The use of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate (TmDOTP5-) as an in vivo 23Na NMR shift reagent for rat liver was evaluated by collecting interleaved 23Na and 31P spectra. Infusion of 80 mM TmDOTP5- without added Ca2+ produced baseline-resolved peaks from intra- and extracellular sodium without producing any changes in phosphate metabolite resonances or intracellular pH. Several key physiological parameters measured in parallel groups of animals confirmed that liver physiology is largely unaffected by this shift reagent. A direct comparison of TmDOTP5- versus DyTTHA3- showed that after infusion of 5-8 times more DyTTHA3-, the extracellular sodium peak shifted by the same amount as with TmDOTP5-, but the two 23Na resonances were very broad and not resolved. The baseline-resolved peaks with TmDOTP5- allowed us to measure the in vivo T1 and T2 relaxation characteristics of intra- and extracellular Na+. The measured T1, T2s, and T2f values and the relative contributions from the slow and fast T2 components for intracellular Na+ in liver did not differ significantly from the values reported for perfused frog heart. The T1 and T2 relaxation curves of the extracellular Na+ resonances fit a monoexponential function. Analysis of the relative contribution of the fast- and slow-relaxing T2 components from intracellular Na+ resulted in a calculated visibility factor of 69 +/- 4% and the intracellular Na+ concentration calculated from the NMR peak intensity ratio, the measured visibility factor, and literature values of intra- and extracellular volume was 19 mM. These results indicate that TmDOTP5- promises to be quite useful as an in vivo shift reagent for liver and other organs.

The most commonly applied model for the description of diffusion-weighted imaging (DWI) data in perfused organs is bicompartmental intravoxel incoherent motion (IVIM) analysis. In this study, we assessed the ground truth of underlying diffusion components in healthy abdominal organs using an extensive DWI protocol and subsequent computation of apparent diffusion coefficient 'spectra', similar to the computation of previously described T 2 relaxation spectra. Diffusion datasets of eight healthy subjects were acquired in a 3-T magnetic resonance scanner using 68 different b values during free breathing (equidistantly placed in the range 0-1005 s/mm 2 ). Signal intensity curves as a function of the b value were analyzed in liver, spleen and kidneys using nonnegative least-squares fitting to a distribution of decaying exponential functions with minimum amplitude energy regularization. In all assessed organs, the typical slow-and fast-diffusing com- In the first description of spin echoes in magnetic resonance (MR), it was noted that the observed echo amplitudes were not only determined by the relaxation times T 1 and T 2 , but also by diffusion. 1 In addition to the unwanted possible effect of diffusion on the measurement of relaxation times, the possibility of measurements of diffusion coefficients was also noted and experimentally realized shortly thereafter. 2 However, it was not until the mid-1980s that diffusion-weighted imaging (DWI) was developed and applied in vivo for the first time. 3 Since then, several models for diffusion in perfused biological tissues have been proposed, with intravoxel incoherent motion (IVIM) being the most established at present.In this model, a slow-decaying component, as a result of passive diffusion in the tissue, and a fast-decaying component, as a result of perfusion,

In vivo sodium-23 and hydrogen-1 magnetic resonance (MR) imaging and spectroscopy of the rat brain during infusion of the shift reagent thulium DOTP5- (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra[methylene phosphonate] was performed to assign the various peaks observed during infusion and to evaluate the shift reagent in discriminating tissue compartments. Na-23 spectra collected during the infusion showed two shifted peaks that were assigned to intravascular Na+ and extracellular muscle Na+, respectively, and one unshifted peak assigned to intra- and extracellular brain Na+ and cerebrospinal fluid Na+. These assignments were validated with H-1 and Na-23 MR imaging and Na-23 chemical shift imaging (CSI). The H-1 and Na-23 images showed that a surface coil placed on a rat head can detect a substantial amount of signal from muscle surrounding the skull. Na-23 CSI spectra from successive 1-mm-thick coronal sections indicated that the shift reagent did not cross the blood-brain barrier. The study also showed that bulk susceptibility shifts are quite small with Tm-DOTP5-. This reagent may be useful in determining compartmental Na+ concentrations and blood flow kinetics in brain and in examining the integrity of the blood-brain barrier.

Since transmembrane sodium gradient is essential to many cell functions, there is continuing interest in methods that differentiate intracellular and extracellular Na+. In the kidney, shift reagent (SR) aided 23Na magnetic resonance spectroscopy (MRS) has been successfully used only in isolated cells, tubules, and the perfused organ. In this report, we demonstrate for the first time that TmDOTP5- can be used to distinguish Na+ compartments in kidneys in vivo. Infusion of 80 mM TmDOTP5- without added Ca2+ produced three resolved 23Na resonances, which we have assigned to intracellular Na+, vascular Na+, and intraluminal Na+. In comparison, infusion of 400 mM DyTTHA3- produced two broad and unresolved resonances. The 31P spectra of the cellular high energy phosphate metabolites indicate that TmDOTP5- is safe for in vivo applications. Washout studies suggest that this SR displays renal clearance similar to that of MR imaging contrast agents. However, the glomerular filtration rate (GFR) in animals infused with TmDOTP5- was reduced by 49% compared with the GFR in control animals, perhaps due to the hypotensive effects of the SR. We conclude that TmDOTP5- is effectively cleared from the blood of live animals but that a different formulation will be required for clinical application.