Mapping of metabolites in whole animals by 31P NMR using surface coils

Ackerman, Joseph J. H.; Grove, Thomas H.; Wong, Gordon G.; Gadian, David G.; Radda, George K.

doi:10.1038/283167a0

Cited by 956 publications

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“…Following initial experiments on animal tissue (Hoult et al 1974;Ackerman et al 1980), magnetic resonance (MR) spectroscopy (MRS) was first applied to human subjects in the early 1980s, using the 31 P nucleus to monitor the levels and fate of high-energy phosphates in skeletal muscle (Chance et al 1981;Cresshull et al 1981;Ross et al 1981). From these first experiments it was clear that 31 P MRS offers a unique non-invasive window on energy metabolism in skeletal muscle.…”

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Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

et al. 1999

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fax +31 24 3540 866, email a.heerschap@rdiag.azn.nl 31 P magnetic resonance spectroscopy (MRS) offers a unique non-invasive window on energy metabolism in skeletal muscle, with possibilities for longitudinal studies and of obtaining important bioenergetic data continuously and with sufficient time resolution during muscle exercise. The present paper provides an introductory overview of the current status of in vivo 31 P MRS of skeletal muscle, focusing on human applications, but with some illustrative examples from studies on transgenic mice. Topics which are described in the present paper are the information content of the 31 P magnetic resonance spectrum of skeletal muscle, some practical issues in the performance of this MRS methodology, related muscle biochemistry and the validity of interpreting results in terms of biochemical processes, the possibility of investigating reaction kinetics in vivo and some indications for fibre-type heterogeneity as seen in spectra obtained during exercise. P magnetic resonance spectroscopy: Skeletal muscle: High-energy phosphates: Energy metabolism: ExerciseFollowing initial experiments on animal tissue (Hoult et al. 1974;Ackerman et al. 1980), magnetic resonance (MR) spectroscopy (MRS) was first applied to human subjects in the early 1980s, using the 31 P nucleus to monitor the levels and fate of high-energy phosphates in skeletal muscle (Chance et al. 1981;Cresshull et al. 1981;Ross et al. 1981). From these first experiments it was clear that 31 P MRS offers a unique non-invasive window on energy metabolism in skeletal muscle. Of particular interest is the possibility of obtaining important bioenergetic data continuously and with sufficient time resolution during muscle exercise. Another important aspect is that longitudinal monitoring is possible. Numerous studies applying this technique to human subjects have been published, and several reviews are available addressing specific results obtained in this way (for example, see Barbiroli, 1992;Cozzone & Bendahan, 1994;Kemp & Radda, 1994;McCully et al. 1994;Radda et al. 1995).The present paper provides an introduction to 31 P MRS as applied to skeletal muscle of human subjects, and also gives some illustrative examples from our recent studies on skeletal muscle of transgenic mouse models lacking creatine kinase (EC 2.7.3.2). Information content of the 31 P magnetic resonance spectrum of skeletal muscleTo appreciate the potential of the method, first, the information content of a spectrum obtained from human skeletal muscle at rest should be examined (see Fig. 1(A)).The most dominant signals in the spectrum are from phosphocreatine (PCr) and the three non-equivalent phosphate groups of ATP. Usually also a signal for inorganic phosphate (Pi) can be observed, and under favourable conditions signals for phosphomonoesters and phosphodiesters are observable as well. What is the origin of the distinct resonance frequencies of the 31 P nuclei in these compounds? In a first approximation the resonance frequency of the nuclear spins is...

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Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

et al. 1999

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“…It has been shown that very rapid, noninvasive measurements of cerebral intracellular metabolites, including intracellular pH, can be accomplished in vivo with 3 1 p NMR techniques, allowing experi ments to be performed that would otherwise not be possible (Chance et al, 1978;Ackerman et al, 1980;Wemmer et al, 1982;Prichard et al, 1983;Hilberman et al, 1984). We have employed such techniques during supercarbia, with the hope of ex tending the intracellular perturbations, experi mental techniques, and physiological conclusions of previous works.…”

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Cerebral Intracellular Changes during Supercarbia: An in vivo ³¹P Nuclear Magnetic Resonance Study in Rats

Litt

González‐Méndez

Severinghaus

et al. 1985

J Cereb Blood Flow Metab

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Summary: 31p nuclear magnetic resonance (NMR) spec troscopy was used noninvasively to measure in vivo changes in intracellular pH and intracellular phosphate metabolites in the brains of rats during supercarbia (P aco2 "" 400 mm Hg). Five intubated rats were mechanically ventilated with inspired gas mixtures containing 70% CO2 and 30% 02' Supercarbia in the rat was observed to cause a greater reduction in cerebral intracellular pH (pH) and increase in Peo2 than observed in other experiments with rats after 15 min of global ischemia. Complete neurologic and metabolic recovery was observed in these animals, de spite an average decrease in pHj of 0.63 ± 0.02 pH unit during supercarbia episodes that raised Paco2 to 490 ± 80 mm Hg. No change was observed in cerebral intra cellular ATP and only a 25% decrease was detected in phosphocreatine. The concentration of free cerebral in- SUPERCARBIA AND BRAIN ENERGY METABOLISMIschemia and hypoventilation in clinical situa tions can cause hypercarbia in brain cells. During these conditions, some cells usually will also suffer from inadequate oxygen availability. Deleterious consequences of hypercarbia are known to arise from secondary physiological phenomena such as seizures, sympathetic stimulation, and certain ef fects of acidosis, such as cardiac irritability and de creased oxygen availability due to a right shift of the hemoglobin dissociation curve (Nunn, 1977). Abbreviations used: Cr, creatine; NMR, nuclear magnetic res onance; PCr, phosphocreatine; pHa, arterial pH; pHi' cerebral intracellular pH; PME, phosphomonoesters. tracellular ADP, which can be calculated if one assumes that the creatine kinase reaction is in equilibrium, de creased to approximately one-third of its control value. The calculated threefold decrease in the concentration of free ADP and twofold increase in the cytosolic phos phorylation potential suggest that there is increased in tracellular oxygenation during supercarbia. Because a more than fourfold increase in intracellular hydrogen ion concentration was tolerated without apparent clinical in jury, we conclude that so long as adequate tissue oxy genation and perfusion are maintained, a severe decrease in intracellular pH need not induce or indicate brain in jury.

