Quantification of the in vivo brain ultrashort-T2* component in healthy volunteers.

PURPOSE: Recent work has shown MRI is able to measure and quantify signals of phospholipid membrane-bound protons associated with myelin in the human brain. This work seeks to develop an improved technique for characterizing this brain ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component in vivo accounting for T 1 $$ {\mathrm{T}}_1 $$ weighting. METHODS: Data from ultrashort echo time scans from 16 healthy volunteers with variable flip angles (VFA) were collected and fitted into an advanced regression model to quantify signal fraction, relaxation time, and frequency shift of the ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component. RESULTS: The fitted components show intra-subject differences of different white matter structures and significantly elevated ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ signal fraction in the corticospinal tracts measured at 0.09 versus 0.06 in other white matter structures and significantly elevated ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ frequency shift in the body of the corpus callosum at - $$ - $$ 1.5 versus - $$ - $$ 2.0 ppm in other white matter structures. CONCLUSION: The significantly different measured components and measured T 1 $$ {\mathrm{T}}_1 $$ relaxation time of the ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component suggest that this method is picking up novel signals from phospholipid membrane-bound protons.

Simultaneous high-resolution T2 -weighted imaging and quantitative T2 mapping at low magnetic field strengths using a multiple TE and multi-orientation acquisition approach.

PURPOSE: Low magnetic field systems provide an important opportunity to expand MRI to new and diverse clinical and research study populations. However, a fundamental limitation of low field strength systems is the reduced SNR compared to 1.5 or 3T, necessitating compromises in spatial resolution and imaging time. Most often, images are acquired with anisotropic voxels with low through-plane resolution, which provide acceptable image quality with reasonable scan times, but can impair visualization of subtle pathology. METHODS: Here, we describe a super-resolution approach to reconstruct high-resolution isotropic T2 -weighted images from a series of low-resolution anisotropic images acquired in orthogonal orientations. Furthermore, acquiring each image with an incremented TE allows calculations of quantitative T2 images without time penalty. RESULTS: Our approach is demonstrated via phantom and in vivo human brain imaging, with simultaneous 1.5 × 1.5 × 1.5 mm3 T2 -weighted and quantitative T2 maps acquired using a clinically feasible approach that combines three acquisition that require approximately 4-min each to collect. Calculated T2 values agree with reference multiple TE measures with intraclass correlation values of 0.96 and 0.85 in phantom and in vivo measures, respectively, in line with previously reported brain T2 values at 150 mT, 1.5T, and 3T. CONCLUSION: Our multi-orientation and multi-TE approach is a time-efficient method for high-resolution T2 -weighted images for anatomical visualization with simultaneous quantitative T2 imaging for increased sensitivity to tissue microstructure and chemical composition.

Motion corrected silent ZTE neuroimaging.

PURPOSE: To develop self-navigated motion correction for 3D silent zero echo time (ZTE) based neuroimaging and characterize its performance for different types of head motion. METHODS: The proposed method termed MERLIN (Motion Estimation & Retrospective correction Leveraging Interleaved Navigators) achieves self-navigation by using interleaved 3D phyllotaxis k-space sampling. Low resolution navigator images are reconstructed continuously throughout the ZTE acquisition using a sliding window and co-registered in image space relative to a fixed reference position. Rigid body motion corrections are then applied retrospectively to the k-space trajectory and raw data and reconstructed into a final, high-resolution ZTE image. RESULTS: MERLIN demonstrated successful and consistent motion correction for magnetization prepared ZTE images for a range of different instructed motion paradigms. The acoustic noise response of the self-navigated phyllotaxis trajectory was found to be only slightly above ambient noise levels (<4 dBA). CONCLUSION: Silent ZTE imaging combined with MERLIN addresses two major challenges intrinsic to MRI (i.e., subject motion and acoustic noise) in a synergistic and integrated manner without increase in scan time and thereby forms a versatile and powerful framework for clinical and research MR neuroimaging applications.

Silent T1 mapping using the variable flip angle method with B1 correction.

