Magnetization Transfer Sequences Research Articles

Quantitative MRI reveals heterogeneous impacts of treatment on diseased bone marrow in a mouse model of myelofibrosis.

Analyzing bone marrow in the hematologic cancer myelofibrosis requires endpoint histology in mouse models and bone marrow biopsies in patients. These methods hinder the ability to monitor therapy over time. Preclinical studies typically begin treatment before mice develop myelofibrosis, unlike patients who begin therapy only after onset of disease. Using clinically relevant, quantitative MRI metrics allowed us to evaluate treatment in mice with established myelofibrosis. We used chemical shift-encoded fat imaging, DWI, and magnetization transfer sequences to quantify bone marrow fat, cellularity, and macromolecular components in a mouse model of myelofibrosis. We monitored spleen volume, the established imaging marker for treatment, with anatomic MRI. After confirming bone marrow disease by MRI, we randomized mice to treatment with an approved drug (ruxolitinib or fedratinib) or an investigational agent, navitoclax, for 33 days. We measured the effects of therapy over time with bone marrow and spleen MRI. All treatments produced heterogeneous responses with improvements in bone marrow evident in subsets of individual mice in all treatment groups. Reductions in spleen volume commonly occurred without corresponding improvement in bone marrow. MRI revealed patterns associated with effective and ineffective responses to treatment in bone marrow and identified regional variations in efficacy within a bone. Quantitative MRI revealed modest, heterogeneous improvements in bone marrow disease when treating mice with established myelofibrosis. These results emphasize the value of bone marrow MRI to assess treatment in preclinical models and the potential to advance clinical trials for patients.

Dual-encoded magnetization transfer and diffusion imaging and its application to tract-specific microstructure mapping

Abstract We present a novel dual-encoded magnetization transfer (MT) and diffusion-weighted sequence and demonstrate its potential to resolve distinct properties of white matter fiber tracts at the sub-voxel level. The sequence was designed and optimized for maximal MT ratio (MTR) efficiency. The resulting whole brain 2.6 mm isotropic protocol to measure tract-specific MTR has a scan time under 7 minutes. Ten healthy subjects were scanned twice to assess repeatability. Two different analysis methods were contrasted: a technique to extract tract-specific MTR using Convex Optimization Modeling for Microstructure Informed Tractography (COMMIT), a global optimization technique; and conventional MTR tractometry. The results demonstrate that the tract-specific method can reliably resolve the MT ratios of major white matter fiber pathways and is less affected by partial volume effects than conventional multi-modal tractometry. By reducing the contamination due to partial volume averaging of tracts, dual-encoded MT and diffusion may increase the sensitivity to microstructure alterations of specific tracts due to disease, aging, or learning, as well as lead to weighted structural connectomes with more anatomical specificity.

Correlation between the elastic modulus of anterior cruciate ligament (ACL) and quantitative ultrashort echo time (UTE) magnetic resonance imaging.

Conventional magnetic resonance imaging (MRI) often acquires no signal in anterior cruciate ligament (ACL) due to the short apparent transverse relaxation time of ACL. Ultrashort echo time (UTE) MRI is capable of imaging ACL with high signal which enables quantitative ACL assessment. This study aimed to investigate the correlations of the mechanical and microstructural properties of human ACL specimens with quantitative three-dimensional UTE Cones (3D-UTE-Cones) MRI measures. ACL specimens were harvested from cadaveric knee joints of 13 (50.9 ± 21.1 years old, 11 males and 2 female) donors. Specimens were scanned using a series of quantitative 3D-UTE-Cones T2 * (UTE-T2 *), T1 (UTE-T1 ), Adiabatic T1ρ (UTE-Adiab-T1ρ ), and magnetization transfer (UTE-MT) sequences in a wrist coil on a clinical 3T scanner. ACL elastic modulus was measured using a uniaxial tensile mechanical test. Histomorphometry analysis was performed to measure the average fascicle specific surface, fascicle size, and number of cells per unit area. Spearman's rank correlations of UTE-MRI biomarkers with mechanical and histomorphometry measures were investigated. The elastic modulus of ACL showed significant moderate correlations with UTE-Adiab-T1ρ (R = -0.59, p = 0.01), macromolecular fraction from MT modeling (R = 0.54, p = 0.01), magnetization transfer ratio (R = 0.53, p = 0.01), UTE-T2* (R = -0.53, p = 0.01), and average fascicle specific surface (R = 0.54, p = 0.01). UTE-MRI showed nonsignificant correlations with histomorphometry measures. UTE-MRI biomarkers may be useful noninvasive tools for the ACL mechanical assessment.

