Transverse Relaxation Time Constant Research Articles

Five multivariate Duchenne muscular dystrophy progression models bridging six-minute walk distance and MRI relaxometry of leg muscles.

The study aimed to provide quantitative information on the utilization of MRI transverse relaxation time constant (MRI-T2) of leg muscles in DMD clinical trials by developing multivariate disease progression models of Duchenne muscular dystrophy (DMD) using 6-min walk distance (6MWD) and MRI-T2. Clinical data were collected from the prospective and longitudinal ImagingNMD study. Disease progression models were developed by a nonlinear mixed-effect modeling approach. Univariate models of 6MWD and MRI-T2 of five muscles were developed separately. Age at assessment was the time metric. Multivariate models were developed by estimating the correlation of 6MWD and MRI-T2 modelvariables. Full model estimation approach for covariate analysis and five-fold cross validation were conducted. Simulations were performed to compare the models and predict the covariate effects on the trajectories of 6MWD and MRI-T2. Sigmoid Imax and Emax models best captured the profiles of 6MWD and MRI-T2 over age. Steroid use, baseline 6MWD, and baseline MRI-T2 were significant covariates. The median age at which 6MWD is half of its maximum decrease in the five models was similar, while the median age at which MRI-T2 is half of its maximum increase varied depending on the type of muscle. The models connecting 6MWD and MRI-T2 successfully quantified how individual characteristics alter disease trajectories. The models demonstrate a plausible correlation between 6MWD and MRI-T2, supporting the use of MRI-T2. The developed models will guide drug developers in using the MRI-T2 to most efficient use in DMD clinical trials.

Neurochemical Differences between 1p/19q Codeleted and Noncodeleted IDH-mutant Gliomas by in Vivo MR Spectroscopy.

Background Noninvasive identification of glioma subtypes is important for optimizing treatment strategies. Purpose To compare the in vivo neurochemical profiles between isocitrate dehydrogenase (IDH) 1-mutant 1p/19q codeleted gliomas and their noncodeleted counterparts measured by MR spectroscopy at 3.0 T with a point-resolved spectroscopy (PRESS) sequence optimized for D-2-hydroxyglutarate (2HG) detection. Materials and Methods Adults with IDH1-mutant gliomas were retrospectively included for this study from two university hospitals (inclusion period: January 2015 to July 2016 and September 2019 to June 2021, respectively) based on availability of 1p/19q codeletion status and a PRESS acquisition optimized for 2HG detection (echo time, 97 msec) at 3.0 T before any treatment. Spectral analysis was performed using LCModel and a simulated basis set. Metabolite quantification was performed using the water signal as a reference and correcting for water and metabolite longitudinal and transverse relaxation time constants. Concentration ratios were computed using total creatine (tCr) and total choline. A two-tailed unpaired t test was used to compare metabolite concentrations obtained in codeleted versus noncodeleted gliomas, accounting for multiple comparisons. Results Thirty-one adults (mean age, 39 years ± 8 [SD]; 19 male) were included, and 19 metabolites were quantified. Cystathionine concentration was higher in codeleted (n = 13) than noncodeleted (n = 18) gliomas when quantification was performed using the water signal or tCr as references (2.33 mM ± 0.98 vs 0.93 mM ± 0.94, and 0.34 mM ± 0.14 vs 0.14 mM ± 0.14, respectively; both P < .001). The sensitivity and specificity of PRESS to detect codeletion by means of cystathionine quantification were 92% and 61%, respectively. Other metabolites did not show evidence of a difference between groups (P > .05). Conclusion Higher cystathionine levels were detected in IDH1-mutant 1p/19q codeleted gliomas than in their noncodeleted counterparts with use of a PRESS sequence optimized for 2HG detection. Of 19 metabolites quantified, only cystathionine showed evidence of a difference in concentration between groups. Clinical trial registry no. NCT01703962 © RSNA, 2023 See also the editorial by Lin in this issue.

Magnetometer-Detected Nuclear Magnetic Resonance of Photochemically Hyperpolarized Molecules.

