Are glutamate and lactate increases ubiquitous to physiological activation? A (1)H functional MR spectroscopy study during motor activation in human brain at 7Tesla.

Recent studies at high field (7Tesla) have reported small metabolite changes, in particular lactate and glutamate (below 0.3μmol/g) during visual stimulation. These studies have been limited to the visual cortex because of its high energy metabolism and good magnetic resonance spectroscopy (MRS) sensitivity using surface coil. The aim of this study was to extend functional MRS (fMRS) to investigate for the first time the metabolite changes during motor activation at 7T. Small but sustained increases in lactate (0.17μmol/g±0.05μmol/g, p<0.001) and glutamate (0.17μmol/g±0.09μmol/g, p<0.005) were detected during motor activation followed by a return to the baseline after the end of activation. The present study demonstrates that increases in lactate and glutamate during motor stimulation are small, but similar to those observed during visual stimulation. From the observed glutamate and lactate increase, we inferred that these metabolite changes may be a general manifestation of the increased neuronal activity. In addition, we propose that the measured metabolite concentration increases imply an increase in ΔCMRO2 that is transiently below that of ΔCMRGlc during the first 1 to 2min of the stimulation.

Coronary MR imaging: lumen and wall.

Coronary MR imaging is a promising noninvasive technique for the combined assessment of coronary artery anatomy and function. Anomalous coronary arteries and aneurysms can reliably be assessed in clinical practice using coronary MR imaging and the presence of significant left main or proximal multivessel coronary artery disease detected. Technical challenges that need to be addressed are further improvements in motion suppression and abbreviated scanning times aimed at improving spatial resolution and patient comfort. The development of new and specific contrast agents, high-field MR imaging with improved spatial resolution, and continued progress in MR imaging methods development will undoubtedly lead to further progress toward the noninvasive and comprehensive assessment of coronary atherosclerotic disease.

Simultaneous B(0)- and B(1)+-map acquisition for fast localized shim, frequency, and RF power determination in the heart at 3 T.

High-field (>or=3 T) cardiac MRI is challenged by inhomogeneities of both the static magnetic field (B(0)) and the transmit radiofrequency field (B(1)+). The inhomogeneous B fields not only demand improved shimming methods but also impede the correct determination of the zero-order terms, i.e., the local resonance frequency f(0) and the radiofrequency power to generate the intended local B(1)+ field. In this work, dual echo time B(0)-map and dual flip angle B(1)+-map acquisition methods are combined to acquire multislice B(0)- and B(1)+-maps simultaneously covering the entire heart in a single breath hold of 18 heartbeats. A previously proposed excitation pulse shape dependent slice profile correction is tested and applied to reduce systematic errors of the multislice B(1)+-map. Localized higher-order shim correction values including the zero-order terms for frequency f(0) and radiofrequency power can be determined based on the acquired B(0)- and B(1)+-maps. This method has been tested in 7 healthy adult human subjects at 3 T and improved the B(0) field homogeneity (standard deviation) from 60 Hz to 35 Hz and the average B(1)+ field from 77% to 100% of the desired B(1)+ field when compared to more commonly used preparation methods.

Digit somatotopy in the human cerebellum: a 7T fMRI study.

The representation of the human body in the human cerebellum is still relatively unknown, compared to the well-studied homunculus in the primary somatosensory cortex. The investigation of the body representation in the cerebellum and its somatotopic organisation is complicated because of the relatively small dimensions of the cerebellum, compared to the cerebrum. Somatotopically organised whole-body homunculi have previously been reported in both humans and rats. However, whether individual digits are represented in the cerebellum in a somatotopically organised way is much less clear. In this study, the high spatial resolution and high sensitivity to the blood oxygenation level dependent (BOLD) signal of 7T fMRI were employed to study the BOLD responses in the human cerebellum to the stroking of the skin of individual digits, the hand and forearm. For the first time, a coarse somatotopic organisation of the digits, ordered from D1-D5, could be visualised in individual human subjects in both the anterior (lobule V) and the posterior (lobule VIII) lobes of the cerebellum using a somatosensory stimulus. The somatotopic gradient in lobule V was found consistently in the posterior to anterior direction, with the thumb most posterior, while the direction of the somatotopic gradient in lobule VIII differed between subjects. No somatotopic organisation was found in Crus I. A comparison of the digit patches with the hand patch revealed that the digit regions are completely covered by the hand region in both the anterior and posterior lobes of the cerebellum, in a non-somatotopic manner. These results demonstrate the promise of ultra-high field, high-resolution fMRI for studies of the cerebellum.

Coronary magnetic resonance imaging.

