Towards portable MRI in the plant sciences.

Plant physiology and structure are constantly changing according to internal and external factors. The study of plant water dynamics can give information on these changes, as they are linked to numerous plant functions. Currently, most of the methods used to study plant water dynamics are either invasive, destructive, or not easily accessible. Portable magnetic resonance imaging (MRI) is a field undergoing rapid expansion and which presents substantial advantages in the plant sciences. MRI permits the non-invasive study of plant water content, flow, structure, stress response, and other physiological processes, as a multitude of information can be obtained using the method, and portable devices make it possible to take these measurements in situ, in a plant's natural environment. In this work, we review the use of such devices applied to plants in climate chambers, greenhouses or in their natural environments. We also compare the use of portable MRI to other methods to obtain the same information and outline its advantages and disadvantages.

Interhemispheric reactivity of the subthalamic nucleus sustains progressive dopamine neuron loss in asymmetrical parkinsonism.

Parkinson's disease (PD) is characterized by the progressive and asymmetrical degeneration of the nigrostriatal dopamine neurons and the unilateral presentation of the motor symptoms at onset, contralateral to the most impaired hemisphere. We previously developed a rat PD model that mimics these typical features, based on unilateral injection of a substrate inhibitor of excitatory amino acid transporters, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), in the substantia nigra (SN). Here, we used this progressive model in a multilevel study (behavioral testing, in vivo 1H-magnetic resonance spectroscopy, slice electrophysiology, immunocytochemistry and in situ hybridization) to characterize the functional changes occurring in the cortico-basal ganglia-cortical network in an evolving asymmetrical neurodegeneration context and their possible contribution to the cell death progression. We focused on the corticostriatal input and the subthalamic nucleus (STN), two glutamate components with major implications in PD pathophysiology. In the striatum, glutamate and glutamine levels increased from presymptomatic stages in the PDC-injected hemisphere only, which also showed enhanced glutamatergic transmission and loss of plasticity at corticostriatal synapses assessed at symptomatic stage. Surprisingly, the contralateral STN showed earlier and stronger reactivity than the ipsilateral side (increased intraneuronal cytochrome oxidase subunit I mRNA levels; enhanced glutamate and glutamine concentrations). Moreover, its lesion at early presymptomatic stage halted the ongoing neurodegeneration in the PDC-injected SN and prevented the expression of motor asymmetry. These findings reveal the existence of endogenous interhemispheric processes linking the primary injured SN and the contralateral STN that could sustain progressive dopamine neuron loss, opening new perspectives for disease-modifying treatment of PD.

Online adaptive identification of multichannel systems for audio applications.

Impulse responses (IRs) estimation of multi-input acoustic systems is a prerequisite for many audio applications. In this paper, an adaptive identification problem based on the Autostep algorithm is extended to the simultaneous estimation of room IRs for multiple input single output linear time invariant systems without any a priori information. To do so, the proposed algorithm is initially evaluated in a simulated room with several sound sources active at the same time. Finally, an experimental validation is proposed for the cases of a semi-anechoic chamber and an arbitrary room. Special attention is dedicated to the algorithm convergence behavior, considering different meta parameters settings. Results are eventually compared with the other normalized version of the least mean square algorithm.

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.

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.

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.

Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse.

Chronic exposure to high circulating levels of glucocorticoids has detrimental effects on health, including metabolic abnormalities, as exemplified in Cushing's syndrome (CS). Magnetic resonance imaging (MRI) studies have found volumetric changes in gray and white matter of the brain in CS patients during the course of active disease, but also in remission. In order to explore this further, we performed MRI-based brain volumetric analyses in the AdKO mouse model for CS, which presents its key traits. AdKO mice had reduced relative volumes in several brain regions, including the corpus callosum and cortical areas. The medial amygdala, bed nucleus of the stria terminalis, and hypothalamus were increased in relative volume. Furthermore, we found a lower immunoreactivity of myelin basic protein (MBP, an oligodendrocyte marker) in several brain regions but a paradoxically increased MBP signal in the male cingulate cortex. We also observed a decrease in the expression of glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) and ionized calcium-binding adapter molecule 1 (IBA1, a marker for activated microglia) in the cingulate regions of the anterior corpus callosum and the hippocampus. We conclude that long-term hypercorticosteronemia induced brain region-specific changes that might include aberrant myelination and a degree of white matter damage, as both repair (GFAP) and immune (IBA1) responses are decreased. These findings suggest a cause for the changes observed in the brains of human patients and serve as a background for further exploration of their subcellular and molecular mechanisms.

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.

Low field, time domain NMR in the agriculture and agrifood sectors: An overview of applications in plants, foods and biofuels.

In this contribution, a selective overview of low field, time-domain NMR (TD-NMR) applications in the agriculture and agrifood sectors is presented. The first applications of commercial TD-NMR instruments were in food and agriculture domains. Many of these earlier methods have now been recognized as standard methods by several international agencies. Since 2000, several new applications have been developed, using state of the art instruments, new pulse sequences and new signal processing methods. TD-NMR is expected, in the coming years, to become even more important in quality control of fresh food and agricultural products, as well as for a wide range of food-processed products. TD-NMR systems provide excellent means to collect data relevant for use in the agricultural environment and the bioenergy industry. Data and information collected by TD-NMR systems thus may support decision makers in business and public organizations.

