An accelerated PETALUTE MRI sequence for in vivo quantification of sodium content in human articular cartilage at 3T.

OBJECTIVE: In this work, we evaluate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence in human articular cartilage in the knee. MATERIALS AND METHODS: We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial - Matched Spokes) and the other matching the total number of samples (Radial - Matched Samples) acquired in k-space. RESULTS: The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM, mean ± standard deviation) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a 41% shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2 × and 4 × acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction. CONCLUSION: We demonstrate improved scan time with equivalent performance using a 3D dual-echo PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.

Demyelination and Impaired Oligodendrogenesis in the Corpus Callosum Following Lead Exposure.

The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate effects of Pb exposure on oligodendrogenesis in SVZ and myelination in corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hrs before sampling) caused mild Pb accumulation in corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared to controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wks) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimers's disease, effect of Pb on myelination was evalued in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1000 ppm Pb in drinking water as PbAc2 for 20 wks) revealed a profound demyelination in corpus callosum compared to controls. Immunostaining of choroid plexus showed diminished signalling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis.

Recurrent inhibition refines mental templates to optimize perceptual decisions.

Translating sensory inputs to perceptual decisions relies on building internal representations of features critical for solving complex tasks. Yet, we still lack a mechanistic account of how the brain forms these mental templates of task-relevant features to optimize decision-making. Here, we provide evidence for recurrent inhibition: an experience-dependent plasticity mechanism that refines mental templates by enhancing γ-aminobutyric acid (GABA)-mediated (GABAergic) inhibition and recurrent processing in superficial visual cortex layers. We combine ultrahigh-field (7 T) functional magnetic resonance imaging at submillimeter resolution with magnetic resonance spectroscopy to investigate the fine-scale functional and neurochemical plasticity mechanisms for optimized perceptual decisions. We demonstrate that GABAergic inhibition increases following training on a visual (i.e., fine orientation) discrimination task, enhancing the discriminability of orientation representations in superficial visual cortex layers that are known to support recurrent processing. Modeling functional and neurochemical plasticity interactions reveals that recurrent inhibitory processing optimizes brain computations for perpetual decisions and adaptive behavior.

An Accelerated PETALUTE MRI Sequence for In Vivo Quantification of Sodium Content in Human Articular Cartilage at 3T.

In this work, we demonstrate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence. We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial-Matched Trajectories) and the other matching the total number of samples (Radial-Matched Samples) acquired in k-space. The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2× and 4× acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction. Together, these results demonstrate improved scan time with equivalent performance of the PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.

Effects of ebselen addition on emotional processing and brain neurochemistry in depressed patients unresponsive to antidepressant medication.

Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias-an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.

Test-Retest Reproducibility of Reduced-Field-of-View Density-Weighted CRT MRSI at 3T.

Quantifying an imaging modality's ability to reproduce results is important for establishing its utility. In magnetic resonance spectroscopic imaging (MRSI), new acquisition protocols are regularly introduced which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-field-of-view density-weighted concentric ring trajectory (rFOV-DW-CRT) MRSI) by calculating the coefficient of variance of data acquired from a test-retest experiment. The posterior cingulate cortex (PCC) and the right superior corona radiata (SCR) were selected as the regions of interest (ROIs) for grey matter (GM) and white matter (WM), respectively. CVs for between-subject and within-subject were consistently around or below 15% for Glx, tCho, and Myo-Ins, and below 5% for tNAA and tCr.

3D ultra-short echo time 31P-MRSI with rosette k-space pattern: Feasibility and comparison with conventional weighted CSI.

Phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) provides valuable non-invasive in vivo information on tissue metabolism but is burdened by poor sensitivity and prolonged scan duration. Ultra-short echo time (UTE) acquisitions minimize signal loss when probing signals with relatively short spin-spin relaxation time (T2), while also preventing first-order dephasing. Here, a three-dimensional (3D) UTE sequence with a rosette k-space trajectory is applied to 31P-MRSI at 3T. Conventional chemical shift imaging (CSI) employs highly regular Cartesian k-space sampling, susceptible to substantial artifacts when accelerated via undersampling. In contrast, this novel sequence's "petal-like" pattern offers incoherent sampling more suitable for compressed sensing (CS). These results showcase the competitive performance of UTE rosette 31P-MRSI against conventional weighted CSI with simulation, phantom, and in vivo leg muscle comparisons.

