Magnetization Transfer Saturation Research Articles

Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis.

In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI). Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity. Compared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change (MD-ApC) = -1.50; p = 0.041] and increase in quantitative T1 (MD-ApC = 0.92; p < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion (β = -0.067; p = 0.039) and QSM (β = -0.077; p = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy. These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.

Advanced MRI Measures of Myelin and Axon Volume Identify Repair in Multiple Sclerosis.

Pathological studies suggest that multiple sclerosis (MS) lesions endure multiple waves of damage and repair; however, the dynamics and characteristics of these processes are poorly understood in patients living with MS. We studied 128 MS patients (75 relapsing-remitting, 53 progressive) and 72 healthy controls who underwent advanced magnetic resonance imaging and clinical examination at baseline and 2 years later. Magnetization transfer saturation and multi-shell diffusion imaging were used to quantify longitudinal changes in myelin and axon volumes within MS lesions. Lesions were grouped into 4 classes (repair, damage, mixed repair damage, and stable). The frequency of each class was correlated to clinical measures, demographic characteristics, and levels of serum neurofilament light chain (sNfL). Stable lesions were the most frequent (n = 2,276; 44%), followed by lesions with patterns of "repair" (n = 1,352; 26.2%) and damage (n = 1,214; 23.5%). The frequency of "repair" lesion was negatively associated with disability (β = -0.04; p < 0.001) and sNfL (β = -0.16; p < 0.001) at follow-up. The frequency of the "damage" class was higher in progressive than relapsing-remitting patients (p < 0.05) and was related to disability (baseline: β = -0.078; follow-up: β = -0.076; p < 0.001) and age (baseline: β = -0.078; p < 0.001). Stable lesions were more frequent in relapsing-remitting than in progressive patients (p < 0.05), and in younger patients versus older (β = -0.07; p < 0.001) at baseline. Further, "mixed" lesions were most frequent in older patients (β = 0.004; p < 0.001) at baseline. These findings show that repair and damage processes within MS lesions occur across the entire disease spectrum and that their frequency correlates with patients disability, age, disease duration, and extent of neuroaxonal damage. ANN NEUROL 2024.

White matter spinal tracts impairment in patients with degenerative cervical myelopathy evaluated with the magnetization transfer saturation MRI technique.

Prospective case-control study. We investigated the use of the magnetization transfer saturation (MTsat) technique to assess the structural integrity of the spinal cord tracts in individuals with clinically significant degenerative cervical myelopathy (DCM) and associated disability. Novosibirsk Neurosurgery Centre, Russia. A total of 53 individuals diagnosed with DCM and 41 patients with cervical radiculopathy underwent high-resolution MRI of the cervical spinal cord via the magnetization transfer technique. The MRI data were processed using the Spinal Cord Toolbox (v5.5), with MTsat values determined for each spinal tract and compared between the two groups. Furthermore, associations between MTsat values and the clinical disability rates of patients were investigated. A significant decrease in the MTsat of the ventral spinocerebellar tract was observed in the DCM group compared to the control group (adjusted p < 0.001). There was a trend towards lower MTsat values in the rubrospinal tract in the DCM group (adjusted p = 0.08). Additionally, a decrease in MTsat values in the lateral funiculi of the spinal cord was found in patients with DCM (adjusted p < 0.01). Furthermore, a trend toward a positive correlation was observed between the JOA score and the MTsat values within the ventral spinocerebellar tract (R = 0.33, adjusted p = 0.051). The findings of our study indicate that demyelination in patients with DCM affects mainly the ventral spinocerebellar and rubrospinal tracts, and the extent of changes in the ventral spinocerebellar tract is related to the severity of the condition.

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the UK

IntroductionPreterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the...

Circadian rapid eye movement sleep expression is associated with brain microstructural integrity in older adults

Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under strong circadian control and circadian dysregulation increases with age, the association between brain aging and circadian REMS regulation has not yet been assessed. Here, we measure the circadian amplitude of REMS through a 40-h in-lab multiple nap protocol in controlled laboratory conditions, and brain microstructural integrity with quantitative multi-parameter mapping (MPM) imaging in 86 older individuals. We show that reduced circadian REMS amplitude is related to lower magnetization transfer saturation (MTsat), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*) values in several white matter regions mostly located around the lateral ventricles, and with lower R1 values in grey matter clusters encompassing the hippocampus, parahippocampus, thalamus and hypothalamus. Our results further highlight the importance of considering circadian regulation for understanding the association between sleep and brain structure in older individuals.

