scholarly journals Diffusely abnormal white matter converts to T2 lesion volume in the absence of acute inflammation

2021 ◽  
Author(s):  
Mahsa Dadar ◽  
Sawsan Mahmoud ◽  
Sridar Narayanan ◽  
D. Louis Collins ◽  
Douglas Arnold ◽  
...  

Diffusely abnormal white matter (DAWM), characterised by biochemical changes of myelin in the absence of frank demyelination, has been associated with clinical progression in secondary progressive MS (SPMS). However, little is known about changes of DAWM over time and their relation to focal white matter lesions (FWML). The objectives of this work were: 1) To characterize the longitudinal evolution of FWML, DAWM, and DAWM that transforms into FWML, and 2) To determine whether gadolinium enhancement, known to be associated with the development of new FWML, is also related to DAWM voxels that transform into FWML. Our data included 4220 MRI scans of 689 SPMS participants, followed for 156 weeks and 2677 scans of 686 RRMS participants, followed for 96 weeks. FWML and DAWM were segmented using a previously validated, automatic thresholding technique based on normalized T2 intensity values. Using longitudinally registered images, DAWM voxels at each visit that transformed into FWML on the last MRI scan as well as their overlap with gadolinium enhancing lesion masks were identified. Our results showed that the average yearly rate of conversion of DAWM-to-FWML was 1.27cc for SPMS and 0.80cc for RRMS. FWML in SPMS participants significantly increased (t=3.9; p=0.0001) while DAWM significantly decreased (t=-4.3 p<0.0001) and the ratio FWML:DAWM increased (t=12.7; p<0.00001). RRMS participants also showed an increase in the FWML:DAWM Ratio (t=6.9; p<0.00001) but without a significant change of the individual volumes. Gadolinium enhancement was associated with 7.3% and 18.7% of focal New T2 lesion formation in the infrequent scans of the RRMS and SPMS cohorts, respectively. In comparison, only 0.1% and 0.0% of DAWM-to-FWML voxels overlapped with gadolinium enhancement. We conclude that DAWM transforms into FWML over time, in both RRMS and SPMS. DAWM appears to represent a form of pre-lesional pathology that contributes to T2 lesion volume increase over time, independent of new focal inflammation and gadolinium enhancement.

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
John Conklin ◽  
Frank L Silver ◽  
David J Mikulis ◽  
Daniel M Mandell

INTRODUCTION: Leukoaraiosis, the presence of “incidental” white matter lesions in the aging brain, is increasingly recognized as a predictor for dementia, ischemic stroke, intracerebral hemorrhage and vascular death. The pathogenesis of leukoaraiosis remains controversial, with abnormalities of small arterioles hypothesized to play an important role. To investigate this hypothesis, we sought to characterize the temporal evolution of the individual lesions making up leukoaraiosis. HYPOTHESIS: Discrete occlusive events at the level of small arterioles play a key role in the pathogenesis of leukoaraiosis. METHODS: Participants were prospectively recruited through an outpatient neurology clinic (inclusion criteria: age > 60 years, Fazekas grade 3 leukoaraiosis burden; exclusion criteria: cortical infarct, cardioembolic disease, dissection, carotid stenosis > 50%). Subjects underwent an identical MRI protocol in each of 16 consecutive weeks, including diffusion tensor imaging (DTI) and multi-echo T2-weighted imaging. Parametric maps of the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and T2 relaxation time were constructed and coregistered (Analysis of Functional NeuroImages, NIH; 3D Slicer, www.slicer.org; Matlab, The MathWorks). Images were reviewed for new diffusion restricting lesions, and such lesions were manually segmented. Plots of lesion ADC, FA and T2 were generated and temporally aligned to the onset of acute diffusion restriction. RESULTS: Five subjects (mean age 69 ± 8 years) met criteria and completed all 16 MRI scans. There were no lacunar or large artery infarcts during the study period. A total of 9 new diffusion restricting white matter lesions were identified (mean volume 0.06 ± 0.03 cc). Evolution of these lesions showed striking similarity to that of cerebral infarction, with acute reduction in ADC, followed by gradual rise in ADC and T2, and corresponding decline in FA. At 8 weeks, new lesions were indistinguishable from pre-existing white matter disease. CONCLUSION: Leukoaraiosis evolves through temporally and spatially discrete acute ischemic injuries. This supports the hypothesized role of small vessel arteriolar pathology as a key pathogenetic mechanism.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Blake Dewey ◽  
Xiang Xu ◽  
Linda Knutson ◽  
Amod Jog ◽  
Jerry Prince ◽  
...  