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“…In the intervening years, NMR spectroscopy has been used in-vitro and in-vivo to study enzymatic reactions (8,9); measure intracellular pH (10,11); study cell membranes (12)(13)(14); follow metabolic pathways in normal, ischemic and neoplastic states (15)(16)(17)(18); and monitor pharmaceutical interventions (19,20). Nuclei investigated include P-31, H-l, C-13, F-19, Na-23, and C1-35.…”

Section: Thank Youmentioning

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“…Three methods are commonly used today. In surface coil technology (18,19), a small receiving coil is used to acquire the resonance signal only from the tissue adjacent to the coil. TMR, or topical magnetic resonance, techniques use specially designed magnets to acquire chemical shift data from a volume lying deep within an animal (22).…”

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confidence: 99%

NMR chemical shift imaging

Brink

Buschmann

Rosen

1989

Computerized Medical Imaging and Graphics

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Medical Engineering and Medical PhysicsI. ABSTRACT Methods of obtaining nuclear magnetic resonance (NMR) images containing chemical shift information are presented. Using a three-dimensional Fourier Transform approach (two spatial axes and one resonance frequency axis), proton chemical shift images were acquired in phantoms and in-vivo using both spin echo and free induction decay (FID) pulse sequences. A proton resonance frequency of 61.5 MHz, corresponding to a magnetic field strength of 1.44 tesla, was used. In simple phantoms, chemical shift images indicate that spectral resolution of 0.7 parts per million (ppm) is readily achieved at all locations within the image matrix, even when using a magnet not specifically designed for chemical shift spectroscopy. In-vivo images of normal human forearms and cat heads yield separable signals from water and lipid protons. In the cat brain, no appreciable NMR signal originates from membrane lipids (e.g., myelin); images acquired using FID pulse sequences imply T 2 relaxation times less than 2 msec for these protons. The measurement of magnetic susceptibility using this technique is also demonstrated. The effect of susceptibility variations in-vivo appears in general to be less than 1 ppm.Proton chemical shift imaging was used to study fatty liver change in the rat. The correlation between lipid group signal intensity from chemical shift images i'n-viv and liver triglyceride levels measured in-vitro was good (r = .97). In-vivo T 1 relaxation time measurements were made on lipid and water protons separately. Values calculated were corrected for the influence of gaussian plane selection and spin echo data acquisition, and demonstrate different T 1 times reflecting two distinct populations of non-exchanging protons. Proton chemical shift imaging offers enhanced sensitivity over conventional NMR imaging techniques in characterizing fatty liver disease.Selective saturation (solvent suppression) techniques were used in an imaging context in both phantoms and in-vivo. Using a three-dimensional chemical shift imaging approach, data presented demonstrate the feasibility of imaging proton metabolites at low concentration. Phantom studies without solvent suppression failed to detect lactate at 80 mM; however with solvent suppression, lactate at 40 mM was imaged in a reasonable time (approximately 50 minutes). Using a conventional two-dimensional NMR imaging technique preceded by a selective (saturating) pulse, signal from water or lipid protons were eliminated (>95% reduction in signal intensity), resulting in images of -CH 2 -or H 2 0 proton distribution with resolution and imaging times equivalent to conventional proton images. With improvements in imaging systems, these techniques may play an important role in the non-invasive evaluation of tissue ischemia using proton NMR. where Y is the gyromagnetic ratio (defined as the ratio of the nuclear magnetic moment to the spin angular momentum) and B is the magnetic field seen by the nucleus (5). This B field is traditionally rewritte...

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Mapping of metabolites in whole animals by 31P NMR using surface coils

Cited by 956 publications

References 18 publications

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Cerebral Intracellular Changes during Supercarbia: An in vivo ³¹P Nuclear Magnetic Resonance Study in Rats

NMR chemical shift imaging

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Mapping of metabolites in whole animals by 31P NMR using surface coils

Cited by 956 publications

References 18 publications

Introduction toin vivo31P magnetic resonance spectroscopy of (human) skeletal muscle

Introduction toin vivo31P magnetic resonance spectroscopy of (human) skeletal muscle

Cerebral Intracellular Changes during Supercarbia: An in vivo 31P Nuclear Magnetic Resonance Study in Rats

NMR chemical shift imaging

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Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Introduction toin vivo³¹P magnetic resonance spectroscopy of (human) skeletal muscle

Cerebral Intracellular Changes during Supercarbia: An in vivo ³¹P Nuclear Magnetic Resonance Study in Rats