PURPOSE: To compare the silent rotating ultrafast imaging sequence (RUFIS) to a traditional Cartesian spoiled gradient-echo (SPGR) acquisition scheme for variable flip angle (VFA) T1 mapping. METHODS: A two-point VFA measurement was performed using RUFIS and Cartesian SPGR in a quantitative phantom and healthy volunteers. To correct for B1 errors, a novel silent magnetization prepared B1 map acquisition (SIMBA) was developed, which combined with RUFIS VFA allows for a completely silent T1 mapping protocol. RESULTS: The silent protocol was found to have comparable repeatability but higher reproducibility in vivo compared to the standard SPGR protocol, and showed no increase in acoustic noise levels above background noise levels compared to a 33 dBA increase for the SPGR acquisition. CONCLUSIONS: VFA T1 mapping using RUFIS is a feasible alternative to SPGR, achieving silent T1 mapping with comparable acquisition time.

Quantitative neuroimaging measures of myelin in the healthy brain and in multiple sclerosis.

Quantitative magnetic resonance imaging (MRI) techniques have been developed as imaging biomarkers, aiming to improve the specificity of MRI to underlying pathology compared to conventional weighted MRI. For assessing the integrity of white matter (WM), myelin, in particular, several techniques have been proposed and investigated individually. However, comparisons between these methods are lacking. In this study, we compared four established myelin-sensitive MRI techniques in 56 patients with relapsing-remitting multiple sclerosis (MS) and 38 healthy controls. We used T2-relaxation with combined GRadient And Spin Echoes (GRASE) to measure myelin water fraction (MWF-G), multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) to measure MWF-D, magnetization-transfer imaging to measure magnetization-transfer ratio (MTR), and T1 relaxation to measure quantitative T1 (qT1 ). Using voxelwise Spearman correlations, we tested the correspondence of methods throughout the brain. All four methods showed associations that varied across tissue types; the highest correlations were found between MWF-D and qT1 (median ρ across tissue classes 0.8) and MWF-G and MWF-D (median ρ = 0.59). In eight WM tracts, all measures showed differences (p < 0.05) between MS normal-appearing WM and healthy control WM, with qT1 showing the highest number of different regions (8), followed by MWF-D and MTR (6), and MWF-G (n = 4). Comparing the methods in terms of their statistical sensitivity to MS lesions in WM, MWF-D demonstrated the best accuracy (p < 0.05, after multiple comparison correction). To aid future power analysis, we provide the average and standard deviation volumes of the four techniques, estimated from the healthy control sample.

Spinal cord grey matter segmentation challenge.

An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication.

Rapid myelin water imaging in human cervical spinal cord.

PURPOSE: Myelin water imaging (MWI) using multi-echo T2 relaxation is a quantitative MRI technique that can be used as an in vivo biomarker for myelin in the central nervous system. MWI using a multi-echo spin echo sequence currently takes more than 20 min to acquire eight axial slices (5 mm thickness) in the cervical spinal cord, making spinal cord MWI impractical for implementation in clinical studies. METHODS: In this study, an accelerated gradient and spin echo sequence (GRASE), previously validated for brain MWI, was adapted for spinal cord MWI. Ten healthy volunteers were scanned with the GRASE sequence (acquisition time 8.5 min) and compared with the multi-echo spin echo sequence (acquisition time 23.5 min). RESULTS: Using region of interest analysis, myelin estimates obtained from the two sequences were found to be in good agreement (mean difference = -0.0092, 95% confidence interval = - 0.0092 ± 0.061; regression slope = 1.01, ρ = 0.9). MWI using GRASE was shown to be highly reproducible with an average coefficient of variation of 6.1%. CONCLUSION: The results from this study show that MWI can be performed in the cervical spinal cord in less than 10 min, allowing for practical implementation in multimodal clinical studies. Magn Reson Med 78:1482-1487, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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.

Silent zero TE MR neuroimaging: Current state-of-the-art and future directions.