3D balanced SSFP UTE MRI for multiple contrasts whole brain imaging.

PURPOSE: This study aimed to develop a new high-resolution MRI sequence for the imaging of the ultra-short transverse relaxation time (uT2) components in the brain, while simultaneously providing proton density (PD) contrast for reference and quantification. THEORY: The sequence combines low flip angle balanced SSFP (bSSFP) and UTE techniques, together with a 3D dual-echo rosette k-space trajectory for readout. METHODS: The expected image contrast was evaluated by simulations. A study cohort of six healthy volunteers and eight multiple sclerosis (MS) patients was recruited to test the proposed sequence. Subtraction between two TEs was performed to extract uT2 signals. In addition, conventional longitudinal relaxation time (T1) weighted, T2-weighted, and PD-weighted MRI sequences were also acquired for comparison. RESULTS: Typical PD-contrast was found in the second TE images, while uT2 signals were selectively captured in the first TE images. The subtraction images presented signals primarily originating from uT2 components, but only if the first TE is short enough. Lesions in the MS subjects showed hyperintense signals in the second TE images but were hypointense signals in the subtraction images. The lesions had significantly lower signal intensity in subtraction images than normal white matter (WM), which indicated a reduction of uT2 components likely associated with myelin. CONCLUSION: 3D isotropic sub-millimeter (0.94 mm) spatial resolution images were acquired with the novel bSSFP UTE sequence within 3 min. It provided easy extraction of uT2 signals and PD-contrast for reference within a single acquisition.

Dissecting the chain of information processing and its interplay with neurochemicals and fluid intelligence across development.

Previous research has highlighted the role of glutamate and gamma-aminobutyric acid (GABA) in perceptual, cognitive, and motor tasks. However, the exact involvement of these neurochemical mechanisms in the chain of information processing, and across human development, is unclear. In a cross-sectional longitudinal design, we used a computational approach to dissociate cognitive, decision, and visuomotor processing in 293 individuals spanning early childhood to adulthood. We found that glutamate and GABA within the intraparietal sulcus (IPS) explained unique variance in visuomotor processing, with higher glutamate predicting poorer visuomotor processing in younger participants but better visuomotor processing in mature participants, while GABA showed the opposite pattern. These findings, which were neurochemically, neuroanatomically and functionally specific, were replicated ~21 mo later and were generalized in two further different behavioral tasks. Using resting functional MRI, we revealed that the relationship between IPS neurochemicals and visuomotor processing is mediated by functional connectivity in the visuomotor network. We then extended our findings to high-level cognitive behavior by predicting fluid intelligence performance. We present evidence that fluid intelligence performance is explained by IPS GABA and glutamate and is mediated by visuomotor processing. However, this evidence was obtained using an uncorrected alpha and needs to be replicated in future studies. These results provide an integrative biological and psychological mechanistic explanation that links cognitive processes and neurotransmitters across human development and establishes their potential involvement in intelligent behavior.

Ensemble Learning for Breast Cancer Lesion Classification: A Pilot Validation Using Correlated Spectroscopic Imaging and Diffusion-Weighted Imaging.

