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Potassium and sodium specific binding in vivo were explored at 21.1T by triple quantum (TQ) magnetic resonance (MR) signals without filtration to achieve high sensitivities and precise quantifications. The pulse sequence used time proportional phase increments (TPPI). During simultaneous phase-time increments, it provided total single quantum (SQ) and TQ MR signals in the second dimension at single and triple quantum frequencies, respectively. The detection of both TQ and SQ signals was performed at identical experimental conditions and the resulting TQ signal equals 60±3% of the SQ signal when all ions experience sufficient time for binding. In a rat head in vivo the TQ percentage relative to SQ for potassium is 41.5±3% and for sodium is 16.1±1%. These percentages were compared to the matching values in an agarose tissue model with MR relaxation times similar to those of mammalian brain tissue. The sodium TQ signal in agarose samples decreased in the presence of potassium, suggesting a competitive binding of potassium relative to sodium ions for the same binding sites. The TQTPPI signals correspond to almost two times more effective binding of potassium than sodium. In vivo, up to ∼69% of total potassium and ∼27% of total sodium can be regarded as bound or experiencing an association time in the range of several milliseconds. Experimental data analyses show that more than half of the in vivo total sodium TQ signal could be from extracellular space, which is an important factor for quantification of intracellular MR signals., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Functional changes of sodium 3D MRI signals were converted into millimolar concentration changes using an open-source fully automated MATLAB toolbox. These concentration changes are visualized via 3D sodium concentration maps, and they are overlaid over conventional 3D proton images to provide high-resolution co-registration for easy correlation of functional changes to anatomical regions. Nearly 5000/h concentration maps were generated on a personal computer (ca. 2012) using 21.1T 3D sodium MRI brain images of live rats with spatial resolution of 0.8×0.8×0.8 mm(3) and imaging matrices of 60×60×60. The produced concentration maps allowed for non-invasive quantitative measurement of in vivo sodium concentration in the normal rat brain as a functional response to migraine-like conditions. The presented work can also be applied to sodium-associated changes in migraine, cancer, and other metabolic abnormalities that can be sensed by molecular imaging. The MATLAB toolbox allows for automated image analysis of the 3D images acquired on the Bruker platform and can be extended to other imaging platforms. The resulting images are presented in a form of series of 2D slices in all three dimensions in native MATLAB and PDF formats. The following is provided: (a) MATLAB source code for image processing, (b) the detailed processing procedures, (c) description of the code and all sub-routines, (d) example data sets of initial and processed data. The toolbox can be downloaded at: http://www.vuiis.vanderbilt.edu/~truongm/COMA3D/., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The first in vivo sodium and proton magnetic resonance (MR) images and localized spectra of rodents were attained using the wide bore (105 mm) high resolution 21.1-T magnet, built and operated at the National High Magnetic Field Laboratory (Tallahassee, FL, USA). Head images of normal mice (C57BL/6J) and Fisher rats (approximately 250 g) were acquired with custom designed radiofrequency probes at frequencies of 237/900 MHz for sodium and proton, respectively. Sodium MR imaging resolutions of approximately 0.125 microl for mouse and rat heads were achieved by using a 3D back-projection pulse sequence. A gain in SNR of approximately 3 for sodium and approximately 2 times for proton were found relative to corresponding MR images acquired at 9.4 T. 3D Fast Low Angle Shot (FLASH) proton mouse images (50x50x50 microm(3)) were acquired in 90 min and corresponding rat images (100x100x100 microm(3)) within a total time of 120 min. Both in vivo large rodent MR imaging and localized spectroscopy at the extremely high field of 21.1 T are feasible and demonstrate improved resolution and sensitivity valuable for structural and functional brain analysis., (Copyright 2010 Elsevier Inc. All rights reserved.)