Introduction: White matter lesions of presumed ischemic origin (WMH) have been associated with increased risk of stroke, cognitive and motor decline, and are a subject of public health research. Engineering new MRI pipelines allowing for determination of mean transit time (MTT), and blood brain barrier permeability (BBBP), within WMH lesions is required for long-term population-based studies of lesion progression in patients with dementia and vascular cognitive impairment. Methods: WMH lesion volumes in 24 asymptomatic individuals was determined using an automated segmentation methodology, S3DL, with manual correction to remove false positives. A double contrast injection scheme was used to measure both K trans using dynamic contrast enhanced (DCE) imaging and K 2 using dynamic susceptibility contrast (DSC) imaging which also provided perfusion-related measures. BBBP was measured as k 2 within segmented WMH lesions and compared with normal white and gray matter. Results: The mean transit time (MTT) was found to be significantly prolonged (8.11, p<0.001Wilcoxon Signed-Rank Test) in WMH lesions when compared to normal appearing white and gray matter. There was no significant difference in DCE-K trans (0.018, p=0.351) between the lesions and the white/gray matter. Permeability measured in the WMH lesions using the DSC-K 2 method was increased and was correlated withincreasing total WMH lesion volume (spearman correlation 0.44; p< 0.046). Conclusion: In this first study using an advanced WMH lesion automated segmentation pipeline, we measured DCE and DSC perfusion and permeability variables within WMH lesions and compared them to normal white and grey matter in healthy people. We observed increasing MTT, within WMH lesions as compared to unaffected white and gray matter. Using the DSC-K 2 method, BBBP was higher within WMH lesions in these asymptomatic people, and correlated with increasing total lesion volume.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Abdul Ghani Mikati ◽  
Luying Li ◽  
Robert Shenkar ◽  
Lingjao Zhang ◽  
Xiaodong Guo ◽  
...  

Introduction: Vascular hyperpermeability in lesions and nonlesional brain is a cardinal feature of cerebral cavernous malformation (CCM) pathogenesis. Thus we implemented a novel magnetic resonance imaging (MRI) technique in order to quantitate vascular permeability in CCMs and non-CCM brain tissue in humans. We hypothesize that permeability of lesions and background brain will differ between familial and sporadic patients and measurements will be consistent between observers and over time. Method: We used a T 1 -weighted dynamic contrast-enhanced quantitative perfusion (DCEQP) protocol in 30 patients (13 sporadic, 12 familial, and 5 non-CCM cases) in conjunction with routine MRI scans. Regions of interest (ROIs) for permeability measurement included the entire lesion and areas of 12.9 mm 2 (16 pixels) of grey and white matter near and far from the lesion. Measurements were repeated by two observers and at two time points on a subset of patients. Results: For each ROI category except white matter near lesions, the mean permeability was higher in the familial than in the sporadic patients with p-values of 0.04, 0.005, 0.05, and 0.007 for CCM lesions, grey matter near, grey matter far (GMF), and white matter far (WMF) from lesions respectively. No difference was seen between sporadic and non-CCM cases, however familial WMF had higher permeability than both those groups (p0.05) except GMF with p=0.04. The intrapatient coefficients of variation between measurements were 0.74 and 0.63 and interpatient coefficients of variation were 1.36 and 1.56 for sporadic and familial cases respectively. Lastly, it was found that 3 of 4 patients with two scans had stable background (WMF) brain permeability over time. Conclusion: Results show the higher lesional and background brain permeability of familial cases, corroborating previous findings in mice. We also demonstrate the feasibility of DCEQP in CCM disease and the potential of permeability as a biomarker of disease activity or response to treatment. It also highlights the need for further investigation into clinical factors that may impact disease activity and permeability measures.


2016 ◽  
Vol 23 (7) ◽  
pp. 973-981 ◽  
Author(s):  
Jan-Mendelt Tillema ◽  
Stephen D Weigand ◽  
Jay Mandrekar ◽  
Yunhong Shu ◽  
Claudia F Lucchinetti ◽  
...  

