pH Dependence of <i>T</i>₂ for Hyperpolarizable ¹³C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging

• Main Authors: Martin Grashei, Christian Hundshammer, Frits H. A. van Heijster, Geoffrey J. Topping, Franz Schilling
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Pharmaceuticals
• Subjects: <i>T</i>₂ relaxation time constant; pH; [1-¹³C]pyruvate; [1-¹³C]acetate; ¹³C-labeled biomolecules; hyperpolarization
• Online Access: https://www.mdpi.com/1424-8247/14/4/327

Hyperpolarized ¹³C magnetic resonance imaging often uses spin-echo-based pulse sequences that are sensitive to the transverse relaxation time <i>T</i>₂. In this context, local <i>T</i>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 <i>T</i>₂) of six ¹³C-labelled molecules. We obtained minimum and maximum <i>T</i>₂ values within pH 1–13 at 14.1 T: [1‑¹³C]acetate (<i>T</i>_2,min = 2.1 s; <i>T</i>_2,max = 27.7 s), [1-¹³C]alanine (<i>T</i>_2,min = 0.6 s; <i>T</i>_2,max = 10.6 s), [1,4‑¹³C₂]fumarate (<i>T</i>_2,min = 3.0 s; <i>T</i>_2,max = 18.9 s), [1-¹³C]lactate (<i>T</i>_2,min = 0.7 s; <i>T</i>_2,max = 12.6 s), [1‑¹³C]pyruvate (<i>T</i>_2,min = 0.1 s; <i>T</i>_2,max = 18.7 s) and ¹³C-urea (<i>T</i>_2,min = 0.1 s; <i>T</i>_2,max = 0.1 s). At 7 T, <i>T</i>₂‑variation in the physiological pH range (pH 6.8–7.8) was highest for [1‑¹³C]pyruvate (Δ<i>T</i>₂ = 0.95 s/0.1pH) and [1‑¹³C]acetate (Δ<i>T</i>₂ = 0.44 s/0.1pH). Concentration, salt concentration, and temperature alterations caused <i>T</i>₂ 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 <i>T</i>₂-mapping were demonstrated with 1.6 pH units accuracy in vitro. A strong proton exchange-based pH dependence of <i>T</i>₂ suggests that pH alterations potentially influence signal strength for hyperpolarized ¹³C-acquisitions.