A Complementary Multitechnique Approach to Assess the Bias in Molecular Weight Determination of Lignin by Derivatization-Free Gel Permeation Chromatography.

The growing interest in lignin valorization in the past decades calls for analytical techniques for lignin characterization, ranging from wet chemistry techniques to highly sophisticated chromatographic and spectroscopic methods. One of the key parameters to consider is the molecular weight profile of lignin, which is routinely determined by size-exclusion chromatography; however, this is by no means straightforward and is prone to being hampered by considerable errors. Our study expands the fundamental understanding of the bias-inducing mechanisms in gel permeation chromatography (GPC), the magnitude of error originating from using polystyrene standards for mass calibration, and an evaluation of the effects of the solvent and type of lignin on the observed bias. The developed partial least-squares (PLS) regression model for lignin-related monomers revealed that lignin is prone to association mainly via hydrogen bonding. This hypothesis was supported by functional group-based analysis of the bias as well as pulse field gradient (pfg) diffusion NMR spectroscopy of model compounds in THF-d8. Furthermore, although the lack of standards hindered drawing conclusions based on functionalities, direct infusion electrospray ionization mass spectrometry indicated that the relative bias decreases considerably for higher molecular weight species. The results from pfg-diffusion NMR spectroscopy on whole lignin samples were comparable when the same solvents were used in both experiments; in addition, the comparison between results obtained by pfg-diffusion NMR in different solvents gives some additional insights into the aggregation.

RF shimming in the cervical spinal cord at 7 T.

PURPOSE: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. METHODS: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. RESULTS: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1 + efficiency, and the vendor-based "patient" and "volume" modes showed the lowest B1 + efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior-inferior axis. CONCLUSION: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.

Single-Standard Quantification Strategy for Lignin Dimers by Supercritical Fluid Chromatography with Charged Aerosol Detection.

The increased interest in utilizing lignin as a feedstock to produce various aromatic compounds requires advanced chemical analysis methods to provide qualitative and quantitative characterization of lignin samples along different technology streamlines. However, due to the lack of commercially available chemical standards, routine quantification of industrially relevant lignin oligomers in complex lignin samples remains a challenge. This study presents a novel method for universal quantification of lignin dimers based on supercritical fluid chromatography with charged aerosol detection (CAD). A series of lignin-derived dimeric compounds that have been reported from reductive catalytic fractionation (RCF) were synthesized and used as standards. The applicability of using linear regression instead of quadratic calibration curves was evaluated over a concentration range of 15-125 mg/L, demonstrating that the former calibration method is as appropriate as the latter. The response factors of lignin dimeric compounds were compared to assess the uniformity of the CAD signal, revealing that the CAD response for the tested lignin dimers did not differ substantially. It was also found that the response factors were not dependent on the number of methoxy groups or linkage motifs, ultimately enabling the use of only one calibrant for these compounds. The importance of chromatographic peak resolution in CAD was stressed, and the use of a digital peak sharpening technique was adopted and applied to address this challenge. The developed method was verified and used for the quantification of lignin dimers in an oil obtained by a RCF of birch sawdust.

Shimming toolbox: An open-source software toolbox for B0 and B1 shimming in MRI.

PURPOSE: Introduce Shimming Toolbox ( https://shimming-toolbox.org), an open-source software package for prototyping new methods and performing static, dynamic, and real-time B0 shimming as well as B1 shimming experiments. METHODS: Shimming Toolbox features various field mapping techniques, manual and automatic masking for the brain and spinal cord, B0 and B1 shimming capabilities accessible through a user-friendly graphical user interface. Validation of Shimming Toolbox was demonstrated in three scenarios: (i) B0 dynamic shimming in the brain at 7T using custom AC/DC coils, (ii) B0 real-time shimming in the spinal cord at 3T, and (iii) B1 static shimming in the spinal cord at 7T. RESULTS: The B0 dynamic shimming of the brain at 7T took about 10 min to perform. It showed a 47% reduction in the standard deviation of the B0 field, associated with noticeable improvements in geometric distortions in EPI images. Real-time dynamic xyz-shimming in the spinal cord took about 5 min and showed a 30% reduction in the standard deviation of the signal distribution. B1 static shimming experiments in the spinal cord took about 10 min to perform and showed a 40% reduction in the coefficient of variation of the B1 field. CONCLUSION: Shimming Toolbox provides an open-source platform where researchers can collaborate, prototype and conveniently test B0 and B1 shimming experiments. Future versions will include additional field map preprocessing techniques, optimization algorithms, and compatibility across multiple MRI manufacturers.

