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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.)

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.)

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 + -T 2 dictionary. A single component analysis with this dictionary is used in an initial step to obtain a B 1 + 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.)

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.)

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.

Purpose: To investigate the effect of the choice of the curve-fitting model on the perfusion fraction (f IVIM ) with regard to tissue type characterization, correlation with microvascular anatomy, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters. Several curve-fitting models coexist in intravoxel incoherent motion (IVIM) MRI to derive the (f IVIM )., Materials and Methods: In all, 29 patients with brain lesions (12 gliomas, 11 meningiomas, three metastases, two gliotic scars, one multiple sclerosis) underwent IVIM-MRI (32 b-values, 0 to 2000 s/mm 2 ) at 3T. f IVIM was determined by classic monoexponential, biexponential, and a novel nonnegative least squares (NNLS) fitting in 352 regions of interest (lesion-containing and normal-appearing tissue) and tested their correlation with DCE-MRI kinetic parameters and microvascular anatomy derived from 57 region of interest (ROI)-based biopsies and their capacities to differentiate histologically different lesions., Results: f IVIM differed significantly between all three models and all tissue types (monoexponential confidence interval in percent [CI 3.4-3.8]; biexponential [CI 11.21-12.45]; NNLS [CI 2.06-2.60]; all P < 0.001). For all models an increase in f IVIM was associated with a shift to larger vessels and higher vessel area / tissue area ratio (regression coefficient 0.07-0.52; P = 0.04-0.001). Correlation with kinetic parameters derived from DCE-MRI was usually not significant. Only biexponential fitting allowed differentiation of both gliosis from edema and high- from low-grade glioma (both P < 0.001)., Conclusion: The curve-fitting model has an important impact on f IVIM and its capacity to differentiate tissues. f IVIM may possibly be used to assess microvascular anatomy and is weakly correlated with DCE-MRI kinetic parameters., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1187-1199., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: Kinetic parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) were suggested as a possible instrument for multi-parametric lesion characterization, but have not found their way into clinical practice yet due to inconsistent results. The quantification is heavily influenced by the definition of an appropriate arterial input functions (AIF). Regarding brain tumor DCE-MRI, there are currently several co-existing methods to determine the AIF frequently including different brain vessels as sources. This study quantitatively and qualitatively analyzes the impact of AIF source selection on kinetic parameters derived from commonly selected AIF source vessels compared to a population-based AIF model., Material and Methods: 74 patients with brain lesions underwent 3D DCE-MRI. Kinetic parameters [transfer constants of contrast agent efflux and reflux K trans and k ep and, their ratio, v e, that is used to measure extravascular-extracellular volume fraction and plasma volume fraction v p ] were determined using extended Tofts model in 821 ROI from 4 AIF sources [the internal carotid artery (ICA), the closest artery to the lesion, the superior sagittal sinus (SSS), the population-based Parker model]. The effect of AIF source alteration on kinetic parameters was evaluated by tissue type selective intra-class correlation (ICC) and capacity to differentiate gliomas by WHO grade [area under the curve analysis (AUC)]., Results: Arterial AIF more often led to implausible v e >100% values (p<0.0001). AIF source alteration rendered different absolute kinetic parameters (p<0.0001), except for k ep . ICC between kinetic parameters of different AIF sources and tissues were variable (0.08-0.87) and only consistent >0.5 between arterial AIF derived kinetic parameters. Differentiation between WHO III and II glioma was exclusively possible with v p derived from an AIF in the SSS (p=0.03; AUC 0.74)., Conclusion: The AIF source has a significant impact on absolute kinetic parameters in DCE-MRI, which limits the comparability of kinetic parameters derived from different AIF sources. The effect is also tissue-dependent. The SSS appears to be the best choice for AIF source vessel selection in brain tumor DCE-MRI as it exclusively allowed for WHO grades II/III and III/IV glioma distinction (by v p ) and showed the least number of implausible v e values., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this "cloudy" enhancement during radio-chemotherapy and its impact on patients' progression-free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T-MRI pre- and post contrast agent with standard T1-weighted (T1w) and with sequences to quantify T1 before radiation, and at 6-week intervals during radio-chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy-enhancing compartment and evaluated the impact of their therapy-related volume change upon PFS. In ∆qT1 maps cloudy-enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy-enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy-enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy-enhancing compartment at first follow-up predicted longer PFS (P = 0.038). Cloudy-enhancing compartment outside the solid contrast-enhancing area of GBM is a new observation which is only visually detectable with qT1-mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio-chemotherapy., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background Context: Magnetic resonance imaging (MRI) is a very useful diagnostic test for cervical spondylotic myelopathy (CSM) because it can identify degenerative changes within the spinal cord (SC), disclose the extent, localization, and the kind of SC compression, and help rule out other SC disorders. However, the relationships between changes in cerebrospinal fluid (CSF) flow, cord motion, the extent and severity of spinal canal stenosis, and the development of CSM symptoms are not well understood., Purpose: To evaluate if changes in the velocity of CSF and SC movements provide additional insight into the pathophysiological mechanisms underlying CSM beyond MRI observations of cord compression., Study Design: Prospective radiologic study of recruited patients., Patient Sample: Thirteen CSM subjects and 15 age and gender matched controls., Outcome Measures: Magnetic resonance imaging measures included CSF and SC movement. Cervical cord condition was assessed by the Japanese Orthopaedic Association (JOA) score, compression ratio (CR), and somatosensory evoked potentials (SSEPs) of the tibial and ulnar nerves., Methods: Phase-contrast imaging at the level of stenosis for patients and at C5 for controls and T2-weighted images were compared with clinical findings., Results: Cerebrospinal fluid velocity was significantly reduced in CSM subjects as compared with controls and was related to cord CR. Changes in CSF velocity and cord compression were not correlated with clinical measures (JOA scores, SSEP) or the presence of T2 hyperintensities. Spinal cord movements, that is, cord displacement and velocity in the craniocaudal axis, were increased in CSM patients. Increased SC movements (ie, total cord displacement) both in the controls and CSM subjects were associated with altered spinal conduction as assessed by SSEP., Conclusions: This study revealed rather unexpected increased cord movements in the craniocaudal axis in CSM patients that may contribute to myelopathic deteriorations in combination with spinal canal compression. Understanding the relevance of cord movements with respect to supporting the clinical CSM diagnosis or disease monitoring requires further long-term follow-up studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To assess the reproducibility of myelin water fraction (MWF) and geometric mean T2 (GMT2 ), which are in vivo markers of pathological changes underlying disability and progression in diseases such as multiple sclerosis., Materials and Methods: Five healthy volunteers were scanned twice within 24 hours at six different sites using the same manufacturer's 3T magnetic resonance (MR) system. T2 distributions were produced by fitting multiecho 3D T2 data using non-negative least squares, with stimulated echo correction. MWF, the fraction of signal with T2 between 15 and 40 msec to the entire signal, and GMT2 , the mean T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white matter., Results: Intrasite coefficients of variation (COVs) were low (mean 3.99% for MWF and 0.51% for GMT2 ), as were intersite COVs (mean 4.68% for MWF, 0.31% for GMT2 ). Scan-rescan intraclass correlation coefficients (ICCs) (0.76 for MWF and 0.93 for GMT2 ) and Bland-Altman plots indicated good agreement between single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for GMT2 ), revealing good intersite reliability., Conclusion: MWF and GMT2 measures are reproducible between scans and across sites with an equivalent MR scanner and sequence protocol. Multicenter clinical trials using quantitative T2 relaxation are feasible., (Copyright © 2013 Wiley Periodicals, Inc.)

