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Purpose: To measure T(1) and T(2) relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels.Materials and Methods: A total of 23 patients with gliomas and 10 volunteers were studied with single-voxel two-dimensional (2D) J-resolved point-resolved spectral selection (PRESS) using a 3T MR scanner. Voxels were chosen in normal appearing white matter (WM) and in regions of tumor. The T(1) and T(2) of choline containing compounds (Cho), creatine (Cr), and N-acetyl aspartate (NAA) were estimated.Results: Metabolite T(1) relaxation values in gliomas were not significantly different from values in normal WM. The T(2) of Cho and Cr were statistically significantly longer for grade 4 gliomas than for normal WM but the T(2) of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P < 0.001).Conclusion: The differential increase in T(2) for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times (TEs) relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MR spectroscopic imaging (MRSI) data, in which limited time is available and only one TE can be used. [ABSTRACT FROM AUTHOR]

Precision medicine research benefits from machine learning in the creation of robust models adapted to the processing of patient data. This applies both to pathology identification in images, i.e., annotation or segmentation, and to computer-aided diagnostic for classification or prediction. It comes with the strong need to exploit and visualize large volumes of images and associated medical data. The work carried out in this paper follows on from a main case study piloted in a cancer center. It proposes an analysis pipeline for patients with osteosarcoma through segmentation, feature extraction and application of a deep learning model to predict response to treatment. The main aim of the AWESOMME project is to leverage this work and implement the pipeline on an easy-to-access, secure web platform. The proposed WEB application is based on a three-component architecture: a data server, a heavy computation and authentication server and a medical imaging web-framework with a user interface. These existing components have been enhanced to meet the needs of security and traceability for the continuous production of expert data. It innovates by covering all steps of medical imaging processing (visualization and segmentation, feature extraction and aided diagnostic) and enables the test and use of machine learning models. The infrastructure is operational, deployed in internal production and is currently being installed in the hospital environment. The extension of the case study and user feedback enabled us to fine-tune functionalities and proved that AWESOMME is a modular solution capable to analyze medical data and share research algorithms with in-house clinicians., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background: Diffusion-weighted imaging (DWI) has been considered for chronic liver disease (CLD) characterization. Grading of liver fibrosis is important for disease management., Purpose: To investigate the relationship between DWI's parameters and CLD-related features (particularly regarding fibrosis assessment)., Study Type: Retrospective., Subjects: Eighty-five patients with CLD (age: 47.9 ± 15.5, 42.4% females)., Field Strength/sequence: 3-T, spin echo-echo planar imaging (SE-EPI) with 12 b-values (0-800 s/mm 2 )., Assessment: Several models statistical models, stretched exponential model, and intravoxel incoherent motion were simulated. The corresponding parameters (D s , σ, DDC, α, f, D, D*) were estimated on simulation and in vivo data using the nonlinear least squares (NLS), segmented NLS, and Bayesian methods. The fitting accuracy was analyzed on simulated Rician noised DWI. In vivo, the parameters were averaged from five central slices entire liver to compare correlations with histological features (inflammation, fibrosis, and steatosis). Then, the differences between mild (F0-F2) or severe (F3-F6) groups were compared respecting to statistics and classification. A total of 75.3% of patients used to build various classifiers (stratified split strategy and 10-folders cross-validation) and the remaining for testing., Statistical Tests: Mean squared error, mean average percentage error, spearman correlation, Mann-Whitney U-test, receiver operating characteristic (ROC) curve, area under ROC curve (AUC), sensitivity, specificity, accuracy, precision. A P-value <0.05 was considered statistically significant., Results: In simulation, the Bayesian method provided the most accurate parameters. In vivo, the highest negative significant correlation (D s , steatosis: r = -0.46, D*, fibrosis: r = -0.24) and significant differences (D s , σ, D*, f) were observed for Bayesian fitted parameters. Fibrosis classification was performed with an AUC of 0.92 (0.91 sensitivity and 0.70 specificity) with the aforementioned diffusion parameters based on the decision tree method., Data Conclusion: These results indicate that Bayesian fitted parameters may provide a noninvasive evaluation of fibrosis with decision tree., Evidence Level: 1 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