Photochemically induced dynamic nuclear polarization (photo-CIDNP) enables nuclear spin ordering by irradiating samples with light. Polarized spins are conventionally detected via high-field chemical-shift-resolved NMR (above 0.1 T). In this Letter, we demonstrate in situ low-field photo-CIDNP measurements using a magnetically shielded fast-field-cycling NMR setup detecting Larmor precession via atomic magnetometers. For solutions comprising mM concentrations of the photochemically polarized molecules, hyperpolarized 1H magnetization is detected by pulse-acquired NMR spectroscopy. The observed NMR line widths are about 5 times narrower than normally anticipated in high-field NMR and are systematically affected by light irradiation during the acquisition period, reflecting a reduction of the transverse relaxation time constant, T2*, on the order of 10%. Magnetometer-detected photo-CIDNP spectroscopy enables straightforward observation of spin-chemistry processes in the ambient field range from a few nT to tens of mT. Potential applications of this measuring modality are discussed.

Scyllo-inositol: Transverse relaxation time constant at 3T and concentration changes associated with aging and alcohol use.

The goals of this study were to measure the apparent transverse relaxation time constant, T2 , of scyllo-inositol (sIns) in young and older healthy adults' brains and to investigate the effect of alcohol usage on sIns in young and older healthy adults' brains, using proton magnetic resonance spectroscopy (MRS) at 3T. Twenty-nine young adults (age 21 ± 1years) and 24 older adults (age 74 ± 3years) participated in this study. MRS data were acquired from two brain regions (the occipital cortex and posterior cingulate cortex) at 3T. The T2 of sIns was measured using a localization by adiabatic selective refocusing (LASER) sequence at various echo times, while the sIns concentrations were measured using a short-echo-time stimulated echo acquisition mode (STEAM) sequence. A trend towards lower T2 relaxation values of sIns in older adults was observed, although these were not significant. sIns concentration was higher with age in both brain regions and was significantly higher in the young when considering alcohol consumption of more than two drinks per week. This study shows that differences in sIns can be found in two distinct regions of the brain across two age groups, potentially reflecting normal aging. In addition, it is important to take into account alcohol consumption when reporting the sIns level in the brain.

Myocardial Tissue Characterization in Cardiac Magnetic Resonance Studies of Patients Recovering From COVID-19: A Meta-Analysis.

Background Meta-analysis can identify biological factors that moderate cardiac magnetic resonance myocardial tissue markers such as native T1 (longitudinal magnetization relaxation time constant) and T2 (transverse magnetization relaxation time constant) in cohorts recovering from COVID-19 infection. Methods and Results Cardiac magnetic resonance studies of patients with COVID-19 using myocardial T1, T2 mapping, extracellular volume, and late gadolinium enhancement were identified by database searches. Pooled effect sizes and interstudy heterogeneity (I2) were estimated with random effects models. Moderators of interstudy heterogeneity were analyzed by meta-regression of the percent difference of native T1 and T2 between COVID-19 and control groups (%ΔT1 [percent difference of the study-level means of myocardial T1 in patients with COVID-19 and controls] and %ΔT2 [percent difference of the study-level means of myocardial T2 in patients with COVID-19 and controls]), extracellular volume, and the proportion of late gadolinium enhancement. Interstudy heterogeneities of %ΔT1 (I2=76%) and %ΔT2 (I2=88%) were significantly lower than for native T1 and T2, respectively, independent of field strength, with pooled effect sizes of %ΔT1=1.24% (95% CI, 0.54%-1.9%) and %ΔT2=3.77% (95% CI, 1.79%-5.79%). %ΔT1 was lower for studies in children (median age: 12.7 years) and athletes (median age: 21 years), compared with older adults (median age: 48 years). Duration of recovery from COVID-19, cardiac troponins, C-reactive protein, and age were significant moderators for %ΔT1 and/or %ΔT2. Extracellular volume, adjusted by age, was moderated by recovery duration. Age, diabetes, and hypertension were significant moderators of the proportion of late gadolinium enhancement in adults. Conclusions T1 and T2 are dynamic markers of cardiac involvement in COVID-19 that reflect the regression of cardiomyocyte injury and myocardial inflammation during recovery. Late gadolinium enhancement and to a lesser extent extracellular volume, are more static biomarkers moderated by preexisting risk factors linked to adverse myocardial tissue remodeling.

