brain volume change (r = -0.63; P = 0.0028). No significant correlation existed between the number of diffuse axonal injury susceptibility-weighted imaging lesions, brain atrophy and functional outcome. Volumetric analysis of diffuse axonal injury on fluid-attenuated inversion recovery imaging and automated brain atrophy calculation are potentially useful tools in the clinical management and follow-up of traumatic brain injury patients with diffuse axonal injury.

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.

Plasma citrulline levels are increased in patients with multiple sclerosis

BackgroundMultiple sclerosis is an inflammatory demyelinating disorder of the central nervous system (CNS). Myelin basic protein (MBP), which is one of the main compounds of CNS myelin, appears to be hypercitrullinated in the brain of patients with MS. We hypothesized that MS is associated with an increased release of citrulline from the brain. MethodsTwenty-five patients with MS, 25 controls without neurological disease (CwND) and 25 subjects with non-MS cerebral white matter lesions were included in this study. Groups were matched for age and gender. Clinical MS disability measures were recorded by means of Expanded Disability Status Scale (EDSS) scores and Multiple Sclerosis Severity Scores (MSSS). Citrulline was assessed in plasma obtained from an antecubital peripheral vein (PV) in all participants. Additional internal jugular vein (IJV) samples were examined in 10 patients with MS and 10 CwND. Twelve patients with MS underwent brain magnetic resonance imaging to determine total brain and T2 fluid-attenuated inversion recovery lesion volume. ResultsMedian [IQR] PV citrulline levels were increased in patients with MS (50.47 [86.61] μM), as compared to CwND (33.58 [43.65] μM, P = 0.042) and subjects with non-MS cerebral white matter lesions (32.41 [28.86] μM, P = 0.006). Citrulline IJV levels and IJV/PV ratios were comparable between patients with MS and CwND. No significant correlations were found between PV citrulline levels and any of the clinical, nor radiological, disease measures. ConclusionPV plasma levels of citrulline are elevated in patients with MS but this does not seem to result from an augmented release from the brain. Increased plasma citrulline may be a promising new biomarker in MS but the origin and significance need to be further elucidated.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial

ObjectivesThe authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BackgroundTAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. MethodsSENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤−1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below −1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. ResultsAmong 234 patients tested, the mean composite z-score was −0.65 SD below the normative mean. Domain scores ranged from −0.15 SD for attention to −1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. ConclusionsThere was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Predicting Outcome after Pediatric Traumatic Brain Injury by Early Magnetic Resonance Imaging Lesion Location and Volume.

Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluid-attenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2±5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5±8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI)=(hyperintensity lesion volume / whole brain volume)×100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups (p<0.05). GOS-E Peds correlated with HLVI-total (r=0.39; p=0.002) and HLVI in all three zones: zone A (r=0.31; p<0.02); zone B (r=0.35; p=0.004); and zone C (r=0.37; p=0.003). In adolescents ages 13-17 years, HLVI-total correlated best with outcome (r=0.5; p=0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r=0.52; p=0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19-16.0) for developing an unfavorable outcome.

Detecting Lesions after Traumatic Brain Injury Using Susceptibility Weighted Imaging: A Comparison with Fluid-Attenuated Inversion Recovery and Correlation with Clinical Outcome

The development and utilization of newer neuroimaging modalities provides the capability to more accurately detect the extent of pathology after TBI. The current study examined the ability of susceptibility-weighted imaging (SWI) to detect lesions after TBI as well as the relationship to subsequent clinical outcome. The performance of SWI was compared to that of fluid-attenuated inversion recovery (FLAIR). This study comprised 79 individuals with mild-to-severe TBI, 38 of whom completed neuropsychological tests of attention, working memory, processing speed, memory, and executive functions. SWI was found to quantify a greater lesion volume over the entire brain, specifically in frontal, central, limbic, subcortical gray, and parietal brain regions, than did FLAIR. Moreover, SWI was able to identify TBI-related lesions in almost one third of patients for whom FLAIR was unable to detect any lesions. Greater overall SWI volume, as well as frontal SWI volume, was found to relate to the severity of TBI. Conversely, no association was found between FLAIR lesion volume and injury severity. In addition, there was some evidence that higher lesion volume, for both SWI and FLAIR, were associated with poorer memory as well as processing speed impairment. This study suggests that SWI may provide additional sensitivity in the detection of lesions after TBI. Consequently, this imaging sequence may provide a more accurate representation of the severity of individuals' injuries and their subsequent neuropsychological outcomes.