Myelin water imaging, a magnetic resonance imaging technique capable of resolving the fraction of water molecules which are located between the layers of myelin, is a valuable tool for investigating both normal and pathological brain structure in vivo. There is a strong need for pulse sequences which improve the quality and applicability of myelin water imaging in a clinical setting. In this study, we validated the use of a fast multi echo T(2) relaxation sequence for myelin water imaging. Using a multiple combined gradient and spin echo (GRASE) technique, we attain whole cerebrum myelin water images in under 15 minutes. Region of interest analysis indicates that this fast GRASE imaging sequence produces results which are in good agreement with pure spin echo measurements (R(2)=0.95, p<0.0001). This drastic improvement in speed and brain coverage compared to current spin echo standards will allow increased inclusion of myelin water imaging in neurological research protocols and opens up the possibility of applications in a clinical setting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We propose a multicomponent fitting algorithm for multiecho T(2) data which allows for correction of T(2) distributions in the presence of stimulated echoes. Tracking the population of spins in many coherence pathways via the iterated method of the Extended Phase Graph algorithm allows for accurate quantification of echo magnitudes. The resulting decay curves allow for correction of errors due to nonideal refocusing pulses as a result of inhomogeneities in the B(1) transmit field. Non-Negative Least Squares fitting is used to quantify the magnitude of T(2) components at various T(2) values. This method, allowing calculation of the T(2) distribution with simultaneous extraction of the refocusing pulse flip angle, requires no change to image acquisition procedures and no extra data input. Validation by means of both simulations and in vivo data shows excellent interscan reproducibility while vastly improving the accuracy of extracted T(2) parameters in voxels where poor B(1) homogeneity leads to refocusing pulse flip angles significantly less than 180°. Most notably, myelin water fraction values in these regions are found to have increased consistency and accuracy., (Copyright © 2011 Wiley Periodicals, Inc.)

