Analyzing equilibrium water exchange between myocardial tissue compartments using dynamical two‐dimensional correlation experiments combined with manganese‐enhanced relaxography

Abstract

Water compartments were identified and equilibrium water exchange was studied in excised rat myocardium enriched with intracellular manganese (Mn 2؉ ). Standard relaxographic measurements were supplemented with diffusion-T 2 and T 1 -T 2 correlation measurements. In nonenriched myocardium, one T 1 component (800 ms) and three T 2 components (32, 120, and 350 ms) were identified. The correlation measurements revealed fast-and slow-diffusing water fractions with mean diffusion coefficients of 1.2 ؋ 10 -5 and 3.0 ؋ 10 -5 cm 2 s -1 . The two shortest T 2 components, which had different diffusivities, both originated from water in intracellular compartments. A component with longer relaxation time (T 1 Ϸ 2200 ms; T 2 Ϸ 1200 ms), originating from extra-tissue water, was also observed. The presence of this component may lead to erroneous estimations of water exchange rates from multiexponential relaxographic analyses of excised tissues. The tissue T 1 value is strongly reduced with increasing enrichment of Mn 2؉ , and eventually a second tissue T 1 component emerges, indicating a shift in the equilibrium water exchange between intra-and extracellular compartments from the fast-exchange limit to the slow-exchange regime. Using a two-site water exchange analysis, the lifetime of intracellular water, In biological tissues water is found in different compartments. In addition, equilibrium water exchange takes place between these compartments. In a single pixel of a proton MR image the observed signal is therefore a sum of signals from water molecules originating from different magnetic environments. In particular, since the MR contrast agent (CA) does not distribute homogeneously in the tissue, intercompartmental equilibrium water exchange can significantly affect the quantitative analysis of various in vivo MR parameters. One method of investigating equilibrium water exchange is to take advantage of the differences in the relaxation times, T i (i ϭ 1 or 2 for longitudinal or transverse relaxation, respectively) between tissue compartments in the presence of a contrast agent (CA) (1), known as "relaxography." The observed relaxation behavior will depend on the difference in relaxation rate between compartments, and to which extent the water in other compartments can access the CA through equilibrium water exchange. Biological tissue has intracellular (ic) and extracellular (ec) water compartments, with relaxation rates (R i ϭ 1/T i ) of R i-ic and R i-ec , respectively. The ec compartment further contains the intravascular (iv) and interstitial (is) compartments, with respective relaxation rates of R i-iv and R i-is. Depending on the type of CA used, equilibrium water exchange between some or all of these compartments have to be taken into consideration when analyzing an MR image.In the last decade there has been a growing interest in the use of manganese-enhanced MRI (MEMRI) to investigate tissue function and cell viability (2). In myocardium, manganese ions (Mn 2ϩ ) are known to enter the cell through calcium (Ca 2ϩ ) ch...

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