Magnetic Resonance Imaging (MRI) scanners produce loud acoustic noise originating from vibrational Lorentz forces induced by rapidly changing currents in the magnetic field gradient coils. Using zero echo time (ZTE) MRI pulse sequences, gradient switching can be reduced to a minimum, which enables near silent operation.Besides silent MRI, ZTE offers further interesting characteristics, including a nominal echo time of TE = 0 (thus capturing short-lived signals from MR tissues which are otherwise MR-invisible), 3D radial sampling (providing motion robustness), and ultra-short repetition times (providing fast and efficient scanning).In this work we describe the main concepts behind ZTE imaging with a focus on conceptual understanding of the imaging sequences, relevant acquisition parameters, commonly observed image artefacts, and image contrasts. We will further describe a range of methods for anatomical and functional neuroimaging, together with recommendations for successful implementation.

Silent myelin-weighted magnetic resonance imaging.

Background: Inhomogeneous Magnetization Transfer (ihMT) is an emerging, uniquely myelin-specific magnetic resonance imaging (MRI) contrast. Current ihMT acquisitions utilise fast Gradient Echo sequences which are among the most acoustically noisy MRI sequences, reducing patient comfort during acquisition. We sought to address this by modifying a near silent MRI sequence to include ihMT contrast. Methods: A Magnetization Transfer preparation module was incorporated into a radial Zero Echo-Time sequence. Repeatability of the ihMT ratio and inverse ihMT ratio were assessed in a cohort of healthy subjects. We also investigated how head orientation affects ihMT across subjects, as a previous study in a single subject suggests this as a potential confound. Results: We demonstrated that ihMT ratios comparable to existing, acoustically loud, implementations could be obtained with the silent sequence. We observed a small but significant effect of head orientation on inverse ihMTR. Conclusions: Silent ihMT imaging is a comparable alternative to conventional, noisy, alternatives. For all future ihMT studies we recommend careful positioning of the subject within the scanner.

The Evaluation of Optic Nerves Using 7 Tesla "Silent" Zero Echo Time Imaging in Patients with Leber's Hereditary Optic Neuropathy with or without Idebenone Treatment.

Magnetic Resonance Imaging (MRI) of the Optic Nerve is difficult due to the fine extended nature of the structure, strong local magnetic field distortions induced by anatomy, and large motion artefacts associated with eye movement. To address these problems we used a Zero Echo Time (ZTE) MRI sequence with an Adiabatic SPectral Inversion Recovery (ASPIR) fat suppression pulse which also imbues the images with Magnetisation Transfer contrast. We investigated an application of the sequence for imaging the optic nerve in subjects with Leber's hereditary optic neuropathy (LHON). Of particular note is the sequence's near-silent operation, which can enhance image quality of the optic nerve by reducing the occurrence of involuntary saccades induced during Magnetic Resonance (MR) scanning.

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.

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.

Assessing structure and function of myelin in cervical spondylotic myelopathy: Evidence of demyelination.

PURPOSE: To assess the extent of demyelination in cervical spondylotic myelopathy (CSM) using myelin water imaging (MWI) and electrophysiologic techniques. METHODS: Somatosensory evoked potentials (SSEPs) and MWI were acquired in 14 patients with CSM and 18 age-matched healthy controls. MWI was performed on a 3.0T whole body magnetic resonance scanner. Myelin water fraction (MWF) was extracted for the dorsal columns and whole cord. SSEPs and MWF were also compared with conventional MRI outcomes, including T2 signal intensity, compression ratio, maximum spinal cord compression (MSCC), and maximum canal compromise (MCC). RESULTS: Group analysis showed marked differences in T2 signal intensity, compression ratio, MSCC, and MCC between healthy controls and patients with CSM. There were no group differences in MWF and SSEP latencies. However, patients with CSM with pathologic SSEPs exhibited reduction in MWF (p < 0.05). MWF was also correlated with SSEP latencies. CONCLUSION: Our findings provide evidence of decreased myelin content in the spinal cord associated with impaired spinal cord conduction in patients with CSM. While conventional MRI are of great value to define the extent of cord compression, they show a limited correlation with functional deficits (i.e., delayed SSEPs). MWI provides independent and complementary readouts to spinal cord compression, with a high specificity to detect impaired conduction.