Publications by authors named "Stefan Ropele"

151 Publications

In vivo assessment of anisotropy of apparent magnetic susceptibility in white matter from a single orientation acquisition.

Neuroimage 2021 Nov 31;241:118442. Epub 2021 Jul 31.

Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Philosophenweg 3, Jena 07743, Germany.

Multiple studies have reported a significant dependence of the effective transverse relaxation rate constant (R) and the phase of gradient-echo based (GRE) signal on the orientation of white matter fibres in the human brain. It has also been hypothesized that magnetic susceptibility, as obtained by single-orientation quantitative susceptibility mapping (QSM), exhibits such a dependence. In this study, we investigated this hypothesized relationship in a cohort of healthy volunteers. We show that R follows the predicted orientation dependence consistently across white matter regions, whereas the apparent magnetic susceptibility is related differently to fibre orientation across the brain and often in a complex non-monotonic manner. In addition, we explored the effect of fractional anisotropy measured by diffusion-weighted MRI on the strength of the orientation dependence and observed only a limited influence in many regions. However, with careful consideration of such an impact and the limitations imposed by the ill-posed nature of the dipole inversion process, it is possible to study magnetic susceptibility anisotropy in specific brain regions with a single orientation acquisition.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118442DOI Listing
November 2021

MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes.

Front Neurosci 2021 12;15:691244. Epub 2021 Jul 12.

Department of Neurology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO, United States.

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).

Results: Radiomic features were predictive of WMH burden ( = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected -values < 0.001, -value = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.

Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.
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http://dx.doi.org/10.3389/fnins.2021.691244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312571PMC
July 2021

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns.

Nat Commun 2021 06 2;12(1):3289. Epub 2021 Jun 2.

Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA.

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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http://dx.doi.org/10.1038/s41467-021-23492-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172535PMC
June 2021

Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis.

Brain 2021 06;144(5):1296-1311

Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response.
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http://dx.doi.org/10.1093/brain/awab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219362PMC
June 2021

Development and evaluation of a manual segmentation protocol for deep grey matter in multiple sclerosis: Towards accelerated semi-automated references.

Neuroimage Clin 2021 6;30:102659. Epub 2021 Apr 6.

Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VUmc, Amsterdam, NL, Netherlands.

Background: Deep grey matter (dGM) structures, particularly the thalamus, are clinically relevant in multiple sclerosis (MS). However, segmentation of dGM in MS is challenging; labeled MS-specific reference sets are needed for objective evaluation and training of new methods.

Objectives: This study aimed to (i) create a standardized protocol for manual delineations of dGM; (ii) evaluate the reliability of the protocol with multiple raters; and (iii) evaluate the accuracy of a fast-semi-automated segmentation approach (FASTSURF).

Methods: A standardized manual segmentation protocol for caudate nucleus, putamen, and thalamus was created, and applied by three raters on multi-center 3D T1-weighted MRI scans of 23 MS patients and 12 controls. Intra- and inter-rater agreement was assessed through intra-class correlation coefficient (ICC); spatial overlap through Jaccard Index (JI) and generalized conformity index (CIgen). From sparse delineations, FASTSURF reconstructed full segmentations; accuracy was assessed both volumetrically and spatially.

Results: All structures showed excellent agreement on expert manual outlines: intra-rater JI > 0.83; inter-rater ICC ≥ 0.76 and CIgen ≥ 0.74. FASTSURF reproduced manual references excellently, with ICC ≥ 0.97 and JI ≥ 0.92.

Conclusions: The manual dGM segmentation protocol showed excellent reproducibility within and between raters. Moreover, combined with FASTSURF a reliable reference set of dGM segmentations can be produced with lower workload.
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http://dx.doi.org/10.1016/j.nicl.2021.102659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082260PMC
July 2021

Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy.

Mult Scler 2021 Apr 19:13524585211008743. Epub 2021 Apr 19.

Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.

Background: Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied.

Objectives: To study how thalamic functional connectivity (FC) is related to disability and thalamic or cortical network atrophy in two large MS cohorts.

Methods: Structural and resting-state functional magnetic resonance imaging (fMRI) was obtained in 673 subjects from Amsterdam (MS:  = 332, healthy controls (HC):  = 96) and Graz (MS:  = 180, HC:  = 65) with comparable protocols, including disability measurements in MS (Expanded Disability Status Scale, EDSS). Atrophy was measured for the thalamus and seven well-recognized resting-state networks. Static and dynamic thalamic FC with these networks was correlated with disability. Significant correlates were included in a backward multivariate regression model.

Results: Disability was most strongly related (adjusted  = 0.57,  < 0.001) to higher age, a progressive phenotype, thalamic atrophy and increased static thalamic FC with the sensorimotor network (SMN). Static thalamus-SMN FC was significantly higher in patients with high disability (EDSS ⩾ 4) and related to network atrophy but not thalamic atrophy or lesion volumes.

Conclusion: The severity of disability in MS was related to increased static thalamic FC with the SMN. Thalamic FC changes were only related to cortical network atrophy, but not to thalamic atrophy.
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http://dx.doi.org/10.1177/13524585211008743DOI Listing
April 2021

Manual and automated tissue segmentation confirm the impact of thalamus atrophy on cognition in multiple sclerosis: A multicenter study.