Macromolecular fraction (MMF) from 3D ultrashort echo time cones magnetization transfer (3D UTE-Cones-MT) imaging predicts meniscal degeneration and knee osteoarthritis

Meniscal degeneration is strongly associated with osteoarthritis (OA). We aimed to evaluate a 3D ultrashort-echo-time Cones magnetization transfer (UTE-Cones-MT) sequence for quantification of macromolecular fraction (MMF) and MT ratio (MTR) in menisci of healthy volunteers and patients with different degrees of OA. Patients with mild OA (n=19; 37-86 years; 10 males) or advanced OA (n=12; 52-88 years; 4 males) and healthy volunteers (n=17; 20-49 years; 7 males) were scanned with T2-FSE and UTE-Cones-MT sequences at 3T. Morphological assessment was performed using meniscal whole-organ magnetic resonance imaging score (WORMS). MMF and MTR were calculated for menisci, and correlated with age and meniscal WORMS scores. The diagnostic efficiency was performed by using receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses. Decreased MMF and MTR were observed in menisci of patients with mild or advanced OA compared with healthy subjects, and in menisci with tears (Grade 2-4) compared with normal menisci (Grade 0). Significant negative correlations were observed between MMF (r=-0.769, P<0.01), MTR (r=-0.320, P<0.01), and meniscal WORMS score. There was a mild negative correlation between MMF (r=-0.438, P<0.01), MTR (r=-0.289, P<0.01), and age. The AUC values of MMF and MTR in the four horns of meniscus and the posterior horn medial meniscus for differentiating OA patients from healthy volunteers were 0.762 and 0.699, and 0.835 and 0.883, respectively. The 3D UTE-Cones-MT biomarkers of MTR and especially MMF can detect compositional changes in meniscus and differentiate healthy subjects from patients with mild or advanced knee OA.

Automated cartilage segmentation and quantification using 3D ultrashort echo time (UTE) cones MR imaging with deep convolutional neural networks.

To develop a fully automated full-thickness cartilage segmentation and mapping of T1, T1ρ, and T2*, as well as macromolecular fraction (MMF) by combining a series of quantitative 3D ultrashort echo time (UTE) cones MR imaging with a transfer learning-based U-Net convolutional neural networks (CNN) model. Sixty-five participants (20 normal, 29 doubtful-minimal osteoarthritis (OA), and 16 moderate-severe OA) were scanned using 3D UTE cones T1 (Cones-T1), adiabatic T1ρ (Cones-AdiabT1ρ), T2* (Cones-T2*), and magnetization transfer (Cones-MT) sequences at 3T. Manual segmentation was performed by two experienced radiologists, and automatic segmentation was completed using the proposed U-Net CNN model. The accuracy of cartilage segmentation was evaluated using the Dice score and volumetric overlap error (VOE). Pearson correlation coefficient and intraclass correlation coefficient (ICC) were calculated to evaluate the consistency of quantitative MR parameters extracted from automatic and manual segmentations. UTE biomarkers were compared among different subject groups using one-way ANOVA. The U-Net CNN model provided reliable cartilage segmentation with a mean Dice score of 0.82 and a mean VOE of 29.86%. The consistency of Cones-T1, Cones-AdiabT1ρ, Cones-T2*, and MMF calculated using automatic and manual segmentations ranged from 0.91 to 0.99 for Pearson correlation coefficients, and from 0.91 to 0.96 for ICCs, respectively. Significant increases in Cones-T1, Cones-AdiabT1ρ, and Cones-T2* (p<0.05) and a decrease in MMF (p<0.001) were observed in doubtful-minimal OA and/or moderate-severe OA over normal controls. Quantitative 3D UTE cones MR imaging combined with the proposed U-Net CNN model allows a fully automated comprehensive assessment of articular cartilage. • 3D UTE cones imaging combined with U-Net CNN model was able to provide fully automated cartilage segmentation. • UTE parameters obtained from automatic segmentation were able to reliably provide a quantitative assessment of cartilage.

Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson's disease.

Cognitive decline is a common feature of Parkinson's disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson's disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomized crossover design, 19 patients with Parkinson's disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7 T imaging of the locus coeruleus using a neuromelanin-sensitive magnetization transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in patients with Parkinson's disease. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalized treatment approaches.

Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease

Diagnosing early stage Parkinson's disease (PD) is still a clinical challenge. Previous studies using iron, neuromelanin (NM) or the Nigrosome-1 (N1) sign in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. Our goal in this study was to extract the NM complex volume, iron content and volume representing the entire SN, and the N1 sign as potential complementary imaging biomarkers using a single 3D magnetization transfer contrast (MTC) gradient echo sequence and to evaluate their diagnostic performance and clinical correlations in early stage PD. A total of 40 early stage idiopathic PD subjects and 40 age- and sex-matched healthy controls (HCs) were imaged at 3T. NM boundaries (representing the SN pars compacta (SNpc) and parabrachial pigmented nucleus) and iron boundaries representing the total SN (SNpc and SN pars reticulata) were determined semi-automatically using a dynamic programming (DP) boundary detection algorithm. Receiver operating characteristic analyses were performed to evaluate the utility of these imaging biomarkers in diagnosing early stage PD. A correlation analysis was used to study the relationship between these imaging measures and the clinical scales. We also introduced the concept of NM and total iron overlap volumes to demonstrate the loss of NM relative to the iron containing SN. Furthermore, all 80 cases were evaluated for the N1 sign independently. The NM and SN volumes were lower while the iron content was higher in the SN for PD subjects compared to HCs. Interestingly, the PD subjects with bilateral loss of the N1 sign had the highest iron content. The area under the curve (AUC) values for the average of both hemispheres for single measures were: .960 for NM complex volume; .788 for total SN volume; .740 for SN iron content and .891 for the N1 sign. Combining NM complex volume with each of the following measures through binary logistic regression led to AUC values for the averaged right and left sides of: .976 for total iron content; .969 for total SN volume, .965 for overlap volume and .983 for the N1 sign. We found a negative correlation between SN volume and UPDRS-III (R2 = .22, p = .002). While the N1 sign performed well, it does not contain any information about iron content or NM quantitatively, therefore, marrying this sign with the NM and iron measures provides a better physiological explanation of what is happening when the N1 sign disappears in PD subjects. In summary, the combination of NM complex volume, SN volume, iron content and the N1 sign as derived from a single MTC sequence provides complementary information for understanding and diagnosing early stage PD.

