ABSTRACT
PURPOSE: To simultaneously acquire spectroscopic signals from two MRS voxels using a multi-banded 2 spin-echo, full-intensity acquired localized (2SPECIAL) sequence, and to decompose the signal to their respective regions by a novel voxel-GRAPPA (vGRAPPA) decomposition approach for in vivo brain applications at 7 T. METHODS: A wideband, uniform rate, smooth truncation (WURST) multi-banded pulse was incorporated into SPECIAL to implement 2SPECIAL for simultaneous multi-voxel spectroscopy (sMVS). To decompose the acquired data, the voxel-GRAPPA decomposition algorithm is introduced, and its performance is compared to the SENSE-based decomposition. Furthermore, the limitations of two-voxel excitation concerning the multi-banded adiabatic inversion pulse, as well as of the combined B0 shim and B1 + adjustments, are evaluated. RESULTS: It was successfully shown that the 2SPECIAL sequence enables sMVS without a significant loss in SNR while reducing the total scan time by 21.6% compared to two consecutive acquisitions. The proposed voxel-GRAPPA algorithm properly reassigns the signal components to their respective origin region and shows no significant differences to the well-established SENSE-based algorithm in terms of leakage (both <10%) or Cramér-Rao lower bounds (CRLB) for in vivo applications, while not requiring the acquisition of additional sensitivity maps and thus decreasing motion sensitivity. CONCLUSION: The use of 2SPECIAL in combination with the novel voxel-GRAPPA decomposition technique allows a substantial reduction of measurement time compared to the consecutive acquisition of two single voxels without a significant decrease in spectral quality or metabolite quantification accuracy and thus provides a new option for multiple-voxel applications.
Subject(s)
Algorithms , Brain , Brain/diagnostic imaging , Brain/metabolism , MotionABSTRACT
PURPOSE: To introduce a study design and statistical analysis framework to assess the repeatability, reproducibility, and minimal detectable changes (MDCs) of metabolite concentrations determined by in vivo MRS. METHODS: An unbalanced nested study design was chosen to acquire in vivo MRS data within different repeatability and reproducibility scenarios. A spin-echo, full-intensity acquired localized (SPECIAL) sequence was employed at 7 T utlizing three different inversion pulses: a hyperbolic secant (HS), a gradient offset independent adiabaticity (GOIA), and a wideband, uniform rate, smooth truncation (WURST) pulse. Metabolite concentrations, Cramér-Rao lower bounds (CRLBs) and coefficients of variation (CVs) were calculated. Both Bland-Altman analysis and a restricted maximum-likelihood estimation (REML) analysis were performed to estimate the different variance contributions of the repeatability and reproducibility of the measured concentration. A Bland-Altmann analysis of the spectral shape was performed to assess the variance of the spectral shape, independent of quantification model influences. RESULTS: For the used setup, minimal detectable changes of brain metabolite concentrations were found to be between 0.40 µmol/g and 2.23 µmol/g. CRLBs account for only 16 % to 74 % of the total variance of the metabolite concentrations. The application of gradient-modulated inversion pulses in SPECIAL led to slightly improved repeatability, but overall reproducibility appeared to be limited by differences in positioning, calibration, and other day-to-day variations throughout different sessions. CONCLUSION: A framework is introduced to estimate the precision of metabolite concentrations obtained by MRS in vivo, and the minimal detectable changes for 13 metabolite concentrations measured at 7 T using SPECIAL are obtained.
Subject(s)
Brain , Brain/diagnostic imaging , Humans , Magnetic Resonance Spectroscopy , Reproducibility of ResultsABSTRACT
PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.
Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Data Analysis , Databases, Factual/standards , Magnetic Resonance Imaging/standards , Magnetic Resonance Spectroscopy/standards , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methodsABSTRACT
INTRODUCTION: Single-voxel 1 H MRS in body applications often suffers from respiratory and other motion induced phase and frequency shifts, which lead to incoherent averaging and hence to suboptimal results. METHODS: Here we show the application of metabolite cycling (MC) for liver STEAM-localized 1 H MRS on a 7 T parallel transmit system, using eight transmit-receive fractionated dipole antennas with 16 additional, integrated receive loops. MC-STEAM measurements were made in six healthy, lean subjects and compared with STEAM measurements using VAPOR water suppression. Measurements were performed during free breathing and during synchronized breathing, for which the subjects did breathe in between the MRS acquisitions. Both intra-session repeatability and inter-session reproducibility of liver lipid quantification with MC-STEAM and VAPOR-STEAM were determined. RESULTS: The preserved water signal in MC-STEAM allowed for robust phase and frequency correction of individual acquisitions before averaging, which resulted in in vivo liver spectra that were of equal quality when measurements were made with free breathing or synchronized breathing. Intra-session repeatability and inter-session reproducibility of liver lipid quantification were better for MC-STEAM than for VAPOR-STEAM. This may also be explained by the more robust phase and frequency correction of the individual MC-STEAM acquisitions as compared with the VAPOR-STEAM acquisitions, for which the low-signal-to-noise ratio lipid signals had to be used for the corrections. CONCLUSION: Non-water-suppressed MC-STEAM on a 7 T system with parallel transmit is a promising approach for 1 H MRS applications in the body that are affected by motion, such as in the liver, and yields better repeatability and reproducibility compared with water-suppressed measurements.
Subject(s)
Liver/diagnostic imaging , Magnetic Resonance Spectroscopy/methods , Adult , Body Composition , Fatty Liver/diagnostic imaging , Female , Humans , Lipids/analysis , Liver/chemistry , Magnetic Resonance Spectroscopy/instrumentation , Male , Middle Aged , Motion , Phantoms, Imaging , Reproducibility of Results , Respiration , Signal-To-Noise RatioABSTRACT
PURPOSE: To compare several different optimization algorithms currently used for localized in vivo B0 shimming, and to introduce a novel, fast, and robust constrained regularized algorithm (ConsTru) for this purpose. METHODS: Ten different optimization algorithms (including samples from both generic and dedicated least-squares solvers, and a novel constrained regularized inversion method) were implemented and compared for shimming in five different shimming volumes on 66 in vivo data sets from both 7 T and 9.4 T. The best algorithm was chosen to perform single-voxel spectroscopy at 9.4 T in the frontal cortex of the brain on 10 volunteers. RESULTS: The results of the performance tests proved that the shimming algorithm is prone to unstable solutions if it depends on the value of a starting point, and is not regularized to handle ill-conditioned problems. The ConsTru algorithm proved to be the most robust, fast, and efficient algorithm among all of the chosen algorithms. It enabled acquisition of spectra of reproducible high quality in the frontal cortex at 9.4 T. CONCLUSIONS: For localized in vivo B0 shimming, the use of a dedicated linear least-squares solver instead of a generic nonlinear one is highly recommended. Among all of the linear solvers, the constrained regularized method (ConsTru) was found to be both fast and most robust. Magn Reson Med 79:1145-1156, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Subject(s)
Algorithms , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Databases, Factual , HumansABSTRACT
PURPOSE: Inhomogeneities of the main magnetic field cause line broadening and location-dependent frequency shifts in brain MRSI. These are often visible despite advanced B0 shimming. The purpose of this work is to propose an advanced B0 correction method that can easily be applied during postprocessing. METHODS: A target-driven overdiscrete reconstruction method previously introduced for MRSI is modified by dividing it into two steps. In a first step, an intermediate spectroscopic image with arbitrarily high resolution is generated, on which B0 correction is performed as an additional processing step based on an additionally acquired B0 map. This frequency-aligns metabolite peaks and destroys noise correlations between neighboring subvoxels. Second, the voxel is shaped by application of the spatial response target. The method was tested with simulated spectroscopic imaging data as well as in a series of MRSI data sets obtained from four healthy volunteers at 7T. RESULTS: A systematic gain in spectral signal-to-noise ratio is achieved, due to spatial averaging now occurring over peak aligned and noise decorrelated subvoxel spectra. At the same time, metabolite peak line widths are reduced. CONCLUSION: In the presence of B0 inhomogeneities across the field of view, the proposed method offers the potential to improve spectral quality with only a minimal additional effort during acquisition. Magn Reson Med 77:44-56, 2017. © 2015 Wiley Periodicals, Inc.
Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Humans , Signal-To-Noise RatioABSTRACT
PURPOSE: To calibrate a pre-emphasis to sufficiently compensate eddy currents for application of dynamic shim updating to fMRI without extension of scan times. METHODS: Eddy current effects induced into all shim terms up to third-order were characterized by spatiotemporal field monitoring, using a third-order field camera. Pre-emphasis settings were derived from the measurements and iteratively evaluated and refined. The calibrated pre-emphasis was applied to slice-wise dynamic shim updating in combination with a dynamic excitation frequency (F0) determination and a slice-wise B0 optimization routine for in vivo echo planar imaging and resting-state functional MRI. RESULTS: The described method for pre-emphasis calibration led to settling times of remaining eddy current effects below 2 ms, allowing for the application of dynamic shim updating to fMRI without extension of scan times or induction of eddy current related artifacts. A dynamic F0 determination compensates frequency shifts induced by the superposition of different shim fields, and therefore, prevents an image shift within the field of view. Hardware limitations necessitate the reduction of the maximum applicable B0 shim field amplitudes and restrict the shim performance. CONCLUSION: The proposed method enables accurate pre-emphasis calibration, and therefore, the application of dynamic shim updating to fMRI.
Subject(s)
Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Signal Processing, Computer-Assisted , Algorithms , Brain/anatomy & histology , Brain/physiology , HumansABSTRACT
PURPOSE: To improve B0 shimming for applications in high- and ultrahigh-field magnetic resonance imaging and magnetic resonance spectroscopy. METHODS: An existing image-based constrained B0 shimming algorithm was enhanced using two techniques: (1) A region of less interest was introduced to control B0 field inhomogeneities in the vicinity of the region of interest; (2) multiple sets of starting values were used for the fitting routine, to avoid "getting trapped" in a local minimum of the optimization function. The influence of constraints during the fitting procedure, due to hardware limitations, on the B0 shim result was investigated. The performance of this algorithm was compared to other B0 shim algorithms for typical shim problems in head and body applications at 3T and 7T. RESULTS: Utilization of a weighted region of less interest lead to a significant gain in B0 homogeneity adjacent to the region of interest. The loss of B0 quality due to the enlarged total shim volume within the region of interest remained minimal, allowing for improved artifact reduction in magnetic resonance spectroscopic imaging. Multiple sets of starting values and consideration of shim field constraints led to an additional gain in B0 shim quality. CONCLUSION: The proposed algorithm allows for more flexible control of B0 inhomogeneities and, hence, enables gains in image and spectral quality for MR applications. RO1AR050597
Subject(s)
Brain Chemistry , Brain/anatomy & histology , Heart/anatomy & histology , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Myocardium/chemistry , Adult , Female , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
PURPOSE: To substantially improve spatial localization in magnetic resonance spectroscopic imaging (MRSI) accelerated by parallel imaging. This is important in order to make MRSI more reliable as a tool for clinical applications. METHODS: The sensitivity encoding acceleration technique with spatial overdiscretization is applied for the reconstruction of parallel MRSI. In addition, the spatial response function is optimized by minimizing its deviation from a previously chosen target function. This modified minimum-norm sensitivity encoding-MRSI reconstruction approach is applied in this article for in vivo pulse-acquire MRSI of human brain at 7T with simulated acceleration factors of 2, 4, and 9 as well as actual 4-fold accelerated MRSI. RESULTS: The sidelobes of the spatial response function are significantly suppressed, which reduces far-reaching voxel bleeding. At the same time, the major enlargement of the effective voxel size, which would be introduced by conventional k-space apodization methods, is largely avoided. Regularization allows for a practical trade-off between noise minimization, effective voxel size, and unaliasing. Although not aiming at increasing the nominal spatial resolution, a better spatial specificity is achieved. CONCLUSION: Simultaneous suppression of short- and far-reaching voxel bleeding in MRSI is analyzed and reconstruction of highly accelerated parallel in vivo MRSI is demonstrated.