Multiecho T(2) relaxation measurements offer specific information about myelin content through the myelin water fraction (MWF), as well as about the water environments through the intra- and extra-cellular (IE), and global, geometric mean T(2) (GMT(2)) times. While these measurements have yielded new insights into brain development and pathologies, they have yet to be thoroughly investigated in the spinal cord. The goals of this study were: (1) to apply a new 3D multiecho T(2) relaxation measurement in the cervical spine with sufficient axial resolution to distinguish grey and white matter; (2) to perform a pilot reliability assessment of the resulting MWF and GMT(2) measures in a target population; and (3) to detect differences in these measures between a younger cohort (20-30 years of age) and an older cohort (50-75 years of age) of healthy adults. The results demonstrated that the MWF in younger healthy adults follows the known pattern of lower myelin content in grey matter (mean (95% confidence interval)) (0.049 (0.030-0.067)) as compared to white matter (0.296 (0.275-0.317), p<0.001). The reliability coefficients were 0.65 and 0.82 for the MWF in the dorsal (DC) and lateral column (LC) white matter, respectively; 0.79 and 0.52 for the IE GMT(2); and 0.74 and 0.73 for the global GMT(2). Significantly lower MWF were found in the older adults than in the younger adults (DC p=0.014; LC p=0.012), as well as lower IE GMT(2) times (DC p=0.008; LC p=0.042), however, the global GMT(2) times did not show any differences. These changes in MWF and IE GMT(2) times, but not in global GMT(2) times, indicate that multiecho T(2) relaxation measures are sensitive to changes in myelin integrity and cell morphology that may not be apparent on conventional T(2) weighted images., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This study compared region of interest (ROI) and voxel-based analysis (VBA) methods to determine the optimal method of myelin water fraction (MWF) analysis. Twenty healthy controls were scanned twice using a multi-echo T(2) relaxation sequence and ROIs were drawn in white and grey matter. MWF was defined as the fractional signal from 15 to 40 ms in the T(2) distribution. For ROI analysis, the mean intensity of voxels within an ROI was fit using non-negative least squares. For VBA, MWF was obtained for each voxel and the mean and median values within an ROI were calculated. There was a slightly higher correlation between Scan 1 and 2 for the VBA method (R(2)=0.98) relative to the ROI method (R(2)=0.95), and the VBA mean square difference between scans was 300% lower, indicating VBA was the most consistent between scans. For the VBA method, mean MWF was found to be more reproducible than median MWF. As the VBA method is more reproducible and gives more options for visualization and analysis of MWF, it is recommended over the ROI method of MWF analysis.

