Imaging chronic active lesions in multiple sclerosis: a consensus statement.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification, and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a Consensus Statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this Consensus Statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.

Denoising of diffusion MRI in the cervical spinal cord - effects of denoising strategy and acquisition on intra-cord contrast, signal modeling, and feature conspicuity.

Quantitative diffusion MRI (dMRI) is a promising technique for evaluating the spinal cord in health and disease. However, low signal-to-noise ratio (SNR) can impede interpretation and quantification of these images. The purpose of this study is to evaluate several dMRI denoising approaches on their ability to improve the quality, reliability, and accuracy of quantitative diffusion MRI of the spinal cord. We evaluate three denoising approaches (Non-Local Means, Marchenko-Pastur PCA, and a newly proposed Patch2Self algorithm) and conduct five experiments to validate the denoising performance on clinical-quality and commonly-acquired dMRI acquisitions: 1) a phantom experiment to assess denoising error and bias; 2) a multi-vendor, multi-acquisition open experiment for both qualitative and quantitative evaluation of noise residuals; 3) a bootstrapping experiment to estimate uncertainty of parametric maps; 4) an assessment of spinal cord lesion conspicuity in a multiple sclerosis group; and 5) an evaluation of denoising for advanced parametric multi-compartment modeling. We find that all methods improve signal-to-noise ratio and conspicuity of MS lesions in individual diffusion weighted images (DWIs), but MPPCA and Patch2Self excel at improving the quality and intra-cord contrast of diffusion weighted images - removing signal fluctuations due to thermal noise while improving precision of estimation of diffusion parameters even with very few DWIs (i.e., 16-32) typical of clinical acquisitions. These denoising approaches hold promise for facilitating reliable diffusion observations and measurements in the spinal cord to investigate biological and pathological processes.

Cervical spinal cord susceptibility-weighted MRI at 7T: Application to multiple sclerosis.

BACKGROUND: Susceptibility-weighted imaging (SWI) has been extensively studied in the brain and in diseases of the central nervous system such as multiple sclerosis (MS) providing unique opportunities to visualize cerebral vasculature and disease-related pathology, including the central vein sign (CVS) and paramagnetic rim lesions (PRLs). However, similar studies evaluating SWI in the spinal cord of patients with MS remain severely limited. PURPOSE: Based on our previous findings of enlarged spinal vessels in MS compared to healthy controls (HCs), we developed high-field SWI acquisition and processing methods for the cervical spinal cord with application in people with MS (pwMS) and HCs. Here, we demonstrate the vascular variability between the two cohorts and unique MS lesion features in the cervical cord. METHODS: In this retrospective, exploratory pilot study conducted between March 2021 and March 2022, we scanned 12 HCs and 9 pwMS using an optimized non-contrast 2D T2*-weighted gradient echo sequence at 7 tesla. The overall appearance of the white and gray matter as well as tissue vasculature were compared between the two cohorts and areas of MS pathology in the patient group were assessed using both the magnitude and processed SWI images. RESULTS: We show improved visibility of vessels and more pronounced gray and white matter contrast in the MS group compared to HCs, hypointensities surrounding the cord in the MS cohort, and identify signal changes indicative of the CVS and paramagnetic rims in 66 % of pwMS with cervical spinal lesions. CONCLUSION: In this first study of SWI at 7T in the human spinal cord, SWI holds promise in advancing our understanding of disease processes in the cervical cord in MS.

J-Difference editing (MEGA) of lactate in the human brain at 3T.

PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.

Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors.

Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.

Integrating the BIDS Neuroimaging Data Format and Workflow Optimization for Large-Scale Medical Image Analysis.

