In vivo measurement of apparent diffusion coefficients of hyperpolarized ¹³C-labeled metabolites

Area of Science:

• Metabolic Imaging
• Biophysics
• Physiology

Background:

• Hyperpolarized magnetic resonance spectroscopy (MRS) offers real-time metabolic insights.
• Combining hyperpolarized MRS with diffusion weighting (dw-MRS) enables apparent diffusion coefficient (ADC) measurement.
• ADC values indicate whether metabolites are intracellular or extracellular.

Purpose of the Study:

• To implement and validate a dw-MRS technique for in vivo metabolite localization.
• To determine the ADCs of hyperinjected [1-13C]pyruvate and its metabolites in rat muscle.
• To differentiate the intra- vs. extracellular distribution of pyruvate, lactate, and alanine.

Main Methods:

• A slice-selective pulsed-gradient spin echo sequence was used for dw-MRS acquisition in rat muscle.
• Hyperpolarized [1-13C]pyruvate was injected intravenously.
• An optimal control optimized universal-rotation pulse minimized signal loss; interleaved non-dw spectra corrected for signal decay.

Main Results:

• ADC values for [1-13C]lactate (0.4–0.7 µm²/ms) and [1-13C]alanine (0.4–0.9 µm²/ms) were significantly lower than for [1-13C]pyruvate (1.1–1.5 µm²/ms).
• Lower ADCs for lactate and alanine suggest restricted diffusion, consistent with intracellular localization.
• Higher ADC for pyruvate indicates its presence in both intracellular and extracellular compartments.

Conclusions:

• Diffusion-weighted hyperpolarized MRS effectively distinguishes between intracellular and extracellular metabolites in vivo.
• This method provides valuable insights into metabolic compartmentalization within tissues.
• The findings confirm lactate and alanine are primarily intracellular, while pyruvate distributes more broadly.