Neuroimage Clin 2021 25;29:102549. Epub 2020 Dec 25.

Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA 02215, USA. Electronic address:

Background And Rationale: Thalamus atrophy has been linked to cognitive decline in multiple sclerosis (MS) using various segmentation methods. We investigated the consistency of the association between thalamus volume and cognition in MS for two common automated segmentation approaches, as well as fully manual outlining.

Methods: Standardized neuropsychological assessment and 3-Tesla 3D-T1-weighted brain MRI were collected (multi-center) from 57 MS patients and 17 healthy controls. Thalamus segmentations were generated manually and using five automated methods. Agreement between the algorithms and manual outlines was assessed with Bland-Altman plots; linear regression assessed the presence of proportional bias. The effect of segmentation method on the separation of cognitively impaired (CI) and preserved (CP) patients was investigated through Generalized Estimating Equations; associations with cognitive measures were investigated using linear mixed models, for each method and vendor.

Results: In smaller thalami, automated methods systematically overestimated volumes compared to manual segmentations [ρ=(-0.42)-(-0.76); p-values < 0.001). All methods significantly distinguished CI from CP MS patients, except manual outlines of the left thalamus (p = 0.23). Poorer global neuropsychological test performance was significantly associated with smaller thalamus volumes bilaterally using all methods. Vendor significantly affected the findings.

Conclusion: Automated and manual thalamus segmentation consistently demonstrated an association between thalamus atrophy and cognitive impairment in MS. However, a proportional bias in smaller thalami and choice of MRI acquisition system might impact the effect size of these findings.
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http://dx.doi.org/10.1016/j.nicl.2020.102549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787946PMC
June 2021

Investigation of Deep-Learning-Driven Identification of Multiple Sclerosis Patients Based on Susceptibility-Weighted Images Using Relevance Analysis.

Front Neurosci 2020 18;14:609468. Epub 2020 Dec 18.

Medical Physics Group, Institute for Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.

The diagnosis of multiple sclerosis (MS) is usually based on clinical symptoms and signs of damage to the central nervous system, which is assessed using magnetic resonance imaging. The correct interpretation of these data requires excellent clinical expertise and experience. Deep neural networks aim to assist clinicians in identifying MS using imaging data. However, before such networks can be integrated into clinical workflow, it is crucial to understand their classification strategy. In this study, we propose to use a convolutional neural network to identify MS patients in combination with attribution algorithms to investigate the classification decisions. The network was trained using images acquired with susceptibility-weighted imaging (SWI), which is known to be sensitive to the presence of paramagnetic iron components and is routinely applied in imaging protocols for MS patients. Different attribution algorithms were used to the trained network resulting in heatmaps visualizing the contribution of each input voxel to the classification decision. Based on the quantitative image perturbation method, we selected DeepLIFT heatmaps for further investigation. Single-subject analysis revealed veins and adjacent voxels as signs for MS, while the population-based study revealed relevant brain areas common to most subjects in a class. This pattern was found to be stable across different echo times and also for a multi-echo trained network. Intensity analysis of the relevant voxels revealed a group difference, which was found to be primarily based on the T1w magnitude images, which are part of the SWI calculation. This difference was not observed in the phase mask data.
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http://dx.doi.org/10.3389/fnins.2020.609468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775402PMC
December 2020

Do increases in deep grey matter volumes after electroconvulsive therapy persist in patients with major depression? A longitudinal MRI-study.

J Affect Disord 2021 02 11;281:908-917. Epub 2020 Nov 11.

Department of Radiology, Division of Neuroradiology, Vascular and Interventional Radiology, 8036 Graz, Medical University of Graz, Austria; Department of Neurology, Division of General Neurology, 8036 Graz, Medical University of Graz, Austria; Research Unit for Neuronal Repair and Plasticity, 8036 Graz, Medical University of Graz, Austria. Electronic address:

Background: Previous MRI studies reported deep grey matter volume increases after electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD). However, the clinical correlates of these changes are still unclear. It remains debated whether such volume changes are transient, and if they correlate with affective changes over time. We here investigated if ECT induces deep grey matter volume increases in MDD-patients; and, if so, whether volume changes persist over more than 9 months and whether they are related to the clinical outcome.

Methods: We examined 16 MDD-patients with 3Tesla MRI before (baseline) and after an ECT-series and followed 12 of them up for 10-36 months. Patients' data were compared to 16 healthy controls. Affective scales were used to investigate the relationship between therapy-outcome and MRI changes.

Results: At baseline, MDD-patients had lower values in global brain volume, white matter and peripheral grey matter compared to healthy controls, but we observed no significant differences in deep grey matter volumes. After ECT, the differences in peripheral grey matter disappeared, and patients demonstrated significant volume increases in the right hippocampus and both thalami, followed by subsequent decreases after 10-36 months, especially in ECT-responders. Controls did not show significant changes over time.

Limitations: Beside the relatively small, yet carefully characterized cohort, we address the variability in time between the third scanning session and the baseline.

