Hyperpolarized ¹³C MRI: State of the Art and Future Directions

Radiology, Год журнала: 2019, Номер 291(2), С. 273 - 284

Опубликована: Март 5, 2019

Hyperpolarized (HP) carbon 13 (13C) MRI is an emerging molecular imaging method that allows rapid, noninvasive, and pathway-specific investigation of dynamic metabolic physiologic processes were previously inaccessible to imaging. This technique has enabled real-time in vivo investigations metabolism are central a variety diseases, including cancer, cardiovascular disease, diseases the liver kidney. review provides overview methods hyperpolarization 13C probes investigated date preclinical models disease. The article then discusses progress been made translating this technology for clinical investigation. In particular, potential roles applications HP [1-13C]pyruvate will be highlighted. future directions enable adoption advance basic understanding metabolism, improve disease diagnosis, accelerate treatment assessment also detailed. ©RSNA, 2019 Online supplemental material available article.

Язык: Английский

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Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system

Neurobiology of Disease, Год журнала: 2021, Номер 152, С. 105290 - 105290

Опубликована: Фев. 6, 2021

In response to various types of environmental and cellular stress, microglia rapidly activate exhibit either pro- or anti-inflammatory phenotypes maintain tissue homeostasis. Activation can result in changes morphology, phagocytosis capacity, secretion cytokines. Furthermore, microglial activation also induces energy demand, which is dependent on the metabolism metabolic substrates including glucose, fatty acids, amino acids. Accumulating evidence demonstrates reprogramming acts as a key driver immune response. For instance, pro-inflammatory states preferentially use glycolysis for production, whereas, cells are mainly powered by oxidative phosphorylation acid oxidation. this review, we summarize recent findings regarding pathways under physiological pathological circumtances. We will then discuss how orchestrate variety central nervous system pathologies. Finally, highlight manipulating reprogram towards beneficial functions, illustrate therapeutic potential inflammation-related neurological diseases.

Язык: Английский

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Neurons require glucose uptake and glycolysis in vivo

Cell Reports, Год журнала: 2023, Номер 42(4), С. 112335 - 112335

Опубликована: Апрель 1, 2023

Neurons require large amounts of energy, but whether they can perform glycolysis or to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through and rely on supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, generated mice with postnatal deletion either dominant neuronal transporter (GLUT3cKO) neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 other hippocampal neurons. GLUT3cKO PKM1cKO age-dependent learning memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows female have increased pyruvate-to-lactate conversion, whereas decreased body weight, brain volume. GLUT3KO also cytosolic ATP at nerve terminals, spatial genomics metabolomics revealing compensatory changes mitochondrial bioenergetics galactose metabolism. Therefore, vivo normal function.

Язык: Английский

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Lactate: A key regulator of the immune response

Immunity, Год журнала: 2025, Номер 58(3), С. 535 - 554

Опубликована: Март 1, 2025

SummaryLactate, the end product of both anaerobic and aerobic glycolysis in proliferating growing cells—with latter process known as Warburg effect—is historically considered a mere waste cell tissue metabolism. However, research over past ten years has unveiled multifaceted functions lactate that critically shape impact cellular biology. Beyond serving fuel source, is now to influence gene expression through histone modification function signaling molecule impacts wide range activities. These properties have been particularly studied context adaptive innate immune responses. Here, we review diverse roles regulation system during homeostasis disease pathogenesis (including cancer, infection, cardiovascular diseases, autoimmunity). Furthermore, describe recently proposed therapeutic interventions for manipulating metabolism human diseases.

Язык: Английский

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Development of methods and feasibility of using hyperpolarized carbon‐13 imaging data for evaluating brain metabolism in patient studies

Magnetic Resonance in Medicine, Год журнала: 2018, Номер 80(3), С. 864 - 873

Опубликована: Янв. 10, 2018

Purpose Hyperpolarized carbon‐13 ( 13 C) metabolic imaging is a noninvasive modality for evaluating real‐time metabolism. The purpose of this study was to develop and implement experimental strategies using [1‐ C]pyruvate probe in vivo metabolism patients with brain tumors other neurological diseases. Methods C radiofrequency coils pulse sequences were tested phantom performed 3 Tesla whole‐body scanner. Samples polarized SPINlab system. Dynamic data acquired from 8 previously diagnosed tumors, who had received treatment being followed serial magnetic resonance scans. Results studies produced good‐quality spectra reduction signal intensity the center attributed reception profiles receive coils. obtained 3‐cm slice through patient's following injection showed anticipated arrival agent, its conversion lactate bicarbonate, subsequent intensity. A similar temporal pattern observed 2D dynamic patient studies, signals corresponding pyruvate, lactate, bicarbonate normal appearing brain, but only pyruvate detected regions anatomical lesion. Physiological monitoring follow‐up confirmed that there no adverse events associated injection. Conclusion This has presented first application hyperpolarized tumor demonstrated safety feasibility evaluate Magn Reson Med 80:864–873, 2018. © 2018 International Society Magnetic Resonance Medicine.

