99 results on '"Ladislav Valkovič"'
Search Results
2. Investigating the Role of the Right Ventricle in Hfpef Using Exercise CMR
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Roshan Xavier, MD, MA, Sher May Ng, MD, MA, Jiliu Pan, MD, MA, Jack Miller, PhD, Ferenc Mózes, PhD, Ladislav Valkovič, PhD, Jenny Rayner, MD, PhD, Marzia Rigolli, MD, PhD, Matthew Fronheiser, PhD, Stefan Neubauer, MD, PhD, Andrew Lewis, MD, PhD, and Oliver Rider, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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3. Multimodal Stress Testing Unmasks Latent Energetic Deficit in Subjects with Subtly Depressed Ejection FBaction
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Per Arvidsson, MD, PhD, Rebecca Chamley, MD, Jenny Rayner, MD, PhD, Jennifer Holland, MD, Ladislav Valkovič, PhD, Will Watson, Sarah Birkhoelzer, MD, Sher May Ng, MD, MA, Roshan Xavier, MD, MA, Stefan Neubauer, MD, PhD, David Holdsworth, MD, PhD, Andrew Lewis, MD, PhD, and Oliver Rider, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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4. Ninerafaxstat Modulates Cardiac Energy Metabolism in Cardio-metabolic Syndromes: A Mechanistic, Hyperpolarized MR Trial
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Moritz Hundertmark, MD, PhD, Oliver Rider, MD, PhD, Jai Patel, MD, Damian Tyler, PhD, Paul Chamberlin, MD, Jack Miller, PhD, Ladislav Valkovič, PhD, Stefan Neubauer, MD, PhD, and Arash Yavari
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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5. The Effects of Haemodialysis on Myocardial Energetics and Rest and Stress Cardiac Function
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Sher May Ng, MD, MA, Roshan Xavier, MD, MA, Jiliu Pan, MD, MA, Jack Miller, PhD, Ferenc Mózes, PhD, Ladislav Valkovič, PhD, Stefan Neubauer, MD, PhD, Andrew Lewis, MD, PhD, and Oliver Rider, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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6. Dynamic Cardiac Magnetic Resonance Measures of Left Atrial Mechanics Across Spectrum of Heart Failure with Preserved Ejection FBaction
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Sher May Ng, MD, MA, Roshan Xavier, MD, MA, Jiliu Pan, MD, MA, Jack Miller, PhD, Ferenc Mózes, PhD, Ladislav Valkovič, PhD, Jenny Rayner, MD, PhD, Marzia Rigolli, MD, PhD, Matthew Fronheiser, PhD, Stefan Neubauer, MD, PhD, Oliver Rider, MD, PhD, and Andrew Lewis, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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7. Novel Endotypes in Hfpef Identified Using Exercise Stress CMR and Machine Learning
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Roshan Xavier, MD, MA, Sher May Ng, MD, MA, Jiliu Pan, MD, MA, Jack Miller, PhD, Ferenc Mózes, PhD, Ladislav Valkovič, PhD, Jenny Rayner, MD, PhD, Marzia Rigolli, MD, PhD, Matthew Fronheiser, PhD, Stefan Neubauer, MD, PhD, Oliver Rider, MD, PhD, and Andrew Lewis, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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8. The Impact of Type 2 Diabetes on the Myocardial Morphological, Functional, and Energetic Recovery in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting Surgery
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Sindhoora Kotha, Henry Procter, Marilena Giannoudi, Nicholas Jex, PhD, Amrit Chowdhary, PhD, Sharmaine Thirunavukarasu, Tobin Joseph, Peter Swoboda, Sven Plein, MD, PhD, John P Greenwood, MD, PhD, Ladislav Valkovič, PhD, Peter Kellman, PhD, and Eylem Levelt
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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9. Cardiac and Skeletal Muscle Energetics in Chronic Heart Failure and Iron Deficiency
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Sarah Birkhoelzer, MD, Per Arvidsson, MD, PhD, Mehrsa Jafarpour, John Henry, MD, Jordan J McGing, PhD, Damian Tyler, PhD, Oliver Rider, MD, PhD, Ladislav Valkovič, PhD, and Jenny Rayner, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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10. Compartment-based reconstruction of acquisition-weighted 31P cardiac MRSI reduces sensitivity to cardiac motion and scan planning
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Andrew Tyler, Moritz J. Hundertmark, Jack J. Miller, Oliver Rider, Damian J. Tyler, and Ladislav Valkovič
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31P ,cardiac ,spectroscopy ,spectroscopy with linear algebra modeling ,magnetic resonance spectroscopic imaging ,cardiac gating ,Physiology ,QP1-981 - Abstract