Coronary magnetic resonance imaging is a powerful non-invasive technique for the combined assessment of coronary artery anatomy and function. In the present review article, challenges in coronary artery imaging are discussed and results obtained in both healthy volunteers and patients with cardiovascular disease are presented. This includes a short overview of coronary artery vessel lumen and wall imaging, contrast agents, permeability of the coronary vessel wall, high-field imaging and imaging of endothelial function.

Detection of neuronal activity and metabolism in a model of dehydration-induced anorexia in rats at 14.1 T using manganese-enhanced MRI and 1H MRS.

In this study, hypothalamic activation was performed by dehydration-induced anorexia (DIA) and overnight food suppression (OFS) in female rats. The assessment of the hypothalamic response to these challenges by manganese-enhanced MRI showed increased neuronal activity in the paraventricular nuclei (PVN) and lateral hypothalamus (LH), both known to be areas involved in the regulation of food intake. The effects of DIA and OFS were compared by generating T-score maps. Increased neuronal activation was detected in the PVN and LH of DIA rats relative to OFS rats. In addition, the neurochemical profile of the PVN and LH were measured by (1) H MRS at 14.1T. Significant increases in metabolite levels were measured in DIA and OFS relative to control rats. Statistically significant increases in γ-aminobutyric acid were found in DIA (p=0.0007) and OFS (p<0.001) relative to control rats. Lactate increased significantly in DIA (p=0.03), but not in OFS, rats. This work shows that manganese-enhanced MRI coupled to (1) H MRS at high field is a promising noninvasive method for the investigation of the neural pathways and mechanisms involved in the control of food intake, in the autonomic and endocrine control of energy metabolism and in the regulation of body weight.

Longitudinal MR assessment of hypoxic ischemic injury in the immature rat brain.

Extremely preterm infants commonly show brain injury with long-term structural and functional consequences. Three-day-old (P3) rat pups share some similarities in terms of cerebral development with the very preterm infant (born at 24-28 weeks of gestation). The aim of this study was to assess longitudinally the cerebral structural and metabolic changes resulting from a moderate neonatal hypoxic ischemic injury in the P3 rat pup using high-field (9.4 T) MRI and localized (1) H magnetic resonance spectroscopy techniques. The rats were scanned longitudinally at P3, P4, P11, and P25. Volumetric measurements showed that the percentage of cortical loss in the long term correlated with size of damage 6 h after hypoxia-ischemia, male pups being more affected than female. The neurochemical profiles revealed an acute decrease of most of metabolite concentrations and an increase in lactate 24 h after hypoxia-ischemia, followed by a recovery phase leading to minor metabolic changes at P25 in spite of an abnormal brain development. Further, the increase of lactate concentration at P4 correlated with the cortical loss at P25, giving insight into the early prediction of long-term cerebral alterations following a moderate hypoxia-ischemia insult that could be of interest in clinical practice.

Coronary magnetic resonance angiography.

Coronary magnetic resonance angiography (MRA) is a powerful noninvasive technique with high soft-tissue contrast for the visualization of the coronary anatomy without X-ray exposure. Due to the small dimensions and tortuous nature of the coronary arteries, a high spatial resolution and sufficient volumetric coverage have to be obtained. However, this necessitates scanning times that are typically much longer than one cardiac cycle. By collecting image data during multiple RR intervals, one can successfully acquire coronary MR angiograms. However, constant cardiac contraction and relaxation, as well as respiratory motion, adversely affect image quality. Therefore, sophisticated motion-compensation strategies are needed. Furthermore, a high contrast between the coronary arteries and the surrounding tissue is mandatory. In the present article, challenges and solutions of coronary imaging are discussed, and results obtained in both healthy and diseased states are reviewed. This includes preliminary data obtained with state-of-the-art techniques such as steady-state free precession (SSFP), whole-heart imaging, intravascular contrast agents, coronary vessel wall imaging, and high-field imaging. Simultaneously, the utility of electron beam computed tomography (EBCT) and multidetector computed tomography (MDCT) for the visualization of the coronary arteries is discussed.

Handling macromolecule signals in the quantification of the neurochemical profile.

In vivo localized proton magnetic resonance spectroscopy (1H MRS) became a powerful and unique technique to non-invasively investigate brain metabolism of rodents and humans. The main goal of 1H MRS is the reliable quantification of concentrations of metabolites (neurochemical profile) in a well-defined region of the brain. The availability of very high magnetic field strengths combined with the possibility of acquiring spectra at very short echo time have dramatically increased the number of constituents of the neurochemical profile. The quantification of spectra measured at short echo times is complicated by the presence of macromolecule signals of particular importance at high magnetic fields. An error in the macromolecule estimation can lead to substantial errors in the obtained neurochemical profile. The purpose of the present review is to overview methods of high field 1H MRS with a focus on the metabolite quantification, in particular in handling signals of macromolecules. Three main approaches of handling signals of macromolecules are described, namely mathematical estimation of macromolecules, measurement of macromolecules in vivo, and direct acquisition of the in vivo spectrum without the contribution of macromolecules.