Fast magnetization transfer saturation imaging of the brain using MP2RAGE T1 mapping.

Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed-sensing MP2RAGE (csMP2RAGE) T1 mapping for accelerating MTsat imaging. VFA, MP2RAGE, and csMP2RAGE were compared against inversion-recovery T1 in an aqueous phantom at 3 T. The same 1-mm VFA, MP2RAGE, and csMP2RAGE protocols were acquired in 4 healthy subjects to compare T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. At these scan times, all approaches provided strong repeatability and accurate T1 times (< 5% difference) in the phantom, but T1 accuracy was more impacted by T2 for VFA than for MP2RAGE. In vivo, VFA estimated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the differences in the T1 measured using VFA, MP2RAGE, and inversion recovery could be explained by the magnetization-transfer effects. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 2.3% for T1 mapping and 7.8% for MTsat imaging. We demonstrated that MP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.

Tensor denoising of quantitative multi-parameter mapping.

Quantitative multi-parameter mapping (MPM) provides maps of physical quantities representing physiologically meaningful tissue characteristics, which allows to investigate microstructure-function relationships reflecting normal or pathologic processes in the brain. However, the achievable spatial resolution and stability of MPM for basic research or clinical applications is severely constrained by SNR limits of the MR acquisition process, resulting in relatively long acquisition times. To increase SNR, we denoise MPM acquisitions using principal component analysis along tensors exploiting the Marchenko-Pastur law (tMPPCA). tMPPCA denoising was applied to three sets of MPM raw data before the quantification of maps of proton density, magnetization transfer saturation, R1, and R2*. The regional SNR gain for high-resolution MPM was investigated as well as reproducibility gains for clinically optimized protocols with moderate and high acceleration factors at different image resolutions. Substantial noise reduction in raw data was achieved, resulting in reduced noise for quantitative mapping up to sixfold without introducing bias of mean values (below 1%). Scan-rescan fluctuations were reduced up to threefold. Denoising allowed to decrease the voxel volume fourfold at the same scan time or reduce the scan time twofold at same voxel volume without loss of sensitivity. tMPPCA denoising can (a) improve of fine spatial and temporal patterns, (b) considerably reduce scan time for clinical applications, or (c) increase resolution to potentially push cutting-edge MPM protocols from the upper to the lower limit of the mesoscopic scale.

Circadian sleep regulation and brain tissue microstructure in cognitively unimpaired older adults

AbstractBackgroundCircadian dysfunction increases with age, leading to changes in the circadian regulation of physiological and biological rhythms, including sleep. Actigraphy studies demonstrated that altered 24‐h rest‐activity patterns, an estimate of circadian sleep‐wake regulation, is related to cognitive decline and tightly linked to Alzheimer’s disease progression. Here, we assessed whether circadian sleep regulation, measured during a multiple naps protocol, is related to brain microstructural integrity in a group of cognitively unimpaired older adults.MethodEighty‐six retired older individuals (mean age [SD] = 69.9 ± 5.2 y.o., 32 females, Table 1) with no major sleep disorders or medical condition, underwent an in‐lab 40‐h multiple naps protocol and brain structural magnetic resonance imaging. As rapid eye movement (REM) sleep is under strong circadian control, circadian REM sleep amplitude was computed by fitting a Gaussian curve on REM sleep duration (% of total sleep time) measured for each nap opportunity. The multiparametric mapping protocol was used to derive indices of brain tissue microstructure using magnetization transfer saturation (MTsat), R1 and R2* maps (hMRI toolbox v0.2.2). Statistical models were adjusted for age, sex, education, and for additional covariates related to sleep architecture and its circadian modulation, including mean REM% and sleep efficiency (SE), the accumulation of REM sleep and sleep need (slope of a fitted first‐order polynomial curve), and circadian SE amplitude.ResultsWhole‐brain voxel‐based quantification analysis revealed that low circadian REM amplitude was related to low MTsat, R1 and R2* values in several white matter regions mostly located around the lateral ventricles (Figure 1A). In addition, a significant association was observed between low circadian REM amplitude and low R1 values in two grey matter clusters encompassing the hippocampus, entorhinal cortex, thalamus and hypothalamus (Figure 1B).ConclusionOur findings provide first evidence that changes in circadian sleep regulation is associated with microstructural changes in key brain regions sensitive to the aging process and involved in sleep‐wake regulation. These results further emphasize the relevance of monitoring circadian sleep regulation for the early detection of individuals at risk for neurodegeneration and cognitive decline.