Multicomponent T(2) relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). The goal of this study was to implement and develop the single-slice T(2)-imaging technique proposed by Poon and Henkelman. For refinement, scan parameters (gradient crusher height and slew rate, bandwidth, echo spacing, matrix size, repetition time, and phase rewinding) were varied in water-based phantoms and in fixed and in vivo brain. Changes in the standard deviation of the residuals of the multiexponential fit, MWF, T(2), and peak width of the intra/extracellular water were monitored to determine which scan parameters minimized artifacts. Subsequently, we compared multicomponent T(2) measurements at 1.5T and 3.0T for 10 healthy volunteers, and investigated the differences in SNR, fit residuals, MWF, and T(2) and peak width of the intra/extracellular water, at higher magnetic field. MWF maps were found to be qualitatively similar between field strengths. MWFs were found to be significantly higher at 3.0T than at 1.5T, but with a strongly significant correlation between measurements (R(2) > 0.92, P < 0.0005). The signal-to-noise ratio (SNR) was nearly double at 3.0T, but the standard deviation of residuals was increased in most cases., ((c) 2009 Wiley-Liss, Inc.)

Purpose: To describe what, if any, specific long T(2)-related abnormalities occur in the white matter of subjects with either phenylketonuria (PKU) or multiple sclerosis (MS)., Materials and Methods: The 48-echo T(2) relaxation data (maximum TE = 1.12 sec) were acquired from 15 PKU subjects, 20 MS subjects, and 15 healthy volunteers. Regions of interest were drawn in diffuse white matter hyperintensities (DiffWM), lesions, normal-appearing white matter (NAWM), and normal white matter. Long T(2) maps (200 msec < T(2) < 800 msec) were created for each subject., Results: A new water reservoir with a markedly prolonged T(2) peak was identified in DiffWM and NAWM in 12 out of 15 subjects with PKU and a long T(2) signal was also seen in 23/97 lesions in 50% of subjects with MS. Additionally, a long T(2) component was observed in the corticospinal tracts of 10 healthy volunteers. The characteristics of the long T(2) signal were unique for each subject group. Potential sources of this signal include vacuolation and increases in extracellular water., Conclusion: This study supports the usefulness of increasing the data acquisition window of the multiecho T(2) relaxation sequence to better characterize the T(2) decay from pathological brain., ((c) 2007 Wiley-Liss, Inc.)

T2 weighting is particularly sensitive, but notoriously unspecific, to a wide range of brain pathologies. However, careful measurement and analysis of the T2 decay curve from brain tissue promise to provide much improved pathological specificity. In vivo T2 measurement requires accurate 180 pulses and appropriate manipulation of stimulated echoes; the most common approach is to acquire multiple echoes from a single slice. The T2 distribution, a plot of component amplitude as a function of T2, can be estimated using an algorithm capable of fitting a multi-exponential T2 decay with no a priori assumptions about the number of exponential components. T2 distributions from normal brain show peaks from myelin water, intra/extracellular water and cerebral spinal fluid; they can be used to provide estimates of total water content (total area under the T2 distribution) and myelin water fraction (MWF, fractional area under the myelin water peak), a measure believed to be related to myelin content. Experiments on bovine brain suggest that magnetization exchange between water pools plays a minor role in the T2 distribution. Different white matter structures have different MWFs. In normal white matter (NWM), MWF is not correlated with the magnetization transfer ratio (MTR) or the diffusion tensor fractional anisotropy (FA); hence it provides unique information about brain microstructure. Normal-appearing white matter (NAWM) in multiple sclerosis (MS) brain possesses a higher water content and lower MWF than controls, consistent with histopathological findings. Multiple sclerosis lesions demonstrate great heterogeneity in MWF, presumably due to varying myelin contents of these focal regions of pathology. Subjects with schizophrenia were found to have significantly reduced MWF in the minor forceps and genu of the corpus callosum when compared to controls, suggesting that reduced frontal lobe myelination plays a role in schizophrenia. In normal controls, frontal lobe myelination was positively correlated with both age and education; this result was not observed in subjects with schizophrenia. A strong correlation between MWF and the optical density from the luxol fast blue histological stain for myelin was observed in formalin-fixed brain, supporting the use of the MWF as an in vivo myelin marker.