Entrained macrocryst minerals as a key to the source region of olivine nephelinites: Humberg, Kaiserstuhl, Germany

Olivine nephelinites commonly contain macrocrysts of olivine and clinopyroxene. Some of these macrocrysts might represent fragments of the source region of the host magma transported to the Earth surface. If this hypothesis is correct these fragments can be used to characterize the composition of the source region and to put constraints on the magma generation process. In this study, we investigate the origin of macrocrysts and mineral aggregates from an olivine nephelinite from the Kaiserstuhl, Germany. We focus on clinopyroxenes (Cpx), which can be divided into three groups. Cpx I is relict Cpx from aggregates with deformed olivine that is depleted in Ca and characterized by strong light rare earth element (LREE) fractionation, low Ti/Eu and negative high field strength element (HFSE) anomalies. Its geochemical signature is consistent with formation by carbonatite metasomatism and with equilibration in the Presence of orthopyroxene. Cpx II is Ca-rich Cpx, forming both aggregates with deformed olivine and individual macrocrysts. The LREE, as for Cpx I, are strongly fractionated. Convex REE patterns may be present. The depletion in HFSE is less pronounced. Cpx III is oscillatory zoned Cpx phenociysis showing enrichment in Ca, convex REE patterns and no HFSE anomalies. The transition in the trace element abundances between the Cpx of the three groups is gradual. However, Cpx I and H did not crystallize from the host magma, as demonstrated by the presence of kink-bands and undulose extinction in the associated olivine and by the composition of alkali aluminosilicate glass inclusions in Cpx H. Based on the Cpx relationships, we interpret the studied suite of macrocrysts and mineral aggregates as a mixture of disintegrated fragments of the source region of the host olivine nephelinite. The process of melt generation was multi-stage. A primary carbonatite melt ascending from deeper levels in the mantle, probably from the dolomite-garnet peridotite stability field, reacted with mantle peridotite along the solidus ledge in the system lherzolite-CO2 (< 20-22 kbar) and started to crystallize carbonate minerals. Because of its low solidus temperature, the resulting carbonate-wehrlite assemblage melted incongruently with the formation of additional clinopyroxene. The carbonatite melt evolved during crystallization of carbonate minerals and concomitant incongruent melting of the carbonate-wehrlite, accompanied by the segregation of incipient alkali aluminosilicate melts. As a consequence of fast reaction rates in the presence of a carbonatite melt, this process probably took place under disequilibrium conditions. Further melting of the assemblage wehrlite + alkali aluminosilicate melt led to the generation of the olivine nephelinite magma. It entrained fragments of the wehrlite and brought them to the surface.

Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Initial experiences with in vivo right coronary artery human MR vessel wall imaging at 3 tesla.

Due to their relatively small size and central location within the thorax, improvement in signal-to-noise (SNR) is of paramount importance for in vivo coronary vessel wall imaging. Thus, with higher field strengths, coronary vessel wall imaging is likely to benefit from the expected "near linear" proportional gain in SNR. In this study, we demonstrate the feasibility of in vivo human high field (3 T) coronary vessel wall imaging using a free-breathing black blood fast gradient echo technique with respiratory navigator gating and real-time motion correction. With the broader availability of more SNR efficient fast spin echo and spiral techniques, further improvements can be expected.

Assignment strategies for large proteins by magic-angle spinning NMR: the 21-kDa disulfide-bond-forming enzyme DsbA.

We present strategies for chemical shift assignments of large proteins by magic-angle spinning solid-state NMR, using the 21-kDa disulfide-bond-forming enzyme DsbA as prototype. Previous studies have demonstrated that complete de novo assignments are possible for proteins up to approximately 17 kDa, and partial assignments have been performed for several larger proteins. Here we show that combinations of isotopic labeling strategies, high field correlation spectroscopy, and three-dimensional (3D) and four-dimensional (4D) backbone correlation experiments yield highly confident assignments for more than 90% of backbone resonances in DsbA. Samples were prepared as nanocrystalline precipitates by a dialysis procedure, resulting in heterogeneous linewidths below 0.2 ppm. Thus, high magnetic fields, selective decoupling pulse sequences, and sparse isotopic labeling all improved spectral resolution. Assignments by amino acid type were facilitated by particular combinations of pulse sequences and isotopic labeling; for example, transferred echo double resonance experiments enhanced sensitivity for Pro and Gly residues; [2-(13)C]glycerol labeling clarified Val, Ile, and Leu assignments; in-phase anti-phase correlation spectra enabled interpretation of otherwise crowded Glx/Asx side-chain regions; and 3D NCACX experiments on [2-(13)C]glycerol samples provided unique sets of aromatic (Phe, Tyr, and Trp) correlations. Together with high-sensitivity CANCOCA 4D experiments and CANCOCX 3D experiments, unambiguous backbone walks could be performed throughout the majority of the sequence. At 189 residues, DsbA represents the largest monomeric unit for which essentially complete solid-state NMR assignments have so far been achieved. These results will facilitate studies of nanocrystalline DsbA structure and dynamics and will enable analysis of its 41-kDa covalent complex with the membrane protein DsbB, for which we demonstrate a high-resolution two-dimensional (13)C-(13)C spectrum.

