pH Dependence of T₂ for Hyperpolarizable ¹³C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging

Hyperpolarized ¹³C magnetic resonance imaging often uses spin-echo-based pulse sequences that are sensitive to the transverse relaxation time T₂. In this context, local T₂-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 T₂) of six ¹³C-labelled molecules. We obtained minimum and maximum T₂ values within pH 1-13 at 14.1 T: [1-¹³C]acetate (T_2,min = 2.1 s; T_2,max = 27.7 s), [1-¹³C]alanine (T_2,min = 0.6 s; T_2,max = 10.6 s), [1,4-¹³C₂]fumarate (T_2,min = 3.0 s; T_2,max = 18.9 s), [1-¹³C]lactate (T_2,min = 0.7 s; T_2,max = 12.6 s), [1-¹³C]pyruvate (T_2,min = 0.1 s; T_2,max = 18.7 s) and ¹³C-urea (T_2,min = 0.1 s; T_2,max = 0.1 s). At 7 T, T₂-variation in the physiological pH range (pH 6.8-7.8) was highest for [1-¹³C]pyruvate (ΔT₂ = 0.95 s/0.1pH) and [1-¹³C]acetate (ΔT₂ = 0.44 s/0.1pH). Concentration, salt concentration, and temperature alterations caused T₂ variations of up to 45.4% for [1-¹³C]acetate and 23.6% for [1-¹³C]pyruvate. For [1-¹³C]acetate, spatially resolved pH measurements using T₂-mapping were demonstrated with 1.6 pH units accuracy in vitro. A strong proton exchange-based pH dependence of T₂ suggests that pH alterations potentially influence signal strength for hyperpolarized ¹³C-acquisitions.