Conclusions: ECT-induced deep grey matter volume increases are transient. Our results suggest that the thalamus might be a key region for the understanding of the mechanisms of ECT action.
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http://dx.doi.org/10.1016/j.jad.2020.11.035DOI Listing
February 2021

Adaptive slice-specific z-shimming for 2D spoiled gradient-echo sequences.

Magn Reson Med 2021 02 10;85(2):818-830. Epub 2020 Sep 10.

Department of Neurology, Medical University of Graz, Graz, Austria.

Purpose: To reduce the misbalance between compensation gradients and macroscopic field gradients, we introduce an adaptive slice-specific z-shimming approach for 2D spoiled multi-echo gradient-echoe sequences in combination with modeling of the signal decay.

Methods: Macroscopic field gradients were estimated for each slice from a fast prescan (15 seconds) and then used to calculate slice-specific compensation moments along the echo train. The coverage of the compensated field gradients was increased by applying three positive and three negative moments. With a forward model, which considered the effect of the slice profile, the z-shim moment, and the field gradient, maps were estimated. The method was evaluated in phantom and in vivo measurements at 3 T and compared with a spoiled multi-echo gradient-echo and a global z-shimming approach without slice-specific compensation.

Results: The proposed method yielded higher SNR in maps due to a broader range of compensated macroscopic field gradients compared with global z-shimming. In global white matter, the mean interquartile range, proxy for SNR, could be decreased to 3.06 s with the proposed approach, compared with 3.37 s for global z-shimming and 3.52 s for uncompensated multi-echo gradient-echo.

Conclusion: Adaptive slice-specific compensation gradients between echoes substantially improved the SNR of maps, and the signal could also be rephased in anatomical areas, where it has already been completely dephased.
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http://dx.doi.org/10.1002/mrm.28468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693070PMC
February 2021

Long-term course and morphological MRI correlates of cognitive function in multiple sclerosis.

Mult Scler 2021 05 14;27(6):954-963. Epub 2020 Jul 14.

Research Unit for Neuronal Plasticity and Repair, Medical University of Graz, Graz, Austria/Department of Neurology, Medical University of Graz, Graz, Austria/Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria.

Background: Cognitive impairment frequently occurs in patients with MS (pwMS). Magnetic resonance imaging (MRI) markers could help to identify patients at risk for decline.

Objective: To characterize the long-term course and morphological MRI correlates of cognitive function in pwMS.

Methods: We invited 116 pwMS who had undergone clinical, cognitive, and MRI evaluations between 2006 and 2012 (baseline, BL) to attend follow-up (FU) testing between 2016 and 2018. Disability (expanded disability status scale (EDSS)), cognition (brief repeatable battery of neuropsychological test (BRB-N)), global and regional T2-lesion load (T2-LL), brain volumes, and cortical thickness were assessed.

Results: Sixty-three pwMS were willing to attend the FU (54%; median EDSS = 2, interquartile range (IQR) = 2) and did not differ from non-participating pwMS regarding BL characteristics. At BL, half of the participants showed cognitive deficits in at least one domain. Across the entire group, we observed no relevant changes in physical disability and cognition over 10 years. BL thalamic volume best predicted cognitive function at FU, in addition to age and BL cognition, explaining 67% of variance. Cognitive decliners (23.8%) were older, had longer disease duration, and a tendency for lower thalamic volume at BL.

Conclusion: Thalamic volume predicted FU cognitive function and distinguished declining from stable pwMS, underlining the potential of MRI to define risk groups.
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http://dx.doi.org/10.1177/1352458520941474DOI Listing
May 2021

Reduced accuracy of MRI deep grey matter segmentation in multiple sclerosis: an evaluation of four automated methods against manual reference segmentations in a multi-center cohort.

J Neurol 2020 Dec 3;267(12):3541-3554. Epub 2020 Jul 3.

Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Background: Deep grey matter (DGM) atrophy in multiple sclerosis (MS) and its relation to cognitive and clinical decline requires accurate measurements. MS pathology may deteriorate the performance of automated segmentation methods. Accuracy of DGM segmentation methods is compared between MS and controls, and the relation of performance with lesions and atrophy is studied.

Methods: On images of 21 MS subjects and 11 controls, three raters manually outlined caudate nucleus, putamen and thalamus; outlines were combined by majority voting. FSL-FIRST, FreeSurfer, Geodesic Information Flow and volBrain were evaluated. Performance was evaluated volumetrically (intra-class correlation coefficient (ICC)) and spatially (Dice similarity coefficient (DSC)). Spearman's correlations of DSC with global and local lesion volume, structure of interest volume (ROIV), and normalized brain volume (NBV) were assessed.

Results: ICC with manual volumes was mostly good and spatial agreement was high. MS exhibited significantly lower DSC than controls for thalamus and putamen. For some combinations of structure and method, DSC correlated negatively with lesion volume or positively with NBV or ROIV. Lesion-filling did not substantially change segmentations.

Conclusions: Automated methods have impaired performance in patients. Performance generally deteriorated with higher lesion volume and lower NBV and ROIV, suggesting that these may contribute to the impaired performance.
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http://dx.doi.org/10.1007/s00415-020-10023-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674567PMC
December 2020

Cross-sectional and Longitudinal Assessment of Brain Iron Level in Alzheimer Disease Using 3-T MRI.