An in vivo probabilistic atlas of the human locus coeruleus at ultra-high field

Early and profound pathological changes are evident in the locus coeruleus (LC) in dementia and Parkinson's disease, with effects on arousal, attention, cognitive and motor control. The LC can be identified in vivo using non-invasive magnetic resonance imaging techniques which have potential as biomarkers for detecting and monitoring disease progression. Technical limitations of existing imaging protocols have impaired the sensitivity to regional contrast variance or the spatial variability on the rostrocaudal extent of the LC, with spatial mapping consistent with post mortem findings. The current study employs a sensitive magnetisation transfer sequence using ultrahigh field 7T MRI to investigate the LC structure in vivo at high-resolution (0.4 × 0.4 × 0.5 mm). Magnetisation transfer images from 53 healthy older volunteers (52 - 84 years) clearly revealed the spatial features of the LC and were used to create a probabilistic LC atlas for older adults. This atlas may be especially relevant for studying disorders associated with older age. To use the atlas does not require use of the same MT sequence of 7T MRI, provided good co-registration and normalisation is achieved. Consistent rostrocaudal gradients of slice-wise volume, contrast and variance along the LC were observed, mirroring distinctive ex vivo spatial distributions of LC cells in its subregions. The contrast-to-noise ratios were calculated for the peak voxels, and for the averaged signals within the atlas, to accommodate the volumetric differences in estimated contrast. The probabilistic atlas is freely available, and the MRI dataset will be made available for non-commercial research, for replication or to facilitate accurate LC localisation and unbiased contrast extraction in future studies.

Quantitative Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone: An Update.

Bone possesses a highly complex hierarchical structure comprised of mineral (~45% by volume), organic matrix (~35%) and water (~20%). Water exists in bone in two forms: as bound water (BW), which is bound to bone mineral and organic matrix, or as pore water (PW), which resides in Haversian canals as well as in lacunae and canaliculi. Magnetic resonance (MR) imaging has been increasingly used for assessment of cortical and trabecular bone. However, bone appears as a signal void on conventional MR sequences because of its short T2*. Ultrashort echo time (UTE) sequences with echo times (TEs) 100–1,000 times shorter than those of conventional sequences allow direct imaging of BW and PW in bone. A series of quantitative UTE MRI techniques has been developed for bone evaluation. UTE and adiabatic inversion recovery prepared UTE (IR-UTE) sequences have been developed to quantify BW and PW. UTE magnetization transfer (UTE-MT) sequences have been developed to quantify collagen backbone protons, and UTE quantitative susceptibility mapping (UTE-QSM) sequences have been developed to assess bone mineral.

Quantitative Magnetic Resonance Imaging of Cortical and Trabecular Bone.

Bone is a composite material consisting of mineral, organic matrix, and water. Water in bone can be categorized as bound water (BW), which is bound to bone mineral and organic matrix, or as pore water (PW), which resides in Haversian canals as well as in lacunae and canaliculi. Bone is generally classified into two types: cortical bone and trabecular bone. Cortical bone is much denser than trabecular bone that is surrounded by marrow and fat. Magnetic resonance (MR) imaging has been increasingly used for noninvasive assessment of both cortical bone and trabecular bone. Bone typically appears as a signal void with conventional MR sequences because of its short T2*. Ultrashort echo time (UTE) sequences with echo times 100 to 1,000 times shorter than those of conventional sequences allow direct imaging of BW and PW in bone. This article summarizes several quantitative MR techniques recently developed for bone evaluation. Specifically, we discuss the use of UTE and adiabatic inversion recovery prepared UTE sequences to quantify BW and PW, UTE magnetization transfer sequences to quantify collagen backbone protons, UTE quantitative susceptibility mapping sequences to assess bone mineral, and conventional sequences for high-resolution imaging of PW as well as the evaluation of trabecular bone architecture.

Amide proton transfer-weighted magnetic resonance imaging of human brain aging at 3 Tesla.

