pH Dependence of T1 for 13C-Labelled Small Molecules Commonly Used for Hyperpolarized Magnetic Resonance Imaging

Hyperpolarization is a method to enhance the nuclear magnetic resonance signal by up to five orders of magnitude. However, the hyperpolarized (HP) state is transient and decays with the spin-lattice relaxation time (T₁), which is on the order of a few tens of seconds. Here, we analyzed the pH-dependence of T₁ for commonly used HP ¹³C-labelled small molecules such as acetate, alanine, fumarate, lactate, pyruvate, urea and zymonic acid. For instance, the T₁ of HP pyruvate is about 2.5 fold smaller at acidic pH (25 s, pH 1.7, B₀=1 T) compared to pH close to physiological conditions (66 s, pH 7.3, B₀=1 T). Our data shows that increasing hydronium ion concentrations shorten the T₁ of protonated carboxylic acids of most of the analyzed molecules except lactate. Furthermore it suggests that intermolecular hydrogen bonding at low pH can contribute to this T₁ shortening. In addition, enhanced proton exchange and chemical reactions at the pK_a appear to be detrimental for the HP-state.     

On bijections of Lorentz manifolds,which leave the class of spacelike paths invariant

Suppose that (M, g) and (M′, g′) are Lorentz manifolds, and that f: M → M′ is a bijection, such that f and f^-1 preserve spacelike paths (f: M → M′ has this property, if for any spacelike path γ: J → M in (M ,g), the composition fγ: J → M′ is a spacelike path in (M′, g′)). Then f is a (manifold-) homeomorphism.This statement is the ‘spacelike’ version of an analogous ‘timelike’ theorem (Hawking, King and McCarthy [6] and Göbel [2] for strongly causal, and Malament [10] for general Lorentz manifolds).With this result it is possible to prove a conjecture of Göbel [3] which states that every bijection between time-orientable n-dimensional (n ? 3) Lorentz manifolds which preserves spacelike paths is a conformal C^∞-diffeomorphism.     

Coefficients of half-integral weight modular forms

In this paper, we study the distribution of the coefficients a(n) of half-integral weight modular forms modulo odd integers M. As a consequence, we obtain improvements of indivisibility results for the central critical values of quadratic twists of L-functions associated with integral weight newforms established in Ono and Skinner (Fourier coefficients of half-integral weight modular forms modulo ?, Ann. of Math. 147 (1998) 453-470). Moreover, we find a simple criterion for proving cases of Newman's conjecture for the partition function.     

Finsler cases of GF-space

Summary Finsler cases of the generalized-Finslerian structure associated with a product manifold are investigated. The indicatrix of any Finsler space thus obtained is found to be conformally flat in dimensionsN > 4. The cases where the indicatrix is of constant curvature are described in detail.     

Restricted 123-avoiding Baxter permutations and the Padovan numbers

Baxter studied a particular class of permutations by considering fixed points of the composite of commuting functions. This class is called Baxter permutations. In this paper we investigate the number of 123-avoiding Baxter permutations of length n that also avoid (or contain a prescribed number of occurrences of) another certain pattern of length k. In several interesting cases the generating function depends only on k and is expressed via the generating function for the Padovan numbers.     

Evidence for nonperturbative string symmetries

String theory appears to admit a group of discrete field transformations — calledS dualities — as exact nonperturbative quantum symmetries. Mathematically, they are rather analogous to the better-knownT duality symmetries, which hold perturbatively. In this Letter the evidence forS duality is reviewed and some speculations are presented.     

Super line bundles

Super line bundles over supermanifolds are introduced as natural generalizations of line bundles over smooth manifolds. Their classification in terms of their obstruction class and the representation of their Chern class in terms of a connection on the super line bundle are discussed. The case where the base supermanifold is De Witt is analyzed in detail, both in the supersmooth and complex superanalytic case.     

More Than 12 % Polarization and 20 Minute Lifetime of 15N in a Choline Derivative Utilizing Parahydrogen and a Rhodium Nanocatalyst in Water

Hyperpolarization techniques are key to extending the capabilities of MRI for the investigation of structural, functional and metabolic processes in vivo. Recent heterogeneous catalyst development has produced high polarization in water using parahydrogen with biologically relevant contrast agents. A heterogeneous ligand‐stabilized Rh catalyst is introduced that is capable of achieving ¹⁵N polarization of 12.2±2.7 % by hydrogenation of neurine into a choline derivative. This is the highest ¹⁵N polarization of any parahydrogen method in water to date. Notably, this was performed using a deuterated quaternary amine with an exceptionally long spin‐lattice relaxation time (T₁) of 21.0±0.4 min. These results open the door to the possibility of ¹⁵N in vivo imaging using nontoxic similar model systems because of the biocompatibility of the production media and the stability of the heterogeneous catalyst using parahydrogen‐induced polarization (PHIP) as the hyperpolarization method.     

Signal Amplification by Reversible Exchange (SABRE): From Discovery to Diagnosis

Signal amplification by reversible exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements possible. This technique has gained significant popularity because of its speed and simplicity. This Minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009 to the point in which 50 % ¹H polarization levels have been achieved in a di‐deuterio‐nicotinate, a key step in the pathway to potential clinical use. Simple routes to highly efficient ¹⁵N hyperpolarization and the creation of hyperpolarized long‐lived magnetic states are illustrated. To conclude, we describe how the recently reported SABRE‐RELAY approach offers a route for parahydrogen to hyperpolarize a much wider array of molecular scaffolds, such as amides, alcohols, carboxylic acids, and phosphates, than was previously thought possible. We predict that collectively these developments ensure that SABRE will significantly impact on both chemical analysis and the diagnosis of disease in the future.     

Rational Design of [13C,D14]Tert‐butylbenzene as a Scaffold Structure for Designing Long‐lived Hyperpolarized 13C Probes

Dynamic nuclear polarization (DNP) is a technique to polarize the nuclear spin population. As a result of the hyperpolarization, the NMR sensitivity of the nuclei in molecules can be dramatically enhanced. Recent application of the hyperpolarization technique has led to advances in biochemical and molecular studies. A major problem is the short lifetime of the polarized nuclear spin state. Generally, in solution, the polarized nuclear spin state decays to a thermal spin equilibrium, resulting in loss of the enhanced NMR signal. This decay is correlated directly with the spin‐lattice relaxation time T₁. Here we report [¹³C,D₁₄]tert‐butylbenzene as a new scaffold structure for designing hyperpolarized ¹³C probes. Thanks to the minimized spin‐lattice relaxation (T₁) pathways, its water‐soluble derivative showed a remarkably long ¹³C T₁ value and long retention of the hyperpolarized spin state.