Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

The CALIPR framework for highly accelerated myelin water imaging with improved precision and sensitivity.

Quantitative magnetic resonance imaging (MRI) techniques are powerful tools for the study of human tissue, but, in practice, their utility has been limited by lengthy acquisition times. Here, we introduce the Constrained, Adaptive, Low-dimensional, Intrinsically Precise Reconstruction (CALIPR) framework in the context of myelin water imaging (MWI); a quantitative MRI technique generally regarded as the most rigorous approach for noninvasive, in vivo measurement of myelin content. The CALIPR framework exploits data redundancy to recover high-quality images from a small fraction of an imaging dataset, which allowed MWI to be acquired with a previously unattainable sequence (fully sampled acquisition 2 hours:57 min:20 s) in 7 min:26 s (4.2% of the dataset, acceleration factor 23.9). CALIPR quantitative metrics had excellent precision (myelin water fraction mean coefficient of variation 3.2% for the brain and 3.0% for the spinal cord) and markedly increased sensitivity to demyelinating disease pathology compared to a current, widely used technique. The CALIPR framework facilitates drastically improved MWI and could be similarly transformative for other quantitative MRI applications.

Comparison of multi echo T2 relaxation and steady state approaches for myelin imaging in the central nervous system.

The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T2 relaxation data to calculate the myelin water fraction (MWF). A fundamentally different approach, abbreviated "mcDESPOT", uses a more efficient steady-state acquisition to generate an equivalent metric (fM). Although previous studies have demonstrated inherent instability and bias in the complex mcDESPOT analysis procedure, fM has often been used as a surrogate for MWF. We produced and compared multivariate atlases of MWF and fM in healthy human brain and cervical spinal cord (available online) and compared their ability to detect multiple sclerosis pathology. A significant bias was found in all regions (p < 10-5), albeit reversed for spinal cord (fM-MWF = - 3.4%) compared to brain (+ 6.2%). MWF and fM followed an approximately linear relationship for regions with MWF < ~ 10%. For MWF > ~ 10%, the relationship broke down and fM no longer increased in tandem with MWF. For multiple sclerosis patients, MWF and fM Z score maps showed overlapping areas of low Z score and similar trends between patients and brain regions, although those of fM generally had greater spatial extent and magnitude of severity. These results will guide future choice of myelin-sensitive quantitative MRI and improve interpretation of studies using either myelin imaging approach.

An atlas for human brain myelin content throughout the adult life span.

Myelin water imaging is a quantitative neuroimaging technique that provides the myelin water fraction (MWF), a metric highly specific to myelin content, and the intra-/extra-cellular T2 (IET2), which is related to water and iron content. We coupled high-resolution data from 100 adults with gold-standard methodology to create an optimized anatomical brain template and accompanying MWF and IET2 atlases. We then used the MWF atlas to characterize how myelin content relates to demographic factors. In most brain regions, myelin content followed a quadratic pattern of increase during the third decade of life, plateau at a maximum around the fifth decade, then decrease during later decades. The ranking of mean myelin content between brain regions remained consistent across age groups. These openly available normative atlases can facilitate evaluation of myelin imaging results on an individual basis and elucidate the distribution of myelin content between brain regions and in the context of aging.

Multi-spin echo T2 relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging.

