Quantitative sodium magnetic resonance imaging in food: Addressing sensitivity issues using single quantum chemical shift imaging at high field.

According to various health organizations, the global consumption of salt is higher than recommended and needs to be reduced. Ideally, this would be achieved without losing the taste of the salt itself. In order to accomplish this goal, both at the industrial and domestic levels, we need to understand the mechanisms that govern the final distribution of salt in food. The in-silico solutions in use today greatly over-simplify the real food structure. Measuring the quantity of sodium at the local level is key to understanding sodium distribution. Sodium magnetic resonance imaging (MRI), a non-destructive approach, is the ideal choice for salt mapping along transformational process. However, the low sensitivity of the sodium nucleus and its short relaxation times make this imaging difficult. In this paper, we show how sodium MRI can be used to highlight salt heterogeneities in food products, provided that the temporal decay is modeled, thus correcting for differences in relaxation speeds. We then propose an abacus which shows the relationship between the signal-to-noise ratio of the sodium MRI, the salt concentration, the B0 field, and the spatial and temporal resolutions. This abacus simplifies making the right choices when implementing sodium MRI.

Characterization of the sodium binding state in several food products by 23 Na nuclear magnetic resonance spectroscopy.

In food, salt has several key roles including conservative and food perception. For this latter, it is well-known that the interaction of sodium with the food matrix modifies the consumer perception. It is then critical to characterize these interactions in various real foods. For this purpose, we exploited the information obtained on both single and double quantum 23 Na nuclear magnetic resonance (NMR) spectroscopies. All salted food samples studied showed strong interactions with the food matrix leading to quadrupolar interactions. However, for some of them, the single quantum analysis did not match the theoretical prediction. This was explained by the presence of another type of sodium population, which did not produce quadrupolar interactions. This finding is of critical importance to perform quantitative magnetic resonance imaging (MRI) and to understand the consumer salty taste perception.

Simultaneous proteoglycans and hypoxia mapping of chondrosarcoma environment by frequency selective CEST MRI.

PURPOSE: To evaluate the relevance of CEST frequency selectivity in simultaneous in vivo imaging of both of chondrosarcoma's phenotypic features, that are, its high proteoglycan concentration and its hypoxic core. METHODS: Swarm rat chondrosarcomas were implanted subcutaneously in NMRI nude mice. When tumors were measurable (12-16 days postoperative), mice were submitted to GAG, guanidyl, and APT CEST imaging. Proteoglycans and hypoxia were assessed in parallel by nuclear imaging exploiting 99m Tc-NTP 15-5 and 18 F-FMISO, respectively. Data were completed by ex vivo analysis of proteoglycans (histology and biochemical assay) and hypoxia (immunofluorescence). RESULTS: Quantitative analysis of GAG CEST evidenced a significantly higher signal for tumor tissues than for muscles. These results were in agreement with nuclear imaging and ex vivo data. For imaging tumoral pH in vivo, the CEST ratio of APT/guanidyl was studied. This highlighted an important heterogeneity inside the tumor. The hypoxic status was confirmed by 18 F-FMISO PET imaging and ex vivo immunofluorescence. CONCLUSION: CEST MRI simultaneously imaged both chondrosarcoma properties during a single experimental run and without the injection of any contrast agent. Both MR and nuclear imaging as well as ex vivo data were in agreement and showed that this chondrosarcoma animal model was rich in proteoglycans. However, even if tumors were lightly hypoxic at the stage studied, acidic areas were highlighted and mapped inside the tumor.

MRSI vs CEST MRI to understand tomato metabolism in ripening fruit: is there a better contrast?

Besides structural information, magnetic resonance imaging (MRI) is crucial to reveal the presence and gradients of metabolites in organs constituted of several tissues. In plant science, such knowledge is key to better understand fruit development and metabolism. Routine methods based on fixation for cytological studies or dissection for metabolite measurements induce biases and plant sample destruction. Magnetic resonance spectroscopy imaging (MSRI) leads to one NMR spectrum per pixel while chemical exchange saturation transfer (CEST) MRI allows mapping metabolites having exchangeable protons. As both methods present different advantages and drawbacks, we compared them to map metabolites in ripe tomato fruits. We demonstrated that MRSI was difficult to interpret due to large spatial chemical shift variations while CEST MRI produced promising image mapping of the main carbohydrates and amino acids. It showed that glucose/fructose was mostly located in the locular tissue, whereas glutamate/glutamine/GABA was found inside the columella.Graphical abstract.