Subject(s)
Algorithms , Artifacts , Brain/metabolism , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Proton Magnetic Resonance Spectroscopy/methods , Brain/anatomy & histology , Humans , Imaging, Three-Dimensional/methods , Molecular Imaging/methods , Reproducibility of Results , Sensitivity and Specificity , Spatio-Temporal Analysis , Tissue DistributionABSTRACT
OBJECTIVE: We propose a method for the reconstruction of parameter-maps in Quantitative Magnetic Resonance Imaging (QMRI). METHODS: Because different quantitative parameter-maps differ from each other in terms of local features, we propose a method where the employed dictionary learning (DL) and sparse coding (SC) algorithms automatically estimate the optimal dictionary-size and sparsity level separately for each parameter-map. We evaluated the method on a T1-mapping QMRI problem in the brain using the BrainWeb data as well as in-vivo brain images acquired on an ultra-high field 7 T scanner. We compared it to a model-based acceleration for parameter mapping (MAP) approach, other sparsity-based methods using total variation (TV), Wavelets (Wl), and Shearlets (Sh) to a method which uses DL and SC to reconstruct qualitative images, followed by a non-linear (DL+Fit). RESULTS: Our algorithm surpasses MAP, TV, Wl, and Sh in terms of RMSE and PSNR. It yields better or comparable results to DL+Fit by additionally significantly accelerating the reconstruction by a factor of approximately seven. CONCLUSION: The proposed method outperforms the reported methods of comparison and yields accurate T1-maps. Although presented for T1-mapping in the brain, our method's structure is general and thus most probably also applicable for the the reconstruction of other quantitative parameters in other organs. SIGNIFICANCE: From a clinical perspective, the obtained T1-maps could be utilized to differentiate between healthy subjects and patients with Alzheimer's disease. From a technical perspective, the proposed unsupervised method could be employed to obtain ground-truth data for the development of data-driven methods based on supervised learning.
Subject(s)
Algorithms , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Image Processing, Computer-Assisted/methodsABSTRACT
Purpose: To improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain 1 H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints. Methods: Full- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared to those other methods was investigated. Results: The developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramér-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. While the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p≤0.0001). Minimally detectable changes are in the range 0.5 - 1.9 mM and percent coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out. Conclusion: Here, the PRaMM model, a method for an improved quantification of metabolites was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.
ABSTRACT
INTRODUCTION: The hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer's disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population. METHODS: Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education. RESULTS: Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13]. CONCLUSION: Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala's value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Follow-Up Studies , Alzheimer Disease/pathology , Longitudinal Studies , Cross-Sectional Studies , Cognitive Dysfunction/pathology , Magnetic Resonance Imaging , Amygdala/diagnostic imaging , Amygdala/pathology , Neuropsychological Tests , Memory Disorders/diagnostic imaging , Memory Disorders/etiologyABSTRACT
Background: Magnetic resonance imaging (MRI) is indispensable for diagnosing neurological conditions such as multiple sclerosis (MS). MRI also supports decisions regarding the choice of disease-modifying drugs (DMDs). Determining in vivo tissue concentrations of DMDs has the potential to become an essential clinical tool for therapeutic drug monitoring (TDM). The aim here was to examine the feasibility of fluorine-19 (19F) MR methods to detect the fluorinated DMD teriflunomide (TF) during normal and pathological conditions. Methods: We used 19F MR spectroscopy to detect TF in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS) in vivo. Prior to the in vivo investigations we characterized the MR properties of TF in vitro. We studied the impact of pH and protein binding as well as MR contrast agents. Results: We could detect TF in vivo and could follow the 19F MR signal over different time points of disease. We quantified TF concentrations in different tissues using HPLC/MS and showed a significant correlation between ex vivo TF levels in serum and the ex vivo19F MR signal. Conclusion: This study demonstrates the feasibility of 19F MR methods to detect TF during neuroinflammation in vivo. It also highlights the need for further technological developments in this field. The ultimate goal is to add 19F MR protocols to conventional 1H MRI protocols in clinical practice to guide therapy decisions.