PURPOSE: Myelin water imaging (MWI) provides a valuable biomarker for myelin, but clinical application has been restricted by long acquisition times. Accelerating the standard multi-echo T2 acquisition with gradient echoes (GRASE) or by 2D multi-slice data collection results in image blurring, contrast changes, and other issues. Compressed sensing (CS) can vastly accelerate conventional MRI. In this work, we assessed the use of CS for in vivo human MWI, using a 3D multi spin-echo sequence. METHODS: We implemented multi-echo T2 relaxation imaging with compressed sensing (METRICS) and METRICS with partial Fourier acceleration (METRICS-PF). Scan-rescan data were acquired from 12 healthy controls for assessment of repeatability. MWI data were acquired for METRICS in 9 m:58 s and for METRICS-PF in 7 m:25 s, both with 1.5 × 2 × 3 mm3 voxels, 56 echoes, 7 ms ΔTE, and 240 × 240 × 170 mm3 FOV. METRICS was compared with a novel multi-echo spin-echo gold-standard (MSE-GS) MWI acquisition, acquired for a single additional subject in 2 h:2 m:40 s. RESULTS: METRICS/METRICS-PF myelin water fraction had mean: repeatability coefficient 1.5/1.1, coefficient of variation 6.2/4.5%, and intra-class correlation coefficient 0.79/0.84. Repeatability metrics comparing METRICS with METRICS-PF were similar, and both sequences agreed with reference values from literature. METRICS images and quantitative maps showed excellent qualitative agreement with those of MSE-GS. CONCLUSION: METRICS and METRICS-PF provided highly repeatable MWI data without the inherent disadvantages of GRASE or 2D multi-slice acquisition. CS acceleration allows MWI data to be acquired rapidly with larger FOV, higher estimated SNR, more isotropic voxels and more echoes than with previous techniques. The approach introduced here generalizes to any multi-component T2 mapping application.

Brain Myelin Water Fraction and Diffusion Tensor Imaging Atlases for 9-10 Year-Old Children.

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-T1 , 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/.

Myelin water imaging data analysis in less than one minute.

PURPOSE: Based on a deep learning neural network (NN) algorithm, a super fast and easy to implement data analysis method was proposed for myelin water imaging (MWI) to calculate the myelin water fraction (MWF). METHODS: A NN was constructed and trained on MWI data acquired by a 32-echo 3D gradient and spin echo (GRASE) sequence. Ground truth labels were created by regularized non-negative least squares (NNLS) with stimulated echo corrections. Voxel-wise GRASE data from 5 brains (4 healthy, 1 multiple sclerosis (MS)) were used for NN training. The trained NN was tested on 2 healthy brains, 1 MS brain with segmented lesions, 1 healthy spinal cord, and 1 healthy brain acquired from a different scanner. RESULTS: Production of whole brain MWF maps in approximately 33 â€‹s can be achieved by a trained NN without graphics card acceleration. For all testing regions, no visual differences between NN and NNLS MWF maps were observed, and no obvious regional biases were found. Quantitatively, all voxels exhibited excellent agreement between NN and NNLS (all R2>0.98, p â€‹< â€‹0.001, mean absolute error <0.01). CONCLUSION: The time for accurate MWF calculation can be dramatically reduced to less than 1 â€‹min by the proposed NN, addressing one of the barriers facing future clinical feasibility of MWI.

Myelin Water Fraction and Intra/Extracellular Water Geometric Mean T2 Normative Atlases for the Cervical Spinal Cord from 3T MRI.

BACKGROUND AND PURPOSE: Acquiring and interpreting quantitative myelin-specific MRI data at an individual level is challenging because of technical difficulties and natural myelin variation in the population. To overcome these challenges, we used multiecho T2 myelin water imaging (MWI) to create T2 metric healthy population atlases that depict the mean and variation of myelin water fraction (MWF), and intra- and extracellular water mobility as described by geometric mean T2 (IEGMT2 ). METHODS: Cervical cord MWI was performed at 3T on 20 healthy individuals (10M/10F, mean age: 36 years) and 3 relapsing remitting multiple sclerosis (RRMS) participants (1M/2F, age: 39/42/37 years). Anatomical data were collected for the purpose of image segmentation and registration. Atlases were created by coregistering and averaging T2 metrics from all controls. Voxel-wise z-score maps from 3 RRMS participants were produced to demonstrate the preliminary utility of the MWF and IEGMT2 atlases. RESULTS: The average MWF atlas provides a representation of myelin in the spinal cord consistent with well-known spinal cord anatomical characteristics. The IEGMT2 atlas also depicted structural variations in the spinal cord. Z-score analysis illustrated distinct abnormalities in MWF and IEGMT2 in the 3 RRMS cases. CONCLUSIONS: Our findings highlight the potential for using a quantitative T2 relaxation metric atlas to visualize and detect pathology in spinal cord. Our MWF and IEGMT2 atlases (URL: https://sourceforge.net/projects/mwi-spinal-cord-atlases/) can serve as normative references in the cervical spinal cord for other studies.