A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically problematic when matching large amount of processing to large datasets. Historically, workflow engines have been focused on refining workflows themselves instead of actual job generation. However, such an approach is incompatible with data centric architecture that hosts heterogeneous medical image computing. Distributed automation for XNAT toolkit (DAX) provides large-scale image storage and analysis pipelines with an optimized job management tool. Herein, we describe developments for DAX that allows for integration of XNAT and BIDS standards. We also improve DAX's efficiencies of diverse containerized workflows in a high-performance computing (HPC) environment. Briefly, we integrate YAML configuration processor scripts to abstract workflow data inputs, data outputs, commands, and job attributes. Finally, we propose an online database-driven mechanism for DAX to efficiently identify the most recent updated sessions, thereby improving job building efficiency on large projects. We refer the proposed overall DAX development in this work as DAX-1 (DAX version 1). To validate the effectiveness of the new features, we verified (1) the efficiency of converting XNAT data to BIDS format and the correctness of the conversion using a collection of BIDS standard containerized neuroimaging workflows, (2) how YAML-based processor simplified configuration setup via a sequence of application pipelines, and (3) the productivity of DAX-1 on generating actual HPC processing jobs compared with earlier DAX baseline method. The empirical results show that (1) DAX-1 converting XNAT data to BIDS has similar speed as accessing XNAT data only; (2) YAML can integrate to the DAX-1 with shallow learning curve for users, and (3) DAX-1 reduced the job/assessor generation latency by finding recent modified sessions. Herein, we present approaches for efficiently integrating XNAT and modern image formats with a scalable workflow engine for the large-scale dataset access and processing.

Multi-shot acquisitions for stimulus-evoked spinal cord BOLD fMRI.

PURPOSE: To demonstrate the feasibility of 3D multi-shot magnetic resonance imaging acquisitions for stimulus-evoked blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in the human spinal cord in vivo. METHODS: Two fMRI studies were performed at 3T. The first study was a hypercapnic gas challenge where data were acquired from healthy volunteers using a multi-shot 3D fast field echo (FFE) sequence as well as single-shot multi-slice echo-planar imaging (EPI). In the second study, another cohort of healthy volunteers performed an upper extremity motor task while fMRI data were acquired using a 3D multi-shot acquisition. RESULTS: Both 2D-EPI and 3D-FFE were shown to be sensitive to BOLD signal changes in the cervical spinal cord, and had comparable contrast-to-noise ratios in gray matter. FFE exhibited much less signal drop-out and weaker geometric distortions compared to EPI. In the motor paradigm study, the mean number of active voxels was highest in the ventral gray matter horns ipsilateral to the side of the task and at the spinal level associated with innervation of finger extensors. CONCLUSIONS: Highly multi-shot acquisition sequences such as 3D-FFE are well suited for stimulus-evoked spinal cord BOLD fMRI.

Does the magnetization transfer effect bias chemical exchange saturation transfer effects? Quantifying chemical exchange saturation transfer in the presence of magnetization transfer.

PURPOSE: Chemical exchange saturation transfer (CEST) is an MRI technique sensitive to the presence of low-concentration solute protons exchanging with water. However, magnetization transfer (MT) effects also arise when large semisolid molecules interact with water, which biases CEST parameter estimates if quantitative models do not account for macromolecular effects. This study establishes under what conditions this bias is significant and demonstrates how using an appropriate model provides more accurate quantitative CEST measurements. METHODS: CEST and MT data were acquired in phantoms containing bovine serum albumin and agarose. Several quantitative CEST and MT models were used with the phantom data to demonstrate how underfitting can influence estimates of the CEST effect. CEST and MT data were acquired in healthy volunteers, and a two-pool model was fit in vivo and in vitro, whereas removing increasing amounts of CEST data to show biases in the CEST analysis also corrupts MT parameter estimates. RESULTS: When all significant CEST/MT effects were included, the derived parameter estimates for each CEST/MT pool significantly correlated (P < .05) with bovine serum albumin/agarose concentration; minimal or negative correlations were found with underfitted data. Additionally, a bootstrap analysis demonstrated that significant biases occur in MT parameter estimates (P < .001) when unmodeled CEST data are included in the analysis. CONCLUSIONS: These results indicate that current practices of simultaneously fitting both CEST and MT effects in model-based analyses can lead to significant bias in all parameter estimates unless a sufficiently detailed model is utilized. Therefore, care must be taken when quantifying CEST and MT effects in vivo by properly modeling data to minimize these biases.