This article proposes a numerical framework to determine the optimal magnetization preparation in a three-dimensional magnetization-prepared rapid gradient-echo (MP-RAGE) sequence to obtain the best achievable contrast between target tissues based on differences in their relaxation times. The benefit lies in the adaptation of the algorithm of optimal control, GRAdient Ascent Pulse Engineering (GRAPE), to the optimization of magnetization preparation in a cyclic sequence without full recovery between each cycle. This numerical approach optimizes magnetization preparation of an arbitrary number of radio frequency pulses to enhance contrast, taking into account the establishment of a steady state in the longitudinal component of the magnetization. The optimal control preparation offers an optimized mixed T 1 / T 2 contrast in this traditional T 1 -weighted sequence. To show the versatility of the proposed method, numerical and in vitro results are described. Examples of contrasts acquired on brain regions of a healthy volunteer are presented for potential applications at 3 T., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

In this second part of a two-part paper, we intend to demonstrate the impact of the previously proposed advanced quality control pipeline. To understand its benefit and challenge the proposed methodology in a real scenario, we chose to compare the outcome when applying it to the analysis of two patient populations with significant but highly different types of fatigue: COVID-19 and multiple sclerosis (MS). 31 P-MRS was performed on a 3 T clinical MRI, in 19 COVID-19 patients, 38 MS patients, and 40 matched healthy controls. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Long and short T R acquisitions were also made at rest for T 1 correction. The advanced data quality control pipeline presented in Part 1 is applied to the selected patient cohorts to investigate its impact on clinical outcomes. We first used power and sample size analysis to estimate objectively the impact of adding the quality control score (QCS). Then, comparisons between patients and healthy control groups using the validated QCS were performed using unpaired t tests or Mann-Whitney tests (p < 0.05). The application of the QCS resulted in increased statistical power, changed the values of several outcome measures, and reduced variability (standard deviation). A significant difference was found between the T 1PCr and T 1Pi values of MS patients and healthy controls. Furthermore, the use of a fixed correction factor led to systematically higher estimated concentrations of PCr and P i than when using individually corrected factors. We observed significant differences between the two patient populations and healthy controls for resting [PCr]-MS only, [P i ], [ADP], [H 2 PO 4 - ], and [H i ], and [H 2 PO 4 - ]-MS only. The dynamic indicators τ PCr , τ Pi , V iPCr , and V max were reduced for COVID-19 and MS patients compared with controls. Our results show that QCS in dynamic 31 P-MRS studies results in smaller data variability and therefore impacts study sample size and power. Although QCS resulted in discarded data and therefore reduced the acceptable data and subject numbers, this rigorous and unbiased approach allowed for proper assessment of muscle metabolites and metabolism in patient populations. The outcomes include an increased metabolite T 1 , which directly affects the T 1 correction factor applied to the amplitudes of the metabolite, and a prolonged τ PCr , indicating reduced muscle oxidative capacity for patients with MS and COVID-19., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Implementing a standardized phosphorus-31 magnetic resonance spectroscopy ( 31 P-MRS) dynamic acquisition protocol to evaluate skeletal muscle energy metabolism and monitor muscle fatigability, while being compatible with various longitudinal clinical studies on diversified patient cohorts, requires a high level of technicality and expertise. Furthermore, processing data to obtain reliable results also demands a great degree of expertise from the operator. In this two-part article, we present an advanced quality control approach for data acquired using a dynamic 31 P-MRS protocol. The aim is to provide decision support to the operator to assist in data processing and obtain reliable results based on objective criteria. We present here, in part 1, an advanced data quality control (QC) approach of a dynamic 31 P-MRS protocol. Part 2 is an impact study that will demonstrate the added value of the QC approach to explore data derived from two clinical populations that experience significant fatigue, patients with coronavirus disease 2019 and multiple sclerosis. In part 1, 31 P-MRS was performed using 3-T clinical MRI in 175 subjects from clinical and healthy control populations conducted in a University Hospital. An advanced data QC score (QCS) was developed using multiple objective criteria. The criteria were based on current recommendations from the literature enriched by new proposals based on clinical experience. The QCS was designed to indicate valid and corrupt data and guide necessary objective data editing to extract as much valid physiological data as possible. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Using QCS enabled rapid identification of subjects with data anomalies, allowing the user to correct the data series or reject them partially or entirely, as well as identify fully valid datasets. Overall, the use of the QCS resulted in the automatic classification of 45% of the subjects, including 58 participants who had data with no criterion violation and 21 participants with violations that resulted in the rejection of all dynamic data. The remaining datasets were inspected manually with guidance, allowing acceptance of full datasets from an additional 80 participants and recovery phase data from an additional 16 subjects. Overall, more anomalies occurred with patient data (35% of datasets) compared with healthy controls (15% of datasets). In conclusion, the QCS ensures a standardized data rejection procedure and rigorous objective analysis of dynamic 31 P-MRS data obtained from patients. This methodology contributes to efforts made to standardize 31 P-MRS practices that have been underway for a decade, with the goal of making it an empowered tool for clinical research., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: While 3D MR spectroscopic imaging (MRSI) provides valuable spatial metabolic information, one of the hurdles for clinical translation is its interpretation, with voxel-wise quality control (QC) as an essential and the most time-consuming step. This work evaluates the accuracy of machine learning (ML) models for automated QC filtering of individual spectra from 3D healthy control and patient datasets., Methods: A total of 53 3D MRSI datasets from prior studies (30 neurological diseases, 13 brain tumors, and 10 healthy controls) were included in the study. Three ML models were evaluated: a random forest classifier (RF), a convolutional neural network (CNN), and an inception CNN (ICNN) along with two hybrid models: CNN + RF, ICNN + RF. QC labels used for training were determined manually through consensus of two MRSI experts. Normalized and cropped real-valued spectra was used as input. A cross-validation approach was used to separate datasets into training/validation/testing sets of aggregated voxels., Results: All models achieved a minimum AUC of 0.964 and accuracy of 0.910. In datasets from neurological disease and controls, the CNN model produced the highest AUC (0.982), while the RF model achieved the highest AUC in patients with brain tumors (0.976). Within tumor lesions, which typically exhibit abnormal metabolism, the CNN AUC was 0.973 while that of the RF was 0.969. Data quality inference times were on the order of seconds for an entire 3D dataset, offering drastic time reduction compared to manual labeling., Conclusion: ML methods accurately and rapidly performed automated QC. Results in tumors highlights the applicability to a variety of metabolic conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vaziri, Liu, Xie, Ratiney, Sdika, Lupo, Xu and Li.)

Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with [1,1,1- 13 C 3 ]-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://clinicaltrials.gov/ct2/show/NCT02145780 and https://clinicaltrials.gov/ct2/show/NCT02225457., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Segrestin, Delage, Nemeth, Seyssel, Disse, Nazare, Lambert-Porcheron, Meiller, Sauvinet, Chanon, Simon, Ratiney, Beuf, Pralong, Yassin, Boizot, Gachet, Burton-Pimentel, Vidal, Meugnier, Vionnet and Laville.)

Magnetic Resonance Elastography (MRE) quantifies the mechanical properties of tissues, typically applying motion encoding gradients (MEG). Multifrequency results allow better characterizations of tissues using data usually acquired through sequential monofrequency experiments. High frequencies are difficult to reach due to slew rate limitations and low frequencies induce long TEs, yielding magnitude images with low SNR. We propose a novel strategy to perform simultaneous multifrequency MRE in the absence of MEGs: using RF pulses designed via the Optimal Control (OC) theory. Such pulses control the spatial distribution of the MRI magnetization phase so that the resulting transverse magnetization reproduces the phase pattern of an MRE acquisition. The pulse is applied with a constant gradient during the multifrequency mechanical excitation to simultaneously achieve slice selection and motion encoding. The phase offset sampling strategy can be adapted according to the excitation frequencies to reduce the acquisition time. Phantom experiments were run to compare the classical monofrequency MRE to the OC based dual-frequency MRE method and showed excellent agreement between the reconstructed shear storage modulus G'. Our method could be applied to simultaneously acquire low and high frequency components, which are difficult to encode with the classical MEG MRE strategy., (© 2022. The Author(s).)