Step Activity Monitoring in Boys with Duchenne Muscular Dystrophy and its Correlation with Magnetic Resonance Measures and Functional Performance.

Muscles of boys with Duchenne muscular dystrophy (DMD) are progressively replaced by fatty fibrous tissues, and weakness leads to loss of ambulation (LoA). Step activity (SA) monitoring is a quantitative measure of real-world ambulatory function. The relationship between quality of muscle health and SA is unknown in DMD. To determine SA in steroid treated boys with DMD across various age groups, and to evaluate the association of SA with quality of muscle health and ambulatory function. Quality of muscle health was measured by magnetic resonance (MR) imaging transverse magnetization relaxation time constant (MRI-T2) and MR spectroscopy fat fraction (MRS-FF). SA was assessed via accelerometry, and functional abilities were assessed through clinical walking tests. Correlations between SA, MR, and functional measures were determined. A threshold value of SA was determined to predict the future LoA. The greatest reduction in SA was observed in the 9- < 11years age group. SA correlated with all functional and MR measures.10m walk/run test had the highest correlation with SA. An increase in muscle MRI-T2 and MRS-FF was associated with a decline in SA. Two years prior to LoA, SA in boys with DMD was 32% lower than age matched boys with DMD who maintained ambulation for more than two-year period. SA monitoring can predict subsequent LoA in Duchenne, as a daily step count of 3200 at baseline was associated with LoA over the next two-years. SA monitoring is a feasible and accessible tool to measure functional capacity in the real-world environment.

Reducing the effects of weak homonuclear dipolar coupling with CPMG pulse sequences for static and spinning solids

The Carr-Purcell/Meiboom-Gill (CPMG) pulse sequence, initially introduced for measuring transverse relaxation time constants (T2), can provide significant signal enhancements for solid-state NMR (SSNMR) spectra. The proper implementation of CPMG for acquiring spectra influenced by chemical shift anisotropies (CSAs), first and/or second order quadrupolar interactions, or paramagnetic broadening has been well documented to date, as have the effects of heteronuclear dipolar coupling on CPMG echo trains and T2 lifetimes. Homonuclear dipolar coupling can also impact T2 lifetimes and CPMG echo trains; these effects have been thoroughly investigated for spectra of homonuclear dipolar coupled spin-1/2 nuclei typically acquired under static conditions that are predominantly influenced by dipolar broadening (e.g., 1H, 19F, etc.). In particular, it has been shown that short refocusing pulses with small flip angles can extend the effective T2 (T2eff, the observed T2 constant as impacted by experimental conditions) measured by CPMG sequences for strong homonuclear dipolar coupled spin-1/2 pairs under static conditions. To date, these effects have not been explored for (i) spin-1/2 nuclei that have significant CSAs and simultaneously feature weak homonuclear dipolar couplings, (ii) for quadrupolar nuclei that are also weakly homonuclear dipolar coupled, and (iii) for either of these cases under magic-angle spinning (MAS) conditions. Herein, we demonstrate that short refocusing pulses that cause small flip angles can reduce the attenuation of signal in CPMG echo trains resulting from dipolar dephasing caused by the weak homonuclear dipolar couplings. For both spin-1/2 and quadrupolar nuclei, this can lead to significant extensions in T2eff and signal enhancements of up to three times compared to conventional CPMG in favourable cases. These phenomena can occur under both static and magic-angle spinning (MAS) conditions, in the latter of which homonuclear couplings are reintroduced by rotational resonance (R2) recoupling. Experimental examples of 13C (I = 1/2), 2H (I = 1), 87Rb (I = 3/2), 23Na (I = 3/2), and 35Cl (I = 3/2) NMR under static and MAS conditions, as well as simulations of these phenomena, are shown and discussed.