The main objective of this work was to evaluate the application of individual and ensemble machine learning models to classify malignant and benign breast masses using features from two-dimensional (2D) correlated spectroscopy spectra extracted from five-dimensional echo-planar correlated spectroscopic imaging (5D EP-COSI) and diffusion-weighted imaging (DWI). Twenty-four different metabolite and lipid ratios with respect to diagonal fat peaks (1.4 ppm, 5.4 ppm) from 2D spectra, and water and fat peaks (4.7 ppm, 1.4 ppm) from one-dimensional non-water-suppressed (NWS) spectra were used as the features. Additionally, water fraction, fat fraction and water-to-fat ratios from NWS spectra and apparent diffusion coefficients (ADC) from DWI were included. The nine most important features were identified using recursive feature elimination, sequential forward selection and correlation analysis. XGBoost (AUC: 93.0%, Accuracy: 85.7%, F1-score: 88.9%, Precision: 88.2%, Sensitivity: 90.4%, Specificity: 84.6%) and GradientBoost (AUC: 94.3%, Accuracy: 89.3%, F1-score: 90.7%, Precision: 87.9%, Sensitivity: 94.2%, Specificity: 83.4%) were the best-performing models. Conventional biomarkers like choline, myo-Inositol, and glycine were statistically significant predictors. Key features contributing to the classification were ADC, 2D diagonal peaks at 0.9 ppm, 2.1 ppm, 3.5 ppm, and 5.4 ppm, cross peaks between 1.4 and 0.9 ppm, 4.3 and 4.1 ppm, 2.3 and 1.6 ppm, and the triglyceryl-fat cross peak. The results highlight the contribution of the 2D spectral peaks to the model, and they demonstrate the potential of 5D EP-COSI for early breast cancer detection.

Event-related functional magnetic resonance spectroscopy.

Proton-Magnetic Resonance Spectroscopy (MRS) is a non-invasive brain imaging technique used to measure the concentration of different neurochemicals. "Single-voxel" MRS data is typically acquired across several minutes, before individual transients are averaged through time to give a measurement of neurochemical concentrations. However, this approach is not sensitive to more rapid temporal dynamics of neurochemicals, including those that reflect functional changes in neural computation relevant to perception, cognition, motor control and ultimately behaviour. In this review we discuss recent advances in functional MRS (fMRS) that now allow us to obtain event-related measures of neurochemicals. Event-related fMRS involves presenting different experimental conditions as a series of trials that are intermixed. Critically, this approach allows spectra to be acquired at a time resolution in the order of seconds. Here we provide a comprehensive user guide for event-related task designs, choice of MRS sequence, analysis pipelines, and appropriate interpretation of event-related fMRS data. We raise various technical considerations by examining protocols used to quantify dynamic changes in GABA, the primary inhibitory neurotransmitter in the brain. Overall, we propose that although more data is needed, event-related fMRS can be used to measure dynamic changes in neurochemicals at a temporal resolution relevant to computations that support human cognition and behaviour.

Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times.

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand.

Microstructural and neurochemical plasticity mechanisms interact to enhance human perceptual decision-making.

Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are typically studied at different scales (large-scale networks, local circuits), limiting our understanding of the adaptive interactions that support learning of complex cognitive skills in the adult brain. Here, we employ multimodal brain imaging to investigate the link between microstructural (myelination) and neurochemical (GABAergic) plasticity for decision-making. We test (in males, due to potential confounding menstrual cycle effects on GABA measurements in females) for changes in MRI-measured myelin, GABA, and functional connectivity before versus after training on a perceptual decision task that involves identifying targets in clutter. We demonstrate that training alters subcortical (pulvinar, hippocampus) myelination and its functional connectivity to visual cortex and relates to decreased visual cortex GABAergic inhibition. Modeling interactions between MRI measures of myelin, GABA, and functional connectivity indicates that pulvinar myelin plasticity interacts-through thalamocortical connectivity-with GABAergic inhibition in visual cortex to support learning. Our findings propose a dynamic interplay of adaptive microstructural and neurochemical plasticity in subcortico-cortical circuits that supports learning for optimized decision-making in the adult human brain.

High-resolution 3D ultra-short echo time MRI with Rosette k-space pattern for brain iron content mapping.