IDEAL-type magnetic resonance spectroscopic imaging (MRSI) sequences require the acquisition of several datasets using optimized sampling in the time domain to reconstruct metabolite maps. Each unitary scan consists of a selective slice (2D) or slab (3D) excitation followed by an evolution time and then the acquisition of the spatially encoded signal. It is critical that the phase variation during the evolution time for each scan is only dependent on chemical shifts. In this paper, we described the apparition of spurious phase due to either the transmit or the receive frequency. The presence of this unwanted phase depends on (i) where the commutation between these two frequencies is performed and (ii) how it is done, as there are two phase commutation modes: continuous and coherent. We present the correction needed in function of the different cases. It appears that some solutions are universal. However, it is critical to know which case is implemented on the MRI scanner, which is not always easy information to have. We illustrated several cases with our preclinical MRI by using the IDEAL spiral method on a 13 C phantom., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cardiac magnetic resonance myocardial perfusion imaging can detect coronary artery disease and is an alternative to single-photon emission computed tomography or positron emission tomography. However, the complex, non-linear MR signal and the lack of robust quantification of myocardial blood flow have hindered its widespread clinical application thus far. Recently, a new Bayesian approach was developed for brain imaging and evaluation of perfusion indexes (Kudo et al., 2014). In addition to providing accurate perfusion measurements, this probabilistic approach appears more robust than previous approaches, particularly due to its insensitivity to bolus arrival delays. We assessed the performance of this approach against a well-known and commonly deployed model-independent method based on the Fermi function for cardiac magnetic resonance myocardial perfusion imaging. The methods were first evaluated for accuracy and precision using a digital phantom to test them against the ground truth; next, they were applied in a group of coronary artery disease patients. The Bayesian method can be considered an appropriate model-independent method with which to estimate myocardial blood flow and delays. The digital phantom comprised a set of synthetic time-concentration curve combinations generated with a 2-compartment exchange model and a realistic combination of perfusion indexes, arterial input dynamics, noise and delays collected from the clinical dataset. The myocardial blood flow values estimated with the two methods showed an excellent correlation coefficient ( r 2 > 0.9) under all noise and delay conditions. The Bayesian approach showed excellent robustness to bolus arrival delays, with a similar performance to Fermi modeling when delays were considered. Delays were better estimated with the Bayesian approach than with Fermi modeling. An in vivo analysis of coronary artery disease patients revealed that the Bayesian approach had an excellent ability to distinguish between abnormal and normal myocardium. The Bayesian approach was able to discriminate not only flows but also delays with increased sensitivity by offering a clearly enlarged range of distribution for the physiologic parameters., Competing Interests: SG and M-PJ were employed by company Siemens Medical Solutions USA, Inc. TB was employed by Olea Medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Daviller, Boutelier, Giri, Ratiney, Jolly, Vallée, Croisille and Viallon.)

Magnetic resonance elastography (MRE) is used to non-invasively quantify viscoelastic properties of tissues based on the measurement of propagation characteristics of shear waves. Because some of these viscoelastic parameters show a frequency dependence, multifrequency analysis allows us to measure the wave propagation dispersion, leading to a better characterization of tissue properties. Conventionally, motion encoding gradients (MEGs) oscillating at the same frequency as the mechanical excitation encode motion. Hence, multifrequency data is usually obtained by sequentially repeating monochromatic wave excitations experiments at different frequencies. The result is that the total acquisition time is multiplied by a factor corresponding to the number of repetitions of monofrequency experiments, which is a major limitation of multifrequency MRE. In order to make it more accessible, a novel single-shot harmonic wideband dual-frequency MRE method is proposed. Two superposed shear waves of different frequencies are simultaneously generated and propagate in a sample. Trapezoidal oscillating MEGs are used to encode mechanical vibrations having frequencies that are an odd multiple of the MEG frequency. The number of phase offsets is optimized to reduce the acquisition time. For this purpose, a sampling method not respecting the Shannon theorem is used to produce a controlled temporal aliasing that allows us to encode both frequencies without any additional examination time. Phantom experiments were run to compare conventional monofrequency MRE with the single-shot dual-frequency MRE method and showed excellent agreement between the reconstructed shear storage moduli G'. In addition, dual-frequency MRE yielded an increased signal-to-noise ratio compared with conventional monofrequency MRE acquisitions when encoding the high frequency component. The novel proposed multifrequency MRE method could be applied to simultaneously acquire more than two frequency components, reducing examination time. Further studies are needed to confirm its applicability in preclinical and clinical models., (© 2020 John Wiley & Sons, Ltd.)