Amide proton transfer-weighted (APTw) imaging has been revealed to hold great potential in the diagnosis of several brain diseases. The purpose of this proof-of-concept study was to evaluate the feasibility and value of APTw magnetic resonance imaging (MRI) in characterizing normal brain aging. A total of 106 healthy subjects were recruited and scanned at 3.0 Tesla, with APTw and conventional magnetization transfer (MT) sequences. Quantitative image analyses were performed in 12 regions of interest (ROIs) for each subject. The APTw or MT ratio (MTR) signal differences among five age groups (young, mature, middle-aged, young-old, and middle-old) were assessed using the one-way analysis of variance, with the Benjamini-Hochberg correction for multiple comparisons. The relationship between APTw and MTR signals and the age dependencies of APTw and MTR signals were assessed using the Pearson correlation and non-linear regression. There were no significant differences between the APTw or MTR values for males and females in any of the 12 ROIs analyzed. Among the five age groups, there were significant differences in the three white matter regions in the temporal, occipital, and frontal lobes. Overall, the mean APTw values in the older group were higher than those in the younger group. Positive correlations were observed in relation to age in most brain regions, including four with significant positive correlations (r=0.2065-0.4182) and five with increasing trends. As a comparison, the mean MTR values did not appear to be significantly different among the five age groups. In addition, the mean APTw and MTR values revealed significant positive correlations in 10 ROIs (r=0.2214-0.7269) and a significant negative correlation in one ROI (entorhinal cortex, r=-0.2141). Our early results show that the APTw signal can be used as a promising and complementary imaging biomarker with which normal brain aging can be evaluated at the molecular level.

High-resolution in vivo imaging of human locus coeruleus by magnetization transfer MRI at 3T and 7T

Locus Coeruleus (LC) is a neuromelanin-rich brainstem structure that is the source of noradrenaline in the cortex and is thought to modulate attention and memory. LC imaging in vivo is commonly performed with a 2D T1-weighted Turbo Spin Echo (TSE) MRI sequence, an approach that suffers from several drawbacks at 3T, including long acquisition times and highly anisotropic spatial resolution. In this study, we developed a high-resolution Magnetization Transfer (MT) sequence for LC imaging at both 7T and 3T and compared its performance to a TSE sequence. Results indicate that LC imaging can be achieved with an MT sequence at both 7 and 3T at higher spatial resolution than the 3T TSE. Furthermore, we investigated whether the currently disputed source of contrast in the LC region with a TSE sequence relates to MT effects or shortened T1 and T2* due to increased iron concentration. Our results suggest that the contrast in the LC area relates to MT effects. To conclude, in this study we managed to image the LC, for the first time, at 7T and at an increased resolution compared to the current state-of-the-art. Imaging the LC is highly relevant for clinical diagnostics as structural tissue properties of the LC may hold promise as a biomarker in neurodegenerative diseases.

Ultrashort echo time magnetization transfer (UTE‐MT) imaging and modeling: magic angle independent biomarkers of tissue properties

MRI biomarkers such as T2 , T2 * and T1rho have been widely used, but are confounded by the magic angle effect. The purpose of this study is to investigate the use of the two-dimensional ultrashort echo time magnetization transfer (UTE-MT) sequence for potential magic angle independent MR biomarkers. Magnetization transfer was investigated in cadaveric Achilles tendon samples using the UTE-MT sequence at five MT powers and five frequency offsets ranging from 2 to 50kHz. The protocol was applied at five sample orientations ranging from 0 to 90° relative to the B0 field. The results were analyzed with a two-pool quantitative MT model. Multiple TE data were also acquired and mono-exponential T2 * was calculated for each orientation. Macromolecular proton fractions and exchange rates derived from UTE-MT modeling did not appreciably change between the various orientations, whereas the T2 * relaxation time demonstrated up to a sixfold increase from 0° to 55°. The UTE-MT technique with two-pool modeling shows promise as a clinically compatible technique that is resistant to the magic angle effect. This method provides information on the macromolecular proton pool that cannot be directly obtained by other methods, including regular UTE techniques.

Magnetization transfer ratio for the assessment of perianal fistula activity in Crohn's disease.