Background and Purpose: Quantitative T1 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 T1 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 T1 , fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Dax ), and radial diffusivity (Drad ) assessed intrasite and intersite reliability.Results: CC and WM T1 showed excellent intrasite reproducibility with low COVs (mean = .90% and .89%, respectively) and good ICCs (CC = .78, WM = .90). T1 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%, Dax = 1.4%, Drad = 2.2%; WM: FA = .9%, MD = .9%, Dax = .7%, Drad = 1.2%) and high intrasite ICCs (CC: FA = .95, MD = .97, Dax = .94, Drad = .97; CC: FA = .9, MD = .66, Dax = .88, Drad = .63), indicating excellent intrasite reproducibility. DTI also showed excellent intersite reliability with low COVs (CC: FA = 2.1%, MD = 4.1%, Dax = 3.4%, Drad = 5.3%, WM: FA = 1.3%, MD = 1.9%, Dax = 1.8%, Drad = 2.1%,) and good ICCs (CC: FA = .90, MD = .84, Dax = .72, Drad = .90; WM: FA = .83, MD = .34, Dax = .62, Drad = .41).Conclusions: T1 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 T1 and DTI to evaluate changes within the CC and WM. [ABSTRACT FROM AUTHOR]

Background: Reduced myelin water fraction (MWF, a marker for myelin), increased geometric mean T2 (ieGMT2, reflecting intra/extracellular water properties), and increased T1 (related to total water content) have been observed in cross-sectional studies of multiple sclerosis (MS) normal-appearing white matter (NAWM). Objective: To assess longitudinal changes of magnetic resonance (MR) measures in relapsing-remitting MS (RRMS) brain NAWM. Methods: A total of 11 subjects with RRMS and 4 controls were scanned on a 3T MRI at baseline and long-term follow-up (LTFU; 3.2–5.8 years) with a 32-echo T2 relaxation and an inversion recovery T1 sequence. For every voxel, MWF, ieGMT2, and T1 were obtained. Mean, peak height, and peak location from NAWM mask-based histograms were determined. Results: In MS subjects, NAWM MWF mean decreased by 8% (p = 0.0016). No longitudinal changes were measured in T1 or ieGMT2. There was no relationship between change in any MR metric and change in EDSS. Control white matter showed no differences over time in any metric. Conclusion: The decreases we observed in MWF suggest that changes in myelin integrity and loss of myelin may be occurring diffusely and over long time periods in the MS brain. The timescale of these changes indicates that chronic, progressive myelin damage is an evolving process occurring over many years. [ABSTRACT FROM AUTHOR]