Radiology 2020 09 30;296(3):619-626. Epub 2020 Jun 30.

From the Department of Neurology (A.D., L.P., M. Soellradl, M. Sackl, C.T., E.H., C.E., S.R., R.S., C.L.), Institute for Medical Informatics, Statistics and Documentation (E.H.), and Division of Neuroradiology, Vascular, and Interventional Radiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Auenbruggerplatz 22, 8036 Graz, Austria; and Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany (B.G., M.D.).

Background Deep gray matter structures in patients with Alzheimer disease (AD) contain higher brain iron concentrations. However, few studies have included neocortical areas, which are challenging to assess with MRI. Purpose To investigate baseline and change in brain iron levels using MRI at 3 T with R2* relaxation rate mapping in individuals with AD compared with healthy control (HC) participants. Materials and Methods In this prospective study, participants with AD recruited between 2010 and 2016 and age-matched HC participants selected from 2010 to 2014 were evaluated. Of 100 participants with AD, 56 underwent subsequent neuropsychological testing and brain MRI at a mean follow-up of 17 months. All participants underwent 3-T MRI, including R2* mapping corrected for macroscopic B0 field inhomogeneities. Anatomic structures were segmented, and median R2* values were calculated in the neocortex and cortical lobes, basal ganglia (BG), hippocampi, and thalami. Multivariable linear regression analysis was applied to study the difference in R2* levels between groups and the association between longitudinal changes in R2* values and cognition in the AD group. Results A total of 100 participants with AD (mean age, 73 years ± 9 [standard deviation]; 58 women) and 100 age-matched HC participants (mean age, 73 years ± 9; 60 women) were evaluated. Median R2* levels were higher in the AD group than in the HC group in the BG (HC, 29.0 sec; AD, 30.2 sec; = .01) and total neocortex (HC, 17.0 sec; AD, 17.4 sec; < .001) and regionally in the occipital (HC, 19.6 sec; AD, 20.2 sec; = .007) and temporal (HC, 16.4 sec; AD, 18.1 sec; < .001) lobes. R2* values in the temporal lobe were associated with longitudinal changes in Consortium to Establish a Registry for Alzheimer's Disease total score (β = -3.23 score/sec, = .003) in participants with AD independent of longitudinal changes in brain volume. Conclusion Iron concentration in the deep gray matter and neocortical regions was higher in patients with Alzheimer disease than in healthy control participants. Change in iron levels over time in the temporal lobe was associated with cognitive decline in individuals with Alzheimer disease. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020192541DOI Listing
September 2020

The influence of iron oxidation state on quantitative MRI parameters in post mortem human brain.

Neuroimage 2020 10 23;220:117080. Epub 2020 Jun 23.

UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada; Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Pediatrics (Division of Neurology), University of British Columbia, Vancouver, BC, Canada.

A variety of Magnetic Resonance Imaging (MRI) techniques are known to be sensitive to brain iron content. In principle, iron sensitive MRI techniques are based on local magnetic field variations caused by iron particles in tissue. The purpose of this study was to investigate the sensitivity of MR relaxation and magnetization transfer parameters to changes in iron oxidation state compared to changes in iron concentration. Therefore, quantitative MRI parameters including R, R, R∗, quantitative susceptibility maps (QSM) and magnetization transfer ratio (MTR) of post mortem human brain tissue were acquired prior and after chemical iron reduction to change the iron oxidation state and chemical iron extraction to decrease the total iron concentration. All assessed parameters were shown to be sensitive to changes in iron concentration whereas only R, R∗ and QSM were also sensitive to changes in iron oxidation state. Mass spectrometry confirmed that iron accumulated in the extraction solution but not in the reduction solution. R∗ and QSM are often used as markers for iron content. Changes in these parameters do not necessarily reflect variations in iron content but may also be a result of changes in the iron's oxygenation state from ferric towards more ferrous iron or vice versa.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117080DOI Listing
October 2020

Gray Matter Covariance Networks as Classifiers and Predictors of Cognitive Function in Alzheimer's Disease.

Front Psychiatry 2020 5;11:360. Epub 2020 May 5.

Department of Neurology, Medical University of Graz, Graz, Austria.

The study of shared variation in gray matter morphology may define neurodegenerative diseases beyond what can be detected from the isolated assessment of regional brain volumes. We, therefore, aimed to (1) identify SCNs (structural covariance networks) that discriminate between Alzheimer's disease (AD) patients and healthy controls (HC), (2) investigate their diagnostic accuracy in comparison and above established markers, and (3) determine if they are associated with cognitive abilities. We applied a random forest algorithm to identify discriminating networks from a set of 20 SCNs. The algorithm was trained on a main sample of 104 AD patients and 104 age-matched HC and was then validated in an independent sample of 28 AD patients and 28 controls from another center. Only two of the 20 SCNs contributed significantly to the discrimination between AD and controls. These were a temporal and a secondary somatosensory SCN. Their diagnostic accuracy was 74% in the original cohort and 80% in the independent samples. The diagnostic accuracy of SCNs was comparable with that of conventional volumetric MRI markers including whole brain volume and hippocampal volume. SCN did not significantly increase diagnostic accuracy beyond that of conventional MRI markers. We found the temporal SCN to be associated with verbal memory at baseline. No other associations with cognitive functions were seen. SCNs failed to predict the course of cognitive decline over an average of 18 months. We conclude that SCNs have diagnostic potential, but the diagnostic information gain beyond conventional MRI markers is limited.
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http://dx.doi.org/10.3389/fpsyt.2020.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214682PMC
May 2020

Early Progressive Changes in White Matter Integrity Are Associated with Stroke Recovery.