Detecting Dye-Contaminated Vegetables Using Low-Field NMR Relaxometry.

Dyeing vegetables with harmful compounds has become an alarming public health issue over the past few years. Excessive consumption of these dyed vegetables can cause severe health hazards, including cancer. Copper sulfate, malachite green, and Sudan red are some of the non-food-grade dyes widely used on vegetables by untrusted entities in the food supply chain to make them look fresh and vibrant. In this study, the presence and quantity of dye-based adulteration in vegetables are determined by applying 1H-nuclear magnetic resonance (NMR) relaxometry. The proposed technique was validated by treating some vegetables in-house with different dyes and then soaking them in various solvents. The resulting solutions were collected and analyzed using NMR relaxometry. Specifically, the effective transverse relaxation time constant, T2,eff, of each solution was estimated using a Carr–Purcell–Meiboom–Gill (CPMG) pulse sequence. Finally, the estimated time constants (i.e., measured signatures) were compared with a library of existing T2,eff data to detect and quantify the presence of unwanted dyes. The latter consists of data-driven models of transverse decay times for various concentrations of each water-soluble dye. The time required to analyze each sample using the proposed approach is dye-dependent but typically no longer than a few minutes. The analysis results can be used to generate warning flags if the detected dye concentrations violate widely accepted standards for food dyes. The proposed low-cost detection approach can be used in various stages of a produce supply chain, including consumer household.

PH Dependence of T2 for Hyperpolarizable 13C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging.

Hyperpolarized 13C magnetic resonance imaging often uses spin-echo-based pulse sequences that are sensitive to the transverse relaxation time T2. In this context, local T2-changes might introduce a quantification bias to imaging biomarkers. Here, we investigated the pH dependence of the apparent transverse relaxation time constant (denoted here as T2) of six 13C-labelled molecules. We obtained minimum and maximum T2 values within pH 1–13 at 14.1 T: [1-13C]acetate (T2,min = 2.1 s; T2,max = 27.7 s), [1-13C]alanine (T2,min = 0.6 s; T2,max = 10.6 s), [1,4-13C2]fumarate (T2,min = 3.0 s; T2,max = 18.9 s), [1-13C]lactate (T2,min = 0.7 s; T2,max = 12.6 s), [1-13C]pyruvate (T2,min = 0.1 s; T2,max = 18.7 s) and 13C-urea (T2,min = 0.1 s; T2,max = 0.1 s). At 7 T, T2-variation in the physiological pH range (pH 6.8–7.8) was highest for [1-13C]pyruvate (ΔT2 = 0.95 s/0.1pH) and [1-13C]acetate (ΔT2 = 0.44 s/0.1pH). Concentration, salt concentration, and temperature alterations caused T2 variations of up to 45.4% for [1-13C]acetate and 23.6% for [1-13C]pyruvate. For [1-13C]acetate, spatially resolved pH measurements using T2-mapping were demonstrated with 1.6 pH units accuracy in vitro. A strong proton exchange-based pH dependence of T2 suggests that pH alterations potentially influence signal strength for hyperpolarized 13C-acquisitions.

Changes in the intracellular microenvironment in the aging human brain

Normal brain aging is associated with changes occurring at all levels. This study investigates age-related differences in the brain intracellular microenvironment by comparing the apparent diffusion coefficients (ADC) and apparent transverse relaxation time constants (T2) of 5 neurochemicals (i.e., total N-acetyl-aspartate, total creatine, total choline, glutamate, and myo-inositol) between young and older adults. Thirty-two young healthy adults (18–22 years) and 26 older healthy adults (70–83 years) were recruited. Three brain regions were studied at 3 T: prefrontal, posterior cingulate and occipital cortices. ADC and T2 were measured using stimulated echo acquisition mode and localization by adiabatic selective refocusing sequences, respectively. This study shows that the diffusivities of several neurochemicals are higher in older than in younger adults. In contrast, shorter apparent T2 values for several metabolites were measured in older adults. Age-related difference in ADC and apparent T2 of metabolites seem to be region-specific. Furthermore, this study shows that it is feasible to observe age-related differences in the cellular microenvironment of neurochemicals in the normal aging brain.

