pH Dependence of T(2) for Hyperpolarizable (13)C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging

Hyperpolarized (13)C magnetic resonance imaging often uses spin-echo-based pulse sequences that are sensitive to the transverse relaxation time T(2). In this context, local T(2)-changes might introduce a quantification bias to imaging biomarkers. Here, we investigated the pH dependence of the apparent transverse relaxation time constant (denoted here as T(2)) of six (13)C-labelled molecules. We obtained minimum and maximum T(2) values within pH 1–13 at 14.1 T: [1-(13)C]acetate (T(2,min) = 2.1 s; T(2,max) = 27.7 s), [1-(13)C]alanine (T(2,min) = 0.6 s; T(2,max) = 10.6 s), [1,4-(13)C(2)]fumarate (T(2,min) = 3.0 s; T(2,max) = 18.9 s), [1-(13)C]lactate (T(2,min) = 0.7 s; T(2,max) = 12.6 s), [1-(13)C]pyruvate (T(2,min) = 0.1 s; T(2,max) = 18.7 s) and (13)C-urea (T(2,min) = 0.1 s; T(2,max) = 0.1 s). At 7 T, T(2)-variation in the physiological pH range (pH 6.8–7.8) was highest for [1-(13)C]pyruvate (ΔT(2) = 0.95 s/0.1pH) and [1-(13)C]acetate (ΔT(2) = 0.44 s/0.1pH). Concentration, salt concentration, and temperature alterations caused T(2) variations of up to 45.4% for [1-(13)C]acetate and 23.6% for [1-(13)C]pyruvate. For [1-(13)C]acetate, spatially resolved pH measurements using T(2)-mapping were demonstrated with 1.6 pH units accuracy in vitro. A strong proton exchange-based pH dependence of T(2) suggests that pH alterations potentially influence signal strength for hyperpolarized (13)C-acquisitions.