Transl Stroke Res 2020 12 4;11(6):1264-1272. Epub 2020 Mar 4.

Department of Neurology, Research Unit for Neuronal Plasticity and Repair, Medical University of Graz, Graz, Austria.

Information on microstructural white matter integrity has been shown to explain post-stroke recovery beyond clinical measures and focal brain damage. Especially, knowledge about early white matter changes might improve prediction of outcome. We investigated 42 acute reperfused ischemic stroke patients (mean age 66.5 years, 40% female, median admission NIHSS 9.5) with a symptomatic MRI-confirmed unilateral middle cerebral artery territory infarction 24-72 h post-stroke and after 3 months. All patients underwent neurological examination and brain MRI. Fifteen older healthy controls (mean age 57.3 years) were also scanned twice. We assessed fractional anisotropy (FA), mean diffusivity (MD), axial (AD), and radial diffusivity (RD). Patients showed significantly decreased white matter integrity in the hemisphere affected by the acute infarction 24-72 h post-stroke, which further decreased over 3 months compared with controls. Less decrease in FA of remote white matter tracts was associated with better stroke recovery even after correcting for infarct location and extent. A regression model including baseline information showed that the modified Rankin Scale and mean FA of the genu of the corpus callosum explained 53.5% of the variance of stroke recovery, without contribution of infarct volume. Furthermore, early dynamic FA changes of the corpus callosum within the first 3 months post-stroke independently predicted stroke recovery. Information from advanced MRI measures on white matter integrity at the acute stage, as well as early dynamic white matter degeneration beyond infarct location and extent, improve our understanding of post-stroke reorganization in the affected hemisphere and contribute to an improved prediction of recovery.
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http://dx.doi.org/10.1007/s12975-020-00797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575507PMC
December 2020

Serum neurofilament light levels in normal aging and their association with morphologic brain changes.

Nat Commun 2020 02 10;11(1):812. Epub 2020 Feb 10.

Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

Neurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also in serum, which allows for repeated assessments. There is still limited knowledge regarding the association of serum NfL (sNfL) with age and subclinical morphologic brain changes and their dynamics in the normal population. We measured sNfL by a single molecule array (Simoa) assay in 335 individuals participating in a population-based cohort study and after a mean follow-up time of 5.9 years (n = 103). Detailed clinical examination, cognitive testing and 3T brain MRI were performed to assess subclinical brain damage. We show that rising and more variable sNfL in individuals >60 years indicate an acceleration of neuronal injury at higher age, which may be driven by subclinical comorbid pathologies. This is supported by a close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner.
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http://dx.doi.org/10.1038/s41467-020-14612-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010701PMC
February 2020

Assessment and correction of macroscopic field variations in 2D spoiled gradient-echo sequences.

Magn Reson Med 2020 08 23;84(2):620-633. Epub 2019 Dec 23.

Department of Neurology, Medical University of Graz, Graz, Austria.

Purpose: To model and correct the dephasing effects in the gradient-echo signal for arbitrary RF excitation pulses with large flip angles in the presence of macroscopic field variations.

Methods: The dephasing of the spoiled 2D gradient-echo signal was modeled using a numerical solution of the Bloch equations to calculate the magnitude and phase of the transverse magnetization across the slice profile. Additionally, regional variations of the transmit RF field and slice profile scaling due to macroscopic field gradients were included. Simulations, phantom, and in vivo measurements at 3 T were conducted for and myelin water fraction (MWF) mapping.

Results: The influence of macroscopic field gradients on and myelin water fraction estimation can be substantially reduced by applying the proposed model. Moreover, it was shown that the dephasing over time for flip angles of 60° or greater also depends on the polarity of the slice-selection gradient because of phase variation along the slice profile.

Conclusion: Substantial improvements in accuracy and myelin water fraction mapping coverage can be achieved using the proposed model if higher flip angles are required. In this context, we demonstrated that the phase along the slice profile and the polarity of the slice-selection gradient are essential for proper modeling of the gradient-echo signal in the presence of macroscopic field variations.
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http://dx.doi.org/10.1002/mrm.28139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216950PMC
August 2020

Morphological MRI phenotypes of multiple sclerosis differ in resting-state brain function.

Sci Rep 2019 11 7;9(1):16221. Epub 2019 Nov 7.

Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, Graz, Austria.