Selective inversion recovery quantitative magnetization transfer imaging: Toward a 3 T clinical application in multiple sclerosis.

BACKGROUND: Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically. OBJECTIVES: We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS. METHODS: A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability. RESULTS: SIR-qMT measures differed between lesional and non-lesional tissue (p < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs (p < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores (p ⩽ 0.002). CONCLUSION: SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.

Spatial distribution of multiple sclerosis lesions in the cervical spinal cord.

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

Diffusion MRI microstructural models in the cervical spinal cord - Application, normative values, and correlations with histological analysis.

Multi-compartment tissue modeling using diffusion magnetic resonance imaging has proven valuable in the brain, offering novel indices sensitive to the tissue microstructural environment in vivo on clinical MRI scanners. However, application, characterization, and validation of these models in the spinal cord remain relatively under-studied. In this study, we apply a diffusion "signal" model (diffusion tensor imaging, DTI) and two commonly implemented "microstructural" models (neurite orientation dispersion and density imaging, NODDI; spherical mean technique, SMT) in the human cervical spinal cord of twenty-one healthy controls. We first provide normative values of DTI, SMT, and NODDI indices in a number of white matter ascending and descending pathways, as well as various gray matter regions. We then aim to validate the sensitivity and specificity of these diffusion-derived contrasts by relating these measures to indices of the tissue microenvironment provided by a histological template. We find that DTI indices are sensitive to a number of microstructural features, but lack specificity. The microstructural models also show sensitivity to a number of microstructure features; however, they do not capture the specific microstructural features explicitly modelled. Although often regarded as a simple extension of the brain in the central nervous system, it may be necessary to re-envision, or specifically adapt, diffusion microstructural models for application to the human spinal cord with clinically feasible acquisitions - specifically, adjusting, adapting, and re-validating the modeling as it relates to both theory (i.e. relevant biology, assumptions, and signal regimes) and parameter estimation (for example challenges of acquisition, artifacts, and processing).

Quantitative magnetization transfer imaging of the human locus coeruleus.

The locus coeruleus (LC) is the major origin of norepinephrine in the central nervous system, and is subject to age-related and neurodegenerative changes, especially in disorders such as Parkinson's disease and Alzheimer's disease. Previous studies have shown that neuromelanin (NM)-sensitive MRI can be used to visualize the LC, and it is hypothesized that magnetization transfer (MT) effects are the primary source of LC contrast. The aim of this study was to characterize the MT effects in LC imaging by applying high spatial resolution quantitative MT (qMT) imaging to create parametric maps of the macromolecular content of the LC and surrounding tissues. Healthy volunteers (n = 26; sex = 17 F/9M; age = 41.0 ±â€¯19.1 years) underwent brain MRI on a 3.0 T scanner. qMT data were acquired using a 3D MT-prepared spoiled gradient echo sequence. A traditional NM scan consisting of a T1-weighted turbo spin echo sequence with MT preparation was also acquired. The pool-size ratio (PSR) was estimated for each voxel using a single-point qMT approach. The LC was semi-automatically segmented on the MT-weighted images. The MT-weighted images provided higher contrast-ratio between the LC and surrounding pontine tegmentum (PT) (0.215 ±â€¯0.031) than the reference images without MT-preparation (-0.005 ±â€¯0.026) and the traditional NM images (0.138 ±â€¯0.044). The PSR maps showed significant differences between the LC (0.090 ±â€¯0.009) and PT (0.188 ±â€¯0.025). The largest difference between the PSR values in the LC and PT was observed in the central slices, which also correspond to those with the highest contrast-ratio. These results highlight the role of MT in generating NM-related contrast in the LC, and should serve as a foundation for future studies aiming to quantify pathological changes in the LC and surrounding structures in vivo.

7T quantitative magnetization transfer (qMT) of cortical gray matter in multiple sclerosis correlates with cognitive impairment.