Parsimonious discretization for characterizing multi-exponential decay in magnetic resonance.

We address the problem of analyzing noise-corrupted magnetic resonance transverse decay signals as a superposition of underlying independently decaying monoexponentials of positive amplitude. First, we indicate the manner in which this is an ill-conditioned inverse problem, rendering the analysis unstable with respect to noise. Second, we define an approach to this analysis, stabilized solely by the nonnegativity constraint without regularization. This is made possible by appropriate discretization, which is coarser than that often used in practice. Thirdly, we indicate further stabilization by inspecting the plateaus of cumulative distributions. We demonstrate our approach through analysis of simulated myelin water fraction measurements, and compare the accuracy with more conventional approaches. Finally, we apply our method to brain imaging data obtained from a human subject, showing that our approach leads to maps of the myelin water fraction which are much more stable with respect to increasing noise than those obtained with conventional approaches.

Uncertainties of calculated Cramér-Rao lower bounds: implications for quantitative MRS.

PURPOSE: To investigate the uncertainties on relative Cramér-Rao lower bound (rCRB) estimates and demonstrate their biasing effects in MRS quantification. THEORY AND METHODS: Simulations were performed to calculate the distribution of the computed rCRB (noted rCRB*) for several rCRB levels. One hundred thousand simulations per rCRB value were performed on simulated NMR signals containing either 1 signal (singlet) or 2 partially overlapping signals. False-positive and false-negative risks were compiled for different threshold levels. rCRB* distribution was experimentally checked on a deuterated water sample using a 9.4 Tesla vertical magnet. RESULTS: Simulations showed that (1) rCRB* distribution is asymmetrical, with a right-tailed distribution increasing the risk of accepting false-positive data (i.e., accepting an rCRB* value whereas the true rCRB value is higher than the threshold level) and (2) distribution broadness increases with increasing rCRB level. Simulations with overlapped peaks lead to more inaccuracy in the rCRB estimation. Probabilities of false detection increase with increasing threshold level. CONCLUSION: Analyzing results thanks to a CRB (or rCRB) based on experimental measurements might lead to misinterpretations. To exploit the rCRB* as rejection criteria, a conservative threshold level of 20% is recommended in order to limit the probability of false alarms.

Differences in BOLD responses in brain reward network reflect the tendency to assimilate a surprising flavor stimulus to an expected stimulus.

External information can modify the subjective value of a tasted stimulus, but little is known about neural mechanisms underlying these behavioral modifications. This study used flavored drinks to produce variable degrees of discrepancy between expected and received flavor. During a learning session, 43 healthy young men learned 4 symbol-flavor associations. In a separate session, associations were presented again during an fMRI scan, but half of the trials introduced discrepancy with previously learned associations. Liking ratings of drinks were collected and were analyzed using a linear model to define the degree to which discrepant symbols affected liking ratings of the subjects during the fMRI session. Based on these results, a GLM analysis of fMRI data was conducted to determine neural correlates of observed behavior. Groups of subjects were composed based on their behavior in response to discrepant symbols, and comparison of brain activity between groups showed that activation in the PCC and the caudate nucleus was more potent in those subjects in which liking was not affected by discrepant symbols. These activations were not found in subjects who assimilated unexpected flavors to flavors preceeded by discrepant symbols. Instead, these subjects showed differences in the activity in the parietal operculum. The activity of reward network appears to be related to assimilation of received flavor to expected flavor in response to symbol-flavor discrepancy.

Incorporation of Rician noise in the analysis of biexponential transverse relaxation in cartilage using a multiple gradient echo sequence at 3 and 7 Tesla.