We aimed to assess differences in resting-state functional connectivity (FC) between distinct morphological MRI-phenotypes in multiple sclerosis (MS). Out of 180 MS patients, we identified those with high T2-hyperintense lesion load (T2-LL) and high normalized brain volume (NBV; a predominately white matter damage group, WMD; N = 37) and patients with low T2-LL and low NBV (N = 37; a predominately grey matter damage group; GMD). Independent component analysis of resting-state fMRI was used to test for differences in the sensorimotor network (SMN) between MS MRI-phenotypes and compared to 37 age-matched healthy controls (HC). The two MS groups did not differ regarding EDSS scores, disease duration and distribution of clinical phenotypes. WMD compared to GMD patients showed increased FC in all sub-units of the SMN (sex- and age-corrected). WMD patients had increased FC compared to HC and GMD patients in the central SMN (leg area). Only in the WMD group, higher EDSS scores and T2-LL correlated with decreased connectivity in SMN sub-units. MS patients with distinct morphological MRI-phenotypes also differ in brain function. The amount of focal white matter pathology but not global brain atrophy affects connectivity in the central SMN (leg area) of the SMN, consistent with the notion of a disconnection syndrome.
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http://dx.doi.org/10.1038/s41598-019-52757-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838050PMC
November 2019

Total gray matter volume is reduced in individuals with bipolar disorder currently treated with atypical antipsychotics.

J Affect Disord 2020 01 19;260:722-727. Epub 2019 Sep 19.

Department of Psychiatry and Psychotherapy, Medical University of Graz, Auenbruggerplatz 31, A-8036, Graz, Austria.

Background/aims: Recent evidence indicates that the intake of atypical antipsychotics (AAP) is associated with gray matter abnormalities in patients with psychiatric disorders. We explored if patients with bipolar disorder (BD) who are medicated with AAP exhibit total gray matter volume (TGV) reduction compared to BD individuals not medicated with AAP and healthy controls (HC).

Methods: In a cross-sectional design, 124 individuals with BD and 86 HC underwent 3T-MRI of the brain and clinical assessment as part of our BIPFAT-study. The TGV was estimated using Freesurfer. We used univariate covariance analysis (ANCOVA) to test for normalized TGV differences and controlled for covariates.

Results: ANCOVA results indicated that 75 BD individuals taking AAP had significantly reduced normalized TGV as compared to 49 BD not taking AAP (F = 9.995, p = .002., Eta = 0.084) and 86 HC (F = 7.577, p = .007, Eta = 0.046).

Limitations: Our cross-sectional results are not suited to draw conclusions about causality. We have no clear information on treatment time and baseline volumes before drug treatment in the studied subjects. We cannot exclude that patients received different psychopharmacologic medications prior to the study point. We did not included dosages into the calculation. Many BD individuals received combinations of psychopharmacotherapy across drug classes. We did not have records displaying quantitative alcohol consumption and drug abuse in our sample.

Conclusions: Our data provide further evidence for the impact of AAP on brain structure in BD. Longitudinal studies are needed to investigate the causal directions of the proposed relationships.
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http://dx.doi.org/10.1016/j.jad.2019.09.068DOI Listing
January 2020

Quantification of cortical damage in multiple sclerosis using DTI remains a challenge.

Brain 2019 07;142(7):1848-1850

Department of Neurology, Medical University of Graz, Austria.

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http://dx.doi.org/10.1093/brain/awz160DOI Listing
July 2019

Low-dose ladostigil for mild cognitive impairment: A phase 2 placebo-controlled clinical trial.

Neurology 2019 10 6;93(15):e1474-e1484. Epub 2019 Sep 6.

From the Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Avraham Pharmaceuticals, Ltd (Y.G.), Yavne; Bar Ilan University (J.R.), Ramat Gan, Israel; University of California (R.G.T.), San Diego; Department of Neurology (R.S., S.R.), Medical University, Graz, Austria; and Hebrew University (M.W.), Jerusalem, Israel.

Objective: Ladostigil reduces oxidative stress and microglial activation in aging rats. We assessed its safety and potential efficacy in a 3-year, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild cognitive impairment (MCI) and medial temporal lobe atrophy.

Methods: Patients 55 to 85 years of age with MCI, Clinical Dementia Rating (CDR) score of 0.5, Mini-Mental State Examination (MMSE) score >24, Wechsler Memory Scale-Revised Verbal Paired Associates I score ≤18, and Medial Temporal Lobe Atrophy Scale score >1 were stratified by ε4 genotype and randomly assigned (1:1) to ladostigil 10 mg/d or placebo. Primary outcomes were safety and onset of Alzheimer disease dementia. Secondary endpoints were Neuropsychological Test Battery (NTB) composite, Disability Assessment in Dementia (DAD), and Geriatric Depression Scale (GDS) scores. Exploratory outcomes were NTB component, CDR, and MMSE scores. Biomarkers included MRI-derived whole-brain, hippocampus, and entorhinal cortex volumes.

Results: Two hundred ten patients from 15 sites in Austria, Germany, and Israel were randomly allocated to placebo (107 patients) or ladostigil (103 patients). After 36 months, 21 of 103 patients on placebo and 14 of 99 patients receiving ladostigil progressed to Alzheimer disease (log-rank test = 0.162). There were no significant effects on the NTB composite, DAD, or GDS score. Whole-brain and hippocampus volumes decreased more in the placebo than in the ladostigil group (whole brain, = 0.025, Cohen d = 0.43; hippocampus, = 0.043, d = 0.43). Serious adverse events were reported by 28 of 107 patients treated with placebo and 26 of 103 with ladostigil.

