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 ...

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.