PURPOSE: Previous work has evaluated the quality of different analytic methods for extracting relaxation times from magnitude imaging data exhibiting Rician noise. However, biexponential analysis of relaxation in tissue, including cartilage, and materials is of increasing interest. We, therefore, analyzed biexponential transverse relaxation decay in the presence of Rician noise and assessed the accuracy and precision of several approaches to determining component fractions and apparent transverse relaxation times. THEORY AND METHODS: Comparisons of four different voxel-by-voxel fitting methods were performed using Monte Carlo simulations, and phantom and ex vivo bovine nasal cartilage (BNC) experiments. In each case, preclinical and clinical imaging field strengths of 7 Tesla (T) and 3T, respectively, and parameters, were investigated across a range of signal-to-noise ratios (SNR). Results were compared with Cramér-Rao lower bound calculations. RESULTS: As expected, at high SNR, all methods performed well. At lower SNR, fits explicitly incorporating the analytic form of the Rician noise maintained performance. The much more efficient correction scheme of Gudbjartsson and Patz performed almost as well in many cases. Ex vivo experiments on phantoms and BNC were consistent with simulation results. CONCLUSION: Explicit incorporation of Rician noise greatly improves accuracy and precision in the analysis of biexponential transverse decay data.

fMRI of human olfaction at the individual level: interindividual variability.

PURPOSE: To determine whether the range of normal variation of human olfactory functional magnetic resonance imaging (fMRI) activations in healthy single subjects is compatible with the detection of atypical patterns. MATERIALS AND METHODS: In an event-related olfactory experiment, the variability of fMRI activation in six bilateral olfactory areas known to be affected in neurodegenerative diseases was measured in a region of interest (ROI) analysis in terms of intensity, localization, and overlap on 51 subjects. fMRI measurements were compared against measurements from a visual experiment performed on 25 subjects. RESULTS: Olfaction induced activations with low intensity, high variability, and a 4-fold lower contrast-to-noise ratio (CNR) than vision. Even in the best case (piriform cortex), mean pairwise activation overlap was still less than 40%. None of the olfactory ROIs showed significant activation for all subjects at the permissive threshold of P < 0.001. A gender-dependent significantly stronger activation was found in the bilateral piriform cortex of male subjects. CONCLUSION: Linking t-statistics and CNR showed that for all olfactory ROIs, CNR is either near or below the estimated threshold of 0.73 found to be necessary to obtain significant activations. In our experimental conditions the low reliability of olfactory activations should prompt major reservations over using fMRI of human olfaction as a diagnostic tool in single subjects.

Volumetric changes and clinical trajectories in Parkinson's disease: a prospective multicentric study.

BACKGROUND: Longitudinal measures of structural brain changes using MRI in relation to clinical features and progression patterns in PD have been assessed in previous studies, but few were conducted in well-defined and large cohorts, including prospective clinical assessments of both motor and non-motor symptoms. OBJECTIVE: We aimed to identify brain volumetric changes characterizing PD patients, and determine whether regional brain volumetric characteristics at baseline can predict motor, psycho-behavioral and cognitive evolution at one year in a prospective cohort of PD patients. METHODS: In this multicentric 1 year longitudinal study, PD patients and healthy controls from the MPI-R2* cohort were assessed for demographical, clinical and brain volumetric characteristics. Distinct subgroups of PD patients according to motor, cognitive and psycho-behavioral evolution were identified at the end of follow-up. RESULTS: One hundred and fifty PD patients and 73 control subjects were included in our analysis. Over one year, there was no significant difference in volume variations between PD and control subjects, regardless of the brain region considered. However, we observed a reduction in posterior cingulate cortex volume at baseline in PD patients with motor deterioration at one year (p = 0.017). We also observed a bilateral reduction of the volume of the amygdala (p = 0.015 and p = 0.041) and hippocampus (p = 0.015 and p = 0.053) at baseline in patients with psycho-behavioral deterioration, regardless of age, dopaminergic treatment and center. CONCLUSION: Brain volumetric characteristics at baseline may predict clinical trajectories at 1 year in PD as posterior cingulate cortex atrophy was associated with motor decline, while amygdala and hippocampus atrophy were associated with psycho-behavioral decline.

B1 mapping with selective pulses.

