Voxel-by-voxel correlations of perfusion, substrate, and metabolite signals in dynamic hyperpolarized¹³C imaging

Abstract

In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment of perfusion and metabolism in vivo. The pre-polarized mixture was administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts and imaged using an interleaved sequence with designed spectral-spatial pulses and flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed for tumour, kidney, and muscle regions of interest. The relationship between perfusion and hyperpolarized signal was explored on a voxel-by-voxel basis in various metabolically active tissues, including tumour, healthy kidneys, and skeletal muscle. Positive pairwise correlations between lactate, pyruvate, and HP001 observed in all 10 tumours suggested that substrate delivery was the dominant factor limiting the conversion of pyruvate to lactate in the tumour model used in this study. On the other hand, in cases where conversion is the limiting factor, such as in healthy kidneys, both pyruvate and lactate can act as excellent perfusion markers. In intermediate cases between the two limits, such as in skeletal muscle, some perfusion information may be inferred from the (pyruvate + lactate) signal distribution. Co-administration of pyruvate with a dynamic nuclear polarization (DNP) perfusion agent is an effective approach for distinguishing between slow metabolism and poor perfusion and a practical strategy for lactate signal normalization to account for substrate delivery, especially in cases of rapid pyruvate-to-lactate conversion and in poorly perfused regions with inadequate pyruvate signal-to-noise ratio for reliable determination of the lactate-to-pyruvate ratio. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetic resonance imaging with hyperpolarized agents: methods and applications

“…Several studies have also looked at biologic factors modulating the observed metabolic signals in breast cancer studies, including perfusion [178], cellular transport [179], and endogenous lactate and lactate dehydrogenase (LDH) concentrations [180]. Both perfusion and cellular expression of monocarboxylate transporters were important factors affecting the observed metabolic signals.…”

Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

“…Extravasation in Equation 1 follows a 2 physical compartment exchange model where is the rate constant for vascular exchange, and is the extravascular volume fraction. Rapid diffusion and cellular transport is assumed to homogenize interstitial space with the intracellular compartment where the enzymes that mediate this reaction reside . Therefore, this model permits chemical conversion of HP pyruvate into lactate only in the extravascular compartment.…”

Improved tolerance to off‐resonance in spectral‐spatial EPI of hyperpolarized [1‐13C]pyruvate and metabolites

“…A 1 M 13 C-bicarbonate phantom was imaged to examine the limitations of the pulse sequence used in our previous preclinical studies (20). A sliceselective spectroscopic acquisition (1.8 ms sinc pulse, 1 cm slice thickness, 16,384 points, 31.25 kHz bandwidth) was included as the third interleaf within each repetition time (TR) to measure the global frequency offset (22). A constant wait time was included at the end of each interleaf to ensure equal spacing within each TR.…”