Background: The relationship between cortical lesions (CLs) and white matter lesions (WMLs) in multiple sclerosis (MS) is poorly understood. Pathological studies support a topographical association between CLs and underlying subcortical WMLs and suggest CLs may play a role in both disease initiation and progression. We hypothesized that cortical MS lesions are physically connected to white matter MS lesions via axonal connections. Objective: To assess the presence of CL-WML connectivity utilizing novel magnetic resonance imaging (MRI) methodology. Methods: In all, 28 relapsing-remitting MS patients and 25 controls received 3 T MRI scans, including double inversion recovery (DIR) for CL detection coupled with diffusion tensor imaging (DTI). CL and WML maps were created, and DTI was used to calculate inter-lesional connectivity and volumetric connectivity indices. Results: All patients showed inter-lesional WML connectivity (median 76% of WMLs connected to another WML; interquartile range (IQR), 58%–88%). On average, 52% of detected CLs per patient were connected to at least one WML (IQR, 42%–71%). Volumetric connectivity analysis showed significantly elevated cortical lesion ratios in MS patients (median, 2.3; IQR, 1.6–3.3) compared to null MS and healthy control datasets ( p < 0.001). Conclusion: These findings provide strong evidence of inter-lesional connectivity between CLs and WMLs, supporting our hypothesis of intrinsic CL-WML connectivity.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Erik Olsson ◽  
Niklas Klasson ◽  
Josef Berge ◽  
Carl Eckerström ◽  
Åke Edman ◽  
...  

Age-related white matter lesions (WML) are a risk factor for stroke, cognitive decline, and dementia. Different requirements are imposed on methods for the assessment of WML in clinical settings and for research purposes, but reliability analysis is of major importance. In this study, WML assessment with three different methods was evaluated. In the Gothenburg mild cognitive impairment study, MRI scans from 152 participants were used to assess WML with the Fazekas visual rating scale on T2 images, a manual volumetric method on FLAIR images, and FreeSurfer volumetry on T1 images. Reliability was acceptable for all three methods. For low WML volumes (2/3 of the patients), reliability was overall lower and nonsignificant for the manual volumetric method. Unreliability in the assessment of patients with low WML with manual volumetry may mainly be due to intensity variation in the FLAIR sequence used; hence, intensity standardization and normalization methods must be used for more accurate assessments. The FreeSurfer segmentations resulted in smaller WML volumes than the volumes acquired with the manual method and showed deviations from visible hypointensities in the T1 images, which quite likely reduces validity.


2011 ◽  
Vol 17 (11) ◽  
pp. 1313-1323 ◽  
Author(s):  
Niraj Mistry ◽  
Emma C Tallantyre ◽  
Jennifer E Dixon ◽  
Nicolas Galazis ◽  
Tim Jaspan ◽  
...  

Background: The ‘normal appearing white matter’ (NAWM) in multiple sclerosis (MS) is known to be abnormal using quantitative magnetic resonance (MR) techniques. The aetiology of the changes in NAWM remains debatable. Objective: To investigate whether high-field and ultra high-field T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) MRI enables detection of MS white matter lesions in areas defined as NAWM using high-field T2-weighted fluid attenuation inversion recovery (FLAIR) MRI; that is, to ascertain whether undetected lesions are likely contributors to the burden of abnormality in similarly defined NAWM. Methods: Fourteen MS patients underwent MRI scans using 3T FLAIR and MPRAGE and 7 Tesla (7T) MPRAGE sequences. Independent observers identified lesions on 3T FLAIR and (7T and 3T) MPRAGE images. The detection of every individual lesion was then compared for each image type. Results: We identified a total of 812 white matter lesions on 3T FLAIR. Using 3T MPRAGE, 186 additional lesions were detected that were not detected using 3T FLAIR. Using 7T MPRAGE, 231 additional lesions were detected that were not detected using 3T FLAIR. Conclusions: MRI with 3T and 7T MPRAGE enables detection of MS lesions in areas defined as NAWM using 3T FLAIR. Focal MS lesions contribute to the abnormalities known to exist in the NAWM.


2021 ◽  
Author(s):  
Chanon Ngamsombat ◽  
Augusto Lio M. Gonçalves Filho ◽  
M. Gabriela Figueiro Longo ◽  
Stephen F. Cauley ◽  
Kawin Setsompop ◽  
...  