Background and Purpose: Late-onset adult Krabbe disease is a very rare demyelinating leukodystrophy, affecting less than 1 in a million people. Hematopoietic stem cell transplantation (HSCT) strategies can stop the accumulation of toxic metabolites that damage myelin-producing cells. We used quantitative advanced imaging metrics to longitudinally assess the impact of HSCT on brain abnormalities in adult-onset Krabbe disease.Methods: A 42-year-old female with late-onset Krabbe disease and an age/sex-matched healthy control underwent annual 3T MRI (baseline was immediately prior to HSCT for the Krabbe subject). Imaging included conventional scans, myelin water imaging, diffusion tensor imaging, and magnetic resonance spectroscopy.Results: Brain abnormalities far beyond those visible on conventional imaging were detected, suggesting a global pathological process occurs in Krabbe disease with adult-onset etiology, with myelin being more affected than axons, and evidence of wide-spread gliosis. After HSCT, our patient showed clinical stability in all measures, as well as improvement in gait, dysarthria, and pseudobulbar affect at 7.5 years post-transplant. No MRI evidence of worsening demyelination and axonal loss was observed up to 4 years post-allograft.Conclusions: Clinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late-onset Krabbe disease. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether differences in hydration state, which could arise from routine clinical procedures such as overnight fasting, affect brain total water content (TWC) and brain volume measured with magnetic resonance imaging (MRI).Materials and Methods: Twenty healthy volunteers were scanned with a 3T MR scanner four times: day 1, baseline scan; day 2, hydrated scan after consuming 3L of water over 12 hours; day 3, dehydrated scan after overnight fasting of 9 hours, followed by another scan 1 hour later for reproducibility. The following MRI data were collected: T2 relaxation (for TWC measurement), inversion recovery (for T1 measurement), and 3D T1 -weighted (for brain volumes). Body weight and urine specific gravity were also measured. TWC was calculated by fitting the T2 relaxation data with a nonnegative least-squares algorithm, with corrections for T1 relaxation and image signal inhomogeneity and normalization to ventricular cerebrospinal fluid. Brain volume changes were measured using SIENA. TWC means were calculated within 14 tissue regions.Results: Despite indications of dehydration as demonstrated by increases in urine specific gravity (P = 0.03) and decreases in body weight (P = 0.001) between hydrated and dehydrated scans, there was no measurable change in TWC (within any brain region) or brain volume between hydration states.Conclusion: We demonstrate that within a range of physiologic conditions commonly encountered in routine clinical scans (no pretreatment with hydration, well hydrated before MRI, and overnight fasting), brain TWC and brain volumes are not substantially affected in a healthy control cohort. J. Magn. Reson. Imaging 2016;44:296-304. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of metal artifact reduction techniques on dGEMRIC T calculation with surgical hardware present. Materials and methods: We examined the effect of stainless-steel and titanium hardware on dGEMRIC T maps. We tested two strategies to reduce metal artifact in dGEMRIC: (1) saturation recovery (SR) instead of inversion recovery (IR) and (2) applying the metal artifact reduction sequence (MARS), in a gadolinium-doped agarose gel phantom and in vivo with titanium hardware. T maps were obtained using custom curve-fitting software and phantom ROIs were defined to compare conditions (metal, MARS, IR, SR). Results: A large area of artifact appeared in phantom IR images with metal when TI ≤ 700 ms. IR maps with metal had additional artifact both in vivo and in the phantom (shifted null points, increased mean T (+151 % IR ROI) and decreased mean inversion efficiency (f; 0.45 ROI, versus 2 for perfect inversion)) compared to the SR maps (ROI: +13 % T SR, 0.95 versus 1 for perfect excitation), however, SR produced noisier T maps than IR (phantom SNR: 118 SR, 212 IR). MARS subtly reduced the extent of artifact in the phantom (IR and SR). Conclusions: dGEMRIC measurement in the presence of surgical hardware at 3T is possible with appropriately applied strategies. Measurements may work best in the presence of titanium and are severely limited with stainless steel. For regions near hardware where IR produces large artifacts making dGEMRIC analysis impossible, SR-MARS may allow dGEMRIC measurements. The position and size of the IR artifact is variable, and must be assessed for each implant/imaging set-up. [ABSTRACT FROM AUTHOR]