Assessment of perianal fistulas is important to guide management of Crohn's disease (CD). Our objectives were to analyze the feasibility of magnetization transfer (MT) imaging to assess fistulas and to evaluate its contribution in assessing disease activity. During 15 months, all patients referred for perianal fistulas in CD underwent 3T-MRI including diffusion, T2/T1-weighted gadolinium-enhanced sequences and MT sequences (one with an off-resonance saturation pulse of 800 and one with 1200 Hz). We collected Van Assche score, fistula activity signs by analyzing T2, diffusion and contrast enhancement. We calculated MT ratio (MTR) with a ROI in the largest fistula. Twenty-nine patients (mean 34.9 years, range 17-53) were included. Van Assche score was 11.7, range 4-21. In 22 patients, the fistula presented with a bright T2 and diffusion signal with contrast enhancement, and was characterized as active. Mean MTR was respectively 47.2 (range 12-68) and 34.3 (range 11-57) at 800 and 1200 Hz. MTR at 800 Hz was significantly lower in non-active (34, range 12-55) than in active fistulas (51, range 24-68) (p < 0.02). MTR is feasible for the assessment of fistulas in CD and in the future could be used to help identify active and non-active fistulas. • MTR is feasible for the assessment of perianal fistulas in CD. • MT allows quantitative imaging of perianal fistula activity in CD. • MTR could be used to help identify active and non-active fistulas in CD.

Quantitative magnetic resonance imaging in patients with cirrhosis: a cross-sectional study.

Cerebral magnetic resonance imaging was undertaken, at 3 Tesla field strength, employing magnetization transfer (MT) and diffusion-weighted imaging (DWI) sequences, in 26 patients with well-compensated cirrhosis, free of overt hepatic encephalopathy. Results were compared to those from 18 aged-matched healthy volunteers. Cerebral magnetization transfer ratios (MTR) were reduced in the frontal white matter, caudate, putamen and globus pallidus in patients with cirrhosis, compared to healthy controls, while the apparent diffusion coefficients (ADC) on DWI were significantly increased in the genu and body of the corpus callosum. An association between previous excessive alcohol consumption and both MTR and ADCs was noted, but this association was lost when controls were exercised for the severity of liver disease and psychometric impairment on multivariate analysis. Eight (31%) of the 26 patients had impaired psychometric performance consistent with a diagnosis of minimal hepatic encephalopathy. No statistically significant difference in regional cerebral MTRs or ADCs was found in relation to neuropsychiatric status, although there was a trend towards lower MTRs in patients with impaired psychometric performance. The alterations in MTR and ADC in the patients with functionally compensated cirrhosis are compatible with theories governing the genesis of hepatic encephalopathy, including changes in astrocyte membrane permeability, with subsequent redistribution of macromolecules.

Off-resonance saturation ratio obtained with ultrashort echo time-magnetization transfer techniques is sensitive to changes in static tensile loading of tendons and degeneration.

To determine if off-saturation ratio (OSR) measured with the ultrashort echo time magnetization transfer (UTE-MT) sequence could differentiate between tendons under different states of tensile load and to compare these changes between normal versus degenerated tendons. Fourteen tendons were imaged at 3 Tesla before and during the application of 0.5-1 kg tension. A two-dimensional (2D) -UTE-MT sequence with 1.5, 3, and 5 kHz frequency offsets was used on nine tendons and a 3D-UTE-MT sequence with 1.5 kHz frequency offset was used on five tendons. OSR was calculated and compared for each condition. Histologic correlation was performed using light microscopy. In general, OSR increased after the application of tension. Mean increase of 2D OSR was 0.035 (95% confidence interval [CI], 0.013-0.056) at 1.5 kHz offset (P < 0.01), 0.031 (95% CI, 0.023-0.040) at 3 kHz offset (P < 0.01), and 0.013 (95% CI, -0.013-0.027) at 5 kHz offset (P = 0.07) from pre- to posttension states. Mean increase of 3D OSR was 0.026 (95% CI, 0.008-0.044) at a 1.5 kHz offset (P = 0.02) from pre- to posttension states. Mean decrease of 2D OSR at 1.5 kHz offset was 0.074-0.087 when comparing normal versus degenerated tendons (P < 0.01). OSR as measured with 2D or 3D UTE-MT sequences can detect the changes in hydration seen when tendons are placed under two different states of tensile load, but these changes are smaller than those encountered when comparing between normal versus pathologic tendons. Lower off-resonance saturation frequencies (3 kHz or less) are more sensitive to these changes than higher off-resonance saturation frequencies.