Motivation:31P magnetic resonance spectroscopic imaging (31P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure in vivo, allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac 31P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction.Methods: Six healthy volunteers were scanned twice in a test–retest procedure to allow quantification of repeatability. Each scan consisted of anatomical localizers and two acquisition-weighted (AW) 31P MRSI acquisitions, which were acquired with and without cardiac gating. Five patients with heart failure with a preserved ejection fraction were then scanned with the same 31P MRSI sequence without cardiac gating. All 31P MRSI datasets were reconstructed with both conventional Fourier transform (FT)-based reconstruction and SLAM reconstruction, which were compared statistically. The effect of shifting the 31P MRSI acquisition field of view was also investigated.Results: In the healthy volunteer cohort, the spectral fit of the SLAM reconstructions had significantly improved Cramer–Rao lower bounds (CRLBs) compared to the FT-based reconstruction of non-cardiac gated data, as well as improved coefficients of variability and repeatability. The SLAM reconstruction found a significant difference in the PCr/ATP ratio between the healthy volunteer and patient cohorts, which the FT-based reconstruction did not find. Furthermore, the SLAM reconstruction was less influenced by the placement of the field of view (FOV) of the 31P MRSI acquisition in post hoc analysis.Discussion: The experimental benefits of the SLAM reconstruction for AW data were demonstrated by the improvements in fit confidence and repeatability seen in the healthy volunteer cohort and post hoc FOV analysis. The benefit of SLAM reconstruction of AW data for clinical studies was then illustrated by the patient cohort, which suggested improved sensitivity to clinically significant changes in the PCr/ATP ratio.
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- 2024
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11. Design and rationale of the EMPA‐VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure
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Moritz J. Hundertmark, Olorunsola F. Agbaje, Ruth Coleman, Jyothis T. George, Rolf Grempler, Rury R. Holman, Hanan Lamlum, Jisoo Lee, Joanne E. Milton, Heiko G. Niessen, Oliver Rider, Christopher T. Rodgers, Ladislav Valkovič, Eleanor Wicks, Masliza Mahmod, and Stefan Neubauer
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Heart failure ,Diabetes ,SGLT2 inhibitors ,31P‐MRS ,Trial design ,Empagliflozin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium‐glucose co‐transporter‐2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR‐Reduced trial and cardiovascular mortality in the EMPA‐REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR). Methods and results The EMPA‐VISION trial is a double‐blind, randomized, placebo‐controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine‐to‐adenosine triphosphate ratio, as measured by 31Phosphorus‐MRS. Conclusions EMPA‐VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR‐Reduced and EMPEROR‐Preserved).
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- 2021
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12. Investigating the effect of trigger delay on cardiac 31P MRS signals
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Stefan Wampl, Tito Körner, Ladislav Valkovič, Siegfried Trattnig, Michael Wolzt, Martin Meyerspeer, and Albrecht Ingo Schmid
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Medicine ,Science - Abstract
Abstract The heart’s geometry and its metabolic activity vary over the cardiac cycle. The effect of these fluctuations on phosphorus (31P) magnetic resonance spectroscopy (MRS) data quality and metabolite ratios was investigated. 12 healthy volunteers were measured using a 7 T MR scanner and a cardiac 31P-1H loop coil. 31P chemical shift imaging data were acquired untriggered and at four different times during the cardiac cycle using acoustic triggering. Signals of adenosine-triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and 2,3-diphosphoglycerate (2,3-DPG) and their fit quality as Cramér-Rao lower bounds (CRLB) were quantified including corrections for contamination by 31P signals from blood, flip angle, saturation and total acquisition time. The myocardial filling factor was estimated from cine short axis views. The corrected signals of PCr and $$\gamma$$ γ -ATP were higher during end-systole and lower during diastasis than in untriggered acquisitions ( $$P
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- 2021
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13. Increased cardiac Pi/PCr in the diabetic heart observed using phosphorus magnetic resonance spectroscopy at 7T.