Characterisation of the neonatal brain using myelin-sensitive magnetisation transfer imaging

Abstract A cardinal feature of the encephalopathy of prematurity is dysmaturation of developing white matter and subsequent hypomyelination. Magnetisation transfer imaging (MTI) offers surrogate markers for myelination, including magnetisation transfer ratio (MTR) and magnetisation transfer saturation (MTsat). Using data from 105 neonates, we characterise MTR and MTsat in the developing brain and investigate how these markers are affected by gestational age at scan and preterm birth. We explore correlations of the two measures with fractional anisotropy (FA), radial diffusivity (RD) and T1w/T2w ratio which are commonly used markers of white matter integrity in early life. We used two complementary analysis methods: voxel-wise analysis across the white matter skeleton, and tract-of-interest analysis across 16 major white matter tracts. We found that MTR and MTsat positively correlate with gestational age at scan. Preterm infants at term-equivalent age had lower values of MTsat in the genu and splenium of the corpus callosum, while MTR was higher in central white matter regions, the corticospinal tract and the uncinate fasciculus. Correlations of MTI metrics with other MRI parameters revealed that there were moderate positive correlations between T1w/T2w and MTsat and MTR at voxel level, but at tract level FA had stronger positive correlations with these metrics. RD had the strongest correlations with MTI metrics, particularly with MTsat in major white matter tracts. The observed changes in MTI metrics are consistent with an increase in myelin density during early postnatal life, and lower myelination and cellular/axonal density in preterm infants at term-equivalent age compared to term controls. Furthermore, correlations between MTI-derived features and conventional measures from diffusion MRI provide new understanding about the contribution of myelination to non-specific imaging metrics that are often used to characterise early brain development.

Multiparametric Quantitative MRI of Peripheral Nerves in the Leg: A Reliability Study.

Patients with polyneuropathies typically have demyelination and/or axonal degeneration in peripheral nerves. Currently, there is a lack of imaging biomarkers to track the changes in these pathologies. To develop and evaluate the reliability of a multiparametric quantitative magnetic resonance imaging (qMRI) method of peripheral nerves in the leg. Prospective. Seventeen healthy volunteers (36.2 ± 13.8 years old, 9 males) with 10 of them scanned twice for test-retest. 3 T, three-dimensional gradient echo and diffusion tensor imaging. A qMRI protocol and processing pipeline was established for quantifying the following nerve parameters that are sensitive to myelin and axonal pathologies: magnetization transfer (MT) ratio (MTR), MT saturation index (MTsat), T2 *, T1 , proton density (PD), fractional anisotropy (FA), and mean/axial/radial diffusivities (MD, AD, and RD). The qMRI protocol also measures the volume of nerve fascicles (fVOL) and the fat fraction (FF) of muscles. The intersession reproducibility and inter-rater reliability of each qMRI parameter were assessed by Bland-Altman analysis and intraclass correlation coefficient (ICC). Pairwise Pearson correlation analyses were performed to investigate the intrinsic association between qMRI parameters. Distal-to-proximal variations were evaluated by paired t-tests with Bonferroni-Holm multiple comparison corrections. P < 0.05 was considered statistically significant. The MTR, MTsat, T2 *, T1 , PD, FA, AD, and fVOL of the sciatic and tibial nerves, and the FF of leg muscles, had an overall good-to-excellent test-retest agreement (ICC varying from 0.78 to 0.99). All the qMRI parameters had good-to-excellent inter-rater reliability (ICC > 0.80). The data demonstrated a pattern of distal-to-proximal changes of an increased nerve MTsat and FA, and a decreased nerve T1 , PD, MD, and RD, as well as a significantly increased muscle FF. The proposed multiparametric qMRI method of the peripheral nerves is highly reproducible and provided healthy control data which will be used in developing monitoring biomarkers in patients with polyneuropathies. 1 TECHNICAL EFFICACY: Stage 2.