Effect of Mineral Composition on Transverse Relaxation Time Distributions and MR Imaging of Tight Rocks from Offshore Ireland

In this paper, we investigate the effect of magnetic field strength on the transverse relaxation time constant (T2) in six distinct core plugs from four different rock types (three sandstones, one basalt, one volcanic tuff and one siltstone), retrieved from offshore Ireland. The CPMG pulse-sequence was used at two different magnetic field strengths: high-field at 4.70 T and low-field at 0.28 T. Axial images of the core plugs were also acquired with the RAREst sequence at high magnetic field strength. Thin-sections of the core plugs were prepared for optical imaging and SEM analysis, and provided qualitative information on the porosity and quantification of the elemental composition of the rock material. The content of iron varied from 4 wt. % to close to zero in the rock samples. Nevertheless, the effective T2 distributions obtained at low-field were used to successfully predict the porosity of the core plugs. Severe signal attenuations from internal magnetic gradients resulted in an underestimation of the porosity at high-field. No definitive trend was identified on the evolution of discrete relaxation time components between magnetic field strengths. The low-field measurements demonstrate that NMR is a powerful quantitative tool for petrophysical rock analysis as compared to thin-section analysis. The results of this study are of interest to the research community who characterizes natural gas hydrates in tight heterogeneous core plugs, and who typically relies on MR imaging to distinguish between solid hydrates and fluid phases. It further exemplifies the importance of selecting appropriate magnetic field strengths when employing NMR/MRI for porosity calculation in tight rock.

Accelerated 129 Xe MRI morphometry of terminal airspace enlargement: Feasibility in volunteers and those with alpha-1 antitrypsin deficiency.

Multi-b diffusion-weighted hyperpolarized inhaled-gas MRI provides imaging biomarkers of terminal airspace enlargement including ADC and mean linear intercept (Lm ), but clinical translation has been limited because image acquisition requires relatively long or multiple breath-holds that are not well-tolerated by patients. Therefore, we aimed to accelerate single breath-hold 3D multi-b diffusion-weighted 129 Xe MRI, using k-space undersampling in imaging direction using a different undersampling pattern for different b-values combined with the stretched exponential model to generate maps of ventilation, apparent transverse relaxation time constant ( ), ADC, and Lm values in a single, short breath-hold; accelerated and non-accelerated measurements were directly compared. We evaluated multi-b (0, 12, 20, 30, and 45.5 s/cm2 ) diffusion-weighted 129 Xe /ADC/morphometry estimates using acceleration factor (AF = 1 and 7) and multi-breath sampling in 3 volunteers (HV), and 6 participants with alpha-1 antitrypsin deficiency (AATD). For the HV subgroup, mean differences of 5%, 2%, and 8% were observed between fully sampled and undersampled k-space for ADC, Lm , and values, respectively. For the AATD subgroup, mean differences were 9%, 6%, and 12% between fully sampled and undersampled k-space for ADC, Lm and values, respectively. Although mean differences of 1% and 4.5% were observed between accelerated and multi-breath sampled ADC and Lm values, respectively, mean ADC/Lm estimates were not significantly different from corresponding mean ADCM /LmM or mean ADCA /LmA estimates (all P > 0.60 , A = undersampled and M = multi-breath sampled). Accelerated multi-b diffusion-weighted 129 Xe MRI is feasible at AF = 7 for generating pulmonary ADC and Lm in AATD and normal lung.