Rapid myelin water imaging for the assessment of cervical spinal cord myelin damage.

BACKGROUND: Rapid myelin water imaging (MWI) using a combined gradient and spin echo (GRASE) sequence can produce myelin specific metrics for the human brain. Spinal cord MWI could be similarly useful, but technical challenges have hindered routine application. GRASE rapid MWI was recently successfully implemented for imaging of healthy cervical spinal cord and may complement other advanced imaging methods, such as diffusion tensor imaging (DTI) and quantitative T1 (qT1). OBJECTIVE: To demonstrate the feasibility of cervical cord GRASE rapid MWI in multiple sclerosis (MS), primary lateral sclerosis (PLS) and neuromyelitis optica spectrum disorder (NMO), with comparison to DTI and qT1 metrics. METHODS: GRASE MWI, DTI and qT1 data were acquired in 2 PLS, 1 relapsing-remitting MS (RRMS), 1 primary-progressive MS (PPMS) and 2 NMO subjects, as well as 6 age (±3 yrs) and sex matched healthy controls (HC). Internal cord structure guided template registrations, used for region of interest (ROI) analysis. Z score maps were calculated for the difference between disease subject and mean HC metric values. RESULTS: PLS subjects had low myelin water fraction (MWF) in the lateral funiculi compared to HC. RRMS subject MWF was heterogeneous within the cord. The PPMS subject showed no trends in ROI results but had a region of low MWF Z score corresponding to a focal lesion. The NMO subject with a longitudinally extensive transverse myelitis lesion had low values for whole cord mean MWF of 12.8% compared to 24.3% (standard deviation 2.2%) for HC. The NMO subject without lesions also had low MWF compared to HC. DTI and qT1 metrics showed similar trends, corroborating the MWF results and providing complementary information. CONCLUSION: GRASE is sufficiently sensitive to detect decreased myelin within MS spinal cord plaques, NMO lesions, and PLS diffuse spinal cord injury. Decreased MWF in PLS is consistent with demyelination secondary to motor neuron degeneration. GRASE MWI is a feasible method for rapid assessment of myelin content in the cervical spinal cord and provides complementary information to that of DTI and qT1 measures.

Myelin Water Atlas: A Template for Myelin Distribution in the Brain.

BACKGROUND AND PURPOSE: Myelin water imaging (MWI) is a magnetic resonance imaging technique that quantifies myelin in-vivo. Although MWI has been extensively applied to study myelin-related diseases in groups, clinical use in individual patients is challenging mainly due to population heterogeneity. The purpose of this study was twofold: (1) create a normative brain myelin water atlas depicting the population mean and regional variability of myelin content; and (2) apply the myelin atlas to assess the degree of demyelination in individuals with multiple sclerosis (MS). METHODS: 3T MWI was performed on 50 healthy adults (25 M/25 F, mean age 25 years [range 17-42 years]). The myelin water atlas was created by averaging coregistered myelin water fraction (MWF) maps from all healthy individuals. To illustrate the preliminary utility of the atlas, white matter (WM) regional MWF variations were evaluated and voxel-wise z-score maps (z < -1.96) from the MWI of three MS participants were produced to assess individually the degree of demyelination. RESULTS: The myelin water atlas demonstrated significant MWF variation across control WM. No significant MWF differences were found between male and female healthy participants. MS z-score maps revealed diffuse regions of demyelination in the two participants with Expanded Disability Status Scale (EDSS) = 2.0 but not in the participant with EDSS = 0. CONCLUSIONS: The myelin water atlas can be used as a reference (URL: https://sourceforge.net/projects/myelin-water-atlas/) to demonstrate areas of demyelination in individual MS participants. Future studies will expand the atlas age range, account for education, and other variables that may affect myelination.