Application of flow sensitive gradients for improved measures of metabolism using hyperpolarized 13 c MRI

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Purpose A multiecho, field of view (FOV)‐oversampled k‐t spiral acquisition and direct iterative decomposition of water and fat with echo asymmetry and least‐squares estimation reconstruction is demonstrated to improve the stability of hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) in the presence of signal ambiguities attributed to low‐SNR (signal‐to‐noise‐ratio) species, local uncertainties in metabolite peaks, and echo‐to‐echo signal inconsistencies. Theory k‐t spiral acquisitions redistribute readout points to be more densely spaced radially in k‐space by acquiring an FOV and matrix that are oversampled by η. These more densely spaced spiral turns constitute effective intraspiral echoes and can supplement conventional interspiral echoes to improve spectral separation and reduce spectral cross‐talk to better resolve 13C‐labeled species for spectroscopic imaging. Methods Digital simulations and imaging phantom experiments were performed for a range of interspiral echo spacings and η using multiecho, k‐t spiral acquisitions. Image spectral cross‐talk artifacts were evaluated both qualitatively and quantitatively as the percent error in measured metabolite ratios. In vivo murine experiments evaluated the feasibility of multiecho, k‐t spiral [1‐13C]pyruvate MRSI to reduce spectral cross‐talk for 3 scenarios of different expected reconstruction stability. Results Digital simulations and imaging phantom experiments both demonstrated reduced or comparable image spectral cross‐talk and percent errors in measured metabolite ratios with increasing η and better choices of echo spacings. In vivo images displayed markedly reduced spectral cross‐talk in lactate images acquired with η = 7 versus η = 1. Conclusion The precision of hyperpolarized 13C metabolic imaging and quantification in the presence of low‐SNR species, local uncertainties in metabolite resonances, and echo‐to‐echo signal inconsistencies can be improved with the use of FOV‐oversampled k‐t spiral acquisitions.

T_{2}^{*}

decay. Additionally, although the 13 C

T_{2}^{*}

is relatively long,

T_{2}^{*}

decay presents a trade‐off between readout duration and spatial resolution. All spiral readouts in this work were designed to maximize SNR per unit time.…”

Section: Discussionmentioning

confidence: 99%

“…To maximize spiral SNR efficiency, the ratio of readout duration to

T_{2}^{*}

decay should be approximately 0.8 . Therefore, a 30‐ms readout duration was used for all simulations using preclinical gradient hardware specifications, thus assuming a realistic

T_{2}^{*}

. Gradient trajectory imperfections were corrected using a thin‐slice–based technique .…”

Section: Methodsmentioning

confidence: 99%

Improved reconstruction stability for chemical shift encoded hyperpolarized ¹³C magnetic resonance spectroscopic imaging using k‐t spiral acquisitions

Macdonald

Barton

Cox

et al. 2019

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“…The bipolar gradient can also induce a diffusion‐related signal loss of static spins. Gordon et al investigated the effects of a bipolar gradient in terms of diffusion sensitivity on static spins. However, the b‐value of the bipolar gradient used in this study was relatively low (∼13.3 s/mm 2 for 3.3 ms of the bipolar gradient), accounting for less than 2% signal loss in stationary tissues .…”

Section: Discussionmentioning

confidence: 99%

Flow‐suppressed hyperpolarized ¹³C chemical shift imaging using velocity‐optimized bipolar gradient in mouse liver tumors at 9.4 T

Lee

Joe

et al. 2016

“…A thermally polarized 13 C urea phantom was placed adjacent to the sample for calibration in the carbon channel. For MRS experiments, 30‐µL aliquots of [1‐ 13 C] pyruvic acid (PA) (Cambridge Isotope Laboratories Inc., Tewksbury, MA) and 15‐mM trityl radical (Ox063, GE Healthcare, Waukesha, WI) were polarized in a HyperSense Dynamic Nuclear Polarizer (Oxford Instruments, Abingdon, United Kingdom) for ~1 h . Samples were dissoluted with 4 mL of solvent containing 1.2 mL 426‐mM NaOH, 1.4 mL 400‐mM Tris buffer, and 1.4 mL 250‐mg/L EDTA.…”

Section: Methodsmentioning

confidence: 99%

A novel bioreactor for combined magnetic resonance spectroscopy and optical imaging of metabolism in 3D cell cultures

Cox

Erickson-Bhatt

Szulczewski

et al. 2019

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Purpose Fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorescent metabolites permits the measurement of cellular metabolism in cell, tissue and animal models. In parallel, magnetic resonance spectroscopy (MRS) of dynamic nuclear (hyper)polarized (DNP) 13C‐pyruvate enables measurement of metabolism at larger in vivo scales. Presented here are the design and initial application of a bioreactor that connects these 2 metabolic imaging modalities in vitro, using 3D cell cultures. Methods The model fitting for FLIM data analysis and the theory behind a model for the diffusion of pyruvate into a collagen gel are detailed. The device is MRI‐compatible, including an optical window, a temperature control system and an injection port for the introduction of contrast agents. Three‐dimensional printing, computer numerical control machining and laser cutting were used to fabricate custom parts. Results Performance of the bioreactor is demonstrated for 4 T1 murine breast cancer cells under glucose deprivation. Mean nicotinamide adenine dinucleotide (NADH) fluorescence lifetimes were 10% longer and hyperpolarized 13C lactate:pyruvate (Lac:Pyr) ratios were 60% lower for glucose‐deprived 4 T1 cells compared to 4 T1 cells in normal medium. Looking at the individual components of the NADH fluorescent lifetime, τ1 (free NADH) showed no significant change, while τ2 (bound NADH) showed a significant increase, suggesting that the increase in mean lifetime was due to a change in bound NADH. Conclusion A novel bioreactor that is compatible with, and can exploit the benefits of, both FLIM and 13C MRS in 3D cell cultures for studies of cell metabolism has been designed and applied.