Magnetic Resonance Imaging of Methane Hydrate Formation and Dissociation in Sandstone with Dual Water Saturation

This paper reports formation and dissociation patterns of methane hydrate in sandstone. Magnetic resonance imaging spatially resolved hydrate growth patterns and liberation of water during dissociation. A stacked core set-up using Bentheim sandstone with dual water saturation was designed to investigate the effect of initial water saturation on hydrate phase transitions. The growth of methane hydrate (P = 8.3 MPa, T = 1–3 °C) was more prominent in high water saturation regions and resulted in a heterogeneous hydrate saturation controlled by the initial water distribution. The change in transverse relaxation time constant, T2, was spatially mapped during growth and showed different response depending on the initial water saturation. T2 decreased significantly during growth in high water saturation regions and remained unchanged during growth in low water saturation regions. Pressure depletion from one end of the core induced a hydrate dissociation front starting at the depletion side and moving through the core as production continued. The final saturation of water after hydrate dissociation was more uniform than the initial water saturation, demonstrating the significant redistribution of water that will take place during methane gas production from a hydrate reservoir.

Effects of PDE5 inhibition on dystrophic muscle following an acute bout of downhill running and endurance training.

Lack of sarcolemma-localized neuronal nitric oxide synthase mu (nNOSμ) contributes to muscle damage and fatigue in dystrophic muscle. In this study, we examined the effects of compensating for lack of nNOSμ with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice (mdx) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T2) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and 31phosphorus MRS (31P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T2 was attenuated (P < 0.05) in treated mdx and wild-type mice compared with untreated mdx. During training, resting T2 values did not change in wild-type and mdx mice from baseline values; however, the running distance completed during training was greater (P < 0.05) in treated mdx (>90% of target distance) and wild-type (100%) than untreated mdx (60%). The post-contractile BOLD response was greater (P < 0.05) in treated mdx that trained than untreated mdx, with no differences in muscle oxidative capacity, as measured by 31P-MRS. Our findings indicate that PDE5 inhibition reduces muscle damage after a single bout of downhill running and improves performance during endurance training in dystrophic mice, possibly because of enhanced microvascular function. NEW & NOTEWORTHY This study examined the combined effects of PDE5 inhibition and exercise in dystrophic muscle using high-resolution magnetic resonance imaging and spectroscopy. Our findings demonstrated that sildenafil citrate reduces muscle damage after a single bout of downhill running, improves endurance-training performance, and enhances microvascular function in dystrophic muscle. Collectively, the results support the combination of exercise and PDE5 inhibition as a therapeutic approach in muscular dystrophies lacking nNOSμ.

DUCHENNE MUSCULAR DYSTROPHY – IMAGING AND BIOMARKERS: P.34MR biomarkers in imaging DMD clinical trial network

MR biomarkers have shown considerable promise as outcome measures in clinical trials for Duchenne muscular dystrophy (DMD). Imaging DMD has developed an extensive clinical trial network with an infrastructure that enables high quality MR data collection across centers. The infrastructure incorporates standardized acquisition procedures, efficient data management, automated processing of images and spectra as a pipeline, phantoms, and quality assurance procedures. MR procedures have been successfully implemented for measuring fat fraction (FF) by both magnetic resonance spectroscopy (1H-MRS) and Dixon imaging, as well as the MRI transverse relaxation time constant (T2), enabling cross validation among measures. In addition, we measure 1H2O T2 using single voxel 1H-MRS as a marker of membrane stability and inflammation. In this study, we describe the infrastructure and MR methods used in these studies, and compare the sensitivity of these measurements to disease progression in a range of lower extremity muscles and ages using data acquired at three centers using 3T MR systems in 138 individuals with DMD (8.8±3.3 years) and 51 unaffected controls (8.8±2.4 years). Our results show a range of involvement and disease progression among muscles, with each MR measure able to robustly discriminate unaffected controls and DMD (p<0.05). Furthermore, the MR measures of muscle FF and MRI T2 were all able to detect longitudinal changes within one year (p<0.05) in the soleus and vastus lateralis. Overall, the Imaging DMD Clinical Trial Network has successfully implemented standardized MR procedures over multiple sites, and presently includes 21 certified MR sites across North America and Europe.