BACKGROUND: The iron concentration increases during normal brain development and is identified as a risk factor for many neurodegenerative diseases, it is vital to monitor iron content in the brain non-invasively. PURPOSE: This study aimed to quantify in vivo brain iron concentration with a 3D rosette-based ultra-short echo time (UTE) magnetic resonance imaging (MRI) sequence. METHODS: A cylindrical phantom containing nine vials of different iron concentrations (iron (II) chloride) from 0.5 millimoles to 50 millimoles and six healthy subjects were scanned using 3D high-resolution (0.94 ×0.94 ×0.94 mm3) rosette UTE sequence at an echo time (TE) of 20 µs. RESULTS: Iron-related hyperintense signals (i.e., positive contrast) were detected based on the phantom scan, and were used to establish an association between iron concentration and signal intensity. The signal intensities from in vivo scans were then converted to iron concentrations based on the association. The deep brain structures, such as the substantia nigra, putamen, and globus pallidus, were highlighted after the conversion, which indicated potential iron accumulations. CONCLUSION: This study suggested that T1-weighted signal intensity could be used for brain iron mapping.

Ultra-short T2 components imaging of the whole brain using 3D dual-echo UTE MRI with rosette k-space pattern.

PURPOSE: This study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically designed for UTE MRI applications. The imaging of the ultra-short transverse relaxation time (uT2 ) of brain was acquired to test the performance of the proposed UTE sequence. THEORY AND METHODS: The rosette trajectory was developed based on rotations of a "petal-like" pattern in the kx -ky plane, with oscillated extensions in the kz -direction for 3D coverage. Five healthy volunteers underwent 10 dual-echo 3D rosette UTE scans with various TEs. Dual-exponential complex model fitting was performed on the magnitude data to separate uT2 signals, with the output of uT2 fraction, uT2 value, and long-T2 value. RESULTS: The 3D rosette dual-echo UTE sequence showed better performance than a 3D radial UTE acquisition. More significant signal intensity decay in white matter than gray matter was observed along with the TEs. The white matter regions had higher uT2 fraction values than gray matter (10.9% ± 1.9% vs. 5.7% ± 2.4%). The uT2 value was approximately 0.10 ms in white matter . CONCLUSION: The higher uT2 fraction value in white matter compared to gray matter demonstrated the ability of the proposed sequence to capture rapidly decaying signals.

Characterizing Off-center MRI with ZTE.

PURPOSE: To maximize acquisition bandwidth in zero echo time (ZTE) sequences, readout gradients are already switched on during the RF pulse, creating unwanted slice selectivity. The resulting image distortions are amplified especially when the anatomy of interest is not located at the isocenter. We aim to characterize off-center ZTE MRI of extremities such as the shoulder, knee, and hip, adjusting the carrier frequency of the RF pulse excitation for each TR. METHODS: In ZTE MRI, radial encoding schemes are used, where the distorted slice profile due to the finite RF pulse length rotates with the k-space trajectory. To overcome these modulations for objects far away from the magnet isocenter, the frequency of the RF pulse is shifted for each gradient setting so that artifacts do not occur at a given off-center target position. The sharpness of the edges in the images were calculated and the ZTE acquisition with off-center excitation was compared to an acquisition with isocenter excitation both in phantom and in vivo off-center MRI of the shoulder, knee, and hip at 1.5 and 3T MRI systems. RESULTS: Distortion and blurriness artifacts on the off-center MRI images of the phantom, in vivo shoulder, knee, and hip images were mitigated with off-center excitation without time or noise penalty, at no additional computational cost. CONCLUSION: The off-center excitation allows ZTE MRI of the shoulder, knee, and hip for high-bandwidth image acquisitions for clinical settings, where positioning at the isocenter is not possible.

Cerebellar GABA Change during Visuomotor Adaptation Relates to Adaptation Performance and Cerebellar Network Connectivity: A Magnetic Resonance Spectroscopic Imaging Study.

