Slice profile effects on quantitative analysis of hyperpolarized pyruvate

Abstract

Magnetic resonance imaging of hyperpolarized pyruvate provides a new imaging biomarker for cancer metabolism, based on the dynamic in vivo conversion of hyperpolarized pyruvate to lactate. Methods for quantification of signal evolution need to be robust and reproducible across a range of experimental conditions. Pharmacokinetic analysis of dynamic spectroscopic imaging data from hyperpolarized pyruvate and its metabolites generally assumes that signal arises from ideal rectangular slice excitation profiles. In this study, we examined whether this assumption could lead to bias in kinetic analysis of hyperpolarized pyruvate and, if so, whether such a bias can be corrected. A Bloch‐McConnell simulator was used to generate synthetic data using a known set of “ground truth” pharmacokinetic parameter values. Signal evolution was then analyzed using analysis software that either assumed a uniform slice profile, or incorporated information about the slice profile into the analysis. To correct for slice profile effects, the expected slice profile was subdivided into multiple sub‐slices to account for variable excitation angles along the slice dimension. An ensemble of sub‐slices was then used to fit the measured signal evolution. A mismatch between slice profiles used for data acquisition and those assumed during kinetic analysis was identified as a source of quantification bias. Results indicate that imperfect slice profiles preferentially increase detected lactate signal, leading to an overestimation of the apparent metabolic exchange rate. The slice profile‐correction algorithm was tested in simulation, in phantom measurements, and applied to data acquired from a patient with prostate cancer. The results demonstrated that slice profile‐induced biases can be minimized by accounting for the slice profile during pharmacokinetic analysis. This algorithm can be used to correct data from either single or multislice acquisitions.

Modeling hyperpolarized lactate signal dynamics in cells, patient‐derived tissue slice cultures and murine models

“…Our fitting approach used a hybrid discrete‐continuous model that specifically includes RF flip angle compensation and can ideally account for these large flip angles. Although the calibration of the RF coil was performed regularly, the flip angle compensation becomes challenging in the presence of flow and RF coil edge or slice profile effects 29 …”

Multi‐band echo‐planar spectroscopic imaging of hyperpolarized 13C probes in a compact preclinical PET/MR scanner

“…Only pyruvate and lactate were considered to be of primary interest for this initial study, although future work could implement revised pulses designed to accurately capture signals from alanine. We also observe that the slice profiles are imperfect, which could affect experimental results 15,16 . Pulses were also tested in EPSI mode using a 3D‐printed multi‐chamber phantom, with individual compartments containing enriched aqueous solutions of [ 13 C]formate, [1‐ 13 C]alanine, and [1‐ 13 ]lactate, respectively.…”

“…We also observe that the slice profiles are imperfect, which could affect experimental results. 15,16 Pulses were also tested in EPSI mode using a 3D-printed multi-chamber phantom, with individual compartments containing enriched aqueous solutions of [ 13 C]formate, [1-13 C]alanine, and [1-13 ]lactate, respectively.…”

The effect of transmit B1 inhomogeneity on hyperpolarized [1‐13C]‐pyruvate metabolic MR imaging biomarkers

“…In this work, we consider two PK models. 4,19,22 Model A (Equation 1) contains two chemical pools (HP pyruvate and lactate) and one physical compartment. This precursor-product relationship between pyruvate and lactate is an approximation that assumes all observed F I G U R E 1 The electromagnetically transparent B 1 + field sensitivity bench measurement setup was used to produce consistent and repeatable positioning and hand measurements.…”

“…In this work, we consider two PK models. 4,19,22 Model A (Equation 1) contains two chemical pools (HP pyruvate and lactate) and one physical compartment. This precursor-product relationship between pyruvate and lactate is an approximation that assumes all observed…”