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Ladislav Valkovič, Andrew Apps, Jane Ellis, Stefan Neubauer, Damian J Tyler, Albrecht Ingo Schmid, Oliver J Rider, and Christopher T Rodgers
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Medicine ,Science - Abstract
Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously demonstrated decreased energy reserves in the form of phosphocreatine to adenosine-tri-phosphate ratio (PCr/ATP) in the hearts of patients with type 2 diabetes (T2DM). Recent 31P-MRS techniques using 7T systems, e.g. long mixing time stimulated echo acquisition mode (STEAM), allow deeper insight into cardiac metabolism through assessment of inorganic phosphate (Pi) content and myocardial pH, which play pivotal roles in energy production in the heart. Therefore, we aimed to further explore the cardiac metabolic phenotype in T2DM using STEAM at 7T. Seventeen patients with T2DM and twenty-three healthy controls were recruited and their cardiac PCr/ATP, Pi/PCr and pH were assessed at 7T. Diastolic function of all patients with T2DM was assessed using echocardiography to investigate the relationship between diastolic dysfunction and cardiac metabolism. Mirroring the decreased PCr/ATP (1.70±0.31 vs. 2.07±0.39; p
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- 2022
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14. Evaluation of Acute Supplementation With the Ketone Ester (R)-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle 31P Magnetic Resonance Spectroscopy
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Donnie Cameron, Adrian Soto-Mota, David R. Willis, Jane Ellis, Nathan E. K. Procter, Richard Greenwood, Neil Saunders, Rolf F. Schulte, Vassilios S. Vassiliou, Damian J. Tyler, Albrecht Ingo Schmid, Christopher T. Rodgers, Paul N. Malcolm, Kieran Clarke, Michael P. Frenneaux, and Ladislav Valkovič
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ketone monoester ,ketone bodies ,phosphorus MRS ,31P-MRS ,heart ,skeletal muscle ,Physiology ,QP1-981 - Abstract
In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23–70 years for cardiac 31P-MRS, and 16 aged 60–75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (−28.8%, p ≪ 0.001; −28.2%, p = 0.02; and −49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in 31P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function.
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- 2022
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15. Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited
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William D. Watson, Peregrine G. Green, Ladislav Valkovič, Neil Herring, Stefan Neubauer, and Oliver J. Rider
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GTN ,cardiac energetics ,31P magnetic resonance spectroscopy ,preload ,cardiomyopathy ,Physiology ,QP1-981 - Abstract
Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion.Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN.Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p
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- 2021
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16. Measuring inorganic phosphate and intracellular pH in the healthy and hypertrophic cardiomyopathy hearts by in vivo 7T 31P-cardiovascular magnetic resonance spectroscopy
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Ladislav Valkovič, William T. Clarke, Albrecht I. Schmid, Betty Raman, Jane Ellis, Hugh Watkins, Matthew D. Robson, Stefan Neubauer, and Christopher T. Rodgers
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31P CMRS ,7T ,Cardiac intracellular pH ,3D-CSI ,Cardiac Pi ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Cardiovascular phosphorus MR spectroscopy (31P-CMRS) is a powerful tool for probing energetics in the human heart, through quantification of phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. In principle, 31P-CMRS can also measure cardiac intracellular pH (pHi) and the free energy of ATP hydrolysis (ΔGATP). However, these require determination of the inorganic phosphate (Pi) signal frequency and amplitude that are currently not robustly accessible because blood signals often obscure the Pi resonance. Typical cardiac 31P-CMRS protocols use low (e.g. 30°) flip-angles and short repetition time (TR) to maximise signal-to-noise ratio (SNR) within hardware limits. Unfortunately, this causes saturation of Pi with negligible saturation of the flowing blood pool. We aimed to show that an adiabatic 90° excitation, long-TR, 7T 31P-CMRS protocol will reverse this balance, allowing robust cardiac pHi measurements in healthy subjects and patients with hypertrophic cardiomyopathy (HCM). Methods The cardiac Pi T1 was first measured by the dual TR technique in seven healthy subjects. Next, ten healthy subjects and three HCM patients were scanned with 7T 31P-MRS using long (6 s) TR protocol and adiabatic excitation. Spectra were fitted for cardiac metabolites including Pi. Results The measured Pi T1 was 5.0 ± 0.3 s in myocardium and 6.4 ± 0.6 s in skeletal muscle. Myocardial pH was 7.12 ± 0.04 and Pi/PCr ratio was 0.11 ± 0.02. The coefficients of repeatability were 0.052 for pH and 0.027 for Pi/PCr quantification. The pH in HCM patients did not differ (p = 0.508) from volunteers. However, Pi/PCr was higher (0.24 ± 0.09 vs. 0.11 ± 0.02; p = 0.001); Pi/ATP was higher (0.44 ± 0.14 vs. 0.24 ± 0.05; p = 0.002); and PCr/ATP was lower (1.78 ± 0.07 vs. 2.10 ± 0.20; p = 0.020), in HCM patients, which is in agreement with previous reports. Conclusion A 7T 31P-CMRS protocol with adiabatic 90° excitation and long (6 s) TR gives sufficient SNR for Pi and low enough blood signal to permit robust quantification of cardiac Pi and hence pHi. Pi was detectable in every subject scanned for this study, both in healthy subjects and HCM patients. Cardiac pHi was unchanged in HCM patients, but both Pi/PCr and Pi/ATP increased that indicate an energetic impairment in HCM. This work provides a robust technique to quantify cardiac Pi and pHi.