Even if cardiovascular magnetic resonance (CMR) perfusion imaging has proven its relevance for visual detection of ischemia, myocardial blood flow (MBF) quantification at the voxel observation scale remains challenging. Integration of an automated segmentation step, prior to perfusion index estimation, might be a significant reconstruction component that could allow sustainable assumptions and constraint enlargement prior to advanced modeling. Current clustering techniques, such as bullseye representation or manual delineation, are not designed to discriminate voxels belonging to the lesion from healthy areas. Hence, the resulting average time-intensity curve, which is assumed to represent the dynamic contrast enhancement inside of a lesion, might be contaminated by voxels with perfectly healthy microcirculation. This study introduces a hierarchical lesion segmentation approach based on time-intensity curve features that considers the spatial particularities of CMR myocardial perfusion. A first k-means clustering approach enables this method to perform coarse clustering, which is refined by a novel spatiotemporal region-growing (STRG) segmentation, thus ensuring spatial and time-intensity curve homogeneity. Over a cohort of 30 patients, myocardial blood flow (MBF) measured in voxels of lesion regions detected with STRG was significantly lower than in regions drawn manually (mean difference = 0.14, 95% CI [0.07, 0.2]) and defined with the bullseye template (mean difference = 0.25, 95% CI [0.17, 0.36]). Over the 90 analyzed slices, the median Dice score calculated against the ground truth ranged between 0.62 and 0.67, the inclusion coefficients ranged between 0.62 and 0.76 and the centroid distances ranged between 0.97 and 3.88 mm. Therefore, though these metrics highlight spatial differences, they could not be used as an index to evaluate the accuracy and performance of the method, which can only be attested by the variability of the MBF clinical index., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Overweight and obesity are major worldwide health concerns characterized by an abnormal accumulation of fat in adipose tissue (AT) and liver., Purpose: To evaluate the volume and the fatty acid (FA) composition of the subcutaneous adipose tissue (SAT) and the visceral adipose tissue (VAT) and the fat content in the liver from 3D chemical-shift-encoded (CSE)-MRI acquisition, before and after a 31-day overfeeding protocol., Study Type: Prospective and longitudinal study., Subjects: Twenty-one nonobese healthy male volunteers., Field Strength/sequence: A 3D spoiled-gradient multiple echo sequence and STEAM sequence were performed at 3T., Assessment: AT volume was automatically segmented on CSE-MRI between L2 to L4 lumbar vertebrae and compared to the dual-energy X-ray absorptiometry (DEXA) measurement. CSE-MRI and MR spectroscopy (MRS) data were analyzed to assess the proton density fat fraction (PDFF) in the liver and the FA composition in SAT and VAT. Gas chromatography-mass spectrometry (GC-MS) analyses were performed on 13 SAT samples as a FA composition countermeasure., Statistical Tests: Paired t-test, Pearson's correlation coefficient, and Bland-Altman plots were used to compare measurements., Results: SAT and VAT volumes significantly increased (P < 0.001). CSE-MRI and DEXA measurements were strongly correlated (r = 0.98, P < 0.001). PDFF significantly increased in the liver (+1.35, P = 0.002 for CSE-MRI, + 1.74, P = 0.002 for MRS). FA composition of SAT and VAT appeared to be consistent between localized-MRS and CSE-MRI (on whole segmented volume) measurements. A significant difference between SAT and VAT FA composition was found (P < 0.001 for CSE-MRI, P = 0.001 for MRS). MRS and CSE-MRI measurements of the FA composition were correlated with the GC-MS results (for ndb: r MRS/GC-MS  = 0.83 P < 0.001, r CSE-MRI/GC-MS  = 0.84, P = 0.001; for nmidb: r MRS/GC-MS  = 0.74, P = 0.006, r CSE-MRI/GC-MS  = 0.66, P = 0.020) DATA CONCLUSION: The follow-up of liver PDFF, volume, and FA composition of AT during an overfeeding diet was demonstrated through different methods. The CSE-MRI sequence associated with a dedicated postprocessing was found reliable for such quantification., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1587-1599., (© 2018 International Society for Magnetic Resonance in Medicine.)

Objectives: The aim of this study was to investigate the feasibility of measuring the effects of a 14-day Periodic Fasting (PF) intervention (<200 cal) on multi-organs of primary interest (liver, visceral/subcutaneous/bone marrow fat, muscle) using non-invasive advanced magnetic resonance spectroscopic (MRS) and imaging (MRI) methods. Methods: One subject participated in a 14-day PF under daily supervision of nurses and specialized physicians, ingesting a highly reduced intake: 200 Kcal/day coupled with active walking and drinking at least 3 L of liquids/day. The fasting was preceded by a 7-day pre-fasting vegetarian period and followed by 14 days of stepwise reintroduction of food. The longitudinal study collected imaging and biological data before the fast, at peak fasting, and 7 days, 1 month, and 4 months after re-feeding. Body fat mass in the trunk, abdomen, and thigh, liver and muscle mass, were respectively computed using advanced MRI and MRS signal modeling. Fat fraction, MRI relativity index T2 * and susceptibility (Chi), as well as Fatty acid composition, were calculated at all-time points. Results: A decrease in body weight (BW: -9.5%), quadriceps muscle volume (-3.2%), Subcutaneous and Visceral Adipose Tissue (SAT -34.4%; VAT -20.8%), liver fat fraction (PDFF = 1.4 vs. 2.6 % at baseline) but increase in Spine Bone Marrow adipose tissue (BMAT) associated with a 10% increase in global adiposity fraction (PDFF: 54.4 vs. 50.9%) was observed. Femoral BMAT showed minimal changes compared to spinal level, with a slight decrease (-3.1%). Interestingly, fatty acid (FA) pattern changes differed depending on the AT locations. In muscle, all lipids increased after fasting, with a greater increase of intramyocellular lipid (IMCL: from 2.7 to 6.3 mmol/kg) after fasting compared to extramyocellular lipid (EMCL: from 6.2 to 9.5 mmol/kg) as well as Carnosine (6.9 to 8.1 mmol/kg). Heterogenous and reverse changes were also observed after re-feeding depending on the organ. Conclusion: These results suggest that investigating the effects of a 14-day PF intervention using advanced MRI and MRS is feasible. Quantitative MR indexes are a crucial adjunct to further understanding the effective changes in multiple crucial organs especially liver, spin, and muscle, differences between adipose tissue composition and the interplay that occurs during periodic fasting.