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel magnetic resonance spectroscopic imaging (MRSI) technique to measure changes in the inhibitory neurotransmitter GABA in the human cerebellum during visuomotor adaptation. Participants (n = 17, six female) used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We spatially resolved adaptation-driven GABA changes at the cerebellar nuclei and cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple right-hand movements increase GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found that GABA in the left cerebellar nuclei and the right cerebellar nuclei diverged, although GABA change from baseline at the right cerebellar nuclei was not different from zero at the group level. Early adaptation-driven GABA fluctuations in the right cerebellar nuclei correlated with adaptation performance. Participants showing greater GABA decrease adapted better, suggesting early GABA change is behaviorally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network. Participants showing greater decreases in GABA showed greater strength increases in cerebellar network connectivity. Results were specific to GABA, to adaptation, and to the cerebellar network. This study provides first evidence for plastic changes in cerebellar neurochemistry during motor adaptation. Characterizing these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate human motor adaptation.SIGNIFICANCE STATEMENT Despite motor adaptation being fundamental to maintaining accurate movements, its neurochemical basis remains poorly understood, perhaps because measuring neurochemicals in the human cerebellum is technically challenging. Using a novel magnetic resonance spectroscopic imaging method, this study provides evidence for GABA changes in the left compared with the right cerebellar nuclei driven by both simple movement and motor adaptation. Although right cerebellar GABA changes were not significantly different from zero at the group level, the adaptation-driven GABA fluctuations in the right cerebellar nuclei correlated with adaptation performance and with functional connectivity change in a cerebellar network. These results show the first evidence for plastic changes in cerebellar neurochemistry during a cerebellar learning task. This provides the basis for developing therapeutic interventions that facilitate these naturally occurring changes to amplify cerebellar-dependent learning.

NIfTI-MRS: A standard data format for magnetic resonance spectroscopy.

PURPOSE: Multiple data formats in the MRS community currently hinder data sharing and integration. NIfTI-MRS is proposed as a standard spectroscopy data format, implemented as an extension to the Neuroimaging informatics technology initiative (NIfTI) format. This standardized format can facilitate data sharing and algorithm development as well as ease integration of MRS analysis alongside other imaging modalities. METHODS: A file format using the NIfTI header extension framework incorporates essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open-source command-line conversion program is implemented to convert single-voxel and spectroscopic imaging data to NIfTI-MRS. Visualization of data in NIfTI-MRS is provided by development of a dedicated plugin for FSLeyes, the FMRIB Software Library (FSL) image viewer. RESULTS: Online documentation and 10 example datasets in the proposed format are provided. Code examples of NIfTI-MRS readers are implemented in common programming languages. Conversion software, spec2nii, currently converts 14 formats where data is stored in image-space to NIfTI-MRS, including Digital Imaging and Communications in Medicine (DICOM) and vendor proprietary formats. CONCLUSION: NIfTI-MRS aims to solve issues arising from multiple data formats being used in the MRS community. Through a single conversion point, processing and analysis of MRS data are simplified, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. Greater standardization and harmonization become possible. By aligning with the dominant format in neuroimaging, NIfTI-MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, for visualization.

Relapsing antibody-negative patients with features of neuromyelitis optica spectrum disorders: Differences in N-acetylaspartate level in the cervical spinal cord indicate distinct underlying processes.

BACKGROUND: Due to lack of biomarkers, antibody-negative patients with features of neuromyelitis optica spectrum disorders (NMOSD) are among the most challenging to diagnose and treat. Using unsupervised clustering, we recently identified 'MS-like', 'spinal MS-like', 'classic NMOSD-like' and 'NMOSD-like with brain involvement' subgroups in this cohort. OBJECTIVE: We used magnetic resonance spectroscopy (MRS) to examine differences in the level of key metabolites in the spinal cord between the four identified subgroups. METHODS: Twenty-five relapsing antibody-negative patients with NMOSD features classified by the unsupervised algorithm to one of the subgroups underwent a prospective cervical spinal cord MRS. Spectra from 16 patients fulfilled quality criteria and were included in the analysis. RESULTS: Total N-acetylaspartate (tNAA), but not total choline (tCho) or myo-inositol (Ins), was significantly different between the four subgroups (p = 0.03). In particular, tNAA was 47.8% lower in the 'MS-like' subgroup as compared with the 'classic NMOSD-like' subgroup (p = 0.02). While we found a negative overall correlation between tNAA and disability score (r = -0.514, p = 0.04) in the whole cohort, the disability score did not differ significantly between the subgroups to explain subgroup differences in tNAA level. CONCLUSIONS: Significant differences in the cervical spinal cord tNAA measurements confirm that the previously identified clinico-radiologic subgroups contain patients with distinct underlying disease processes.