The magmatic to hydrothermal evolution of the intrusive Mont Saint-Hilaire Complex: Insights into the late-stage evolution of peralkaline rocks

The Cretaceous Mont Saint-Hilaire complex (Quebec, Canada) comprises three major rock units that were emplaced in the following sequence: (I) gabbros; (II) diorites; (III) diverse partly agpaitic foid syenites. The major element compositions of the rock-forming minerals, age-corrected Nd and oxygen isotope data for mineral separates and trace element data of Fe-Mg silicates from the various lithologies imply a common source for all units. The distribution of the rare earth elements in clinopyroxene from the gabbros indicates an ocean island basalt type composition for the parental magma. Gabbros record temperatures of 1200 to 800 degrees C, variable silica activities between 0 center dot 7 and 0 center dot 3, and f(O2) values between -0 center dot 5 and +0 center dot 7 (log delta FMQ, where FMQ is fayalite-magnetite-quartz). The diorites crystallized under uniform a(SiO2) (a(SiO2) = 0 center dot 4-0 center dot 5) and more reduced f(O2) conditions (log delta FMQ similar to-1) between similar to 1100 and similar to 800 degrees C. Phase equilibria in various foid syenites indicate that silica activities decrease from 0 center dot 6-0 center dot 3 at similar to 1000 degrees C to < 0 center dot 3 at similar to 550 degrees C. Release of an aqueous fluid during the transition to the hydrothermal stage caused a(SiO2) to drop to very low values, which results from reduced SiO(2) solubilities in aqueous fluids compared with silicate melts. During the hydrothermal stage, high water activities stabilized zeolite-group minerals. Fluid inclusions record a complex post-magmatic history, which includes trapping of an aqueous fluid that unmixed from the restitic foid syenitic magma. Cogenetic aqueous and carbonic fluid inclusions reflect heterogeneous trapping of coexisting immiscible external fluids in the latest evolutionary stage. The O and C isotope characteristics of fluid-inclusion hosted CO(2) and late-stage carbonates imply that the surrounding limestones were the source of the external fluids. The mineral-rich syenitic rocks at Mont Saint-Hilaire evolved as follows: first, alkalis, high field strength and large ion lithophile elements were pre-enriched in the (late) magmatic and subsequent hydrothermal stages; second, percolation of external fluids in equilibrium with the carbonate host-rocks and mixing processes with internal fluids as well as fluid-rock interaction governed dissolution of pre-existing minerals, element transport and precipitation of mineral assemblages determined by locally variable parameters. It is this hydrothermal interplay between internal and external fluids that is responsible for the mineral wealth found at Mont Saint-Hilaire.

Phase-based manganese enhanced MRI, a new methodology to enhance brain cytoarchitectural contrast and study manganese uptake.

PURPOSE: As the magnetic susceptibility induced frequency shift increases linearly with magnetic field strength, the present work evaluates manganese as a phase imaging contrast agent and investigates the dose dependence of brain enhancement in comparison to T1 -weighted imaging after intravenous administration of MnCl2 . METHODS: Experiments were carried out on 12 Sprague-Dawley rats. MnCl2 was infused intravenously with the following doses: 25, 75, 125 mg/kg (n=4). Phase, T1 -weighted images and T1 maps were acquired before and 24h post MnCl2 administration at 14.1 Tesla. RESULTS: Manganese enhancement was manifested in phase imaging by an increase in frequency shift differences between regions rich in calcium gated channels and other tissues, together with local increase in signal to noise ratio (from the T1 reduction). Such contrast improvement allowed a better visualization of brain cytoarchitecture. The measured T1 decrease observed across different manganese doses and in different brain regions were consistent with the increase in the contrast to noise ratio (CNR) measured by both T1 -weighted and phase imaging, with the strongest variations being observed in the dentate gyrus and olfactory bulb. CONCLUSION: Overall from its high sensitivity to manganese combined with excellent CNR, phase imaging is a promising alternative imaging protocol to assess manganese enhanced MRI at ultra high field. Magn Reson Med 72:1246-1256, 2014. © 2013 Wiley Periodicals, Inc.