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Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons in the brain, brainstem, and spinal cord. It has been proposed that bone marrow (BM)-derived cells might supply motor neurons and other cells with a cellular milieu more conducive to survival in ALS. Direct injection of stem cells in ALS is problematic because of the large expanse of the neuraxis that would need to be injected. We reasoned that transiently increasing the number of circulating hematopoietic stem cells might be a useful therapeutic approach. However, agents stimulating the activation and mobilization of hematopoietic stem cells may have adverse effects such as activation of microglial cells. We conducted a small pilot trial of the collection and reinfusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) in ALS patients and found no adverse effects, paving the way for a properly powered therapeutic trial with an optimized regimen of G-CSF. Muscle Nerve, 2007. [ABSTRACT FROM AUTHOR]

Purpose: T 1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T 1 mapping technique, using acquisition details from a seminal T 1 mapping paper on a standardized phantom and in human brains., Methods: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T 1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed., Results: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org., Conclusion: The T 1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T 1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T 1 variations in vivo., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that leads to severe fibrosis and cirrhosis. The aim of this study was to determine the diagnostic value of T1 and T2 mapping as well as extracellular volume fraction (ECV) for non-invasive assessment of liver fibrosis in AIH patients., Methods: In this prospective study, 27 patients (age range: 19-77 years) with AIH underwent liver MRI. T1 and T2 relaxation times as well as ECV were quantified by mapping techniques. The presence of significant fibrosis (≥ F2) was defined as magnetic resonance elastography (MRE)-based liver stiffness ≥ 3.66 kPa. MRE was used as reference standard, against which the diagnostic performance of MRI-derived mapping parameters was tested. Diagnostic performance was compared by utilizing receiver-operating characteristic (ROC) analysis., Results: MRE-based liver stiffness correlated with both, hepatic native T1 (r = 0.69; P < 0.001) as well as ECV (r = 0.80; P < 0.001). For the assessment of significant fibrosis, ECV yielded a sensitivity of 85.7% (95% confidence interval (CI): 60.1-96.0%) and a specificity of 84.6% (CI 60.1-96.0%); hepatic native T1 yielded a sensitivity of 85.7% (CI 60.1-96.0%); and a specificity of 76.9% (CI 49.7-91.8%). Diagnostic performance of hepatic ECV (area under the curve (AUC): 0.885), native hepatic T1 (AUC: 0.846) for assessment of significant fibrosis was similar compared to clinical fibrosis scores (APRI (AUC: 0.852), FIB-4 (AUC: 0.758), and AAR (0.654) (P > 0.05 for each comparison))., Conclusion: Quantitative mapping parameters such as T1 and ECV can identify significant fibrosis in AIH patients. Future studies are needed to explore the value of parametric mapping for the evaluation of different disease stages.