Purpose: This article proposes a rigorous optimal control framework for the design of preparation schemes that optimize MRI contrast based on relaxation time differences., Methods: Compared to previous optimal contrast preparation schemes, a drastic reduction of the optimization parameter number is performed. The preparation scheme is defined as a combination of several block pulses whose flip angles, phase terms and inter-pulse delays are optimized to control the magnetization evolution., Results: The proposed approach reduces the computation time of B 0 -robust preparation schemes to around a minute (whereas several hours were required with previous schemes), with negligible performance loss. The chosen parameterization allows to formulate the total preparation duration as a constraint, which improves the overall compromise between contrast performance and preparation time. Simulation, in vitro and in vivo results validate this improvement, illustrate the straightforward applicability of the proposed approach, and point out its flexibility in terms of achievable contrasts. Major improvement is especially achieved for short-T 2 enhancement, as shown by the acquisition of a non-trivial contrast on a rat brain, where a short-T 2 white matter structure (corpus callosum) is enhanced compared to surrounding gray matter tissues (hippocampus and neocortex)., Conclusions: This approach proposes key advances for the design of optimal contrast preparation sequences, that emphasize their ability to generate non-standard contrasts, their potential benefit in a clinical context, and their straightforward applicability on any MR system., (© 2018 International Society for Magnetic Resonance in Medicine.)

Introduction: The composition of fatty acids in the body is gaining increasing interest, and can be followed up noninvasively by quantitative magnetic resonance spectroscopy (MRS). However, current MRS quantification methods have been shown to provide different quantitative results in terms of lipid signals, with possible varying outcomes for a given biological examination. Quantitative magnetic resonance imaging using multigradient echo sequence (MGE-MRI) has recently been added to MRS approaches. In contrast, these methods fit the undersampled magnetic resonance temporal signal with a simplified model function (expressing the triglyceride [TG] spectrum with only three TG parameters), specific implementations and prior knowledge. In this study, an adaptation of an MGE-MRI method to MRS lipid quantification is proposed., Methods: Several versions of the method - with time data fully or undersampled, including or excluding the spectral peak T 2 knowledge in the fitting - were compared theoretically and on Monte Carlo studies with a time-domain, peak-fitting approach. Robustness, repeatability and accuracy were also inspected on in vitro oil acquisitions and test-retest in vivo subcutaneous adipose tissue acquisitions, adding results from the reference LCModel method., Results: On simulations, the proposed method provided TG parameter estimates with the smallest variability, but with a possible bias, which was mitigated by fitting on undersampled data and considering peak T 2 values. For in vitro measurements, estimates for all approaches were correlated with theoretical values and the best concordance was found for the usual MRS method (LCModel and peak fitting). Limited in vivo test-retest variability was found (4.1% for PUFAindx, 0.6% for MUFAindx and 3.6% for SFAindx), as for LCModel (7.6% for PUFAindx, 7.8% for MUFAindx and 3.0% for SFAindx)., Conclusion: This study shows that fitting the three TG parameters directly on MRS data is one valuable solution to circumvent the poor conditioning of the MRS quantification problem., (© 2018 John Wiley & Sons, Ltd.)

