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Record W2787727062 · doi:10.1161/circresaha.117.312535

Noninvasive Immunometabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance

2018· article· en· W2787727062 on OpenAlexaff
Andrew Lewis, Jack J. Miller, Angus Lau, M. Kate Curtis, Oliver J. Rider, Robin P. Choudhury, Stefan Neubauer, Charles H. Cunningham, Carolyn A. Carr, Damian J. Tyler

Bibliographic record

VenueCirculation Research · 2018
Typearticle
Languageen
FieldMedicine
TopicCardiac Fibrosis and Remodeling
Canadian institutionsUniversity of Toronto
FundersEngineering and Physical Sciences Research CouncilNovo Nordisk FondenBritish Heart FoundationNovo NordiskNational Institute for Health and Care Research
KeywordsInflammationMedicineMagnetic resonance imagingHyperpolarization (physics)Macrophage polarizationMacrophageProinflammatory cytokineInternal medicineChemistryIn vitroNuclear magnetic resonance spectroscopyBiochemistry

Abstract

fetched live from OpenAlex

Rationale: Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping. Objective: To determine whether hyperpolarized MR using [1- 13 C]pyruvate can assess the local cardiac inflammatory response after MI. Methods and Results: We performed hyperpolarized [1- 13 C]pyruvate MR studies in small and large animal models of MI and in macrophage-like cell lines and measured the resulting [1- 13 C]lactate signals. MI caused intense [1- 13 C]lactate signal in healing myocardial segments at both day 3 and 7 after rodent MI, which was normalized at both time points after monocyte/macrophage depletion. A near-identical [1- 13 C]lactate signature was also seen at day 7 after experimental MI in pigs. Hyperpolarized [1- 13 C]pyruvate MR spectroscopy in macrophage-like cell suspensions demonstrated that macrophage activation and polarization with lipopolysaccharide almost doubled hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose in activated cells normalized lactate label flux rates and markedly inhibited the production of key proinflammatory cytokines. Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1- 13 C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines. Cine MRI demonstrated improvements in systolic function in 2-DG (2-deoxyglucose)–treated rats at 3 months. Conclusions: Hyperpolarized MR using [1- 13 C]pyruvate provides a novel method for the assessment of innate immune cell-driven inflammation in the heart after MI, with broad potential applicability across other cardiovascular disease states and suitability for early clinical translation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.857
Threshold uncertainty score0.470

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.065
GPT teacher head0.364
Teacher spread0.299 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations80
Published2018
Admission routes1
Has abstractyes

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