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- 2019
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17. Multinuclear MRS at 7T Uncovers Exercise Driven Differences in Skeletal Muscle Energy Metabolism Between Young and Seniors
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Patrik Krumpolec, Radka Klepochová, Ivica Just, Marjeta Tušek Jelenc, Ivan Frollo, Jozef Ukropec, Barbara Ukropcová, Siegfried Trattnig, Martin Krššák, and Ladislav Valkovič
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magnetic resonance spectroscopy ,muscle energy metabolism ,saturation transfer ,phosphomonoesters ,carnosine ,Physiology ,QP1-981 - Abstract
Purpose: Aging is associated with changes in muscle energy metabolism. Proton (1H) and phosphorous (31P) magnetic resonance spectroscopy (MRS) has been successfully applied for non-invasive investigation of skeletal muscle metabolism. The aim of this study was to detect differences in adenosine triphosphate (ATP) production in the aging muscle by 31P-MRS and to identify potential changes associated with buffer capacity of muscle carnosine by 1H-MRS.Methods: Fifteen young and nineteen elderly volunteers were examined. 1H and 31P-MRS spectra were acquired at high field (7T). The investigation included carnosine quantification using 1H-MRS and resting and dynamic 31P-MRS, both including saturation transfer measurements of phosphocreatine (PCr), and inorganic phosphate (Pi)-to-ATP metabolic fluxes.Results: Elderly volunteers had higher time constant of PCr recovery (τPCr) in comparison to the young volunteers. Exercise was connected with significant decrease in PCr-to-ATP flux in both groups. Moreover, PCr-to-ATP flux was significantly higher in young compared to elderly both at rest and during exercise. Similarly, an increment of Pi-to-ATP flux with exercise was found in both groups but the intergroup difference was only observed during exercise. Elderly had lower muscle carnosine concentration and lower postexercise pH. A strong increase in phosphomonoester (PME) concentration was observed with exercise in elderly, and a faster Pi:PCr kinetics was found in young volunteers compared to elderly during the recovery period.Conclusion: Observations of a massive increment of PME concentration together with high Pi-to-ATP flux during exercise in seniors refer to decreased ability of the muscle to meet the metabolic requirements of exercise and thus a limited ability of seniors to effectively support the exercise load.
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- 2020
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18. Differences in Muscle Metabolism Between Triathletes and Normally Active Volunteers Investigated Using Multinuclear Magnetic Resonance Spectroscopy at 7T
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Radka Klepochová, Ladislav Valkovič, Thomas Hochwartner, Christoph Triska, Norbert Bachl, Harald Tschan, Siegfried Trattnig, Michael Krebs, and Martin Krššák
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proton and phosphorus magnetic resonance spectroscopy ,skeletal muscle ,oxygen uptake ,muscle training status ,energy metabolism ,Physiology ,QP1-981 - Abstract
Purpose: The influence of endurance training on skeletal muscle metabolism can currently be studied only by invasive sampling or through a few related parameters that are investigated by either proton (1H) or phosphorus (31P) magnetic resonance spectroscopy (MRS). The aim of this study was to compare the metabolic differences between endurance-trained triathletes and healthy volunteers using multi-parametric data acquired by both, 31P- and 1H-MRS, at ultra-high field (7T) in a single experimental protocol. This study also aimed to determine the interrelations between these MRS-derived metabolic parameters.Methods: Thirteen male triathletes and ten active male volunteers participated in the study. Proton MRS data from the vastus lateralis yielded concentrations of acetylcarnitine, carnosine, and intramyocellular lipids (IMCL). For the measurement of phosphodiesters (PDEs), inorganic phosphate (Pi), phosphocreatine (PCr), and maximal oxidative capacity (Qmax) phosphorus MRS data were acquired at rest, during 6 min of submaximal exercise and following immediate recovery.Results: The triathletes exhibited significantly higher IMCL levels, higher initial rate of PCr resynthesis (VPCr) during the recovery period, a shorter PCr recovery time constant (τPCr), and higher Qmax. Multivariate stepwise regression analysis identified PDE as the strongest independent predictor of whole-body maximal oxygen uptake (VO2max).Conclusion: In conclusion, we cannot suggest a single MRS-based parameter as an exclusive biomarker of muscular fitness and training status. There is, rather, a combination of different parameters, assessable during a single multi-nuclear MRS session that could be useful for further cross-sectional and/or focused interventional studies on skeletal muscle fitness and training effects.