The visual scene-network-comprising the parahippocampal place area (PPA), retrosplenial cortex (RSC), and occipital place area (OPA)-shows a prolonged functional development. Structural development of white matter that underlies the scene-network has not been investigated despite its potential influence on scene-network function. The key factor for white matter maturation is myelination. However, research on myelination using the gold standard method of post-mortem histology is scarce. In vivo alternatives diffusion-weighted imaging (DWI) and myelin water imaging (MWI) so far report broad-scale findings that prohibit inferences concerning the scene-network. Here, we combine MWI, DWI tractography, and fMRI to investigate myelination in scene-network tracts in middle childhood, late childhood, and adulthood. We report increasing myelin from middle childhood to adulthood in right PPA-OPA, and trends towards increases in the left and right RSC-OPA tracts. Investigating tracts to regions highly connected with the scene-network, such as early visual cortex and the hippocampus, did not yield any significant age group differences. Our findings indicate that structural development coincides with functional development in the scene-network, possibly enabling structure-function interactions., Competing Interests: Declaration of competing interest BM works at Philips GmbH, Hamburg, Germany. Philips is the manufacturer and support service provider for the MRI machine used in this study. BM developed and implemented the GRASE sequence at the scanner and co-developed and provided the MWF maps generating algorithm. BM and Philips GmbH had no role in the funding, conceptualization, design, or statistical analysis of the study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) affects more than six million people, but reliable MRI biomarkers with which to diagnose patients have not been established. Magnetic resonance fingerprinting (MRF) is a recent quantitative technique that can provide relaxometric maps from a single sequence. The purpose of this study is to assess the potential of MRF to identify PD in patients and their disease severity, as well as to evaluate comfort during MRF. Twenty-five PD patients and 25 matching controls underwent 3 T MRI, including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 maps were generated by voxel-wise matching the measured MRF signal to a precomputed dictionary. All participants also received standard inversion recovery T1 and multi-echo T2 mapping. An ROI-based analysis of relaxation times was performed. Differences between patients and controls as well as techniques were determined by logistic regression, Spearman correlation and t-test. Patients were asked to estimate the subjective comfort of the MRF sequence. Both MRF-based T1 and T2 mapping discriminated patients from controls: T1 relaxation times differed most in cortical grey matter (PD 1337 ± 38 vs. control 1386 ± 37 ms; mean ± SD; P = .0001) and, in combination with normal-appearing white matter, enabled correct discrimination in 85.7% of cases (sensitivity 83.3%; specificity 88.0%; receiver-operating characteristic [ROC]) area under the curve [AUC] 0.87), while for T2 mapping the left putamen was the strongest classifier (40.54 ± 6.28 vs. 34.17 ± 4.96 ms; P = .0001), enabling differentiation of groups in 84.0% of all cases (sensitivity 80.0%; specificity 88.0%; ROC AUC 0.87). Relaxation time differences were not associated with disease severity. Standard mapping techniques generated significantly different relaxation time values and identified other structures as different between groups other than MRF. Twenty-three out of 25 PD patients preferred the MRF examination instead of a standard MRI. MRF-based mapping can identify PD patients with good comfort but needs further assessment regarding disease severity identification and its potential for comparability with standard mapping technique results., (© 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Magnetic resonance imaging (MRI) provides a means to non-invasively investigate the neurological links with dyslexia, a learning disability that affects one's ability to read. Most previous brain MRI studies of dyslexia and reading skill have used structural or diffusion imaging to reveal regional brain abnormalities. However, volumetric and diffusion MRI lack specificity in their interpretation at the microstructural level. Myelin is a critical neural component for brain function and plasticity, and as such, deficits in myelin may impact reading ability. MRI can estimate myelin using myelin water fraction (MWF) imaging, which is based on evaluation of the proportion of short T2 myelin-associated water from multi-exponential T2 relaxation analysis, but has not yet been applied to the study of reading or dyslexia. In this study, MWF MRI, intelligence, and reading assessments were acquired in 20 participants aged 10-18 years with a wide range of reading ability to investigate the relationship between reading ability and myelination. Group comparisons showed markedly lower MWF by 16-69% in poor readers relative to good readers in the left and right thalamus, as well as the left posterior limb of the internal capsule, left/right anterior limb of the internal capsule, left/right centrum semiovale, and splenium of the corpus callosum. MWF over the entire group also correlated positively with three different reading scores in the bilateral thalamus as well as white matter, including the splenium of the corpus callosum, left posterior limb of the internal capsule, left anterior limb of the internal capsule, and left centrum semiovale. MWF imaging from T2 relaxation suggests that myelination, particularly in the bilateral thalamus, splenium, and left hemisphere white matter, plays a role in reading abilities. Myelin water imaging thus provides a potentially valuable in vivo imaging tool for the study of dyslexia and its remediation., (Copyright © 2020 Beaulieu, Yip, Low, Mädler, Lebel, Siegel, Mackay and Laule.)

Demyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF). However, long computation times and high noise sensitivity hinder the translation of MWF imaging to clinical practice. In this work, we introduce a more efficient and noise robust method to determine the MWF using a joint sparsity constraint and a pre-computed B 1 + dictionary. A single component analysis with this dictionary is used in an initial step to obtain a B 2 dictionary. A single component analysis with this dictionary is used in an initial step to obtain a B 1 distribution is then determined from a reduced dictionary corresponding to the estimated B + map. The T 2 distribution is then determined from a reduced dictionary corresponding to the estimated B 1 + map using a combination of a non-negativity and a joint sparsity constraint. The non-negativity constraint ensures that a feasible solution with non-negative contribution of each T 2 component is obtained. The joint sparsity constraint restricts the T 2 distribution to a small set of T 2 relaxation times shared between all voxels and reduces the noise sensitivity. The applied Sparsity Promoting Iterative Joint NNLS (SPIJN) algorithm can be implemented efficiently, reducing the computation time by a factor of 50 compared to the commonly used regularized non-negative least squares algorithm. The proposed method was validated in simulations and in 8 healthy subjects with a 3D multi-echo gradient- and spin echo scan at 3 ​T. In simulations, the absolute error in the MWF decreased from 0.031 to 0.013 compared to the regularized NNLS algorithm for SNR ​= ​250. The in vivo results were consistent with values reported in literature and improved MWF-quantification was obtained especially in the frontal white matter. The maximum standard deviation in mean MWF in different regions of interest between subjects was smaller for the proposed method (0.0193) compared to the regularized NNLS algorithm (0.0266). In conclusion, the proposed method for MWF estimation is less computationally expensive and less susceptible to noise compared to state of the art methods. These improvements might be an important step towards clinical translation of MWF measurements., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The corpus callosum serves the functional integration and interaction between the two hemispheres. Many studies investigate callosal microstructure via diffusion tensor imaging (DTI) fractional anisotropy (FA) in geometrically parcellated segments. However, FA is influenced by several different microstructural properties such as myelination and axon density, hindering a neurobiological interpretation. This study explores the relationship between FA and more specific measures of microstructure within the corpus callosum in a sample of 271 healthy participants. DTI tractography was used to assess 11 callosal segments and gain estimates of FA. We quantified axon density and myelination via neurite orientation dispersion and density imaging (NODDI) to assess intra-neurite volume fraction and a multiecho gradient spin-echo sequence estimating myelin water fraction. The results indicate three common factors in the distribution of FA, myelin content and axon density, indicating potentially shared rules of topographical distribution. Moreover, the relationship between measures varied across the corpus callosum, suggesting that FA should not be interpreted uniformly. More specific magnetic resonance imaging-based quantification techniques, such as NODDI and multiecho myelin water imaging, may thus play a key role in future studies of clinical trials and individual differences., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background and Purpose: Myelin water imaging (MWI) and diffusion tensor imaging (DTI) provide information about myelin and axon-related brain microstructure, which can be useful for investigating normal brain development and many childhood brain disorders. While pediatric DTI atlases exist, there are no pediatric MWI atlases available for the 9-10 years old age group. As myelination and structural development occurs throughout childhood and adolescence, studies of pediatric brain pathologies must use age-specific MWI and DTI healthy control data. We created atlases of myelin water fraction (MWF) and DTI metrics for healthy children aged 9-10 years for use as normative data in pediatric neuroimaging studies., Methods: 3D-T 1 , DTI, and MWI scans were acquired from 20 healthy children (mean age: 9.6 years, range: 9.2-10.3 years, 4 females). ANTs and FSL registration were used to create quantitative MWF and DTI atlases. Region of interest (ROI) analysis in nine white matter regions was used to compare pediatric MWF with adult MWF values from a recent study and to investigate the correlation between pediatric MWF and DTI metrics., Results: Adults had significantly higher MWF than the pediatric cohort in seven of the nine white matter ROIs, but not in the genu of the corpus callosum or the cingulum. In the pediatric data, MWF correlated significantly with mean diffusivity, but not with axial diffusivity, radial diffusivity, or fractional anisotropy., Conclusions: Normative MWF and DTI metrics from a group of 9-10 year old healthy children provide a resource for comparison to pathologies. The age-specific atlases are ready for use in pediatric neuroimaging research and can be accessed: https://sourceforge.net/projects/pediatric-mri-myelin-diffusion/., (© 2020 by the American Society of Neuroimaging.)

Purpose: Limbic encephalitis (LE) is an immune-related disease with limbic symptoms, variable and asymmetric magnetic resonance imaging (MRI) aspects and antibody profiles. This study investigated the diagnostic value of quantitative relaxation times T2 (qT2) and MRI signal intensities (SI) in LE., Methods: The prospective 3T-MRI study included 39 epilepsy patients with initially suspected LE and 20 healthy controls. Values and asymmetry indices of qT2, T2-weighted (T2-w) and proton density (PD)-w SI of manually delineated and automatically segmented amygdala and hippocampus were measured. Additionally, two raters made a blinded visual analysis on FLAIR (fluid attenuation inversion recovery) and T2-w images., Results: According to diagnostic guidelines, 22 patients had probable LE and 17 patients had possible LE. The qT2 was higher (p < 0.01) in patients than in controls (mean ± SD, amygdala 98 ± 7 ms vs. 90 ± 5 ms, hippocampus 101 ± 7 ms vs. 92 ± 3 ms), but was not different between probable and possible LE or between sides (left and right). The PD-w SI and T2-w SI were lower in patients than in controls but were not different between patient subgroups or between sides. Diagnostic performance of visual analysis was relatively poor., Conclusions: Epilepsy patients with suspected LE had elevated qT2 in amygdala and hippocampus, whereas the expected T2-w SI increase was not found; however, the diagnostic value of qT2 remains questionable since it did not discriminate probable from possible LE.