An 8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla.

The quality of cervical spinal cord images can be improved by the use of tailored radiofrequency (RF) coil solutions for ultrahigh field imaging; however, very few commercial and research 7-T RF coils currently exist for the spinal cord, and in particular, those with parallel transmission (pTx) capabilities. This work presents the design, testing, and validation of a pTx/Rx coil for the human neck and cervical/upper thoracic spinal cord. The pTx portion is composed of eight dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made up of twenty semiadaptable overlapping loops to produce high signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while also being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1 + uniformity, power efficiency, and/or specific absorption rate efficiency. B1 + homogeneity, SNR, and g-factor were evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.

Multimodal Imaging Brain Markers in Early Adolescence Are Linked with a Physically Active Lifestyle.

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence.SIGNIFICANCE STATEMENT An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development.

Model-based dynamic off-resonance correction for improved accelerated fMRI in awake behaving nonhuman primates.

PURPOSE: To estimate dynamic off-resonance due to vigorous body motion in accelerated fMRI of awake behaving nonhuman primates (NHPs) using the echo-planar imaging reference navigator, in order to attenuate the effects of time-varying off-resonance on the reconstruction. METHODS: In NHP fMRI, the animal's head is usually head-posted, and the dynamic off-resonance is mainly caused by motion in body parts that are distant from the brain and have low spatial frequency. Hence, off-resonance at each frame can be approximated as a spatially linear perturbation of the off-resonance at a reference frame, and is manifested as a relative linear shift in k-space. Using GRAPPA operators, we estimated these shifts by comparing the navigator at each time frame with that at the reference frame. Estimated shifts were then used to correct the data at each frame. The proposed method was evaluated in phantom scans, simulations, and in vivo data. RESULTS: The proposed method is shown to successfully estimate spatially low-order dynamic off-resonance perturbations, including induced linear off-resonance perturbations in phantoms, and is able to correct retrospectively corrupted data in simulations. Finally, it is shown to reduce ghosting artifacts and geometric distortions by up to 20% in simultaneous multislice in vivo acquisitions in awake-behaving NHPs. CONCLUSION: A method is proposed that does not need sequence modification or extra acquisitions and makes accelerated awake behaving NHP imaging more robust and reliable, reducing the gap between what is possible with NHP protocols and state-of-the-art human imaging.

Elevated iron concentration in putamen and cortical speech motor network in developmental stuttering.

Theoretical accounts of developmental stuttering implicate dysfunctional cortico-striatal-thalamo-cortical motor loops through the putamen. However, the analysis of conventional MRI brain scans in individuals who stutter has failed to yield strong support for this theory in terms of reliable differences in the structure or function of the basal ganglia. Here, we performed quantitative mapping of brain tissue, which can be used to measure iron content alongside markers sensitive to myelin and thereby offers particular sensitivity to the measurement of iron-rich structures such as the basal ganglia. Analysis of these quantitative maps in 41 men and women who stutter and 32 individuals who are typically fluent revealed significant group differences in maps of R2*, indicative of higher iron content in individuals who stutter in the left putamen and in left hemisphere cortical regions important for speech motor control. Higher iron levels in brain tissue in individuals who stutter could reflect elevated dopamine levels or lysosomal dysfunction, both of which are implicated in stuttering. This study represents the first use of these quantitative measures in developmental stuttering and provides new evidence of microstructural differences in the basal ganglia and connected frontal cortical regions.