Multiparametric Quantitative MRI of Peripheral Nerves to Differentiate Axonal from Demyelinating Neuropathies (P11-8.002)

<h3>Objective:</h3> To develop a multiparametric quantitative MRI (qMRI) method to track pathological changes of peripheral nerves in patients with peripheral neuropathies. <h3>Background:</h3> Irrespective of the causes or types of polyneuropathies, peripheral nerves are mainly afflicted by two kinds of pathologies – axonal loss and demyelination. It is critical to differentiate the two as treatments are different for the two conditions. While nerve conduction studies (NCS) have been used to differentiate the two pathologies in the distal nerves, there are no tools to probe the pathologies in the proximal peripheral nerves. This is particularly needed when distal nerves become non-responsive in NCS. <h3>Design/Methods:</h3> We have developed a multiparametric qMRI method that quantifies the sciatic and tibial nerves with 10 parameters that are sensitive to different aspects of myelin and axonal pathologies: magnetization transfer ratio (MTR), magnetization transfer saturation index (MTsat), longitudinal relaxation time (T1), proton density (PD), effective transverse relaxation time (T2*), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and nerve fascicular volume (fVol). In this pilot study, we studied 4 patients with Charcot-Marie-Tooth type-1A (CMT1A), 2 patients with CMT type-2S (CMT2S), and 17 healthy controls. <h3>Results:</h3> Compared with healthy controls, patients with CMT2S (reportedly as axonal type) had comparable MTR, MTsat, T1, PD and fVol, but reduced T2*. While patients with CMT1A (dysmyelinating type) had reduced MTR and MTsat, increased fVol, T1 and PD, and comparable T2*. All the 6 patients shared changes of reduced FA which was driven by a reduced AD and an increased RD. <h3>Conclusions:</h3> The data show different qMRI patterns between axonal and demyelinating neuropathies. The differential changes will be further verified in a larger cohort of patients with peripheral neuropathies. <b>Disclosure:</b> Dr. Chen has nothing to disclose. Mr. Baraz has nothing to disclose. Ms. Xuan has nothing to disclose. Sadaf Saba has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Castoro has nothing to disclose. Yang Xuan has nothing to disclose. Dr. Roth has nothing to disclose. The institution of Dr. Dortch has received research support from NIH. The institution of Dr. Dortch has received research support from DOD. Dr. Li has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. The institution of Dr. Li has received research support from NIH. Dr. Li has a non-compensated relationship as a Board of Directors with ANA that is relevant to AAN interests or activities.

Association between sleep slow-wave activity and in-vivo estimates of myelin in healthy young men

Sleep has been suggested to contribute to myelinogenesis and associated structural changes in the brain. As a principal hallmark of sleep, slow-wave activity (SWA) is homeostatically regulated but also differs between individuals. Besides its homeostatic function, SWA topography is suggested to reflect processes of brain maturation. Here, we assessed whether interindividual differences in sleep SWA and its homeostatic response to sleep manipulations are associated with in-vivo myelin estimates in a sample of healthy young men. Two hundred twenty-six participants (18–31 y.) underwent an in-lab protocol in which SWA was assessed at baseline (BAS), after sleep deprivation (high homeostatic sleep pressure, HSP) and after sleep saturation (low homeostatic sleep pressure, LSP). Early-night frontal SWA, the frontal-occipital SWA ratio, as well as the overnight exponential SWA decay were computed over sleep conditions. Semi-quantitative magnetization transfer saturation maps (MTsat), providing markers for myelin content, were acquired during a separate laboratory visit. Early-night frontal SWA was negatively associated with regional myelin estimates in the temporal portion of the inferior longitudinal fasciculus. By contrast, neither the responsiveness of SWA to sleep saturation or deprivation, its overnight dynamics, nor the frontal/occipital SWA ratio were associated with brain structural indices. Our results indicate that frontal SWA generation tracks inter-individual differences in continued structural brain re-organization during early adulthood. This stage of life is not only characterized by ongoing region-specific changes in myelin content, but also by a sharp decrease and a shift towards frontal predominance in SWA generation.

