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PurposeMagnetic resonance spectroscopy of hyperpolarized substrates allows for the observation of label exchange catalyzed by enzymes providing a powerful tool to investigate tissue metabolism and potentially kinetics in vivo. However, the accuracy of current methods to calculate kinetic parameters has been limited by T1 relaxation effects, extracellular signal contributions, and reduced precision at lower signal-to-noise ratio.Theory and methodsTo address these challenges, we investigated a new modeling technique using metabolic activity decomposition-stimulated echo acquisition mode. The metabolic activity decomposition-stimulated echo acquisition mode technique separates exchanging from nonexchanging metabolites providing twice the information as conventional techniques.ResultsThis allowed for accurate measurements of rates of conversion and of multiple T1 values simultaneously using a single acquisition.ConclusionThe additional measurement of T1 values for the reaction metabolites provides further biological information about the cellular environment of the metabolites. The new technique was investigated through simulations and in vivo studies of transgenic mouse models of cancer demonstrating improved assessments of kinetic rate constants and new T1 relaxation value measurements for hyperpolarized (13) C-pyruvate, (13) C-lactate, and (13) C-alanine.

PurposeTo implement and evaluate combined parallel magnetic resonance imaging (MRI) and partial Fourier acquisition and reconstruction for rapid hyperpolarized carbon-13 ((13) C) spectroscopic imaging. Short acquisition times mitigate hyperpolarized signal losses that occur due to T1 decay, metabolism, and radiofrequency (RF) saturation. Human applications additionally require rapid imaging to permit breath-holding and to minimize the effects of physiologic motion.Materials and methodsNumerical simulations were employed to validate and characterize the reconstruction. In vivo MR spectroscopic images were obtained from a rat following injection of hyperpolarized (13) C pyruvate using an 8-channel array of carbon-tuned receive elements.ResultsFor small spectroscopic matrix sizes, combined parallel imaging and partial Fourier undersampling resulted primarily in decreased spatial resolution, with relatively less visible spatial aliasing. Parallel reconstruction qualitatively restored lost image detail, although some pixel spectra had persistent numerical error. With this technique, a 30 × 10 × 16 matrix of 4800 3D MR spectroscopy imaging voxels from a whole rat with isotropic 8 mm(3) resolution was acquired within 11 seconds.ConclusionParallel MRI and partial Fourier acquisitions can provide the shorter imaging times and wider spatial coverage that will be necessary as hyperpolarized (13) C techniques move toward human clinical applications.

High resolution compressed sensing hyperpolarized (13)C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in (13)C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D (13)C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor-bearing rats following injection of hyperpolarized [1-(13)C]-pyruvate using a 3T scanner. The (13)C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high-resolution compressed sensing (13)C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct (13)C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of (13)C metabolic profiles between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue.

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of (13)C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-(13)C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-(13)C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in (13)C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of (13)C metabolism in vivo at very high signal-to-noise ratio (SNR). In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine whether the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+181±69%, P=.025) was measured when [1-(13)C]pyruvate was injected after DCA administration, and increased glutamate (+74±23%, P=.004), acetoacetate (+504±281%, P=.009) and acetylcarnitine (+377±157%, P=.003) were detected when [2-(13)C]pyruvate was used.

The use of in vivo 13C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active 13C substrates, allowing for rapid assessment of 13C metabolism in vivo. The present study applied hyperpolarized 13C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states.[1-13C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI).Significant differences in lactate to alanine ratio (P

The emerging ride-sourcing service has become an important element of urban mobility. A challenging question underlying the provision of such service is how and to what extent the built environment affects origin-destination (OD) travel flows. This paper employs the geographically weighted regression (GWR) model to analyze the OD-based ride-sourcing travel flow. It makes a comparison with the existing ordinary least square (OLS) model and spatial autocorrelation model (SAM). We have collected ride-sourcing order data in Hangzhou, China, to provide an accurate source for acquiring ride-sourcing travel flow. We investigate the effects of the residential area, points of interest (POIs), and transit stations on ride-sourcing travel flow among traffic analysis zones (TAZs). The results show the following: (a) GWR has better goodness-of-fit than SAM and OLS. (b) Residential area, enterprise, and bus stations have positive correlations with ride-sourcing OD flows, but education and subway stations have negative correlations. We have further investigated the issue and found that it is not a causal relationship between the bus station and OD flow, due to collinearity between the two variables. The bus station builds on locations with high demand, but its capacity is not large enough to reduce the ride-sourcing flow to a low level, which results in a positive coefficient. (c) Based on the estimated coefficients, the prediction of ride-sourcing flows is feasible, supporting the impact analysis for urban land use and transportation planning. This paper contributes to understanding OD-based ride-sourcing travel flow distributions and provides a framework of long-term OD flow prediction for urban land use and transportation planning., Author(s): Chuqiao Chen [1]; Simon Hu [2]; Washington Y. Ochieng [3]; Na Xie [4]; Xiqun (Michael) Chen (corresponding author) [1] 1. Introduction The government agencies and urban planning department attach [...]