Mapping Human Laryngeal Motor Cortex during Vocalization.

The representations of the articulators involved in human speech production are organized somatotopically in primary motor cortex. The neural representation of the larynx, however, remains debated. Both a dorsal and a ventral larynx representation have been previously described. It is unknown, however, whether both representations are located in primary motor cortex. Here, we mapped the motor representations of the human larynx using functional magnetic resonance imaging and characterized the cortical microstructure underlying the activated regions. We isolated brain activity related to laryngeal activity during vocalization while controlling for breathing. We also mapped the articulators (the lips and tongue) and the hand area. We found two separate activations during vocalization-a dorsal and a ventral larynx representation. Structural and quantitative neuroimaging revealed that myelin content and cortical thickness underlying the dorsal, but not the ventral larynx representation, are similar to those of other primary motor representations. This finding confirms that the dorsal larynx representation is located in primary motor cortex and that the ventral one is not. We further speculate that the location of the ventral larynx representation is in premotor cortex, as seen in other primates. It remains unclear, however, whether and how these two representations differentially contribute to laryngeal motor control.

Correction of inter-scan motion artifacts in quantitative R1 mapping by accounting for receive coil sensitivity effects.

PURPOSE: Inter-scan motion causes differential receive field modulation between scans, leading to errors when they are combined to quantify MRI parameters. We present a robust and efficient method that accounts for inter-scan motion by removing this modulation before parameter quantification. THEORY AND METHODS: Five participants moved between two high-resolution structural scans acquired with different flip angles. Before each high-resolution scan, the effective relative sensitivity of the receive head coil was estimated by combining two rapid low-resolution scans acquired receiving on each of the body and head coils. All data were co-registered and sensitivity variations were removed from the high-resolution scans by division with the effective relative sensitivity. R1 maps with and without this correction were calculated and compared against reference maps unaffected by inter-scan motion. RESULTS: Even after coregistration, inter-scan motion significantly biased the R1 maps, leading to spurious variation in R1 in brain tissue and deviations with respect to a no-motion reference. The proposed correction scheme reduced the error to within the typical scan-rescan error observed in datasets unaffected by motion. CONCLUSION: Inter-scan motion negatively impacts the accuracy and precision of R1 mapping. We present a validated correction method that accounts for position-specific receive field modulation. Magn Reson Med 76:1478-1485, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The mouse motor system contains multiple premotor areas and partially follows human organizational principles.

While humans are known to have several premotor cortical areas, secondary motor cortex (M2) is often considered to be the only higher-order motor area of the mouse brain and is thought to combine properties of various human premotor cortices. Here, we show that axonal tracer, functional connectivity, myelin mapping, gene expression, and optogenetics data contradict this notion. Our analyses reveal three premotor areas in the mouse, anterior-lateral motor cortex (ALM), anterior-lateral M2 (aM2), and posterior-medial M2 (pM2), with distinct structural, functional, and behavioral properties. By using the same techniques across mice and humans, we show that ALM has strikingly similar functional and microstructural properties to human anterior ventral premotor areas and that aM2 and pM2 amalgamate properties of human pre-SMA and cingulate cortex. These results provide evidence for the existence of multiple premotor areas in the mouse and chart a comparative map between the motor systems of humans and mice.

8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla.

The quality of cervical spinal cord images can be improved by the use of tailored radiofrequency coil solutions for ultra-high field imaging; however, very few commercial and research 7 Tesla radiofrequency coils currently exist for the spinal cord, and in particular those with parallel transmit capabilities. This work presents the design, testing and validation of a pTx/Rx coil for the human neck and cervical/upper-thoracic spinal cord. The pTx portion is composed of 8 dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made of 20 semi-adaptable overlapping loops to produce high Signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B 1 + uniformity, power efficiency and/or specific absorption rate (SAR) efficiency. B 1 + homogeneity, SNR and g-factor was evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper-thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.

