spin-echo (SE) measurements were used to estimate the apparent transverse relaxation time constant (T 2 † ) of water and metabolites in human brain at 4T and 7T. A significant reduction in the T 2 † values of proton resonances (water, N-acetylaspartate, and creatine/phosphocreatine) was observed with increasing magnetic field strength and was attributed mainly to increased dynamic dephasing due to increased local susceptibility gradients. At high field, signal loss resulting from T 2 † decay can be substantially reduced using a Carr-Purcell-type SE sequence.Magn Theoretical and experimental studies have shown at least a linear increase in sensitivity with magnetic field strength (1,2). On the other hand, the transverse relaxation rate is known to increase with magnetic field strength (3,4), which can result in reduced sensitivity in spin-echo (SE) experiments. The apparent transverse relaxation time (T 2 † ) is related to the intrinsic transverse relaxation time (T 2 ) through the following equation:The first term on the right side of Eq.[1] is the inverse of the intrinsic T 2 and is governed by a number of possible mechanisms, including 1) homonuclear dipole-dipole interaction between protons, which is strongly dependent on rotational correlation time c ; 2) hyperfine (contact) interaction, namely, the change of transverse relaxation time due to interaction with a paramagnetic center; and 3) cross-relaxation, which can be significant in dipole-coupled systems. The second and third terms, T 2,Diffusion and T 2,Exchange , are the transverse relaxation times related to diffusion and exchange of spins between regions with different magnetic field strengths, respectively. These contributions describe the dynamic dephasing regime, whereby the net magnetization is reduced by diffusion and exchange between regions with different magnetic field strengths, which causes the phases of the different spin packets to average out. The opposite situation is defined as the static dephasing regime. NMR signal loss due to static dephasing can be refocused by SE sequences and is therefore not considered here.It is important to investigate: 1) how the increase of field strength causes T 2 † shortening, and 2) how the signal loss from T 2 † decay can be compensated for. Key experiments for answering these questions involve measuring T 2 † at different field strengths and attempting to estimate T 2 . The theory of NMR signal formation in the presence of local magnetic field inhomogeneity was first derived by Carr and Purcell (5), and later generalized by Torrey (6), who incorporated the diffusion effects into the Bloch equations to take into account the actual field distribution. The CarrPurcell (CP) method is the most valuable technique for determining transverse relaxation times. CP experiments are performed by applying a /2 pulse followed by a series of pulses spaced with time interval cp . The value of T 2 † determined with a CP technique can vary with cp because dynamic dephasing and homonuclear spin-spin coupling can cause signi...

A majority of ATP in the brain is formed in the mitochondria through oxidative phosphorylation of ADP with the F1F0-ATP (ATPase) enzyme. This ATP production rate plays central roles in brain bioenergetics, function and neurodegeneration. In vivo 31 P magnetic resonance spectroscopy combined with magnetization transfer (MT) is the sole approach able to noninvasively determine this ATP metabolic rate via measuring the forward ATPase reaction flux (F f,ATPase). However, previous studies indicate lack of quantitative agreement between F f,ATPase and oxidative metabolic rate in heart and liver. In contrast, recent work has shown that F f,ATPase might reflect oxidative phosphorylation rate in resting human brains. We have conducted an animal study, using rats under varied brain activity levels from light anesthesia to isoelectric state, to examine whether the in vivo 31 P MT approach is suitable for measuring the oxidative phosphorylation rate and its change associated with varied brain activity. Our results conclude that the measured F f,ATPase reflects the oxidative phosphorylation rate in resting rat brains, that this flux is tightly correlated to the change of energy demand under varied brain activity levels, and that a significant amount of ATP energy is required for ''housekeeping'' under the isoelectric state. These findings reveal distinguishable characteristics of ATP metabolism between the brain and heart, and they highlight the importance of in vivo 31 P MT approach to potentially provide a unique and powerful neuroimaging modality for noninvasively studying the cerebral ATP metabolic network and its central role in bioenergetics associated with brain function, activation, and diseases.A denosine triphosphate (ATP), a high-energy phosphate (HEP) compound, is the universal energy currency in living cells for supporting the energy needs of various cellular activities and functions. In the brain, a majority of ATP is formed in the mitochondria through oxidative phosphorylation of adenosine diphosphate (ADP) catalyzed by the enzyme of ATP synthase (ATPase) (1). A large portion of ATP energy is used in cytosol to pump sodium and potassium across the cellular membrane for maintaining transmembrane ion gradients and to support neurotransmitters cycling and, thus, sustaining electrophysiological activity and cell signaling in the brain. The ATP metabolism regulating both ATP production and utilization plays a fundamental role in cerebral bioenergetics, brain function, and neurodegenerative diseases (2-6).The brain ATP metabolism is mainly controlled by ATPase and creatine kinase (CK) reactions that are coupled together and constitute a complex chemical exchange system involving ATP, phosphocreatine (PCr), and intracellular inorganic phosphate (Pi) (i.e., a PCr^ATP^Pi chemical exchange system) (7-10). One vital function of this ATP metabolic network is to maintain a stable cellular ATP concentration by adjusting the reaction rates to ensure a continuous energy supply for sustaining electrophysiological activity and ...