Knowledge of B1⁺ distribution is crucial for many applications, such as quantitative MRI. A novel method has been developed to improve the accuracy of the conventionally applied double-angle method for B1⁺ mapping. It solves the remaining issues raised by the use of selective pulses for slice selection to accelerate the acquisition process. A general approach for reconstructing B1⁺ maps is presented first. It takes B1⁺-induced slice profile distortions over off-resonance frequencies into account. It is then shown how the ratio between the prescribed flip angles can be adjusted to reach a compromise between the level of noise propagated onto B1⁺ maps and the width of the range in which the field can be mapped. Lastly, several solutions are proposed for reducing the B1⁺-dependent pollution of regions distal to the image slice which participates significantly in the inaccuracy of B1⁺ mapping. These methods were experimentally tested by comparison with gold standard B1⁺ maps obtained on a phantom using a non-selective and thus much slower technique. As they are independent and lead to significant improvements, these solutions can be combined to achieve high precision and fast B1⁺ mapping using spin-echo DAM.

Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease.

Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference. R2∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (PSN_D and PSN_ND < 0.0001). After stratification into four subgroups according to the disease duration, no significant R2∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson's disease patients to controls. R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(ISQR)∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease.

Puncture, MRI and NMR relaxometry data for multiscale analysis of the degradation of apple structure due to thermal treatment.

The data presented here are related to the research paper entitled "Multiscale NMR analysis of the degradation of apple structure due to thermal treatment" whose aim was to investigate the critical temperature at which the cell membranes of a Golden Delicious apple is highly damaged. Apple sticks were analyzed raw and cooked at 45, 50, 53, 60 °C and 70 °C. The firmness data refers to the puncture tests that were done using a Ta-Plus texturometer. The nuclear magnetic resonance (NMR) relaxometry and imaging data were both acquired with a 9.4 T 400WB instrument. For these three raw data collections, analysis results are also provided. These data are complementary as they cover the different scales from molecular to nearly the whole food system to enlighten the process of membrane degradation during thermal processing of apple. Our NMR data could be reused to optimize inversion algorithms dealing with ill-posed inverse problems. Both firmness and NMR data could be added to databases on food structure studies, either in physico-chemical data handbooks or review studies. Finally, these data could also be reused for the optimization of food thermal processing control.

Spurious phase correction in rapid metabolic imaging.

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 13C phantom.

Circadian Variation of Root Water Status in Three Herbaceous Species Assessed by Portable NMR.

Roots are at the core of plant water dynamics. Nonetheless, root morphology and functioning are not easily assessable without destructive approaches. Nuclear Magnetic Resonance (NMR), and particularly low-field NMR (LF-NMR), is an interesting noninvasive method to study water in plants, as measurements can be performed outdoors and independent of sample size. However, as far as we know, there are no reported studies dealing with the water dynamics in plant roots using LF-NMR. Thus, the aim of this study is to assess the feasibility of using LF-NMR to characterize root water status and water dynamics non-invasively. To achieve this goal, a proof-of-concept study was designed using well-controlled environmental conditions. NMR and ecophysiological measurements were performed continuously over one week on three herbaceous species grown in rhizotrons. The NMR parameters measured were either the total signal or the transverse relaxation time T2. We observed circadian variations of the total NMR signal in roots and in soil and of the root slow relaxing T2 value. These results were consistent with ecophysiological measurements, especially with the variation of fluxes between daytime and nighttime. This study assessed the feasibility of using LF-NMR to evaluate root water status in herbaceous species.

Characterisation of spinal cord in a mouse model of spastic paraplegia related to abnormal axono-myelin interactions by in vivo quantitative MRI.

In inherited neurodegenerative disorders the engineering of genetically modified mice for the causative genes have provided new insights in the understanding of axono-glial interactions. Patients lacking the major proteins of the central nervous system myelin, the proteolipoproteins (PLP1) exhibit an ascending axonopathy, named spastic paraplegia type 2. Our objective was to examine the interest of using quantitative MRI for non invasive detection of spinal cord (SC) consequences of the PLP1 defect in a mouse model of SPG2 (PLP1-/Y). For this purpose an MRI acquisition and retrospective correction chain was set up to map apparent diffusion coefficients (ADC) and T2 in the mouse cervical SC which improve the intra- and inter-animal homogeneity. This reliable imaging processing protocol allowed to detect significant changes between PLP1-/Y and wild type 15-month old SC, mainly no longer detected ex vivo after SC fixation. On the basis of ADC(//) and ADC( perpendicular) variations, white matter (WM) damages were characterised on both the myelin and axonal components. The microstructural changes observed in the Plp1 deficient grey matter (GM) were concomitantly related to the isotropic increase of GM ADC. The T2 reduction measured in the WM as well as the GM of the mutant SC seems to be also an interesting marker of the SC axono-glial dysfunction. The present study demonstrated the interest of quantitative MRI for phenotyping in vivo the WM and GM changes in SC neurodegenerative disorders related to myelin and impaired glia-axonal interaction.