AbstractBACKGROUND AND PURPOSETo evaluate an ultrafast 3D-FLAIR sequence using Wave-CAIPI encoding (Wave-FLAIR) compared to standard 3D-FLAIR in the visualization and volumetric estimation of cerebral white matter lesions in a clinical setting.MATERIALS AND METHODS42 consecutive patients underwent 3T brain MRI including standard 3D-FLAIR (acceleration factor R=2, scan time TA=7:15 minutes) and resolution-matched ultrafast Wave-FLAIR sequences (R=6, TA=2:45 minutes for the 20-ch coil; R=9, TA=1:50 minutes for the 32-ch coil) as part of clinical evaluation for demyelinating disease. Automated segmentation of cerebral white matter lesions was performed using the Lesion Segmentation Tool in SPM. Student’s t-test, intra-class correlation coefficient (ICC), relative lesion volume difference (LVD) and Dice similarity coefficients (DSC) were used to compare volumetric measurements between sequences. Two blinded neuroradiologists evaluated the visualization of white matter lesions, artifact and overall diagnostic quality using a predefined 5-point scale.RESULTSStandard and Wave-FLAIR sequences showed excellent agreement of lesion volumes with an ICC of 0.99 and DSC of 0.97±0.05 (range 0.84 to 0.99). Wave-FLAIR was non-inferior to standard-FLAIR for visualization of lesions and motion. The diagnostic quality for Wave-FLAIR was slightly greater than standard-FLAIR for infratentorial lesions (p<0.001), and there was less pulsation artifact on Wave-FLAIR compared to standard FLAIR (p<0.001).CONCLUSIONSUltrafast Wave-FLAIR provides superior visualization of infratentorial lesions while preserving overall diagnostic quality and yields comparable white matter lesion volumes to those estimated using standard-FLAIR. The availability of ultrafast Wave-FLAIR may facilitate the greater use of 3D-FLAIR sequences in the evaluation of patients with suspected demyelinating disease.


US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 82
Author(s):  
Brian K Day ◽  
David W Dodick ◽  
Todd J Schwedt ◽  
◽  
◽  
...  

Migraine is a very common disorder that imposes substantial individual and societal costs. A better understanding of migraine mechanisms may lead to the development of new therapies and thus improve the management of migraine patients. Magnetic resonance imaging (MRI) techniques and positron emission tomography (PET) have revolutionized our understanding of migraine pathophysiology as a primary central nervous system (CNS) disorder, advanced the search for a central migraine generator, clarified the role of cortical spreading depression (CSD) and central sensitization in the pathogenesis of migraine, and revealed some potential sites of action of migraine medications. Structural imaging has shed light on relationships between migraine and stroke, white matter lesions, iron deposition, microstructural brain damage, and other gray and white matter aberrations. Emerging neuroimaging techniques, such as arterial spin labeling (ASL) and functional connectivity MRI (fcMRI), are beginning to provide further evidence of functional brain alterations in migraine patients. Ultimately, it is hoped that advanced neuroimaging will benefit the individual migraine patient by enhancing our diagnostic abilities, allowing for development of better treatments and serving as an important tool in medical decision-making.


1996 ◽  
Vol 168 (4) ◽  
pp. 477-485 ◽  
Author(s):  
John O'brien ◽  
Patricia Desmond ◽  
David Ames ◽  
Isaac Schweitzer ◽  
Susan Harrigan ◽  
...  

BackgroundWhite matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease.MethodT2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM–III–R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0–3 scale by two radiologists blind to clinical diagnosis.ResultsAfter controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML.ConclusionAn association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.


2006 ◽  
Vol 189 (1) ◽  
pp. 81-82 ◽  
Author(s):  
Selim M. El-Badri ◽  
David A. Cousins ◽  
Sean Parker ◽  
Heather C. Ashton ◽  
Victor L. McAllister ◽  
...  

SummaryTemporal lobe and limbic structures may be abnormal in bipolar disorder. T2-weighted magnetic resonance imaging (MRI) scans frequently show deep white matter lesions. MRI was performed on 50 young (19–39 years) euthymic patients with bipolar disorder and 26 controls. Mean temporal lobe volumes were reduced in patients (right, 9.42 cm3; left, 6.33 cm3) but this could not be ascribed to a specific structure. Deep white matter lesions were present in 5 patients but no controls raising questions of their aetiological significance.


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