In vivo (31)P spectra were acquired from the human primary visual cortex at 7 T. The relaxation times of the cerebral metabolites, intracellular pH, rate constant (k(f)) of the creatine kinase (CK) reaction, and nuclear Overhauser enhancement (NOE) on the detected phosphorus moieties from irradiation of the water spins were measured from normal subjects. With a 5-cm-diameter surface coil, 3D (31)P chemical shift imaging was performed with a spatial resolution of 7.5 ml and an acquisition resolution of 8 min, resulting in a signal-to-noise ratio (SNR) for phosphocreatine (PCr) resonance of 32. The apparent T(1) and T(2) of PCr measured at 7 T were 3.37 +/- 0.29 s and 132.0 +/- 12.8 ms, respectively, which were considerably longer than those of adenosine triphosphate (ATP) (T(1): 1.02-1.27 s; T(2): 25-26 ms). The NOE measured in this study was 24.3% +/- 1.6% for PCr, and 10% for ATP. The k(f) measured in the human primary visual cortex was 0.24 +/- 0.03 s(-1). The results from this study suggest that ultra-high-field strength is advantageous for performing in vivo (31)P magnetic resonance spectroscopy (MRS) in the human brain.

Quantitative assessment of cerebral glucose consumption rate (CMR) and tricarboxylic acid cycle flux (V) is crucial for understanding neuroenergetics under physiopathological conditions. In this study, we report a novel in vivo Deuterium (H) MRS (DMRS) approach for simultaneously measuring and quantifying CMR and V in rat brains at 16.4 Tesla. Following a brief infusion of deuterated glucose, dynamic changes of isotope-labeled glucose, glutamate/glutamine (Glx) and water contents in the brain can be robustly monitored from their well-resolved H resonances. Dynamic DMRS glucose and Glx data were employed to determine CMR and V concurrently. To test the sensitivity of this method in response to altered glucose metabolism, two brain conditions with different anesthetics were investigated. Increased CMR (0.46 vs. 0.28 µmol/g/min) and V (0.96 vs. 0.6 µmol/g/min) were found in rats under morphine as compared to deeper anesthesia using 2% isoflurane. This study demonstrates the feasibility and new utility of the in vivo DMRS approach to assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an alternative MRS tool for in vivo study of metabolic coupling relationship between aerobic and anaerobic glucose metabolisms in brain under physiopathological states.