Subject(s)
Crotonates/metabolism , Fluorine Radioisotopes/metabolism , Fluorine/metabolism , Hydroxybutyrates/metabolism , Inflammation/diagnosis , Nitriles/metabolism , Toluidines/metabolism , Animals , Contrast Media/metabolism , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/diagnosis , Encephalomyelitis, Autoimmune, Experimental/metabolism , Female , Fluorine-19 Magnetic Resonance Imaging/methods , Inflammation/metabolism , Magnetic Resonance Spectroscopy/methods , Mice , Mice, Inbred C57BL , Multiple Sclerosis/diagnosis , Multiple Sclerosis/metabolism , RatsABSTRACT
Fluorine (19F) magnetic resonance imaging (MRI) is severely limited by a low signal-to noise ratio (SNR), and tapping it for 19F drug detection in vivo still poses a significant challenge. However, it bears the potential for label-free theranostic imaging. Recently, we detected the fluorinated dihydroorotate dehydrogenase (DHODH) inhibitor teriflunomide (TF) noninvasively in an animal model of multiple sclerosis (MS) using 19F MR spectroscopy (MRS). In the present study, we probed distinct modifications to the CF3 group of TF to improve its SNR. This revealed SF5 as a superior alternative to the CF3 group. The value of the SF5 bioisostere as a 19F MRI reporter group within a biological or pharmacological context is by far underexplored. Here, we compared the biological and pharmacological activities of different TF derivatives and their 19F MR properties (chemical shift and relaxation times). The 19F MR SNR efficiency of three MRI methods revealed that SF5-substituted TF has the highest 19F MR SNR efficiency in combination with an ultrashort echo-time (UTE) MRI method. Chemical modifications did not reduce pharmacological or biological activity as shown in the in vitro dihydroorotate dehydrogenase enzyme and T cell proliferation assays. Instead, SF5-substituted TF showed an improved capacity to inhibit T cell proliferation, indicating better anti-inflammatory activity and its suitability as a viable bioisostere in this context. This study proposes SF5 as a novel superior 19F MR reporter group for the MS drug teriflunomide.
Subject(s)
Crotonates , Dihydroorotate Dehydrogenase , Animals , Hydroxybutyrates , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Nitriles , ToluidinesABSTRACT
The low-temperature dielectric relaxation of collagen and elastin was studied over a wide range of hydrations h. The hydration-shell response increases weakly with temperature, is thermally activated, and conforms to energy barrier scaling. This demonstrates the existence of a decoupled, secondary relaxation akin to that in binary structural glasses. Indications for fragile-to-strong transitions and other changes of mechanism are not found for hydrated collagen and elastin. For low h, the dielectric strength increases superlinearly with h; concomitantly, the water molecules trigger significant mobility of the protein surface.
Subject(s)
Collagen/chemistry , Connective Tissue/chemistry , Elastin/chemistry , Water/chemistry , Animals , Cattle , Tendons/chemistryABSTRACT
INTRODUCTION: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists. METHODS: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization. RESULTS: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials. DISCUSSION: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration.
ABSTRACT
Conditions such as type II diabetes are linked with elevated lipid levels in the heart, and significantly increased risk of heart failure; however, metabolic processes underlying the development of cardiac disease in type II diabetes are not fully understood. Here we present a non-invasive method for in vivo investigation of cardiac lipid metabolism: namely, IVS-McPRESS. This technique uses metabolite-cycled, non-water suppressed 1H cardiac magnetic resonance spectroscopy with prospective and retrospective motion correction. High-quality IVS-McPRESS data acquired from healthy volunteers allowed us to investigate the frequency shift of extramyocellular lipid signals, which depends on the myocardial fibre orientation. Assuming consistent voxel positioning relative to myofibres, the myofibre angle with the magnetic field was derived from the voxel orientation. For separation and individual analysis of intra- and extramyocellular lipid signals, the angle myocardial fibres in the spectroscopy voxel take with the magnetic field should be within ±24.5°. Metabolite and lipid concentrations were analysed with respect to BMI. Significant correlations between BMI and unsaturated fatty acids in intramyocellular lipids, and methylene groups in extramyocellular lipids were found. The proposed IVS-McPRESS technique enables non-invasive investigation of cardiac lipid metabolism and may thus be a useful tool to study healthy and pathological conditions.