Dual Component Analysis for In Vivo T₂* Decay of Hyperpolarized ¹³C Metabolites

PURPOSE: To investigate the exchange and redistribution of hyperpolarized ¹³C metabolites between different pools by temporally analyzing the relative fraction of dual T₂* components of hyperpolarized ¹³C metabolites. MATERIALS AND METHODS: A dual exponential decay analysis of T₂* is performed for [1-¹³C] pyruvate and [1-¹³C] lactate using nonspatially resolved dynamic ¹³C MR spectroscopy from mice brains with tumors (n = 3) and without (n = 4) tumors. The values of shorter and longer T₂* components are explored when fitted from averaged spectrum and temporal variations of their fractions. RESULTS: The T₂* values were not significantly different between the tumor and control groups, but the fraction of longer T₂* [1-¹³C] lactate components was more than 10% in the tumor group over that of the controls (P < 0.1). The fraction of shorter T₂* components of [1-¹³C] pyruvate showed an increasing tendency while that of the [1-¹³C] lactate was decreasing over time. The slopes of the changing fraction were steeper for the tumor group than the controls, especially for lactate (P < 0.01). In both pyruvate and lactate, the fraction of the shorter T₂* component was always greater than the longer T₂* component over time. CONCLUSIONS: The exchange and redistribution of pyruvate and lactate between different pools was investigated by dual component analysis of the free induction decay signal from hyperpolarized ¹³C experiments. Tumor and control groups showed differences in their fractions rather than the values of longer and shorter T₂* components. Fraction changing dynamics may provide an aspect for extravasation and membrane transport of pyruvate and lactate, and will be useful to determine the appropriate time window for acquisition of hyperpolarized ¹³C images.

Alternating Acquisition Technique for Quantification of in vitro Hyperpolarized 1-13C Pyruvate Metabolism

PURPOSE: To develop a technique for quantifying the 13C-metabolites by performing frequency-selective hyperpolarized 13C magnetic resonance spectroscopy (MRS) in vitro which combines simple spectrally-selective excitation with spectrally interleaved acquisition. METHODS: Numerical simulations were performed with varying noise level and K(p) values to compare the quantification accuracies of the proposed and the conventional methods. For in vitro experiments, a spectrally-selective excitation scheme was enabled by narrow-band radiofrequency (RF) excitation pulse implemented into a free-induction decay chemical shift imaging (FIDCSI) sequence. Experiments with LDH / NADH enzyme mixture were performed to validate the effectiveness of the proposed acquisition method. Also, a modified two-site exchange model was formulated for metabolism kinetics quantification with the proposed method. RESULTS: From the simulation results, significant increase of the lactate peak signal to noise ratio (PSNR) was observed. Also, the quantified K(p) value from the dynamic curves were more accurate in the case of the proposed acquisition method compared to the conventional non-selective excitation scheme. In vitro experiment results were in good agreement with the simulation results, also displaying increased PSNR for lactate. Fitting results using the modified two-site exchange model also showed expected results in agreement with the simulations. CONCLUSION: A method for accurate quantification of hyperpolarized pyruvate and the downstream product focused on in vitro experiment was described. By using a narrow-band RF excitation pulse with alternating acquisition, different resonances were selectively excited with a different flip angle for increased PSNR while the hyperpolarized magnetization of the substrate can be minimally perturbed with a low flip angle. Baseline signals from neighboring resonances can be effectively suppressed to accurately quantify the metabolism kinetics.

