Diffusion MR of hyperpolarized 13C molecules in solution

Abstract

We combined the high MR signal enhancement achieved using dissolution dynamic nuclear polarization (DNP) with a pulsed gradient double spin echo diffusion MR sequence to rapidly and accurately measure the diffusion coefficients of various hyperpolarized 13C molecules in solution. Furthermore, with a diffusion-weighted imaging sequence we generate diffusion coefficient maps of multiple hyperpolarized metabolites simultaneously. While hyperpolarized experiments can measure rapid, non-equilibrium processes by avoiding signal averaging, continuous signal loss due to longitudinal relaxation (T1) complicates quantitation. By correcting for this signal loss, we demonstrate the feasibility of using hyperpolarized 13C diffusion weighted MR to accurately measure real-time (seconds) molecular transport phenomena. Potential applications include rapidly measuring molecular binding, cellular membrane transport, in vivo metabolite distribution and establishing a magnetic field independent hyperpolarized parameter.

Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

“…Previous studies have quantified these non-diffusion related signal changes and corrected the diffusion weighted acquisitions accordingly [10,11]. To simplify the quantification of the diffusion coefficients, multiple interspersed normalization scans were acquired temporally close to the diffusion weighted scans and thereby eliminate the effects of these non-diffusion weighted signal changes.…”

“…1a [10]. The pulsed gradient double spin echo sequence was chosen for the diffusion weighting of hyperpolarized 13 C metabolites, given that it has several advantages.…”

“…Recently, there have been several publications that have used diffusion weighted MR to measure the diffusion coefficients of hyperpolarized 13 C metabolites, in solution [10], in cell suspensions [11] and in vivo [12–14]. These studies showed how changes in the ADCs could indicate the extra- and intracellular localization of the hyperpolarized 13 C metabolites.…”

Chemistry and biochemistry of13C hyperpolarized magnetic resonance using dynamic nuclear polarization

“…For the purposes of quantifying in vivo kinetics, it is important to note that relaxation parameters are difficult to assess for different tissues and this must be accounted for to develop quantitative rates. Diffusion and perfusion of substrates as well as products 64,121,209 will also influence the observed signals and these limitations must be addressed to calculate absolute rates in vivo . While rates, in the classical sense, are important for understanding the underlying biochemical mechanism of conversion, a high range of contrast between normal and malignant tissues can be determined using simple approaches such as resonance ratios.…”

Mis‐estimation and bias of hyperpolarized apparent diffusion coefficient measurements due to slice profile effects

“…While it did not completely mitigate mis-estimation over the entire ADC range, an exhaustive search jointly optimizing for both b-value ordering and b-values may be able to further reduce this bias. Prior work has largely avoided the bias introduced by slice profile effects by employing a mixed b-value ordering scheme (12), placing the transition regions where there is little to no hyperpolarized signal (10), or by acquiring multiple b = 0 images (8,9,22). While the multiple b = 0 approach implicitly accounts for slice profile effects, it increases the scan time and makes inefficient use of the hyperpolarization.…”