Purpose To assess the reproducibility of myelin water fraction (MWF) and geometric mean T2 (GMT2), which are in vivo markers of pathological changes underlying disability and progression in diseases such as multiple sclerosis. Materials and Methods Five healthy volunteers were scanned twice within 24 hours at six different sites using the same manufacturer's 3T magnetic resonance (MR) system. T2 distributions were produced by fitting multiecho 3D T2 data using non-negative least squares, with stimulated echo correction. MWF, the fraction of signal with T2 between 15 and 40 msec to the entire signal, and GMT2, the mean T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white matter. Results Intrasite coefficients of variation (COVs) were low (mean 3.99% for MWF and 0.51% for GMT2), as were intersite COVs (mean 4.68% for MWF, 0.31% for GMT2). Scan-rescan intraclass correlation coefficients (ICCs) (0.76 for MWF and 0.93 for GMT2) and Bland-Altman plots indicated good agreement between single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for GMT2), revealing good intersite reliability. Conclusion MWF and GMT2 measures are reproducible between scans and across sites with an equivalent MR scanner and sequence protocol. Multicenter clinical trials using quantitative T2 relaxation are feasible. J. Magn. Reson. Imaging 2013;38:1445-1453. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Immobility in bed and decreased mobility cause adaptations to most human body systems. The effect of immobility on fat accumulation in hemopoietic bone marrow has never been measured prospectively. The reversibility of marrow fat accumulation and the effects on hemopoiesis are not known. In the present study, 24 healthy women (age: 25-40 yr) underwent -6° head-down bed rest for 60 days. We used MRI to noninvasively measure the lumbar vertebral fat fraction at various time points. We also measured hemoglobin, erythropoietin, reticulocytes, leukocytes, platelet count, peripheral fat mass, leptin, cortisol, and Creactive protein during bed rest and for 1 yr after bed rest ended. Compared with baseline, the mean (± SE) fat fraction was increased after 60 days of bed rest (+ 2.5 ± 1.1%, P < 0.05); the increase persisted 1 yr after the resumption of regular activities (+2.3 ± 0.8%, P < 0.05). Mean hemoglobin levels were significantly decreased 6 days after bed rest ended (-1.36 ± 0.20 g/dl, P < 0.05) but had recovered at 1 yr, with significantly lower mean circulating erythropoietin levels (-3.8 ± 1.2 mU/mI, P < 0.05). Mean numbers of neutrophils and lymphocytes remained significantly elevated at 1 yr (+617 ± 218 neutrophils/μ.l and +498 ± 112 lymphocytes/μ.l, both P < 0.05). These results constitute direct evidence that bed rest irreversibly accelerated fat accumulation in hemopoietic bone marrow. The 2.5% increase in fat fraction after 60 days of bed rest was 25-fold larger than expected from historical ambulatory controls. Sixty days of bed rest accelerated by 4 yr the normal bone marrow involution. Bed rest and marrow adiposity were associated with hemopoietic stimulation. One year after subjects returned to normal activities, hemoglobin levels were maintained, with 43% lower circulating erythropoietin levels, and leukocytes remained significantly elevated across lineages. Lack of mobility alters hemopoiesis, possibly through marrow fat accumulation, with potentially wide-ranging clinical consequences. [ABSTRACT FROM AUTHOR]

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 (1H‐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 1H‐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 T1 and T2 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 1H‐MRS acquisition from a single manufacturer's MRI scanner is highly reproducible and reliable for multi‐site clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: The current study examined auditory processing deficits in dyslexia using a dichotic pitch stimulus and functional MRI. Cortical activation by the dichotic pitch task occurred in bilateral Heschl’s gyri, right planum temporale, and right superior temporal sulcus. Adolescents with dyslexia, relative to age-matched controls, illustrated greater activity in left Heschl’s gyrus for random noise, less activity in right Heschl’s gyrus for all auditory conditions, and less activity in right superior temporal sulcus for a dichotic melody. Subsequent analyses showed that these group differences were attributable to dyslexic readers who performed poorly on the psychophysical task. Furthermore, behavioral performance on phonological reading was correlated to activity from dichotic conditions in right Heschl’s gyrus and right superior temporal sulcus. It is postulated that these differences between reader groups is primarily due to a noise exclusion deficit shown previously in dyslexia. [Copyright &y& Elsevier]

Abstract: While conventional magnetic resonance imaging (MRI) has long been used to study multiple sclerosis (MS), more sensitive and specific approaches to studying both MS lesions and normal appearing white matter (NAWM) are needed to gain a better understanding of the pathogenesis of the disease. Two MRI techniques thought to offer insight regarding myelin and axonal integrity are T 2 relaxation and diffusion tensor imaging (DTI). In this study, metrics obtained from T 2 relaxation (specifically myelin water content (MWC) and long-T 2 fraction) and DTI experiments (in particular the fractional anisotropy, mean diffusivity , parallel diffusivity λ ||, and perpendicular diffusivity λ ⊥) were compared for 19 MS patients within both lesion and contralateral NAWM with the goal of better understanding how each of the measures are affected by pathology. In particular, it was successfully determined that the detection of a long-T 2 signal within an MS lesion is indicative of a different underlying pathology than is present in lesions without long-T 2 signal. All of the diffusion metrics were significantly different in lesions with a long-T 2 signal than in those without. While no significant correlations were found between MWC and , λ || or λ ⊥ in NAWM (R 2 =0.02–0.04, p >0.07), and only weak correlations were found in lesions without long-T 2 signal (R 2 =0.05–0.14, p <0.04), strong correlations were observed in lesions exhibiting long-T 2 signal (R 2 =0.54–0.61, p <0.0001). [Copyright &y& Elsevier]