This article presents a new motion encoding strategy to perform magnetic resonance elastography (MRE). Instead of using standard motion encoding gradients, a tailored RF pulse is designed to simultaneously perform selective excitation and motion encoding in presence of a constant gradient. The RF pulse is designed with a numerical optimal control algorithm, in order to obtain a magnetization phase distribution that depends on the displacement characteristics inside each voxel. As a consequence, no post-excitation encoding gradients are required. This offers numerous advantages, such as reducing eddy current artifacts, and relaxing the constraint on the gradients maximum switch rate. It also allows to perform MRE with ultra-short TE acquisition schemes, which limits T 2 decay and optimizes signal-to-noise ratio. The pulse design strategy is developed and analytically analyzed to clarify the encoding mechanism. Finally, simulations, phantom and ex vivo experiments show that phase-to-noise ratios are improved when compared to standard MRE encoding strategies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow-up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues. An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B 1 magnetic field, and a dedicated ERC was used for signal reception. Colon-wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 μL to 2 μL while keeping acquisition times below 3 min. The acquired spectra show various biochemical contents such as α- and β-methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon-wall complex exhibits both high lipid and high water contents. To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies., (Copyright © 2017 John Wiley & Sons, Ltd.)

This paper investigates the use of Optimal Control (OC) theory to design Radio-Frequency (RF) pulses that actively control the spatial distribution of the MRI magnetization phase. The RF pulses are generated through the application of the Pontryagin Maximum Principle and optimized so that the resulting transverse magnetization reproduces various non-trivial and spatial phase patterns. Two different phase patterns are defined and the resulting optimal pulses are tested both numerically with the ODIN MRI simulator and experimentally with an agar gel phantom on a 4.7T small-animal MR scanner. Phase images obtained in simulations and experiments are both consistent with the defined phase patterns. A practical application of phase control with OC-designed pulses is also presented, with the generation of RF pulses adapted for a Magnetic Resonance Elastography experiment. This study demonstrates the possibility to use OC-designed RF pulses to encode information in the magnetization phase and could have applications in MRI sequences using phase images., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This work investigates the use of MRI radio-frequency (RF) pulses designed within the framework of optimal control theory for image contrast optimization. The magnetization evolution is modeled with Bloch equations, which defines a dynamic system that can be controlled via the application of the Pontryagin Maximum Principle (PMP). This framework allows the computation of optimal RF pulses that bring the magnetization to a given state to obtain the desired contrast after acquisition. Creating contrast through the optimal manipulation of Bloch equations is a new way of handling contrast in MRI, which can explore the theoretical limits of the system. Simulation experiments carried out on-resonance quantify the contrast improvement when compared to standard T 1 or T 2 weighting strategies. The use of optimal pulses is also validated for the first time in both in vitro and in vivo experiments on a small-animal 4.7T MR system. Results demonstrate their robustness to static field inhomogeneities as well as the fact that they can be embedded in standard imaging sequences without affecting standard parameters such as slice selection or echo type. In vivo results on rat and mouse brains illustrate the ability of optimal contrast pulses to create non-trivial contrasts on well-studied structures (white matter versus gray matter)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (P<0.05), the occipital white matter (P<0.005) and the thalamus (P<0.05). The proton spectrum of the centrum semiovale was characterized by significantly lower taurine/H2O and macromolecules/H2O ratios (P<0.05) at a TE of 30 ms, and reduced (creatine+phosphocreatine)/H2O and (glutamine+glutamate)/H2O ratios (P<0.05) at a TE of 135 ms in the preterm neonates than in full-term neonates. Our findings indicate that premature neonates with normal conventional MRI present a delay in brain maturation affecting the white matter and the thalamus. Their brain metabolic profile is characterized by lower levels of creatine, glutamine plus glutamate, and macromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis., Competing Interests: NG is a member of the scientific board of Olea Medical. Some travel and accommodation expenses related to scientific congress attendance are paid by Olea Medical (NG).