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- 2018
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19. OXSA: An open-source magnetic resonance spectroscopy analysis toolbox in MATLAB.
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Lucian A B Purvis, William T Clarke, Luca Biasiolli, Ladislav Valkovič, Matthew D Robson, and Christopher T Rodgers
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Medicine ,Science - Abstract
In vivo magnetic resonance spectroscopy provides insight into metabolism in the human body. New acquisition protocols are often proposed to improve the quality or efficiency of data collection. Processing pipelines must also be developed to use these data optimally. Current fitting software is either targeted at general spectroscopy fitting, or for specific protocols. We therefore introduce the MATLAB-based OXford Spectroscopy Analysis (OXSA) toolbox to allow researchers to rapidly develop their own customised processing pipelines. The toolbox aims to simplify development by: being easy to install and use; seamlessly importing Siemens Digital Imaging and Communications in Medicine (DICOM) standard data; allowing visualisation of spectroscopy data; offering a robust fitting routine; flexibly specifying prior knowledge when fitting; and allowing batch processing of spectra. This article demonstrates how each of these criteria have been fulfilled, and gives technical details about the implementation in MATLAB. The code is freely available to download from https://github.com/oxsatoolbox/oxsa.
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- 2017
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20. Using a whole-body 31P birdcage transmit coil and 16-element receive array for human cardiac metabolic imaging at 7T.
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Ladislav Valkovič, Iulius Dragonu, Salam Almujayyaz, Alex Batzakis, Liam A J Young, Lucian A B Purvis, William T Clarke, Tobias Wichmann, Titus Lanz, Stefan Neubauer, Matthew D Robson, Dennis W J Klomp, and Christopher T Rodgers
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Medicine ,Science - Abstract
Cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) provides unique insight into the mechanisms of heart failure. Yet, clinical applications have been hindered by the restricted sensitivity of the surface radiofrequency-coils normally used. These permit the analysis of spectra only from the interventricular septum, or large volumes of myocardium, which may not be meaningful in focal disease. Löring et al. recently presented a prototype whole-body (52 cm diameter) transmit/receive birdcage coil for 31P at 7T. We now present a new, easily-removable, whole-body 31P transmit radiofrequency-coil built into a patient-bed extension combined with a 16-element receive array for cardiac 31P-MRS.A fully-removable (55 cm diameter) birdcage transmit coil was combined with a 16-element receive array on a Magnetom 7T scanner (Siemens, Germany). Electro-magnetic field simulations and phantom tests of the setup were performed. In vivo maps of B1+, metabolite signals, and saturation-band efficiency were acquired across the torsos of eight volunteers.The combined (volume-transmit, local receive array) setup increased signal-to-noise ratio 2.6-fold 10 cm below the array (depth of the interventricular septum) compared to using the birdcage coil in transceiver mode. The simulated coefficient of variation for B1+ of the whole-body coil across the heart was 46.7% (surface coil 129.0%); and the in vivo measured value was 38.4%. Metabolite images of 2,3-diphosphoglycerate clearly resolved the ventricular blood pools, and muscle tissue was visible in phosphocreatine (PCr) maps. Amplitude-modulated saturation bands achieved 71±4% suppression of phosphocreatine PCr in chest-wall muscles. Subjects reported they were comfortable.This easy-to-assemble, volume-transmit, local receive array coil combination significantly improves the homogeneity and field-of-view for metabolic imaging of the human heart at 7T.
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- 2017
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21. CROP - The Clinico-Radiologico-Ophthalmological Paradox in Multiple Sclerosis: Are Patterns of Retinal and MRI Changes Heterogeneous and Thus Not Predictable?