The effect of salt content on the structure of iota-carrageenan systems: (23)Na DQF NMR and rheological studies.

(23)Na NMR spectroscopy has been used to study the effects of Na(+) ion concentrations on the structure of 1% (w/w) iota-carrageenan systems, a natural gelling polysaccharide used as a thickener in the food industry. Rheological and (23)Na T(1) relaxation time measurements revealed that gel formation correlates with decreases in ion mobility over the range of 0-3% (w/w) sodium content. (23)Na single-quantum (SQ) and double-quantum-filtered (DQF) NMR experiments performed on these systems provided evidence for a 'bound' sodium ion fraction in a specifically ordered environment. These results have allowed us to propose a model for the carrageenan gelation mechanism in the presence of Na(+) ions.

Structural and functional alterations in the retrosplenial cortex following neuropathic pain.

Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions. In this article, we conducted a longitudinal and multimodal study to assess how chronic pain affects the brain. Using the spared nerve injury model which promotes both long-lasting mechanical and thermal allodynia/hyperalgesia but also pain-associated comorbidities, we showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 1 and 2 months after injury. We found that both functional metrics and connectivity of the part A of the retrosplenial granular cortex (RSgA) were significantly correlated with the development of neuropathic pain behaviours. In addition, we found that the functional RSgA connectivity to the subiculum and the prelimbic system are significantly increased in spared nerve injury animals and correlated with peripheral pain thresholds. These brain regions were previously linked to the development of comorbidities associated with neuropathic pain. Using a voxel-based morphometry approach, we showed that neuropathic pain induced a significant increase of the gray matter concentration within the RSgA, associated with a significant activation of both astrocytes and microglial cells. Together, functional and morphological imaging metrics of the RSgA could be used as a predictive biomarker of neuropathic pain.

Antioxidant and Cardioprotective Effects of EPA on Early Low-Severity Sepsis through UCP3 and SIRT3 Upholding of the Mitochondrial Redox Potential.

Sepsis still causes death, often through cardiac failure and mitochondrial dysfunction. Dietary ω3 polyunsaturated fatty acids are known to protect against cardiac dysfunction and sepsis lethality. This study set out to determine whether early low-severity sepsis alters the cardiac mitochondrial function in animals fed a Western-type diet and whether dietary eicosapentaenoic acid (EPA) administration protects the myocardium against the deleterious effects of sepsis and if so to seek possible mechanisms for its effects. Rats were divided into two groups fed either an ω3 PUFA-deficient diet ("Western diet," DEF group) or an EPA-enriched diet (EPA group) for 5 weeks. Each group was subdivided into two subgroups: sham-operated rats and rats subjected to cecal ligation and puncture (CLP). In vivo cardiac mechanical function was examined, and mitochondria were harvested to determine their functional activity. Oxidative stress was evaluated together with several factors involved in the regulation of reactive oxygen species metabolism. Sepsis had little effect on cardiac mechanical function but strongly depressed mitochondrial function in the DEF group. Conversely, dietary EPA greatly protected the mitochondria through a decreased oxidative stress of the mitochondrial matrix. The latter was probably due to an increased uncoupling protein-3 expression, already seen in the sham-operated animals. CLP rats in the EPA group also displayed increased mitochondrial sirtuin-3 protein expression that could reinforce the upholding of oxidative phosphorylation. Dietary EPA preconditioned the heart against septic damage through several modifications that protect mitochondrial integrity. This preconditioning can explain the cardioprotective effect of dietary EPA during sepsis.