Determination of Optimal Scan Time for the Measurement of Downstream Metabolites in Hyperpolarized 13C MRSI

PURPOSE: For a single time-point hyperpolarized 13C magnetic resonance spectroscopy imaging (MRSI) of animal models, scan-time window after injecting substrates is critical in terms of signal-to-noise ratio (SNR) of downstream metabolites. Prescans of time-resolved magnetic resonance spectroscopy (MRS) can be performed to determine the scan-time window. In this study, based on two-site exchange model, protocol-specific simulation approaches were developed for 13C MRSI and the optimal scan-time window was determined to maximize the SNR of downstream metabolites. MATERIALS AND METHODS: The arterial input function and conversion rate constant from injected substrates (pyruvate) to downstream metabolite (lactate) were precalibrated, based on pre-scans of time-resolved MRS. MRSI was simulated using twosite exchange model with considerations of scan parameters of MRSI. Optimal scantime window for mapping lactate was chosen from simulated lactate intensity maps. The performance was validated by multiple in vivo experiments of BALB/C nude mice with MDA-MB-231 breast tumor cells. As a comparison, MRSI were performed with other scan-time windows simply chosen from the lactate signal intensities of prescan time-resolved MRS. RESULTS: The optimal scan timing for our animal models was determined by simulation, and was found to be 15 s after injection of the pyruvate. Compared to the simple approach, we observed that the lactate peak signal to noise ratio (PSNR) was increased by 230%. CONCLUSIONS: Optimal scan timing to measure downstream metabolites using hyperpolarized 13C MRSI can be determined by the proposed protocol-specific simulation approaches.

Influencia de la difusión en imágenes de resonancia magnética de gases / Diffusion influence on gas magnetic resonance imaging

La resolución en experimentos de resonancia magnética nuclear (RMN) con gases que hacen uso de gradientes de campo magnético, suele verse reducida debido a la rápida difusión de los mismos. En este artículo se presenta una solución a este problema basada en la mezcla de gases hiperpolarizados con láser (3He o Xe) con otros gases más pesados o más ligeros. De este modo, el coeficiente de difusión es modificado hasta en un orden de magnitud. La señal de imágenes en una dimensión de 3He es descrita en función de la concentración en una mezcla binaria de gases, y se muestra la existencia de una concentración óptima para ciertos parámetros de resolución en las imágenes. Los experimentos muestran que con dicha concentración, se consiguen ganancias de hasta 10 veces la señal del 3He puro, concordando con la teoría para difusión no restringida. Finalmente, se ilustra el método en imágenes 2D de 3He mezclado con diversos gases en un pulmón, que contiene cavidades restrictivas de diversos tamaños.

Resolution of nuclear magnetic resonance (NMR) experiments with gases employing magnetic field gradients is greatly reduced due to their rapid diffusion. In this paper, we present a solution to this problem basedon a mixture of gases hyperpolarized with laser (LP) (3He or Xe) with other heavier and lighter buffer gases. In this way the diffusion coefficient can be modified up to one order of magnitude. The signal of 1D images of 3He is described as a function of the concentration in a binary mixture of gases, and we show the existence of an optimum concentration for some image resolution parameters. Experimentsshow that with this concentration, the signal can gain an increase of up to 10 times the signal with pure 3He, in agreement with the theory of non-restricted diffusion. Finally, the method is illustrated with 2D images of LP-3He mixed with several gases in a lung containing restrictive cavities with different sizes.

A resolução nos experimentos de ressonância magnética nuclear (RMN) com gases que usam gradientes de campo magnético, frequentemente é reduzida por causa da rápida difusão dos mesmos. Neste artigo apresenta-se uma solução para este problema baseada na mistura de gases hiperpolarizados com laser (3He ou Xe) com outros gases mais pesados ou mais leves. Desta forma, o coeficiente de difusão é modificado até uma ordem de magnitude. O sinal de imagensnuma dimensão de 3He é descrita em função da concentração numa mistura binária de gases, e se mostra a existência de uma concentraçãootimizada para certos parâmetros de resolução das imagens. Os experimentos mostram que com essa concentração, conseguem-se ganânciasde até 10 vezes o sinal do 3He puro, concordando com a teoria para a difusão não restringida. Finalmente, ilustra-se o método em imagens2D de 3He misturando com diversos gases num pulmão, que contem cavidades restritivas de diversos tamanhos.