Metabolic clearance rate modeling: A translational approach to quantifying cerebral metabolism using hyperpolarized [1-13C]pyruvate

Hyperpolarized carbon-13 MRI is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a model-free formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel model-free perfusion and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. Simulations showed that the proposed model was robust to perturbations in T1, transmit B1, and kPL. A significant difference in ipsilateral vs contralateral pyruvate derived cerebral blood flow (CBF) was detected in rats (140 ± 2 vs 89 ± 6 mL/100g/min, p < 0.01, respectively) and pigs (139 ± 12 vs 95 ± 5 mL/100g/min, p = 0.04, respectively), along with an increase in fractional metabolism (26 ± 5 vs 4 ± 2 %, p < 0.01, respectively) in the rodent brain. In addition, a significant increase in ipsilateral vs contralateral MCR (0.034 ± 0.007 vs 0.017 ± 0.02 s-1, p = 0.03, respectively) and a decrease in mean transit time (MTT) (31 ± 8 vs 60 ± 2, p = 0.04, respectively) was observed in the porcine brain. In conclusion, MCR mapping is a simple and robust approach to the post-processing of hyperpolarized magnetic resonance imaging.

[1]  T. Santarius,et al.  Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study , 2022, Radiology. Imaging cancer.

[2]  D. Tyler,et al.  Assessing the effect of anesthetic gas mixtures on hyperpolarized 13 C pyruvate metabolism in the rat brain , 2022, Magnetic resonance in medicine.

[3]  J. Wason,et al.  Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients , 2021, Cancer Research.

[4]  D. Vigneron,et al.  Metabolic MRI with hyperpolarized [1-13C]pyruvate separates benign oligemia from infarcting penumbra in porcine stroke , 2021, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  V. Kersemans,et al.  Electromagnetically Transparent Graphene Respiratory Sensors for Multimodal Small Animal Imaging , 2020, Advanced healthcare materials.

[6]  Shuyu Tang,et al.  A variable resolution approach for improved acquisition of hyperpolarized 13C metabolic MRI , 2020, Magnetic resonance in medicine.

[7]  Theodoros N. Arvanitis,et al.  Combining multi-site Magnetic Resonance Imaging with machine learning predicts survival in paediatric brain tumours , 2020, 2004.09849.

[8]  Christoffer Laustsen,et al.  Hyperpolarized 13C MRI: A novel approach for probing cerebral metabolism in health and neurological disease , 2020, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  Evis Sala,et al.  Imaging breast cancer using hyperpolarized carbon-13 MRI , 2020, Proceedings of the National Academy of Sciences.

[10]  Albert P. Chen,et al.  Lactate topography of the human brain using hyperpolarized 13C-MRI , 2020, NeuroImage.

[11]  C. Laustsen,et al.  Detection of acute kidney injury with hyperpolarized [13C, 15N]Urea and multiexponential relaxation modeling , 2019, Magnetic resonance in medicine.

[12]  John Kurhanewicz,et al.  First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. , 2019, Journal of magnetic resonance.

[13]  G. Rosenberg,et al.  Neuroinflammation: friend and foe for ischemic stroke , 2019, Journal of Neuroinflammation.

[14]  Paul Kinchesh,et al.  Reduced respiratory motion artefact in constant TR multi-slice MRI of the mouse , 2019, Magnetic resonance imaging.

[15]  James A Bankson,et al.  Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate , 2019, Magnetic resonance in medicine.

[16]  Frank Riemer,et al.  Quantifying normal human brain metabolism using hyperpolarized [1–13C]pyruvate and magnetic resonance imaging , 2019, NeuroImage.

[17]  F. Gallagher,et al.  13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI , 2018, Scientific Reports.

[18]  Ilwoo Park,et al.  Development of methods and feasibility of using hyperpolarized carbon‐13 imaging data for evaluating brain metabolism in patient studies , 2018, Magnetic resonance in medicine.

[19]  S. Jakobsen,et al.  Hyperpolarized [1-13C]-acetate Renal Metabolic Clearance Rate Mapping , 2017, Scientific Reports.

[20]  C. Laustsen,et al.  Can Hyperpolarized 13C-Urea be Used to Assess Glomerular Filtration Rate? A Retrospective Study , 2017, Tomography.

[21]  M. V. van Osch,et al.  Advances in arterial spin labelling MRI methods for measuring perfusion and collateral flow , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  J. Ardenkjaer-Larsen,et al.  Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury , 2017, Scientific Reports.

[23]  Graham A. Wright,et al.  Hyperpolarized 13C Metabolic MRI of the Human Heart , 2016, Circulation research.

[24]  D. Tyler,et al.  Simultaneous in vivo assessment of cardiac and hepatic metabolism in the diabetic rat using hyperpolarized MRS , 2016, NMR in biomedicine.

[25]  Christoffer Laustsen,et al.  Hyperpolarized 13C,15N2‐Urea MRI for assessment of the urea gradient in the porcine kidney , 2016, Magnetic resonance in medicine.

[26]  C. Laustsen,et al.  Early diabetic kidney maintains the corticomedullary urea and sodium gradient , 2016, Physiological reports.

[27]  Martin J. Graves,et al.  A comparison of quantitative methods for clinical imaging with hyperpolarized 13C‐pyruvate , 2016, NMR in biomedicine.

[28]  Joanna M. Wardlaw,et al.  Tracer kinetic modelling for DCE-MRI quantification of subtle blood–brain barrier permeability , 2016, NeuroImage.

[29]  Stuart Gilchrist,et al.  A resistive heating system for homeothermic maintenance in small animals , 2015, Magnetic resonance imaging.

[30]  James M. Provenzale,et al.  Principles of T2*‐weighted dynamic susceptibility contrast MRI technique in brain tumor imaging , 2015, Journal of magnetic resonance imaging : JMRI.

[31]  Florian Wiesinger,et al.  Multisite Kinetic Modeling of 13C Metabolic MR Using [1-13C]Pyruvate , 2014, Radiology research and practice.

[32]  A. Haase,et al.  Apparent rate constant mapping using hyperpolarized [1–13C]pyruvate , 2014, NMR in biomedicine.

[33]  S W Hetts,et al.  Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery , 2013, American Journal of Neuroradiology.

[34]  Max Wintermark,et al.  Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery. , 2013, Journal of the American College of Radiology : JACR.

[35]  Albert P. Chen,et al.  Hyperpolarized 13C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart , 2012, European journal of heart failure.

[36]  Glyn Johnson,et al.  An improved model for describing the contrast bolus in perfusion MRI. , 2011, Medical physics.

[37]  M. Janier,et al.  Validation of Renal Oxidative Metabolism Measurement by Positron-Emission Tomography , 2007, Hypertension.

[38]  J. Svensson,et al.  Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C , 2004, Magnetic resonance in medicine.

[39]  B. Rosen,et al.  Tracer arrival timing‐insensitive technique for estimating flow in MR perfusion‐weighted imaging using singular value decomposition with a block‐circulant deconvolution matrix , 2003, Magnetic resonance in medicine.

[40]  M. Phelps,et al.  A simplified method for quantification of myocardial blood flow using nitrogen-13-ammonia and dynamic PET. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[41]  T. A. Bronikowski,et al.  Model-free deconvolution techniques for estimating vascular transport functions. , 1983, International journal of bio-medical computing.

[42]  O Muzik,et al.  Validation of nitrogen-13-ammonia tracer kinetic model for quantification of myocardial blood flow using PET. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.