Real‐time monitoring by proton relaxometry of radical polymerization reactions of acrylamide in aqueous solution

AbstractThe potential of time‐domain nuclear magnetic resonance (TD‐NMR) for the real‐time monitoring of solution radical polymerizations is demonstrated. A model system composed of a redox‐pair initiator system, acrylamide as monomer and water as solvent was investigated. A second‐generation continuous wave free precession technique was employed to measure the longitudinal relaxation time constant (T1) of the samples throughout the polymerization reactions. This parameter was shown to be sensitive to the reactant feed free‐radical enhancement of the water molecule relaxation time, making it a good probe to monitor monomer conversion in real time in an automated, non‐destructive fashion. It was found that the T1 value was better than the transverse relaxation time constant (T2) for describing the evolution of the polymerization reactions, due to its greater sensitivity to paramagnetic effects. The TD‐NMR signal variation observed was linked to the formation, propagation and termination steps of the radical polymerization kinetics scheme. These first results may contribute to the application of real‐time monitoring of radical polymerization reactions employing low‐cost and robust TD‐NMR spectrometers. © 2018 Society of Chemical Industry

Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy.

ObjectiveTo provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design.MethodsMR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests.ResultsSignificant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68–0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63–0.73) and peroneals (|ρ| = 0.59–0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation.DiscussionLower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain metabolites at 3T.

The transverse relaxation times T2 of 17 metabolites in vivo at 3T is reported and region specific differences are addressed. An echo-time series protocol was applied to one, two, or three volumes of interest with different fraction of white and gray matter including a total number of 106 healthy volunteers and acquiring a total number of 128 spectra. The data were fitted with the 2D fitting tool ProFit2, which included individual line shape modeling for all metabolites and allowed the T2 calculation of 28 moieties of 17 metabolites. The T2 of 10 metabolites and their moieties have been reported for the first time. Region specific T2 differences in white and gray matter enriched tissue occur in 16 of 17 metabolites examined including single resonance lines and coupled spin systems. The relaxation time T2 is regions specific and has to be considered when applying tissue composition correction for internal water referencing. Magn Reson Med 80:452-461, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Transverse relaxation time constants of the five major metabolites in human brain measured in vivo using LASER and PRESS at 3 T.

The goal of this study was to measure and compare the apparent transverse relaxation time constants (T2 ) of five intracellular metabolites using localization by adiabatic selective refocusing (LASER) and point-resolved spectroscopy (PRESS) sequences in the human brain at 3 T. Five healthy subjects were studied at 3 T. 1 H spectra from the prefrontal cortex were acquired at six different echo times using LASER and PRESS sequences. Postprocessed data were analyzed with LCModel, and the resulting amplitudes were fitted using a mono-exponential decay function to determine the T2 of metabolites. Twenty-one percent higher apparent T2 values for the singlet resonances of N-acetyl aspartate, total creatine, and total choline were measured with LASER as compared with PRESS, whereas comparable apparent T2 values were measured for strongly coupled metabolites, glutamate, and myo-inositol, with both sequences. Reliable T2 measurements were obtained with both sequences for the five major intracellular metabolites. The LASER sequence appears to be more efficient in suppressing the diffusion component for singlets (having nonexchangeable protons) compared to J-coupled metabolites. Magn Reson Med 79:1260-1265, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Spectral characteristics of semisolid protons in human brain white matter at 7 T.

To inform the quantification of MRI magnetization transfer contrast at high field by measuring the spectral characteristics of 1 H protons in semisolids in human brain at 7 T, while avoiding prohibitive radiofrequency (RF) tissue heating and confounding effects from chemical exchange. Saturation-recovery type experiments were performed using brief, frequency-specific RF pulses that saturate semisolid proton magnetization. Analysis of the subsequent recovery of water proton magnetization with a two-pool model of exchange allowed the study of spectral characteristics of semisolid protons. We show that in white matter, the semisolid proton spectrum can be approximated with a symmetric, super-Lorentzian line at -2.58 ± 0.05 ppm from the water resonance and an average transverse relaxation time constant (T2 ) of 9.6 ± 0.6 μs. These results are consistent with studies at lower field that have indicated a major contribution from methylene protons to magnetization transfer contrast, and will facilitate the design and quantification of magnetization transfer studies at 7 T. Magn Reson Med 78:1950-1958, 2017. © 2017 International Society for Magnetic Resonance in Medicine.