Cardiac applications of hyperpolarised magnetic resonance

Timm, Kerstin N.; Miller, Jack J.; Henry, John A.; Tyler, Damian J.

doi:10.1016/j.pnmrs.2018.05.002

Cited by 15 publications

(16 citation statements)

References 247 publications

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“…Until recently the low natural abundance of 13 C nuclei had prevented real-time measurements of metabolic fluxes in vivo. However, over the last decade, hyperpolarized MRS by dissolution dynamic nuclear polarization of 13 C-labeled substrates 18 has revolutionized cardiac metabolic flux measurements in preclinical models 19 and in the human heart 20,21 . For example, increased lactate labeling from hyperpolarized [1-13 C]pyruvate was recently shown to be a marker of innate immune cell driven inflammation in a rodent model of myocardial infarction 22 .…”

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confidence: 99%

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

et al. 2020

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Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity.

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confidence: 99%

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

et al. 2020

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“…Hyperpolarization by dynamic nuclear polarization of 13 C-labeled substrates provides signal enhancements by several orders of magnitude, 1 which allows for real-time imaging of the injected 13 C substrate and its downstream metabolites using MRI. 2,3 Hyperpolarized 13 C imaging has been used to probe cardiac metabolism of various pathologies, [4][5][6] and recent trials indicate the value of the method in humans. [7][8][9] The assessment of in vivo metabolism to distinguish between healthy and pathologic myocardium requires sufficient spatio-temporal resolution, which, however, is limited by the available polarization and concentration of the metabolic products.…”

Section: Introductionmentioning

confidence: 99%

Joint image and field map estimation for multi‐echo hyperpolarized ¹³C metabolic imaging of the heart

Traechtler

Vishnevskiy

Füetterer

et al. 2021

Magnetic Resonance in Med

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Image reconstruction of metabolic images from hyperpolarized 13 C multiecho data acquisition is sensitive to susceptibility-induced phase offsets, which are particularly challenging in the heart. A model-based framework for joint estimation of metabolite images and field map from echo shift-encoded data is proposed. Using simulations, it is demonstrated that correction of signal spilling due to incorrect decomposition of metabolites and geometrical distortions over a wide range of offresonance gradients is possible. In vivo feasibility is illustrated using hyperpolarized [1-13 C]pyruvate in the pig heart. Methods: The model-based reconstruction for multi-echo, multicoil data was implemented as a nonconvex minimization problem jointly optimizing for metabolic images and B 0. A comprehensive simulation framework for echo shift-encoded hyperpolarized [1-13 C]pyruvate imaging was developed and applied to assess reconstruction performance and distortion correction of the proposed method. In vivo data were obtained in four pigs using hyperpolarized [1-13 C]pyruvate on a clinical 3T MR system with a six-channel receiver coil. Dynamic images were acquired during suspended ventilation using cardiac-triggered multi-echo single-shot echo-planar imaging in short-axis orientation. Results: Simulations revealed that off-resonance gradients up to ±0.26 ppm/pixel can be corrected for with reduced signal spilling and geometrical distortions yielding an accuracy of ≥90% in terms of Dice similarity index. In vivo, improved geometrical consistency (10% Dice improvement) compared to image reconstruction without field map correction and with reference to anatomical data was achieved. Conclusion: Joint image and field map estimation allows addressing off-resonanceinduced geometrical distortions and metabolite spilling in hyperpolarized 13 C metabolic imaging of the heart.

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“…Hyperpolarized MRS is a novel technique, which can increase the in vivo sensitivity of MRS to detect 13 C‐labeled metabolic substrates by more than 10 000‐fold 14 . It therefore enables unprecedented real‐time visualization of the biochemical mechanisms of normal and abnormal metabolism, with measurement of instantaneous substrate uptake and enzymatic transformation in vivo 15 . Following the injection of 13 C pyruvate labeled at the first carbon position ([1‐ 13 C]pyruvate), it is possible to see the metabolic production of carbon dioxide and bicarbonate ( 13 CO 2 and H 13 CO 3 − ) through the PDH enzyme complex, yielding a marker of oxidation from carbohydrate sources.…”

Section: Introductionmentioning

confidence: 99%

Hyperpolarized magnetic resonance shows that the anti‐ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post‐ischemic function in the diabetic heart

et al. 2021

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The diabetic heart has a decreased ability to metabolize glucose. The anti‐ischemic drug meldonium may provide a route to counteract this by reducing l‐carnitine levels, resulting in improved cardiac glucose utilization. Therefore, the aim of this study was to use the novel technique of hyperpolarized magnetic resonance to investigate the in vivo effects of treatment with meldonium on cardiac metabolism and function in control and diabetic rats. Thirty‐six male Wistar rats were injected either with vehicle, or with streptozotocin (55 mg/kg) to induce a model of type 1 diabetes. Daily treatment with either saline or meldonium (100 mg/kg/day) was undertaken for three weeks. in vivo cardiac function and metabolism were assessed with CINE MRI and hyperpolarized magnetic resonance respectively. Isolated perfused hearts were challenged with low‐flow ischemia/reperfusion to assess the impact of meldonium on post‐ischemic recovery. Meldonium had no significant effect on blood glucose concentrations or on baseline cardiac function. However, hyperpolarized magnetic resonance revealed that meldonium treatment elevated pyruvate dehydrogenase flux by 3.1‐fold and 1.2‐fold in diabetic and control animals, respectively, suggesting an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that meldonium reduced the normalized acetylcarnitine signal by 2.1‐fold in both diabetic and control animals. The increase in pyruvate dehydrogenase flux in vivo was accompanied by an improvement in post‐ischemic function ex vivo, as meldonium elevated the rate pressure product by 1.3‐fold and 1.5‐fold in the control and diabetic animals, respectively. In conclusion, meldonium improves in vivo pyruvate dehydrogenase flux in the diabetic heart, contributing to improved cardiac recovery after ischemia.

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Cardiac applications of hyperpolarised magnetic resonance

Cited by 15 publications

References 247 publications

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

Joint image and field map estimation for multi‐echo hyperpolarized ¹³C metabolic imaging of the heart

Hyperpolarized magnetic resonance shows that the anti‐ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post‐ischemic function in the diabetic heart

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Cardiac applications of hyperpolarised magnetic resonance

Cited by 15 publications

References 247 publications

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

Joint image and field map estimation for multi‐echo hyperpolarized 13C metabolic imaging of the heart

Hyperpolarized magnetic resonance shows that the anti‐ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post‐ischemic function in the diabetic heart

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Joint image and field map estimation for multi‐echo hyperpolarized ¹³C metabolic imaging of the heart