Conclusion: Ladostigil was safe and well tolerated but did not delay progression to dementia. Its association with reduced brain and hippocampus volume loss suggests a potential effect on atrophy.

Clinicaltrialsgov Identifier: NCT01429623.

Classification Of Evidence: This study provides Class II evidence that for patients with MCI and medial temporal lobe atrophy, ladostigil did not significantly decrease the risk of the development of Alzheimer disease.
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http://dx.doi.org/10.1212/WNL.0000000000008239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010322PMC
October 2019

Optimization of ultrastructural preservation of human brain for transmission electron microscopy after long post-mortem intervals.

Acta Neuropathol Commun 2019 09 3;7(1):144. Epub 2019 Sep 3.

Research Unit Electron Microscopic Techniques, Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftigtalstrasse 6, 8010, Graz, Austria.

Electron microscopy (EM) provides the necessary resolution to visualize the finer structures of nervous tissue morphology, which is important to understand healthy and pathological conditions in the brain. However, for the interpretation of the micrographs the tissue preservation is crucial. The quality of the tissue structure is mostly influenced by the post mortem interval (PMI), the time of death until the preservation of the tissue. Therefore, the aim of this study was to optimize the preparation-procedure for the human frontal lobe to preserve the ultrastructure as well as possible despite the long PMIs. Combining chemical pre- and post-fixation with cryo-fixation and cryo-substitution ("hybrid freezing"), it was possible to improve the preservation of the neuronal profiles of human brain samples compared to the "standard" epoxy resin embedding method. In conclusion short PMIs are generally desirable but up to a PMI of 16 h the ultrastructure can be preserved on an acceptable level with a high contrast using the "hybrid freezing" protocol described here.
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http://dx.doi.org/10.1186/s40478-019-0794-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724377PMC
September 2019

Investigating the origin and evolution of cerebral small vessel disease: The RUN DMC - InTENse study.

Eur Stroke J 2018 Dec 9;3(4):369-378. Epub 2018 May 9.

Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.

Background: Neuroimaging in older adults commonly reveals signs of cerebral small vessel disease (SVD). SVD is believed to be caused by chronic hypoperfusion based on animal models and longitudinal studies with inter-scan intervals of years. Recent imaging evidence, however, suggests a role for acute ischaemia, as indicated by incidental diffusion-weighted imaging lesions (DWI+ lesions), in the origin of SVD. Furthermore, it becomes increasingly recognised that focal SVD lesions likely affect the structure and function of brain areas remote from the original SVD lesion. However, the temporal dynamics of these events are largely unknown.

Aims: (1) To investigate the monthly incidence of DWI+ lesions in subjects with SVD; (2) to assess to which extent these lesions explain progression of SVD imaging markers; (3) to investigate their effects on cortical thickness, structural and functional connectivity and cognitive and motor performance; and (4) to investigate the potential role of the innate immune system in the pathophysiology of SVD.

Design/methods: The RUN DMC - InTENse study is a longitudinal observational study among 54 non-demented RUN DMC survivors with mild to severe SVD and no other presumed cause of ischaemia. We performed MRI assessments monthly during 10 consecutive months (totalling up to 10 scans per subject), complemented with clinical, motor and cognitive examinations.

Discussion: Our study will provide a better understanding of the role of DWI+ lesions in the pathophysiology of SVD and will further unravel the structural and functional consequences and clinical importance of these lesions, with an unprecedented temporal resolution. Understanding the role of acute, potentially ischaemic, processes in SVD may provide new strategies for therapies.
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http://dx.doi.org/10.1177/2396987318776088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571506PMC
December 2018

Lifespan normative data on rates of brain volume changes.

Neurobiol Aging 2019 09 22;81:30-37. Epub 2019 May 22.

Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. Electronic address:

We provide here normative values of yearly percentage brain volume change (PBVC/y) as obtained with Structural Imaging Evaluation, using Normalization, of Atrophy, a widely used open-source software, developing a PBVC/y calculator for assessing the deviation from the expected PBVC/y in patients with neurological disorders. We assessed multicenter (34 centers, 11 acquisition protocols) magnetic resonance imaging data of 720 healthy participants covering the whole adult lifespan (16-90 years). Data of 421 participants with a follow-up > 6 months were used to obtain the normative values for PBVC/y and data of 392 participants with a follow-up <1 month were selected to assess the intrasubject variability of the brain volume measurement. A mixed model evaluated PBVC/y dependence on age, sex, and magnetic resonance imaging parameters (scan vendor and magnetic field strength). PBVC/y was associated with age (p < 0.001), with 60- to 70-year-old participants showing twice more volume decrease than participants aged 30-40 years. PBVC/y was also associated with magnetic field strength, with higher decreases when measured by 1.5T than 3T scanners (p < 0.001). The variability of PBVC/y normative percentiles was narrower as the interscan interval was longer (e.g., 80th normative percentile was 50% smaller for participants with 2-year than with 1-year follow-up). The use of these normative data, eased by the freely available calculator, might help in better discriminating pathological from physiological conditions in the clinical setting.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.05.010DOI Listing
September 2019

Are morphologic features of recent small subcortical infarcts related to specific etiologic aspects?