In vivo multi-parameter mapping of the habenula using MRI

The habenula is a small, epithalamic brain structure situated between the mediodorsal thalamus and the third ventricle. It plays an important role in the reward circuitry of the brain and is implicated in psychiatric conditions, such as depression. The importance of the habenula for human cognition and mental health make it a key structure of interest for neuroimaging studies. However, few studies have characterised the physical properties of the human habenula using magnetic resonance imaging because its challenging visualisation in vivo, primarily due to its subcortical location and small size. To date, microstructural characterization of the habenula has focused on quantitative susceptibility mapping. In this work, we complement this previous characterisation with measures of longitudinal and effective transverse relaxation rates, proton density and magnetisation transfer saturation using a high-resolution quantitative multi-parametric mapping protocol at 3T, in a cohort of 26 healthy participants. The habenula had consistent boundaries across the various parameter maps and was most clearly visualised on the longitudinal relaxation rate maps. We have provided a quantitative multi-parametric characterisation that may be useful for future sequence optimisation to enhance visualisation of the habenula, and additionally provides reference values for future studies investigating pathological differences in habenula microstructure.

Identifying and Overcoming Artifacts in 1 H-Based Saturation Transfer NOE NMR Experiments.

Magnetization transfer experiments are versatile nuclear magnetic resonance (NMR) tools providing site-specific information. We have recently discussed how saturation magnetization transfer (SMT) experiments could leverage repeated repolarizations arising from exchanges between labile and water protons to enhance connectivities revealed via the nuclear Overhauser effect (NOE). Repeated experience with SMT has shown that a number of artifacts may arise in these experiments, which may confound the information being sought - particularly when seeking small NOEs among closely spaced resonances. One of these pertains to what we refer to as "spill-over" effects, originating from the use of long saturation pulses leading to changes in the signals of proximate peaks. A second, related but in fact different effect, derives from what we describe as NOE "oversaturation", a phenomenon whereby the use of overtly intense RF fields overwhelms the cross-relaxation signature. The origin and ways to avoid these two effects are described. A final source of potential artifact arises in applications where the labile 1Hs of interest are bound to 15N-labeled heteronuclei. SMT's long 1H saturation times will then be usually implemented while under 15N decoupling based on cyclic schemes leading to decoupling sidebands. Although these sidebands usually remain invisible in NMR, they may lead to a very efficient saturation of the main resonance when touched by SMT frequencies. All of these phenomena are herein experimentally demonstrated, and solutions to overcome them are proposed.

Parkinson’s disease may disrupt overlapping subthalamic nucleus and pallidal motor networks

There is an ongoing debate about differential clinical outcome and associated adverse effects of deep brain stimulation (DBS) in Parkinson’s disease (PD) targeting the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). Given that functional connectivity profiles suggest beneficial DBS effects within a common network, the empirical evidence about the underlying anatomical circuitry is still scarce. Therefore, we investigate the STN and GPi-associated structural covariance brain patterns in PD patients and healthy controls.We estimate GPi’s and STN’s whole-brain structural covariance from magnetic resonance imaging (MRI) in a normative mid- to old-age community-dwelling cohort (n = 1184) across maps of grey matter volume, magnetization transfer (MT) saturation, longitudinal relaxation rate (R1), effective transversal relaxation rate (R2*) and effective proton density (PD*). We compare these with the structural covariance estimates in patients with idiopathic PD (n = 32) followed by validation using a reduced size controls’ cohort (n = 32).In the normative data set, we observed overlapping spatially distributed cortical and subcortical covariance patterns across maps confined to basal ganglia, thalamus, motor, and premotor cortical areas. Only the subcortical and midline motor cortical areas were confirmed in the reduced size cohort. These findings contrasted with the absence of structural covariance with cortical areas in the PD cohort.We interpret with caution the differential covariance maps of overlapping STN and GPi networks in patients with PD and healthy controls as correlates of motor network disruption. Our study provides face validity to the proposed extension of the currently existing structural covariance methods based on morphometry features to multiparameter MRI sensitive to brain tissue microstructure.