Язык: Английский

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Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis

Journal of Clinical Investigation, Год журнала: 2019, Номер 129(8), С. 3277 - 3292

Опубликована: Май 21, 2019

The migration of leukocytes into the CNS drives neuropathology multiple sclerosis (MS). This penetration likely utilizes energy resources that remain to be defined. Using experimental autoimmune encephalomyelitis (EAE) model MS, we determined macrophages within perivascular cuff post-capillary venules are highly glycolytic as manifested by strong expression lactate dehydrogenase A (LDHA) converts pyruvate lactate. These expressed prominent levels monocarboxylate transporter-4 (MCT-4) specialized in secreting from cells. functional relevance glycolysis was confirmed siRNA-mediated knockdown LDHA and MCT-4, which decreased secretion macrophage transmigration. MCT-4 turn regulated EMMPRIN (CD147) through co-expression/co-immunoprecipitation studies, silencing. MCT-4/EMMPRIN interaction affirmed lower transmigration culture using inhibitor, α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration clinical severity EAE. Relevance MS corroborated brains. results detail metabolism for cuffs parenchyma identifies diet potential modulators neuro-inflammation MS.

Язык: Английский

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Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment

Pharmacology & Therapeutics, Год журнала: 2020, Номер 211, С. 107550 - 107550

Опубликована: Апрель 20, 2020

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory e.g. rheumatoid arthritis but also, less obviously, many other common conditions, cardiovascular disease and diabetes. Together, chronic contribute to the majority of global morbidity mortality. However, our understanding underlying processes by which immune response activated sustained limited lack cellular molecular information obtained situ. Molecular imaging visualization, detection quantification molecules body. The ability reveal on biomarkers, pathways cells can improve diagnosis, guide monitor therapeutic intervention identify new targets for research. optimum modality will possess high sensitivity resolution be capable non-invasive quantitative biomarkers while maintaining an acceptable safety profile. mainstays current clinical are computed tomography (CT), magnetic resonance (MRI), ultrasound (US) nuclear such as positron emission (PET). none these have yet progressed routine use inflammation, therefore approaches required meet this goal. This review sets out respective merits limitations both established emerging modalities clinically useful tools addition potential theranostic applications.

Язык: Английский

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Deuterium metabolic imaging and hyperpolarized 13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism

NeuroImage, Год журнала: 2022, Номер 257, С. 119284 - 119284

Опубликована: Май 6, 2022

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive non-ionizing of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, inborn errors Here we directly compare these at 3 T the first time humans show how they simultaneously probe both oxidative non-oxidative DMI was undertaken 1–2 h after oral administration [6,6′-2H2]glucose, 13C-MRI performed immediately following intravenous injection [1–13C]pyruvate ten nine normal volunteers within each arm respectively. used to generate maps deuterium-labelled water, glucose, lactate, glutamate/glutamine (Glx) spectral separation demonstrated that is feasible T. 13C-HPMRI generated carbon-13 labelled pyruvate, bicarbonate. The ratio 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with higher than equivalent 2H-lactate/2H-Glx 0.18 0.09) using DMI. These differences can be explained by route administering probe, timing ingestion or injection, as well biological uptake cellular physiology between molecules. results demonstrate provide different yet complementary readouts reductive a clinically timescale. Furthermore, clinical field strength ten-minute scan time, it demonstrates its routine tool future.

Язык: Английский

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The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat

Mitochondrion, Год журнала: 2023, Номер 70, С. 59 - 102

Опубликована: Март 1, 2023

Язык: Английский

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Hyperpolarized [1- ¹³ C]pyruvate-to-[1- ¹³ C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane

Proceedings of the National Academy of Sciences, Год журнала: 2020, Номер 117(36), С. 22378 - 22389

Опубликована: Авг. 24, 2020

Significance Hyperpolarized [1- 13 C]pyruvate magnetic resonance spectroscopic imaging (MRSI), which measures C]pyruvate-to-[1- C]lactate conversion, has been widely explored as a metabolic-imaging modality interpreted to reflect LDHA activity and glycolytic flux. However, we show definitively that hyperpolarized conversion rates are primarily functional readout of transmembrane influx mediated by MCT1, providing mechanistic reinterpretation redirection clinical translation.

Язык: Английский

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