The ability to quantitate early effects of tumor therapeutic response using noninvasive imaging would have a major impact in clinical oncology. One area of active research interest is the ability to use MR techniques to detect subtle changes in tumor cellular density. In this study, sodium and proton diffusion MRI were compared for their ability to detect early cellular changes in tumors treated with a cytotoxic chemotherapy. Subcutaneous 9L gliosarcomas were treated with a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea. Both sodium and diffusion imaging modalities were able to detect changes in tumor cellularity as early as 2 days after treatment, which continued to evolve as increased signal intensities reached a maximum approximately 8 days posttreatment. Early changes in tumor sodium and apparent diffusion coefficient values were predictive of subsequent tumor shrinkage, which occurred approximately 10 days later. Overall, therapeutical induced changes in sodium and diffusion values were found to have similar dynamic and spatial changes. These findings suggest that these imaging modalities detected similar early cellular changes after treatment. The results of this study support the continued clinical testing of diffusion MRI for evaluation of early tumor treatment response and demonstrate the complementary insights of sodium MRI for oncology applications.

Background: The accumulation of intracellular sodium during myocardial ischemia couples an inappropriate calcium influx and depressed cardiac recovery during subsequent reperfusion. The effects of the selective sodium/ hydrogen exchange inhibitor HOE 694 are evaluated during myocardial ischemia and reperfusion., Methods: Ten isolated rat hearts were subjected to a 2-minute infusion of St. Thomas' cardioplegia +/- 1 mumol/L HOE 694 followed by 50 minutes' normothermic (37 degrees C) global ischemia. Intracellular sodium accumulation was continuously measured using triple quantum filtered 23Na nuclear magnetic resonance spectroscopy without chemical shift reagents. Hemodynamic variables were assessed before and after ischemia., Results: The addition of 1 mumol/L HOE 694 to St. Thomas cardioplegic solution (n = 5) attenuated the accumulation of intracellular sodium after 50 minutes' ischemia (160.5% +/- 9.1% versus 203.4% +/- 10.9% [mean +/- standard error], HOE 694 versus control, respectively; p = 0.014) and after the initial reperfusion period (first 30 minutes) (288.7% +/- 10.2% versus 335.9% +/- 10.3%; p = 0.008). HOE 694-treated hearts showed significantly improved postischemic recovery of left ventricular developed pressure (53.5% +/- 8.4% versus 26.4% +/- 6.6%; p = 0.036) and rate-pressure product (40.2% +/- 6.9% versus 13.2% +/- 5%; p = 0.014). Postischemic recovery of coronary flow was not significantly different between the two groups (68.6% +/- 5.9% versus 55.5% +/- 4.6%, HOE 694 versus control, respectively; p = 0.11)., Conclusions: The addition of 1 mumol/L HOE 694 to cardioplegic solution attenuates the increase of intracellular sodium during myocardial ischemia and early reperfusion. This is coupled with an improved recovery of contractile function, possibly as a result of decreased sodium and calcium overload of ischemic myocardium.

A class of fast magnetic spectroscopic imaging methods using continuously oscillating gradients for four-dimensional (three spatial and one spectral) localization is introduced. Sampling may start immediately following the application of an RF excitation pulse, thus enabling measurement of spin density, chemical shift, and relaxation rates of short-T2 species. For spatial localization, steady-state sinusoidal gradient waveforms are used to sample a ball in k space. The two types of trajectories presented include: (1) continuously oscillating gradients with continuously rotating direction used for steady-state free-precession imaging and (2) continuously oscillating gradients followed by a spoiler directed along discrete projections. Design criteria are given and spatial-spectral and spatial-temporal reconstruction methods are developed. Theoretical point-spread functions and signal-to-noise ratios are derived while considering T2*, off-resonance effects, and RF excitation options. Experimental phantom, in vivo, and in vitro 1H and 23Na images collected at 2.35 T are presented. The 1H images were acquired with isotropic spatial resolution ranging from 0.03 to 0.27 cm3 and gradient-oscillation frequencies ranging from 600 to 700 Hz, thus allowing for the separation of water and lipid signals within a voxel. The 23Na images, acquired with 500 and 800 Hz gradient waveforms and 0.70 cm3 isotropic resolution, were resolved in the time domain, yielding spatially localized FIDs.