Handedness is the clearest example of behavioral lateralization in humans. It is not known whether the obvious asymmetry manifested by hand preference is associated with similar asymmetry in brain activation during movement. We examined the functional activation in cortical motor areas during movement of the dominant and nondominant hand in groups of right-handed and left-handed subjects and found that use of the dominant hand was associated with a greater volume of activation in the contralateral motor cortex. Furthermore, there was a separate relation between the degree of handedness and the extent of functional lateralization in the motor cortex. The patterns of functional activation associated with the direction and degree of handedness suggest that these aspects are independent and are coded separately in the brain.

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O spin relaxation times and sensitivity of detection were measured for natural abundance H 2 17 O in the rat brain at 4.7 and 9.4 Tesla. The relaxation times were found to be magnetic field independent (T 2 ‫؍‬ 3.03 ؎ 0.08 ms, T * 2 ‫؍‬ 1.79 ؎ 0.04 ms, and T 1 ‫؍‬ 4.47 ؎ 0.14 ms at 4.7T (N ‫؍‬ 5); T 2 ‫؍‬ 3.03 ؎ 0.09 ms, T * 2 ‫؍‬ 1.80 ؎ 0.06 ms, and T 1 ‫؍‬ 4.84 ؎ 0.18 ms at 9.4T (N ‫؍‬ 5)), consistent with the concept that the dominant relaxation mechanism is the quadrupolar interaction for this nucleus. The

We have combined neutron scattering and piezoresponse force microscopy to study the relation between the exchange bias observed in CoFeB/BiFeO3 heterostructures and the multiferroic domain structure of the BiFeO3 films. We show that the exchange field scales with the inverse of the ferroelectric and antiferromagnetic domain size, as expected from Malozemoff's model of exchange bias extended to multiferroics. Accordingly, polarized neutron reflectometry reveals the presence of uncompensated spins in the BiFeO3 film at the interface with the CoFeB. In view of these results we discuss possible strategies to switch the magnetization of a ferromagnet by an electric field using BiFeO3.PACS numbers: 75.50. Ee, 75.70.Cn, 75.70.Kw The renaissance of multiferroics [1, 2], i.e. materials in which at least two ferroic or antiferroic orders coexist, is motivated by fundamental aspects as well as their possible application in spintronics [3]. Such compounds are rare and the very few that possess simultaneously a finite magnetization and polarization usually order below about 100K [4,5,6]. Ferroelectric antiferromagnets (FEAF) are less scarce, and some exhibit a coupling between their two order parameters. This magnetoelectric (ME) coupling allows the reversal of the ferroelectric (FE) polarization by a magnetic field [7] or the control of the magnetic order parameter by an electric field [8].The practical interest of conventional antiferromagnets (AF) is mainly for exchange bias in spin-valve structures. The phenomenon of exchange bias (EB) [9] manifests itself by a shift in the hysteresis loop of a ferromagnet (FM) in contact with an AF and arises from the exchange coupling at the FM/AF interface [10,11]. Combining this effect with the ME coupling in a FEAF/FM bilayer can allow the reversal of the FM magnetization via the application of an electric field through the FEAF, as reported recently at 2K in YMnO 3 /NiFe structures [12].To exploit these functionalities in devices one needs to resort to FEAF materials with high transition temperatures. BiFeO 3 (BFO) is a FE perovskite with a Curie temperature of 1043K [13] that orders antiferromagnetically below T N =643K (T N : Néel temperature) [14]. BFO thin films have a very low magnetization (∼0.01 µ B /Fe) compatible with an AF order [15,16], and remarkable FE properties with polarization values up to 100 µC.cm −2 range [17]. Recently, we reported that BFO films can be used to induce an EB on adjacent CoFeB layers at room temperature [18]. This observation together with the demonstration of a coupling between the AF and FE domains [8] paves the way towards the room-temperature electrical control of magnetization with BFO. However, several questions remain before this can be achieved. Key issues concern the precise magnetic structure of BFO thin films, and the mechanisms of EB in BFO-based heterostructures.In this Letter, we report on the determination of the magnetic structure of BFO films by means of neutron diffraction (ND), and the analysis of the EB effect in CoFeB/BFO ...