Relationships Between Retinal Axonal and Neuronal Measures and Global Central Nervous System Pathology in Multiple Sclerosis

To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS). Cross-sectional study. Johns Hopkins University, Baltimore, Maryland. A total of 84 patients with MS and 24 healthy control subjects. High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes. Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer+inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P=.01 and P=.04, respectively) and caudate (P=.04 and P=.03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P=.007) and inversely associated with normal-appearing white matter volume (P=.005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.

Fluid-Attenuated Inversion Recovery Hyperintensity in Acute Ischemic Stroke May Not Predict Hemorrhagic Transformation

Background: Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3–6 h from stroke onset and its relationship to parenchymal hematoma (PH). Methods: Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3–6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis. Results: There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (ĸ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3–4.5 h and 4.5–6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not. Conclusions: Visible FLAIR hyperintensity is almost universal 3–6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.

Abstract #7: Voxel Based Morphometry with DARTEL in Multiple Sclerosis

Background Voxel based morphometry (VBM) is an automated tool used to assess the topography and magnitude of cerebral atrophy from MRI scans. However, VBM output is highly dependent on the input provided by registration and segmentation algorithms. Diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) is a new tool which has recently been developed to improve registration in healthy volunteers (HV) and neurodegenerative diseases. This has not yet been applied to multiple sclerosis (MS). Objective To assess regional gray matter (GM) and white matter (WM) atrophy using VBM combined with DARTEL in MS patients. Methods Using a 3T MRI scanner, fluid-attenuated inversion-recovery (FLAIR) and 3D spoiled gradient recalled (SPGR) scans were acquired from 26 relapsing remitting (RR) MS patients [age (mean ± SD) 39.2 ± 9.4 years, disease duration 8.5 ± 5.9 years, Expanded Disability Status Scale (EDSS) score 1.2 ± 0.9, FLAIR lesion volume (FLV) 15.0 ± 14.7 mL] and 28 sex- and age-matched HV. MS lesions on SPGR and FLAIR images were traced using a semi-automated thresholding tool. VBM was performed using DARTEL with statistical parametric mapping (SPM8) software from SPGR images. An analysis of covariance was used to assess differences in GM and WM volume between MS patients and HV. Age, gender, and intracranial volume were included as covariates. Results Compared with HV, MS patients showed significant GM atrophy in the bilateral thalami, bilateral caudate, and right putamen. Furthermore, WM atrophy was found in the brainstem, corpus callosum, fornix, and bilateral temporal and occipital lobes. FLV significantly correlated with GM atrophy in the thalami and with WM atrophy in the brainstem, temporal lobes, and corpus callosum. Conclusions VBM-DARTEL reveals widespread WM and GM cerebral atrophy affecting many areas of the brain, which is associated with overt lesions in MS patients. This pilot study suggests that VBM-DARTEL is a promising tool to derive meaningful disease specific information in MS. Acknowledgements This work was supported by research grants from the National Institutes of Health ( NIH R01 NS055083-01 ) and the National Multiple Sclerosis Society ( RG3705A1 , RG3798A2 ).

