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• W4366996238 abstract "<italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>Objective:</i> Hyperpolarized [1- <sup xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>13</sup> C]-pyruvate magnetic resonance imaging is an emerging metabolic imaging method that offers unprecedented spatiotemporal resolution for monitoring tumor metabolism <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>in vivo.</i> To establish robust imaging biomarkers of metabolism, we must characterize phenomena that may modulate the apparent pyruvate-to-lactate conversion rate ( <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL)</i> . Here, we investigate the potential effect of diffusion on pyruvate-to-lactate conversion, as failure to account for diffusion in pharmacokinetic analysis may obscure true intracellular chemical conversion rates. <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>Methods:</i> Changes in hyperpolarized pyruvate and lactate signal were calculated using a finite-difference time domain simulation of a two-dimensional tissue model. Signal evolution curves with intracellular <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL</i> values from 0.02 to 1.00 s <sup xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>-1</sup> were analyzed using spatially invariant one-compartment and two-compartment pharmacokinetic models. A second spatially variant simulation incorporating compartmental instantaneous mixing was fit with the same one-compartment model. <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>Results:</i> When fitting with the one-compartment model, apparent <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL</i> underestimated intracellular <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL</i> by approximately 50% at an intracellular <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL</i> of 0.02 s <sup xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>-1</sup> . This underestimation increased for larger <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL</i> values <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>.</i> However, fitting the instantaneous mixing curves showed that diffusion accounted for only a small part of this underestimation. Fitting with the two-compartment model yielded more accurate intracellular <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>k_PL</i> values. <italic xmlns:mml=http://www.w3.org/1998/Math/MathML xmlns:xlink=http://www.w3.org/1999/xlink>Significance:</i> This work suggests diffusion is not a significant rate-limiting factor in pyruvate-to-lactate conversion given that our model assumptions hold true. In higher order models, diffusion effects may be accounted for by a term characterizing metabolite transport. Pharmacokinetic models used to analyze hyperpolarized pyruvate signal evolution should focus on carefully selecting the analytical model for fitting rather than accounting for diffusion effects." @default.
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• W4366996238 date "2023-10-01" @default.
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• W4366996238 title "A Simulation of the Effects of Diffusion on Hyperpolarized [1-¹³C]-Pyruvate Signal Evolution" @default.
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• W4366996238 doi "https://doi.org/10.1109/tbme.2023.3269665" @default.
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