Cognitive impairment (CI) is a major manifestation of multiple sclerosis (MS) and is responsible for extensively hindering patient quality of life. Cortical gray matter (cGM) damage is a significant contributor to CI, but is poorly characterized by conventional MRI let alone with quantitative MRI, such as quantitative magnetization transfer (qMT). Here we employed high-resolution qMT at 7T via the selective inversion recovery (SIR) method, which provides tissue-specific indices of tissue macromolecular content, such as the pool size ratio (PSR) and the rate of MT exchange (kmf). These indices could represent expected demyelination that occurs in the presence of gray matter damage. We utilized selective inversion recovery (SIR) qMT which provides a low SAR estimate of macromolecular-bulk water interactions using a tailored, B1 and B0 robust inversion recovery (IR) sequence acquired at multiple inversion times (TI) at 7T and fit to a two-pool model of magnetization exchange. Using this sequence, we evaluated qMT indices across relapsing-remitting multiple sclerosis patients (N = 19) and healthy volunteers (N = 37) and derived related associations with neuropsychological measures of cognitive impairment. We found a significant reduction in kmf in cGM of MS patients (15.5%, p = 0.002), unique association with EDSS (ρ = -0.922, p = 0.0001), and strong correlation with cognitive performance (ρ = -0.602, p = 0.0082). Together these findings indicate that the rate of MT exchange (kmf) may be a significant biomarker of cGM damage relating to CI in MS.

Measurement of T2* in the human spinal cord at 3T.

PURPOSE: To measure the transverse relaxation time T2* in healthy human cervical spinal cord gray matter (GM) and white matter (WM) at 3T. METHODS: Thirty healthy volunteers were recruited. Axial images were acquired using an averaged multi-echo gradient-echo (mFFE) T2*-weighted sequence with 5 echoes. We used the signal equation for an mFFE sequence with constant dephasing gradients after each echo to jointly estimate the spin density and T2* for each voxel. RESULTS: No global difference in T2* was observed between all GM (41.3 ± 5.6 ms) and all WM (39.8 ± 5.4 ms). No significant differences were observed between left (43.2 ± 6.8 ms) and right (43.4 ± 5.5 ms) ventral GM, left (38.3 ± 6.1 ms) and right (38.6 ± 6.5 ms) dorsal GM, and left (39.4 ± 5.8 ms) and right (40.3 ± 5.8 ms) lateral WM. However, significant regional differences were observed between ventral (43.4 ± 5.7 ms) and dorsal (38.4 ± 6.0 ms) GM (p < 0.05), as well as between ventral (42.9 ± 6.5 ms) and dorsal (37.9 ± 6.2 ms) WM (p < 0.05). In analyses across slices, inferior T2* was longer than superior T2* in GM (44.7 ms vs. 40.1 ms; p < 0.01) and in WM (41.8 ms vs. 35.9 ms; p < 0.01). CONCLUSIONS: Significant differences in T2* are observed between ventral and dorsal GM, ventral and dorsal WM, and superior and inferior GM and WM. There is no evidence for bilateral asymmetry in T2* in the healthy cord. These values of T2* in the spinal cord are notably lower than most reported values of T2* in the cortex.

Trajectory optimized NUFFT: Faster non-Cartesian MRI reconstruction through prior knowledge and parallel architectures.

PURPOSE: The non-uniform fast Fourier transform (NUFFT) involves interpolation of non-uniformly sampled Fourier data onto a Cartesian grid, an interpolation that is slowed by complex, non-local data access patterns. A faster NUFFT would increase the clinical relevance of the plethora of advanced non-Cartesian acquisition methods. METHODS: Here we customize the NUFFT procedure for a radial trajectory and GPU architecture to eliminate the bottlenecks encountered when allowing for arbitrary trajectories and hardware. We call the result TRON, for TRajectory Optimized NUFFT. We benchmark the speed and accuracy TRON on a Shepp-Logan phantom and on whole-body continuous golden-angle radial MRI. RESULTS: TRON was 6-30× faster than the closest competitor, depending on test data set, and was the most accurate code tested. CONCLUSIONS: Specialization of the NUFFT algorithm for a particular trajectory yielded significant speed gains. TRON can be easily extended to other trajectories, such as spiral and PROPELLER. TRON can be downloaded at http://github.com/davidssmith/TRON.

Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T1- and T2-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM. OBJECTIVE: To study cortical GM pathology related to CI in MS using glutamate-sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0 Tesla (7T). METHODS: A total of 20 patients with relapsing-remitting MS and 20 healthy controls underwent cognitive testing, anatomical imaging, and GluCEST imaging. Glutamate-sensitive image contrast was quantified for cortical GM, compared between cohorts, and correlated with clinical measures of CI. RESULTS AND CONCLUSION: Glutamate-sensitive contrast was significantly increased in the prefrontal cortex of MS patients with accumulated disability (p < 0.05). In addition, glutamate-sensitive contrast in the prefrontal cortex was significantly correlated with symbol digit modality test (rS = -0.814) and choice reaction time (rS = 0.772) scores in patients (p < 0.05), suggesting that GluCEST MRI may have utility as a marker for GM pathology and CI.

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Spinal cord MRI at 7T.

Magnetic resonance imaging (MRI) of the human spinal cord at 7T has been demonstrated by a handful of research sites worldwide, and the spinal cord remains one of the areas in which higher fields and resolution could have high impact. The small diameter of the cord (∼1 cm) necessitates high spatial resolution to minimize partial volume effects between gray and white matter, and so MRI of the cord can greatly benefit from increased signal-to-noise ratio and contrasts at ultra-high field (UHF). Herein we review the current state of UHF spinal cord imaging. Technical challenges to successful UHF spinal cord MRI include radiofrequency (B1) nonuniformities and a general lack of optimized radiofrequency coils, amplified physiological noise, and an absence of methods for robust B0 shimming along the cord to mitigate image distortions and signal losses. Numerous solutions to address these challenges have been and are continuing to be explored, and include novel approaches for signal excitation and acquisition, dynamic shimming and specialized shim coils, and acquisitions with increased coverage or optimal slice angulations.

Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain.

PURPOSE: To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T. THEORY AND METHODS: SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low-power, on-resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (tI/ tD ) to estimate a subset of qMT parameters, including the macromolecular-to-free pool-size-ratio (PSR), the R1 of free water (R1f ), and the rate of MT exchange (kmf ). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér-Rao lower bound theory and data reduction strategies to select optimal tI /tD combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient. RESULTS: Two optimal sampling schemes were determined: (i) a 5-point scheme (kmf estimated) and (ii) a 4-point scheme (kmf assumed). In phantoms, the 5/4-point schemes yielded parameter estimates with similar SNRs as our previous 16-point scheme, but with 4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing kmf reduced the sensitivity of PSR to partial-volume averaging, yielding more consistent estimates throughout the brain. CONCLUSIONS: qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB0 , B1+, and T1 ) when optimized tI -tD combinations are selected.

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T.

PURPOSE: The ability to evaluate pathological changes in the spinal cord in multiple sclerosis (MS) is limited because T1 - and T2 -w MRI imaging are not sensitive to biochemical changes in vivo. Amide proton transfer (APT) chemical exchange saturation transfer (CEST) can indirectly detect amide protons associated with proteins and peptides, potentially providing more pathological specificity. Here, we implement APT CEST in the cervical spinal cord of healthy and MS cohorts at 3T. METHODS: APT CEST of the cervical spinal cord was obtained in a cohort of 10 controls and 10 MS patients using a novel respiratory correction methodology. APT was quantified using two methods: 1) APTw , based off the conventional magnetization transfer ratio asymmetry, and 2) ΔAPT, a spatial characterization of APT changes in MS patients relative to the controls. RESULTS: Respiratory correction yielded highly reproducible z-spectra in white matter (intraclass correlation coefficient = 0.82). APTw signals in normal-appearing white matter (NAWM) of MS patients were significantly different from healthy controls (P = 0.04), whereas ΔAPT of MS patients highlighted large APT differences in NAWM. CONCLUSION: Respiration correction in the spinal cord is necessary to accurately quantify APT CEST, which can provide unique biochemical information regarding disease processes within the spinal cord. Magn Reson Med 79:806-814, 2018. © 2017 International Society for Magnetic Resonance in Medicine.