Non-negative least squares fitting of multi-exponential T2 decay data: Are we able to accurately measure the fraction of myelin water?

The ability to determine the myelin water fraction (MWF) in vivo is essential to assessments of neurodevelopmental myelination and myelin damage in neurodegenerative diseases. The analysis of multi-exponential T2 decay data relies on the non-negative-least-squares (NNLS) fitting, which may be sensitive to the chosen fitting parameters. We performed simulations to explore the outcomes of NNLS under different parameter selection. The lowest allowed T2 was found to have the largest effect on correctly estimating the T2 of different water pools as well as the MWF. Lower refocusing FAs led to further underestimation of the MWF

Inter-Vendor Reproducibility of Myelin Water Imaging Using a 3D Gradient and Spin Echo Sequence

Myelin water imaging can be achieved using multicomponent T2 relaxation analysis to quantify in vivo measurement of myelin content, termed the myelin water fraction (MWF). Therefore, myelin water imaging can be a valuable tool to better understand the underlying white matter pathology in demyelinating diseases, such as multiple sclerosis. To apply myelin water imaging in multisite studies and clinical applications, it must be acquired in a clinically feasible scan time (less than 15 min) and be reproducible across sites and scanner vendors. Here, we assessed the reproducibility of MWF measurements in regional and global white matter in 10 healthy human brains across two sites with two different 3 T magnetic resonance imaging scanner vendors (Philips and Siemens), using a 32-echo gradient and spin echo (GRASE) sequence. A strong correlation was found between the MWF measurements in the global white matter (Pearson’s r = 0.91; p < 0.001) for all participants across the two sites. The mean intersite MWF coefficient of variation across participants was 2.77% in the global white matter and ranged from 4.47% (splenium of the corpus callosum) to 17.89% (genu of the corpus callosum) in white matter regions of interest. Bland-Altman analysis showed a good agreement in MWF measurements between the two sites with small bias of 0.002. Overall, MWF estimates were in good agreement across the two sites and scanner vendors. Our findings support the use of quantitative multi-echo T2 relaxation metrics, such as the MWF, in multicenter studies and clinical trials to gain deeper understanding about the pathological processes resulting from the underlying disease progression in neurodegenerative diseases

Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data

Multi‐compartment T2 mapping has gained particular relevance for the study of myelin water in the brain. As a facilitator of rapid saltatory axonal signal transmission, myelin is a cornerstone indicator of white matter development and function. Regularized non‐negative least squares fitting of multi‐echo T2 data has been widely employed for the computation of the myelin water fraction (MWF), and the obtained MWF maps have been histopathologically validated. MWF measurements depend upon the quality of the data acquisition, B1+ homogeneity and a range of fitting parameters. In this special issue article, we discuss the relevance of these factors for the accurate computation of multi‐compartment T2 and MWF maps. We generated multi‐echo spin‐echo T2 decay curves following the Carr‐Purcell‐Meiboom‐Gill approach for various myelin concentrations and myelin T2 scenarios by simulating the evolution of the magnetization vector between echoes based on the Bloch equations. We demonstrated that noise and imperfect refocusing flip angles yield systematic underestimations in MWF and intra−/extracellular water geometric mean T2 (gmT2). MWF estimates were more stable than myelin water gmT2 time across different settings of the T2 analysis. We observed that the lower limit of the T2 distribution grid should be slightly shorter than TE1. Both TE1 and the acquisition echo spacing also have to be sufficiently short to capture the rapidly decaying myelin water T2 signal. Among all parameters of interest, the estimated MWF and intra−/extracellular water gmT2 differed by approximately 0.13–4 percentage points and 3–4 ms, respectively, from the true values, with larger deviations observed in the presence of greater B1+ inhomogeneities and at lower signal‐to‐noise ratio. Tailoring acquisition strategies may allow us to better characterize the T2 distribution, including the myelin water, in vivo

Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain

Purpose: The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T1D. Methods: ihMT ratio (ihMTR) and MWF maps were acquired at 7 T from formalin-fixed human brain samples at 22.5 °C, 30 °C and 37 °C. The impact of temperature on unfiltered ihMTR, filtered ihMTR and MWF was investigated and compared to myelin basic protein staining. Results: Unfiltered ihMTR exhibited no temperature dependence, whereas filtered ihMTR increased with increasing temperature. MWF decreased at higher temperature, with an increasing prevalence of areas where the myelin water signal was unreliably determined, likely related to a reduction in T2 peak separability at higher temperatures ex vivo. MWF and ihMTR showed similar per-sample correlation with myelin staining at room temperature. At 37 °C, filtered ihMTR was more strongly correlated with myelin staining and had increased dynamic range compared to unfiltered ihMTR. Conclusions: Given the temperature dependence of filtered ihMT, increased dynamic range, and strong myelin specificity that persists at higher temperatures, we recommend carefully controlled temperatures close to 37 °C for filtered ihMT acquisitions. Unfiltered ihMT may also be useful, due to its independence from temperature, higher amplitude values, and sensitivity to short T1D components. Ex vivo myelin water imaging should be performed at room temperature, to avoid fitting issues found at higher temperatures

Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults

Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica

AbstractBackgroundThe optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury.ObjectiveTo determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls.Methods12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density.ResultsMultiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean=0.99mm3, SD=0.06) compared to those without (mean=0.97mm3, SD=0.06; p=0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean=0.098, SD=0.01, multiple sclerosis with optic neuritis history: mean=0.096, SD=0.01, multiple sclerosis without optic neuritis history: mean=0.098, SD=0.02; F3,55=3.35, p=0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent (retinal nerve fiber layer thickness and ganglion cell layer thickness: r=0.25, p=0.05, total macular volume and inner plexiform layer volume: r=0.27, p=0.04).ConclusionsThe relationship between reductions in OCT measures of neuro-axonal health in the anterior visual pathway and MRI-based measures of myelin health in the posterior visual pathway suggests that these measures may be linked through bidirectional axonal degeneration

Inter-Vendor Reproducibility of Myelin Water Imaging Using a 3D Gradient and Spin Echo Sequence

Myelin water imaging can be achieved using multicomponent T2 relaxation analysis to quantify in vivo measurement of myelin content, termed the myelin water fraction (MWF). Therefore, myelin water imaging can be a valuable tool to better understand the underlying white matter pathology in demyelinating diseases, such as multiple sclerosis. To apply myelin water imaging in multisite studies and clinical applications, it must be acquired in a clinically feasible scan time (less than 15 min) and be reproducible across sites and scanner vendors. Here, we assessed the reproducibility of MWF measurements in regional and global white matter in 10 healthy human brains across two sites with two different 3 T magnetic resonance imaging scanner vendors (Philips and Siemens), using a 32-echo gradient and spin echo (GRASE) sequence. A strong correlation was found between the MWF measurements in the global white matter (Pearson's r = 0.91; p < 0.001) for all participants across the two sites. The mean intersite MWF coefficient of variation across participants was 2.77% in the global white matter and ranged from 4.47% (splenium of the corpus callosum) to 17.89% (genu of the corpus callosum) in white matter regions of interest. Bland-Altman analysis showed a good agreement in MWF measurements between the two sites with small bias of 0.002. Overall, MWF estimates were in good agreement across the two sites and scanner vendors. Our findings support the use of quantitative multi-echo T2 relaxation metrics, such as the MWF, in multicenter studies and clinical trials to gain deeper understanding about the pathological processes resulting from the underlying disease progression in neurodegenerative diseases

MSJ770085_supplementary_appendix – Supplemental material for A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab

<p>Supplemental material, MSJ770085_supplementary_appendix for A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab by Irene M Vavasour, Roger Tam, David KB Li, Cornelia Laule, Carolyn Taylor, Shannon H Kolind, Alex L MacKay, Adil Javed and Anthony Traboulsee in Multiple Sclerosis Journal</p

Increased spinal cord movements in cervical spondylotic myelopathy

BACKGROUND CONTEXT: Magnetic resonance imaging is a very useful diagnostic test for cervical spondylotic myelopathy (CSM) since it can identify degenerative changes within the spinal cord (SC), disclose the extent, localisation and 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. PUPOSE: The purpose of this study was 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/Setting: Prospective radiological study of recruited patients PATIENT SAMPLE: 13 CSM subjects and 15 age and gender matched controls OUTCOME MEASURES: MRI measures included CSF and spinal cord movement. Cervical cord condition was assessed by the Japanese Orthopaedic Association (JOA) score, compression ratio and somatosensory evoked potentials (SSEP) of the tibial and ulnar nerves. METHODS: Phase contrast imaging at the level of stenosis for patients and level C5 for controls as well as T2-weighted imaging were compared to clinical findings. This study was funded by the Cervical Spine Research Society ($60000). RESULTS: CSF velocity was significantly reduced in CSM subjects as compared to controls, and was related to cord compression ratio. 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, i.e. cord displacement and velocity in the cranio-caudal axis, were increased in CSM patients. Increased spinal cord movements (i.e. 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 cranio-caudal axis in CSM patients, which 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