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.

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.

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.

Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized 13C-methylglyoxal.

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo.

mGlu5 receptor antagonist blocks bromocriptine-induced conditioned place preference in bilateral mesolimbic-lesioned rat.

Dopamine dysregulation syndrome (DDS) has been attributed to both dopamine replacement therapies (DRT) and the mesencephalic dopaminergic lesion. The DRT reinforcement effect is due to its action on the reward system, particularly on the nucleus accumbens (NAc). This nucleus receives two major projections, a glutamatergic from the prefrontal cortex and a dopaminergic from the posterior ventral tegmental area (pVTA). The latter modulate the former within the NAc. pVTA has been demonstrated to be implicated in the motivational effect of bromocriptine (dopamine 2 receptor (D2R) agonist) in bilateral pVTA-lesioned animals. Therefore the potential implication of the metabotropic glutamate receptor 5 (mGluR5) antagonist (MTEP: 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine) on bromocriptine-induced conditioned place preference (CPP) was explored. Results showed that the administration of the MTEP blocked completely the bromocriptine-induced CPP in bilateral pVTA-lesioned rats. Both the CPP acquisition and expression were abolished. These effects are due, at least to an increase of the glutamate concentration and that of mGlu5 receptor expression in the NAc shell of the pVTA-lesioned animals. Altogether these data demonstrated the importance of the mGlu5 receptor in the bromocriptine induced-reinforcement and that DDS is probably due to DRT effect on this glutamate receptor.

Pulsed Field Gradient NMR with Sigmoid Shape Gradient Sampling To Produce More Detailed Diffusion Ordered Spectroscopy Maps of Real Complex Mixtures: Examples with Medicine Analysis.

NMR diffusion measurements are based on signal attenuation. In the case of complex mixtures for which some molecules are diffusing quickly while others are significantly slower, it is challenging to obtain a diffusion ordered spectroscopy (DOSY)-type 2D map giving reliable information on all molecules. In this paper, we propose a new gradient sampling approach based on a sigmoid shape allowing the acquisition of a significant number of points for both the fast and slow diffusing molecules. We applied this new gradient sampling strategy to deformulate two medicines whose composition was known (Esomeprazole) or unknown (Mebendazole). PFG NMR associated with a sigmoid gradient ramp is an exciting strategy to study drugs as a whole, i.e., the active ingredient(s) and excipients.

FmRα analysis: Rapid and direct estimation of relaxation and kinetic parameters from dynamic nuclear polarization time courses.

PURPOSE: To introduce a direct method for estimating relaxation and kinetic parameter values from rapid dissolution dynamic nuclear polarization (RD-DNP) NMR time courses. THEORY AND METHODS: The analysis relied on a kinetic model that is often used to analyze data in these studies-a unidirectional (bio)chemical reaction with rate constant k1 , coupled to longitudinal relaxation of the magnetization of substrate and product that is characterized by the time constant T1 . The latter value was estimated from the width of the product curve (peak) at the height α relative to the maximum height. We showed α ∼ 0.8 under most conditions, so we measured the interval between the falling and rising parts of the curve at the relative height 0.8. We called this the "fall-minus-rise time at height α," or FmRα , and found that FmR0.8 ∼ T1 . The ratio ß = (product signal/substrate signal) when the product is maximal was shown to be equal to k1 T1 . Therefore, k1 = ß/FmR0.8 . RESULTS: FmRα analysis was demonstrated with (13) C NMR RD-DNP data recorded from hemolysates and from previously published data. CONCLUSION: FmRα analysis enables immediate estimates of kinetic and relaxation parameters from (13) C NMR RD-DNP data. The values can be used as initial estimates in more extensive computer-based data-regression analysis.

Evaluation of a benchtop cryogen-free low-field ¹H NMR spectrometer for the analysis of sexual enhancement and weight loss dietary supplements adulterated with pharmaceutical substances.

Nuclear magnetic resonance (NMR) spectroscopy is a unique tool for detection, structural characterization, and quantification of compounds in complex mixtures. However, due to cost constraints, NMR is rarely used in routine quality control (QC) analysis. The recent release of benchtop cryogen-free low-field NMR spectrometers represents a technological break in the NMR field. In this paper, we evaluated the potential of a benchtop cryogen-free 60 MHz spectrometer for uncovering adulteration of "100% natural" sexual enhancement and weight loss dietary supplements. We demonstrated that the adulterant(s) can readily be detected in ≈20 min of recording after a very simple and rapid sample preparation. We also showed that the quantification by the internal standard method can be done on the low-field NMR spectrometer and leads to results similar to those obtained with high-field NMR. Considering the cost and space efficiency of these spectrometers, we anticipate their introduction in QC laboratories as well as in governmental agencies, especially in the field of fraud detection.