If sensitivity and spectral quality are sufficient, 1H magnetic resonance spectroscopy (MRS) can yield site-specific signatures that directly report metabolic concentrations, biochemistry and kinetics. Here, very high magnetic fields (21.1T) are combined with highly selective spectral excitations to enable relaxation-enhanced (RE) MRS that delivers spectra exhibiting signal-to-noise ratios >50:1 in under 6 seconds for ~5×5×5 mm3 voxels, with flat baselines and no interference from water.

With this spectral quality, MRS was used to interrogate a number of metabolic properties in stroked animal models.

• Metabolic confinements imposed by randomly-oriented microarchitectures were detected and found to change under ischemia.

• Intensities of downfield resonances were found to be selectively altered in stroked hemispheres.

• Longitudinal relaxation time of lactic acid was found to increase by over 50% its control value as early as 3 hours post-ischemia, paralleling the onset of cytotoxic edema.

These results demonstrate the revolutionary potential of probing metabolic properties via 1H MRS at ultra-high fields.

Metabolic properties in stroked rats revealed by relaxation-enhanced MR spectroscopy at 21.1 T

Noam Shemesh1, Jens T Rosenberg2,3, Jean-Nicolas Dumez1, Jose Muniz2,3, Samuel C Grant2,3, Lucio Frydman1,2

1. Weizmann Institute of Science; 2. National High Magnetic Field Laboratory; 3. Florida State University

Funding Grants: G. Boebinger (NSF DMR-1157490); N. Shemesh (VSP); S. Grant (UCGP, AHA 10GRNT3860040); L. Frydman (ISF 1142/13, EC Marie Curie Action ITN METAFLUX 264780)

Facilities: NMR Facility and Animal Facility Instrument/Magnet: 21.1 Tesla Magnet Citations: Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields. Shemesh N, Rosenberg JT, Dumez JN, Muniz JA, Grant SC, Frydman L., Nature Communications 5, 4958 (2014)Metabolic T1 dynamics and longitudinal relaxation enhancement in vivo at ultrahigh magnetic fields on ischemia. Shemesh N, Rosenberg JT, Dumez JN, Grant SC, Frydman L., Journal of Cerebral Blood Flow Metabolism. 34(11): 1810-7 (2014)

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centered in a stroked hemisphere of an in vivo rat brain. SNR of NAA exceeds 50:1, and little remains of the water resonance despite being ~10,000 times stronger. (b) Spectra acquired in 5 minutes from the ipsi- & contralateral hemispheres of a stroked rat, with localized voxels indicated on MRI.

RE-MRS from ipsilateral hemisphere of a stroked rat. Note the oscillations of the peaks upon varying angular ψ, which displays restricted diffusion in non-spherical, randomly oriented regions.

(a) (b)

Complete, broadband spectrum of brain metabolites were used to define bands for choline (Cho), creatine (Cre), N-acetyl-aspartate (NAA) and lactic acid (Lac) that were excited selectively by Shinnar-Le Roux (SLR) pulses to achieve passbands for RE-MRS. (a) 1H MRS recorded in 6 s from a 125-μL voxel

Angularity between directions in double pulsed field gradient scan