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

Abstract

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 (T2,min = 2.1 s; T2,max = 27.7 s), [1-13C]alanine (T2,min = 0.6 s; T2,max = 10.6 s), [1,4‑13C2]fumarate (T2,min = 3.0 s; T2,max = 18.9 s), [1-13C]lactate (T2,min = 0.7 s; T2,max = 12.6 s), [1‑13C]pyruvate (T2,min = 0.1 s; T2,max = 18.7 s) and 13C-urea (T2,min = 0.1 s; T2,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.

Parahydrogen‐Polarized [1‐13C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging

“…Pyruvate polarized with PHIP shows a longer T 1 and shorter T 2 compared to d‐DNP in vitro, where the shortening of T 1 for d‐DNP is most likely caused by the paramagnetic impurities of the d‐DNP formulation. Given that T 2 of [1‐ 13 C]pyruvate is highly pH dependent, especially in the region of 6.5 – 7.5 [ 28 ] and, in addition, the solvent composition strongly affects its T 2 values [ 28 ] we also expect T 2 differences for the PHIP and d‐DNP preparations. Additionally, an increase in T 1 by using a deuterated solvent (110.9 s) versus non deuterated solvent (56.8 s) was shown for d‐DNP.…”

Spectrally selective bSSFP using off‐resonant RF excitations permits high spatiotemporal resolution 3D metabolic imaging of hyperpolarized [1‐13C]Pyruvate‐to‐[1‐13C]lactate conversion

“…Simulated bSSFP response profiles are approximations to in vivo conditions, in part due to choice of relaxation times, which were T 1 = 25 s and T 2 = 300 ms in this work, based on a literature review. Little published information is directly relevant to in vivo measurements at 7 T, and reported relaxation times vary between field strengths, between compounds, 17 between subjects in the same study 31 or in vitro conditions, between tissues, 32 with pH, 33 with temperature, 34 and with concentrations of the metabolite or salt, 34 macromolecules or other relaxation‐modulating compounds. Sensitivity to differences in relaxation times, thus, were also simulated.…”

Dynamic T2* relaxometry of hyperpolarized [1‐13C]pyruvate MRI in the human brain and kidneys

“…These studies noted that the short T 2 components of metabolites were driven by the intracellular matrices. 14 Other studies also showed [1- 13 C]lactate had very different apparent T 2 values between extracellular and intracellular compartments; that is, [1- 13 C]lactate has longer T 2 (1.7-2.2 s) 15 in a HP [1- 13 C]lactate injection study than that as a downstream metabolite (0.5-1.1 s) 16,17 in a HP [1- 13 C]pyruvate injection study. This provides evidence that the microenvironment may strongly influence the transverse relaxation of HP metabolites.…”