Two-dimensional spectroscopy offers the possibility to unambiguously distinguish metabolites by spreading out the multiplet structure of J-coupled spin systems into a second dimension. Quantification methods that perform parametric fitting of the 2D MRS signal have recently been proposed for resolved PRESS (JPRESS) but not explicitly for Localized Correlation Spectroscopy (LCOSY). Here, through a whole metabolite quantification approach, correlation spectroscopy quantification performances are studied. The ability to quantify metabolite relaxation constant times is studied for three localized 2D MRS sequences (LCOSY, LCTCOSY and the JPRESS) in vitro on preclinical MR systems. The issues encountered during implementation and quantification strategies are discussed with the help of the Fisher matrix formalism. The described parameterized models enable the computation of the lower bound for error variance--generally known as the Cramér Rao bounds (CRBs), a standard of precision--on the parameters estimated from these 2D MRS signal fittings. LCOSY has a theoretical net signal loss of two per unit of acquisition time compared to JPRESS. A rapid analysis could point that the relative CRBs of LCOSY compared to JPRESS (expressed as a percentage of the concentration values) should be doubled but we show that this is not necessarily true. Finally, the LCOSY quantification procedure has been applied on data acquired in vivo on a mouse brain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Importance: Predicting disease evolution is becoming essential for optimizing treatment decision making in multiple sclerosis (MS). Multiple sclerosis pathologic damage typically includes demyelination, neuro-axonal loss, and astrogliosis., Objective: To evaluate the potential of magnetic resonance markers of central nervous system injury to predict brain-volume loss and clinical disability in multiple sclerosis., Design, Setting, and Participants: Participants were selected from the Multiple Sclerosis Center at the University of California-San Francisco. The preliminary data set included 59 patients with MS and 43 healthy control individuals. The confirmatory data set included 220 patients from an independent, large genotype-phenotype research project., Main Outcomes and Measures: Baseline N-acetylaspartate (NAA) level, myo-inositol (mI) in normal-appearing white and gray matter, myelin water fraction in normal-appearing white matter, markers of axonal damage, astrogliosis, and demyelination were evaluated as predictors in a preliminary data set. Potential predictors were subsequently tested for replication in a confirmatory data set. Clinical scores and percentage of brain-volume change were obtained annually over 4 years as outcomes. Predictors of outcomes were assessed using linear models, linear mixed-effects models, and logistic regression., Results: N-acetylaspartate and mI both had statistically significant effects on brain volume, prompting the use of the mI:NAA ratio in normal-appearing white matter as a predictor. The ratio was a predictor of brain-volume change in both cohorts (annual slope in the percentage of brain-volume change/unit of increase in the ratio: -1.68; 95% CI, -3.05 to -0.30; P = .02 in the preliminary study cohort and -1.08; 95% CI, -1.95 to -0.20; P = .02 in the confirmatory study cohort). Furthermore, the mI:NAA ratio predicted clinical disability (Multiple Sclerosis Functional Composite evolution: -0.52 points annually, P < .001; Multiple Sclerosis Functional Composite sustained progression: odds ratio, 2.76/SD increase in the ratio; 95% CI, 1.32 to 6.47; P = .01) in the preliminary data set and predicted Multiple Sclerosis Functional Composite evolution (-0.23 points annually; P = .01), Expanded Disability Status Scale evolution (0.57 points annually; P = .04), and Expanded Disability Status Scale sustained progression (odds ratio, 1.46; 95% CI, 1.10 to 1.94; P = .009) in the confirmatory data set. Myelin water fraction did not show predictive value., Conclusions and Relevance: The mI:NAA ratio in normal-appearing white matter has consistent predictive power on brain atrophy and neurological disability evolution. The combined presence of astrogliosis and axonal damage in white matter has cardinal importance in disease severity.

Multidimensional NMR spectroscopy is widely used for studies of molecular and biomolecular structure. A major disadvantage of multidimensional NMR is the long acquisition time which, regardless of sensitivity considerations, may be needed to obtain the final multidimensional frequency domain coefficients. In this article, a method for under-sampling multidimensional NMR acquisition of sparse spectra is presented. The approach is presented in the case of two-dimensional NMR acquisitions. It relies on prior knowledge about the support in the two-dimensional frequency domain to recover an over-determined system from the under-determined system induced in the linear acquisition model when under-sampled acquisitions are performed. This over-determined system can then be solved with linear least squares. The prior knowledge is obtained efficiently at a low cost from the one-dimensional NMR acquisition, which is generally acquired as a first step in multidimensional NMR. If this one-dimensional acquisition is intrinsically sparse, it is possible to reconstruct the corresponding two-dimensional acquisition from far fewer observations than those imposed by the Nyquist criterion, and subsequently to reduce the acquisition time. Further improvements are obtained by optimizing the sampling procedure for the least-squares reconstruction using the sequential backward selection algorithm. Theoretical and experimental results are given in the case of a traditional acquisition scheme, which demonstrate reliable and fast reconstructions with acceleration factors in the range 3-6. The proposed method outperforms the CS methods (OMP, L1) in terms of the reconstruction performance, implementation and computation time. The approach can be easily extended to higher dimensions and spectroscopic imaging., (Copyright © 2014 John Wiley & Sons, Ltd.)