Lactate topography of the human brain using hyperpolarized 13C-MRI

Lee, Casey Y.; Soliman, Hany; Geraghty, Benjamin; Chen, Albert P.; Connelly, Kim A.; Endre, Ruby; Perks, William J.; Heyn, Chris; Black, Sandra E.; Cunningham, Charles H.

doi:10.1016/j.neuroimage.2019.116202

Cited by 82 publications

(94 citation statements)

References 32 publications

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“…41 Variable resolution acquisitions in healthy human subjects showed cardiac structure and neuro-vasculature in the pyruvate data set that would otherwise be missed due to partial-volume effects and illustrates the level of detail that can be achieved with hyperpolarized substrates in a clinical setting, approaching that of 1 H MRSI and some positron emission tomography (PET) radiotracers. [42][43][44][45] A variable resolution approach would also be beneficial when the biodistribution of metabolites is the primary interest 34 or when performing co-polarization studies with inert perfusion agents, such as 13 C urea, 46 and would provide an opportunity to acquire F I G U R E 6 AUC images from a healthy cardiac volunteer. The pyruvate data, acquired at finer resolution, provides improved contrast between the left and right ventricles and the myocardium and papillary muscles.…”

Section: Discussionmentioning

confidence: 99%

A variable resolution approach for improved acquisition of hyperpolarized ¹³C metabolic MRI

Gordon

Autry

Tang

et al. 2020

Magnetic Resonance in Med

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Purpose To ameliorate tradeoffs between a fixed spatial resolution and signal‐to‐noise ratio (SNR) for hyperpolarized 13C MRI. Methods In MRI, SNR is proportional to voxel volume but retrospective downsampling or voxel averaging only improves SNR by the square root of voxel size. This can be exploited with a metabolite‐selective imaging approach that independently encodes each compound, yielding high‐resolution images for the injected substrate and coarser resolution images for downstream metabolites, while maintaining adequate SNR for each. To assess the efficacy of this approach, hyperpolarized [1‐13C]pyruvate data were acquired in healthy Sprague‐Dawley rats (n = 4) and in two healthy human subjects. Results Compared with a constant resolution acquisition, variable‐resolution data sets showed improved detectability of metabolites in pre‐clinical renal studies with a 3.5‐fold, 8.7‐fold, and 6.0‐fold increase in SNR for lactate, alanine, and bicarbonate data, respectively. Variable‐resolution data sets from healthy human subjects showed cardiac structure and neuro‐vasculature in the higher resolution pyruvate images (6.0 × 6.0 mm2 for cardiac and 7.5 × 7.5 mm2 for brain) that would otherwise be missed due to partial‐volume effects and illustrates the level of detail that can be achieved with hyperpolarized substrates in a clinical setting. Conclusion We developed a variable‐resolution strategy for hyperpolarized 13C MRI using metabolite‐selective imaging and demonstrated that it mitigates tradeoffs between a fixed spatial resolution and SNR for hyperpolarized substrates, providing both high resolution pyruvate and coarse resolution metabolite data sets in a single exam. This technique shows promise to improve future studies by maximizing metabolite SNR while minimizing partial‐volume effects from the injected substrate.

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Section: Discussionmentioning

confidence: 99%

A variable resolution approach for improved acquisition of hyperpolarized ¹³C metabolic MRI

Gordon

Autry

Tang

et al. 2020

Magnetic Resonance in Med

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“…[4][5][6][7][8] In addition to the record of safety, this study was able to provide evidence that HP-13 C imaging can capture metabolically relevant data. As reported in adults, [4][5][6][7][8] HP [1-13 C]pyruvate displayed transport across the BBB and subsequent conversion to [1-13 C]lactate and [ 13 C] bicarbonate over experimental time scales of approximately 60-72 seconds. Given the quality of these data, as measured by aSNR, HP- 13 C imaging appears to hold promise for investigating aberrant metabolism in pediatric brain tumors.…”

Section: Discussionmentioning

confidence: 75%

“…HP- 13 C MR imaging has enabled the noninvasive investigation of in vivo brain metabolism using molecular probes whose signal is transiently enhanced via dynamic nuclear polarization. 3 In studies of the adult brain, [4][5][6][7][8] intravenously injected HP [1-13 C]pyruvate was shown to safely transport across the BBB and undergo enzymatic conversion to downstream metabolites [1-13 C]lactate and [ 13 C]bicarbonate, which serve as respective markers of glycolysis 9 and oxidative phosphorylation. 10 Given the metabolic alterations associated with cancer, 11,12 several of these imaging studies were designed to demonstrate the feasibility of HP-13 C MR imaging in patients with gliomas 4,5 and also characterize serial imaging.…”