Several very rare forms of dementia are associated with characteristic focal atrophy predominantly of the frontal and/or temporal lobes and currently lack imaging solutions to monitor disease. Magnetic resonance fingerprinting (MRF) is a recently developed technique providing quantitative relaxivity maps and images with various tissue contrasts out of a single sequence acquisition. This pilot study explores the utility of MRF-based T1 and T2 mapping to discover focal differences in relaxation times between patients with frontotemporal lobe degenerative dementia and healthy controls. 8 patients and 30 healthy controls underwent a 3 T MRI including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 relaxation maps were generated based on an extended phase graphs algorithm-founded dictionary involving inner product pattern matching. A region of interest (ROI)-based analysis of T1 and T2 relaxation times was performed with FSL and ITK-SNAP. Depending on the brain region analyzed, T1 relaxation times were up to 10.28% longer in patients than in controls reaching significant differences in cortical gray matter (P = .047) and global white matter (P = .023) as well as in both hippocampi (P = .001 left; P = .027 right). T2 relaxation times were similarly longer in the hippocampus by up to 19.18% in patients compared with controls. The clinically most affected patient had the most control-deviant relaxation times. There was a strong correlation of T1 relaxation time in the amygdala with duration of the clinically manifest disease (Spearman Rho = .94; P = .001) and of T1 relaxation times in the left hippocampus with disease severity (Rho = .90, P = .002). In conclusion, MRF-based relaxometry is a promising and time-saving new MRI tool to study focal cerebral alterations and identify patients with frontotemporal lobe degeneration. To validate the results of this pilot study, MRF is worth further exploration as a diagnostic tool in neurodegenerative diseases., (© 2019 John Wiley & Sons, Ltd.)

Introduction: Clinical trials that involve participants from multiple sites necessitate standardized and reliable quantitative MRI outcomes to detect significant group differences over time. Metabolite concentrations measured by proton MRS ( 1 H-MRS) provide valuable information about in vivo metabolism of the central nervous system, but can vary based on the acquisition and quantitation methods used by different MR sites. Therefore, we investigated the intra- and inter-site reproducibility of metabolite concentrations measured by 1 H-MRS on MRI scanners from a single manufacturer across six sites., Methods: Five healthy controls were scanned twice within 24 h at six participating 3 T MR sites with large single-voxel PRESS (TE/TR/NSA = 36 ms/4000 ms/56) and anatomical images for voxel positioning and correction of partial volume relaxation. Absolute metabolite concentrations were calculated relative to the T 1 and T 2 relaxation corrected signal from water. Intra- and inter-site reproducibility was assessed using Bland-Altman plots and intra- and inter-site coefficient of variation (CoV) as well as intra- and inter-site intra-class correlation coefficient., Results: The median intra-site CoVs for the five major metabolite concentrations ([NAA], [tCr], [Glu], [tCho] and [Ins]) were between 2.5 and 5.3%. Inter-site CoVs were also low, with the median CoVs for all metabolites between 3.7 and 6.4%. Metabolite concentrations were robust to small inconsistencies in voxel placement and site was not the driving factor in the variance of the measurement of any metabolite concentration. Between-subject differences accounted for the majority of the concentration variability for creatine, choline and myo-inositol (42-65% of the variance)., Conclusion: A large single-voxel 1 H-MRS acquisition from a single manufacturer's MRI scanner is highly reproducible and reliable for multi-site clinical trials., (© 2019 John Wiley & Sons, Ltd.)