Cervical cord lesion load is associated with disability independently from atrophy in MS.

To investigate whether spinal cord (SC) lesion load, when quantified on axial images with high in-plane resolution, is associated with disability in multiple sclerosis (MS). Twenty-eight healthy controls and 92 people with MS had cervical SC 3T MRI with axial phase sensitive inversion recovery, T2, and magnetization transfer (MT) sequences. We outlined all visible focal lesions from C2 to C4 to obtain lesion load and also measured upper cervical cord area. We measured MT ratio in normal-appearing cord tissue and in lesions. Disability was recorded using the Expanded Disability Status Scale (EDSS) and MS Functional Composite. We used linear regression models to determine associations with disability. SC lesion load was significantly higher in both secondary progressive MS (SPMS) (p = 0.008) and primary progressive MS (PPMS) (p = 0.02) compared to relapsing-remitting MS (RRMS); in each comparison, adjustment was made for age, sex, and brain volume. These differences were not evident when EDSS was added as a covariate. SC area was significantly lower in both SPMS (p < 0.001) and PPMS (p = 0.009) compared to RRMS. In a multiple regression model, cord lesion load (p < 0.001), cord area (p = 0.003), age (p < 0.001), and sex (p = 0.001) were independently associated with EDSS (R(2) = 0.58). Cord lesion load (p = 0.003), cord area (p = 0.034), and brain parenchymal fraction (p = 0.007) were independently associated with the 9-hole peg test (R(2) = 0.42). When quantified on axial MRI with high in-plane resolution, upper cervical cord lesion load is significantly and independently correlated with physical disability and is higher in progressive forms of MS than RRMS.

Adiposity is associated with structural properties of the adolescent brain

Obesity, a major risk factor for cardiometabolic disease, is associated with variations in a number of structural properties in the adult brain, as assessed with magnetic resonance imaging (MRI). In this study, we investigated the cross-sectional relationship between visceral fat (VF), total body fat (TBF) and three MRI parameters in the brains of typically developing adolescents: (i) T1-weighted (T1W) signal intensity; (ii) T1W signal contrast between white matter (WM) and gray matter (GM); and (iii) magnetization transfer ratio (MTR). In a community-based sample of 970 adolescents (12–18years old, 466 males), VF was quantified using MRI, and total body fat was measured using a multifrequency bioimpedance. T1W images of the brain were used to determine signal intensity in lobar GM and WM, as well as WM:GM signal contrast. A magnetization transfer (MT) sequence of MTON and MTOFF was used to obtain MTR in GM and WM. We found that both larger volumes of VF and more TBF were independently associated with higher signal intensity in WM and higher WM:GM signal contrast, as well as higher MTR in both GM and WM. These relationships were independent of a number of potential confounders, including age, sex, puberty stage, household income and height. Our results suggest that both visceral fat and fat deposited elsewhere in the body are associated independently with structural properties of the adolescent brain. We speculate that these relationships suggest the presence of adiposity-related variations in phospholipid composition of brain lipids.

Dysfunctional NF-κB and brain myelin formation

Dysfunctional NF-κB and brain myelin formation

“NMR Chemosensing” Using Monolayer-Protected Nanoparticles as Receptors

A new sensing protocol based on NMR magnetization transfer sequences and the molecular recognition abilities of nanoparticles allows the detection and identification of organic molecules in complex mixtures.