Ther Adv Neurol Disord 2019 22;12:1756286419835716. Epub 2019 Apr 22.

Department of Neurology, Medical University of Graz, Austria.

Background: Recent small subcortical infarcts (RSSIs) mostly result from the occlusion of a single, small, brain artery due to intrinsic cerebral small-vessel disease (CSVD). Some RSSIs may be attributable to other causes such as cardiac embolism or large-artery disease, and their association with coexisting CSVD and vascular risk factors may vary with morphological magnetic resonance imaging (MRI) features.

Methods: We retrospectively identified all inpatients with a single symptomatic MRI-confirmed RSSI between 2008 and 2013. RSSIs were rated for size, shape, location (i.e. anterior: basal ganglia and centrum semiovale posterior cerebral circulation: thalamus and pons) and MRI signs of concomitant CSVD. In a further step, clinical data, including detailed diagnostic workup and vascular risk factors, were analyzed with regard to RSSI features.

Results: Among 335 RSSI patients (mean age 71.1 ± 12.1 years), 131 (39%) RSSIs were >15 mm in axial diameter and 66 (20%) were tubular shaped. Atrial fibrillation (AF) was present in 44 (13.1%) and an ipsilateral vessel stenosis > 50% in 30 (9%) patients. Arterial hypertension and CSVD MRI markers were more frequent in patients with anterior-circulation RSSIs, whereas diabetes was more prevalent in posterior-circulation RSSIs. Larger RSSIs occurred more frequently in the basal ganglia and pons, and the latter were associated with signs of large-artery atherosclerosis. Patients with concomitant AF had no specific MRI profile.

Conclusion: Our findings suggest the contribution of different pathophysiological mechanisms to the occurrence of RSSIs in the anterior and posterior cerebral circulation. While there appears to be some general association of larger infarcts in the pons with large-artery disease, we found no pattern suggestive of AF in RSSIs.
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http://dx.doi.org/10.1177/1756286419835716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477767PMC
April 2019

The role of iron and myelin in orientation dependent R of white matter.

NMR Biomed 2019 07 30;32(7):e4092. Epub 2019 Apr 30.

Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada.

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R relaxation rate. However, their quantification based on R maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R shows a linear increase with increasing iron content. In white matter, R is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R decay in white matter. Applying our model to fibre orientation-dependent in vivo R data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non-lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin-induced orientation-dependent and iron-induced orientation-independent components is able to fit in vivo R data.
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http://dx.doi.org/10.1002/nbm.4092DOI Listing
July 2019

Quantifying blood-brain barrier leakage in small vessel disease: Review and consensus recommendations.

Alzheimers Dement 2019 06 25;15(6):840-858. Epub 2019 Apr 25.

Centre for Clinical Brain Science, University of Edinburgh, Edinburgh, UK; Dementia Research Institute, University of Edinburgh, Edinburgh, UK; Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.

Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia.
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http://dx.doi.org/10.1016/j.jalz.2019.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565805PMC
June 2019

Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration.

Alzheimers Dement (Amst) 2019 Dec 26;11:191-204. Epub 2019 Feb 26.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Introduction: Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease.

Methods: Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis.

Results: A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository.

Conclusions: The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease.
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http://dx.doi.org/10.1016/j.dadm.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396326PMC
December 2019

Magnetic resonance elastography of the human brain using a multiphase DENSE acquisition.

Magn Reson Med 2019 06 29;81(6):3578-3587. Epub 2019 Jan 29.

Department of Neurology, Medical University of Graz, Graz, Austria.

Purpose: In magnetic resonance elastography (MRE), a series of time-shifted images is acquired at specific phase offsets in relation to an induced mechanical excitation. To efficiently gather the set of phase offset images and to overcome limitations due to prolonged TEs and related susceptibility artifacts at low-frequency MRE, we developed an improved displacement encoding with a stimulated echoes (DENSE) method.

Methods: The proposed multiphase DENSE-MRE acquisition scheme allows full sampling of the wave propagation in 1 encoding direction during each TR using multiple readouts at specific phase offsets. With this approach, all phase offsets can be imaged in 1 TR without the need for whole sequence repetitions at time-shifted offsets relative to the excitation motion. We tested this technique in phantom experiments with 60 Hz and in the brain of 4 volunteers using 20-Hz harmonic excitation.

Results: Three-dimensional wave propagation could be acquired in 7 minutes 30 seconds. Following background phase elimination, clear wave images were obtained, showing the propagation of the waves over time. Calculated shear modulus maps of the phantom matched well to the maps obtained by conventional gradient-echo MRE. In the brain, low-frequency DENSE-MRE images were free of susceptibility-induced artifacts and the calculated maps showed a median global complex shear modulus magnitude of 0.72 kPa and phase angle of 1.03 rad across volunteers.

Conclusion: The proposed multiphase DENSE approach allows efficient low-frequency MRE with short TEs and is well-suited for low-frequency MRE of the human brain.
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http://dx.doi.org/10.1002/mrm.27672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590321PMC
June 2019
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