Reliability of Measuring Lesion Volumes in Transient Ischemic Attack and Minor Stroke

Lesion volume measurements in disabling ischemic stroke have excellent reliability, but it is not clear whether this is also true for small lesions. We assessed the reliability of measuring baseline and follow-up lesion volumes in transient ischemic attack and minor stroke. Patients who presented with a transient ischemic attack or minor stroke (NIHSS < or = 3) who had brain MRI within 24 hours from symptom onset and at 30-day follow-up and had an acute lesion on baseline MRI were included. Using semiautomated software, 4 stroke fellows independently assessed ischemic lesions twice on acute diffusion-weighted imaging and follow-up fluid-attenuated inversion recovery. Eighty patients were included, with a median baseline NIHSS of 1. Mean baseline diffusion-weighted imaging lesion volume was 3.4+/-7.4 mL (87.5% had <5 mL). There was excellent inter-rater/intrarater reliability, with intraclass correlation coefficients of 0.94/0.96 for acute diffusion-weighted imaging, 0.74/0.92 for follow-up fluid-attenuated inversion recovery, and 0.81/0.93 for growth. We found excellent concordance between and within raters for acute diffusion-weighted imaging and 30-day follow-up fluid-attenuated inversion recovery lesion volume measurements in patients with transient ischemic attack and minor stroke.

FLAIR lesion volume in multiple sclerosis: Relation to processing speed and verbal memory

Information processing speed and episodic memory are two commonly affected cognitive abilities in MS. Insights into the mechanisms of and relationships between these abilities have recently come from structural neuroimaging techniques, but few studies have used fluid-attenuated inversion recovery (FLAIR), a neuroimaging sequence known to be sensitive to cortical and juxtacortical lesions in MS. We hypothesized that a volumetric index of FLAIR total lesion volume (TLV) would be associated with slowed processing speed and verbal memory dysfunction in MS. Twenty MS patients underwent FLAIR imaging and were administered measures of verbal memory and processing speed. Correlational and regression analyses indicated that TLV was directly and independently related to measures of processing speed and verbal memory, and TLV accounted for 56% of the variance in cognitive performance. These findings, considered in the context of prior work, suggest that FLAIR TLV is a useful predictor of commonly impaired cognitive functions in MS, and shows promise as a functionally relevant biomarker for disease status.

Thalamic Involvement in Multiple Sclerosis: A Diffusion‐Weighted Magnetic Resonance Imaging Study

Injury to deep gray matter structures in multiple sclerosis (MS) has been suggested by recent neuro-imaging and neuropathology studies. Diffusion-weighted magnetic resonance imaging (MRI) can assess tissue damage with greater sensitivity than conventional MRI. The authors' objective was to assess thalamic gray matter damage by diffusion-weighted imaging in MS patients. This was a retrospective study performed at a tertiary care, university-affiliated comprehensive MS center of 82 MS patients and 43 controls. The main outcome measures were thalamic apparent diffusion coefficients (ADCs), whole-brain atrophy (brain parenchymal fraction), fluid-attenuated inversion recovery (FLAIR) hypertense lesion volume, and clinical course. ADCs in the left thalamus were higher in MS patients (0.741 +/- 0.044 x 10(-3) mm2/s) than controls (0.723 +/- 0.036 x 10(-3) mm2/s) (P = .027) and higher in secondary progressive MS patients (0.761 +/- 0.044 x 10(-3) mm2/s) than relapsing-remitting MS patients (0.735 +/- 0.032 x 10(-3) mm2/s) (P = .029). ADCs in the right thalamus were higher in secondary progressive MS patients (0.784 +/- 0.069 x 10(-3) mm2/s) than controls (0.757 +/- 0.038 x 10(-3) mm2/s) (P = .033). In the MS group, left thalamus ADCs correlated negatively with brain parenchymal fraction (r = -0.30, P = .008), total left hemispheric FLAIR lesion volume correlated with ADCs in the left (r = 0.35, P = .001) and right (r = 0.39, P < .001) thalami, and total right hemispheric FLAIR lesion volume correlated with ADCs in the left (r = 0.31, P = .006) and right thalami (r = 0.22, P = .048). MS patients have increased water diffusion in the thalamus that is partly associated with clinical course, lesion load, and whole-brain atrophy. Both indirect and direct mechanisms of gray matter injury may play a role in the pathophysiology of MS.