Hebbian activity-dependent plasticity in white matter.

Synaptic plasticity is required for learning and follows Hebb's rule, the computational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain's white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb's rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes and can be observed in human white matter fibers.

Quantitative MRI reveals differences in striatal myelin in children with DLD.

Developmental language disorder (DLD) is a common neurodevelopmental disorder characterised by receptive or expressive language difficulties or both. While theoretical frameworks and empirical studies support the idea that there may be neural correlates of DLD in frontostriatal loops, findings are inconsistent across studies. Here, we use a novel semiquantitative imaging protocol - multi-parameter mapping (MPM) - to investigate microstructural neural differences in children with DLD. The MPM protocol allows us to reproducibly map specific indices of tissue microstructure. In 56 typically developing children and 33 children with DLD, we derived maps of (1) longitudinal relaxation rate R1 (1/T1), (2) transverse relaxation rate R2* (1/T2*), and (3) Magnetization Transfer saturation (MTsat). R1 and MTsat predominantly index myelin, while R2* is sensitive to iron content. Children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, as well as in the left ventral sensorimotor cortex and Heschl's gyrus. They also had globally lower R1 values. No group differences were noted in R2* maps. Differences in MTsat and R1 were coincident in the caudate nucleus bilaterally. These findings support our hypothesis of corticostriatal abnormalities in DLD and indicate abnormal levels of myelin in the dorsal striatum in children with DLD.

Seven percent of children struggle to learn their native language for no obvious reason. This condition is called Developmental Language Disorder (DLD). Children with DLD often have difficulty learning to read and write. They are at higher risk for academic underachievement and may struggle to find good jobs. Their language difficulties also contribute to difficulties making friends and emotional challenges. Scientists suspect children with DLD may have differences in areas deep in the brain that help people learn habits and rules. A new magnetic resonance imaging technique called multiparameter mapping (MPM) can help scientists determine if this is true. The technique measures the properties of brain tissue. It is particularly useful for measuring the amounts of a fatty protective sheath on brain cells called myelin. Myelin helps brain cells send information faster. Using MPM, Krishnan et al. show that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits. In the experiments, 56 children with typical language development and 33 children with DLD were scanned using MPM. Krishnan et al. then compared the two groups and found reduced myelin in these critical areas associated with learning a language in most of the children with DLD. But not all children with DLD had these differences. More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain. Further research may help scientists find new treatments that target these brain differences.

A macroscopic link between interhemispheric tract myelination and cortico-cortical interactions during action reprogramming.

Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them. As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects. We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics. These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.

A laser wakefield acceleration facility using SG-II petawatt laser system.

Laser wakefield acceleration (LWFA) using PW-class laser pulses generally requires cm-scale laser-plasma interaction Rayleigh length, which can be realized by focusing such pulses inside a long underdense plasma with a large f-number focusing optic. Here, we present a new PW-based LWFA instrument at the SG-II 5 PW laser facility, which employs f/23 focusing. The setup also adapted an online probing of the plasma density via Nomarski interferometry using a probe laser beam having 30 fs pulse duration. By focusing 1-PW, 30-fs laser pulses down to a focal spot of 230 µm, the peak laser intensity reached a mild-relativistic level of 2.6 × 1018 W/cm2, a level modest for standard LWFA experiments. Despite the large aspect ratio of >25:1 (transverse to longitudinal dimensions) of the laser pulse, electron beams were observed in our experiment only when the laser pulse experienced relativistic self-focusing at high gas-pressure thresholds, corresponding to plasma densities higher than 3 × 1018 cm-3.

Reassessing associations between white matter and behaviour with multimodal microstructural imaging.

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2∗). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40-200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM's relationship with behaviour, suggesting that variable biological effects may be shaping their interaction.