Dynamics of progressive degeneration of major spinal pathways following spinal cord injury: A longitudinal study

BackgroundFollowing spinal cord injury (SCI), disease processes spread gradually along the spinal cord forming a spatial gradient with most pronounced changes located at the lesion site. However, the dynamics of this gradient in SCI patients is not established. ObjectiveThis study tracks the spatiotemporal dynamics of remote anterograde and retrograde spinal tract degeneration in the upper cervical cord following SCI over two years utilizing quantitative MRI. MethodsTwenty-three acute SCI patients (11 paraplegics, 12 tetraplegics) and 21 healthy controls were scanned with a T1-weighted sequence for volumetry and a FLASH sequence for myelin-sensitive magnetization transfer saturation (MTsat) of the upper cervical cord. We estimated myelin content from MTsat maps within the corticospinal tracts (CST) and dorsal columns (DC) and measured spinal cord atrophy by means of left–right width (LRW) and anterior-posterior width (APW) on the T1-weighted images across cervical levels C1-C3. MTsat in the CST and LRW were considered proxies for retrograde degeneration, while MTsat in the DC and APW provided evidence for anterograde degeneration, respectively. Using regression models, we compared the temporal and spatial trajectories of these MRI readouts between tetraplegics, paraplegics, and controls over a 2-year period and assessed their associations with clinical improvement. ResultsLinear rates and absolute differences in myelin-sensitive MTsat indicated retrograde and anterograde neurodegeneration in the CST and DC, respectively. Changes in MTsat within the CST and in LRW progressively developed over time forming a gradient towards lower cervical levels by 2 years after injury, especially in tetraplegics (change per cervical level in MTsat: −0.247 p.u./level, p = 0.034; in LRW: −0.323 mm/level, p = 0.024). MTsat within the DC was already decreased at cervical levels C1-C3 at baseline (1.5 months after injury) in both tetra- and paraplegics, while linear decreases in APW over time were similar across C1-C3, preserving the spatial gradient. The relative improvement in light touch score was associated with MTsat within the DC at baseline (rs = 0.575, p = 0.014). ConclusionRostral and remote to the injury, the CST and DC show ongoing structural changes, indicative of myelin reductions and atrophy within 2 years after SCI. While anterograde degeneration in the DC was already detectable uniformly at C1-C3 early following SCI, retrograde degeneration in the CST developed over time revealing specific spatial and temporal neurodegenerative gradients. Disentangling and quantifying such dynamic pathological processes may provide biomarkers for regenerative and remyelinating therapies along entire spinal pathways.

Magnetization transfer saturation reveals subclinical optic nerve injury in pediatric-onset multiple sclerosis

Background: The presence of subclinical optic nerve (ON) injury in youth living with pediatric-onset MS has not been fully elucidated. Magnetization transfer saturation (MTsat) is an advanced magnetic resonance imaging (MRI) parameter sensitive to myelin density and microstructural integrity, which can be applied to the study of the ON. Objective: The objective of this study was to investigate the presence of subclinical ON abnormalities in pediatric-onset MS by means of magnetization transfer saturation and evaluate their association with other structural and functional parameters of visual pathway integrity. Methods: Eleven youth living with pediatric-onset MS (ylPOMS) and no previous history of optic neuritis and 18 controls underwent standardized brain MRI, optical coherence tomography (OCT), Magnetoencephalography (MEG)-Visual Evoked Potentials (VEPs), and visual battery. Data were analyzed with mixed effect models. Results: While ON volume, OCT parameters, occipital MEG-VEPs outcomes, and visual function did not differ significantly between ylPOMS and controls, ylPOMS had lower MTsat in the supratentorial normal appearing white matter (−0.26 nU, p = 0.0023), and in both in the ON (−0.62 nU, p < 0.001) and in the normal appearing white matter of the optic radiation (−0.56 nU, p = 0.00071), with these being positively correlated (+0.57 nU, p = 0.00037). Conclusions: Subclinical microstructural injury affects the ON of ylPOMS. This may appear as MTsat changes before being detectable by other currently available testing.

Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis.

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (${R_{1}}$), effective transverse relaxation rate (${R_{2}}^{\ast }$), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (${R_{2}}^{\ast }$ at 3T, ${R_{1}}$ at 7T), endothelial cells (${R_{1}}$ and MTsat at 3T), microglia (${R_{1}}$ and MTsat at 3T, ${R_{1}}$ at 7T), and oligodendrocytes and oligodendrocyte precursor cells (${R_{1}}$ at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.

Effects of Arterial Stiffness on Cerebral WM Integrity in Older Adults: A Neurite Orientation Dispersion and Density Imaging and Magnetization Transfer Saturation Imaging Study.

Arterial stiffness is reported to be able to cause axonal demyelination or degeneration. The present study aimed to use advanced MR imaging techniques to examine the effect of arterial stiffness on the WM microstructure among older adults. Arterial stiffness was measured using the cardio-ankle vascular elasticity index (CAVI). The high-CAVI (mean CAVI ≥ 9 points) and the low-CAVI groups (mean CAVI < 9 points) were created. The neuronal fiber integrity of the WM was evaluated by neurite orientation dispersion and density imaging and magnetization transfer saturation imaging. Tract-Based Spatial Statistics and the tracts-of-interest analysis were performed. Specific WM regions (corpus callosum, internal capsule, anterior thalamic radiation, corona radiata, superior longitudinal fasciculus, forceps minor, and inferior fronto-occipital fasciculus) were selected in the tracts-of-interest analysis. In Tract-Based Spatial Statistics, the high-CAVI group showed a significantly lower myelin volume fraction value in the broad WM and significantly higher radial diffusivity and isotropic volume fraction values in the corpus callosum, forceps minor, inferior fronto-occipital fasciculus, internal capsule, corona radiata, and anterior thalamic radiation than the low-CAVI group. In tracts-of-interest analysis using multivariate linear regression, significant associations were found between the mean CAVI and radial diffusivity in the anterior thalamic radiation and the corona radiata; isotropic volume fraction in the anterior thalamic radiation and the corona radiata; and myelin volume fraction in the superior longitudinal fasciculus (P < .05). Additionally, partial correlation coefficients were observed for the significant associations of executive function with radial diffusivity and myelin volume fraction (P < .05). Arterial stiffness could be associated with demyelination rather than axonal degeneration.

Reliability of multi-parameter mapping (MPM) in the cervical cord: A multi-center multi-vendor quantitative MRI study

MRI based multicenter studies which target neurological pathologies affecting the spinal cord and brain – including spinal cord injury (SCI) – require standardized acquisition protocols and image processing methods. We have optimized and applied a multi-parameter mapping (MPM) protocol that simultaneously covers the brain and the cervical cord within a traveling heads study across six clinical centers (Leutritz et al., 2020). The MPM protocol includes quantitative maps (magnetization transfer saturation (MT), proton density (PD), longitudinal (R1), and effective transverse (R2*) relaxation rates) sensitive to myelination, water content, iron concentration, and morphometric measures, such as cross-sectional cord area. Previously, we assessed the repeatability and reproducibility of the brain MPM data acquired in the five healthy participants who underwent two scan-rescans (Leutritz et al., 2020). This study focuses on the cervical cord MPM data derived from the same acquisitions to determine its repeatability and reproducibility in the cervical cord. MPM matrices of the cervical cord were generated and processed using the hMRI and the spinal cord toolbox. To determine reliability of the cervical MPM data, the intra-site (i.e., scan-rescan) coefficient of variation (CoV), inter-site CoV, and bias within region of interests (C1, C2 and C3 levels) were determined. The range of the mean intra- and inter-site CoV of MT, R1 and PD was between 2.5% and 12%, and between 1.1% and 4.0% for the morphometric measures. In conclusion, the cervical MPM data showed a high repeatability and reproducibility for key imaging biomarkers and hence can be employed as a standardized tool in multi-center studies, including clinical trials.