Myelination of axons in the central nervous system is critical for human cognition and behavior. The predominant protein in myelin is proteolipid protein-making PLP1, the gene that encodes for proteolipid protein, one of the primary candidate genes for white matter structure in the human brain. Here, we investigated the relation of genetic variation within PLP1 and white matter microstructure as assessed with myelin water fraction imaging, a neuroimaging technique that has the advantage over conventional diffusion tensor imaging in that it allows for a more direct assessment of myelin content. We observed significant asymmetries in myelin water fraction that were strongest and rightward in the parietal lobe. Importantly, these parietal myelin water fraction asymmetries were associated with genetic variation in PLP1. These findings support the assumption that genetic variation in PLP1 affects white matter myelination in the healthy human brain.

Background and Purpose: Quantitative T 1 and diffusion tensor imaging (DTI) may provide information about pathological changes underlying disability and progression in diseases like multiple sclerosis (MS). Imaging the corpus callosum (CC), a primary site of damage in MS with a critical role in interhemispheric connectivity, may be useful for assessing overall brain health, prognosis, and therapy efficacy. We assessed the feasibility of multisite clinical trials using advanced MRI by examining the intra and intersite reproducibility of T 1 and DTI measurements in the CC and segmented white matter (WM)., Methods: Five healthy volunteers were scanned twice within 24 hours at six 3T sites. Coefficients of variation (COVs) and intraclass correlation coefficients (ICCs) for CC and WM T 1 , fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (D ax ), and radial diffusivity (D rad ) assessed intrasite and intersite reliability., Results: CC and WM T 1 showed excellent intrasite reproducibility with low COVs (mean = .90% and .89%, respectively) and good ICCs (CC = .78, WM = .90). T 1 also demonstrated intersite reliability (low COVs: CC = 2.4%, WM = 1.8%; moderate ICCs: CC = .43, WM = .69). DTI had low intrasite COVs (CC: FA = 1.3%, MD = 1.5%, D ax = 1.4%, D rad = 2.2%; WM: FA = .9%, MD = .9%, D ax = .7%, D rad = 1.2%) and high intrasite ICCs (CC: FA = .95, MD = .97, D ax = .94, D rad = .97; CC: FA = .9, MD = .66, D ax = .88, D rad = .63), indicating excellent intrasite reproducibility. DTI also showed excellent intersite reliability with low COVs (CC: FA = 2.1%, MD = 4.1%, D ax = 3.4%, D rad = 5.3%, WM: FA = 1.3%, MD = 1.9%, D ax = 1.8%, D rad = 2.1%,) and good ICCs (CC: FA = .90, MD = .84, D ax = .72, D rad = .90; WM: FA = .83, MD = .34, D ax = .62, D rad = .41)., Conclusions: T 1 and DTI measures are reproducible using equivalent MRI scanners and sequence protocols. Using a similar MR system, it is feasible to carry out multicenter studies using T 1 and DTI to evaluate changes within the CC and WM., (© 2018 by the American Society of Neuroimaging.)

Purpose: To compare the recently introduced inhomogeneous magnetization transfer (ihMT) technique with more established MRI techniques including myelin water imaging (MWI) and diffusion tensor imaging (DTI), and to evaluate the microstructural attributes correlating with this new contrast method in the human brain white matter., Methods: Eight adult healthy volunteers underwent T 1 -weighted, ihMT, MWI, and DTI imaging on a 3T human scanner. The ihMT ratio (ihMTR), myelin water fraction (MWF), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) values were calculated from different white matter tracts. The angle ( θ ) between the directions of the principal eigenvector, as measured by DTI, and the main magnetic field was calculated for all voxels from various fiber tracts. The ihMTR was correlated with MWF and DTI metrics., Results: A strong correlation was found between ihMTR and MWF (ρ = 0.77, P < 0.0001). This was followed by moderate to weak correlations between ihMTR and DTI metrics: RD (ρ = -0.30, P < 0.0001), FA (ρ = 0.20, P < 0.0001), MD (ρ = -0.19, P < 0.0001), AD (ρ = 0.02, P < 0.0001). A strong correlation was found between ihMTR and θ (ρ = -0.541, P < 0.0001)., Conclusion: The strong correlation with myelin water imaging and its low coefficient of variation suggest that ihMT has the potential to become a new structural imaging marker of myelin. The substantial orientational dependence of ihMT should be taken into account when evaluating and quantitatively interpreting ihMT results., (© 2018 International Society for Magnetic Resonance in Medicine.)