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confidence: 99%

Pilot Study of Hyperpolarized ¹³C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

Autry

Park

Kline³

et al. 2020

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Pediatric CNS tumors commonly present challenges for radiographic interpretation on conventional MR imaging. This study sought to investigate the safety and tolerability of hyperpolarized carbon-13 (HP-13 C) metabolic imaging in pediatric patients with brain tumors. MATERIALS AND METHODS: Pediatric patients 3 to 18 years of age who were previously diagnosed with a brain tumor and could undergo MR imaging without sedation were eligible to enroll in this safety study of HP [1-13 C]pyruvate. Participants received a onetime injection of HP [1-13 C]pyruvate and were imaged using dynamic HP-13 C MR imaging. We assessed 2 dose levels: 0.34 mL/kg and the highest tolerated adult dose of 0.43 mL/kg. Participants were monitored throughout imaging and for 60 minutes postinjection, including pre-and postinjection electrocardiograms and vital sign measurements.

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“…The power of dynamic metabolic probing using HP 13 C MR is compelling, as it allows measuring previously inaccessible metabolic reactions non-invasively. HP 13 C metabolic imaging is a rapidly growing field, and is now being used in multiple clinical trials across the globe, targeting several organs including brain, heart, prostate and kidney [46][47][48][49][50][51][52][53][54][55][56][57] . It is very likely that, given the constant improvements reported both on the acquisition and processing sides, this methodology will soon approach feasibility for widespread clinical adoption.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive Differentiation of M1 and M2 Activation in Macrophages using Hyperpolarized¹³C MRS of Pyruvate and DHA at 1.47 Tesla

Qiao

Page

Chaumeil

2020

Preprint

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Macrophage activation, first generalized to the M1/M2 dichotomy, is a complex and central process of the innate immune response. Simply, M1 describes the classical pro-inflammatory activation, leading to tissue damage, and M2 the alternative activation promoting tissue repair. Given the central role of macrophages in multiple diseases, the ability to non-invasively differentiate between M1 and M2 activation states would be highly valuable for monitoring disease progression and therapeutic responses. Since M1/M2 activation patterns are associated with differential metabolic reprogramming, we hypothesized that hyperpolarized 13C magnetic resonance spectroscopy (HP 13C MRS), an innovative metabolic imaging approach, could distinguish between macrophage activation states noninvasively. The metabolic conversions of HP [1-13C]pyruvate to HP [1-13C]lactate and HP [1-13C]dehydroascorbic acid to HP [1-13C]ascorbic acid were monitored in live M1 and M2 activated J774a.1 macrophages non-invasively by HP 13C MRS on a 1.47 Tesla NMR system. Our results show that both metabolic conversions were significantly increased in M1 macrophages compared to M2 and non-activated cells. Biochemical assays and high resolution 1H MRS were also performed to investigate the underlying changes in enzymatic activities and metabolite levels linked to M1/M2 activation. Altogether, our results demonstrate the potential of HP 13C MRS for monitoring macrophage activation states non-invasively.

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Lactate topography of the human brain using hyperpolarized 13C-MRI

Cited by 82 publications

References 32 publications

A variable resolution approach for improved acquisition of hyperpolarized ¹³C metabolic MRI

A variable resolution approach for improved acquisition of hyperpolarized ¹³C metabolic MRI

Pilot Study of Hyperpolarized ¹³C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

Non-invasive Differentiation of M1 and M2 Activation in Macrophages using Hyperpolarized¹³C MRS of Pyruvate and DHA at 1.47 Tesla

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Lactate topography of the human brain using hyperpolarized 13C-MRI

Cited by 82 publications

References 32 publications

A variable resolution approach for improved acquisition of hyperpolarized 13C metabolic MRI

A variable resolution approach for improved acquisition of hyperpolarized 13C metabolic MRI

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

Non-invasive Differentiation of M1 and M2 Activation in Macrophages using Hyperpolarized13C MRS of Pyruvate and DHA at 1.47 Tesla

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A variable resolution approach for improved acquisition of hyperpolarized ¹³C metabolic MRI

A variable resolution approach for improved acquisition of hyperpolarized ¹³C metabolic MRI

Pilot Study of Hyperpolarized ¹³C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers

Non-invasive Differentiation of M1 and M2 Activation in Macrophages using Hyperpolarized¹³C MRS of Pyruvate and DHA at 1.47 Tesla