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Fahmy Aboulenein-Djamshidian, Martin Krššák, Nermin Serbecic, Helmut Rauschka, Sven Beutelspacher, Ivica Just Kukurová, Ladislav Valkovič, Adnan Khan, Daniela Prayer, and Wolfgang Kristoferitsch
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Medicine ,Science - Abstract
To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration.28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study.There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability.Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.
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- 2015
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22. Detection and alterations of acetylcarnitine ( <scp>AC</scp> ) in human liver by <scp> 1 H MRS </scp> at <scp>3T</scp> after supplementation with <scp>l</scp> ‐carnitine
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Dragana Savic, Ferenc E. Mózes, Peregrine G. Green, Matthew K. Burrage, Mette Skalshøi Kjær, Leanne Hodson, Stefan Neubauer, Michael Pavlides, and Ladislav Valkovič
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Radiology, Nuclear Medicine and imaging - Published
- 2022
23. Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging
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Shveta Monga, Ladislav Valkovič, Damian Tyler, Craig A. Lygate, Oliver Rider, Saul G. Myerson, Stefan Neubauer, and Masliza Mahmod
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Predictive Value of Tests ,Humans ,Radiology, Nuclear Medicine and imaging ,Aortic Valve Stenosis ,Cardiology and Cardiovascular Medicine ,Magnetic Resonance Imaging - Abstract
Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS). Proton MRS allows the assessment of myocardial triglyceride content and creatine concentration. Phosphorous MRS allows noninvasive in vivo quantification of the phosphocreatine-to-adenosine triphosphate ratio, a measure of cardiac energy status that is reduced in patients with severe AS. This review summarizes the changes to cardiac substrate and high-energy phosphorous metabolism and how they affect cardiac function in AS. The authors focus on the role of MRS to assess these metabolic changes, and potentially guide future (cellular) metabolic therapy in AS.
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- 2022
24. Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin:The Randomized, Controlled EMPA-VISION Trial
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Moritz J. Hundertmark, Amanda Adler, Charalambos Antoniades, Ruth Coleman, Julian L. Griffin, Rury R. Holman, Hanan Lamlum, Jisoo Lee, Daniel Massey, Jack J.J.J. Miller, Joanne E. Milton, Shveta Monga, Ferenc E. Mózes, Areesha Nazeer, Betty Raman, Oliver Rider, Christopher T. Rodgers, Ladislav Valkovič, Eleanor Wicks, Masliza Mahmod, and Stefan Neubauer
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sodium-glucose transporter proteins ,Physiology (medical) ,empagliflozin ,heart failure ,Cardiology and Cardiovascular Medicine ,magnetic resonance spectroscopy - Abstract
BACKGROUND: Sodium–glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness. METHODS: EMPA-VISION is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr:ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated. RESULTS: Empagliflozin treatment did not change cardiac energetics (ie, PCr:ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin – placebo], –0.25 [95% CI, –0.58 to 0.09]; P =0.14) or HFpEF (adjusted mean treatment difference, –0.16 [95% CI, –0.60 to 0.29]; P =0.47]. Likewise, there were no changes in PCr:ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, –0.13 [95% CI, –0.35 to 0.09]; P =0.23) or HFpEF (adjusted mean treatment difference, –0.22 [95% CI, –0.66 to 0.23]; P =0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed. CONCLUSIONS: In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03332212.
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- 2023
25. Maternal cardiac changes in women with obesity and gestational diabetes mellitus
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Sharmaine Thirunavukarasu, Faiza Ansari, Richard Cubbon, Karen Forbes, Chiara Bucciarelli-Ducci, David E. Newby, Marc R. Dweck, Oliver J. Rider, Ladislav Valkovič, Christopher T. Rodgers, Damian J. Tyler, Amrit Chowdhary, Nicholas Jex, Sindhoora Kotha, Lara Morley, Hui Xue, Peter Swoboda, Peter Kellman, John P. Greenwood, Sven Plein, Thomas Everett, Eleanor Scott, Eylem Levelt, Thirunavukarasu, Sharmaine [0000-0003-2535-8407], Levelt, Eylem [0000-0002-3799-7102], and Apollo - University of Cambridge Repository
- Subjects
Advanced and Specialized Nursing ,Diabetes, Gestational ,Adenosine Triphosphate ,Pregnancy ,Endocrinology, Diabetes and Metabolism ,Pregnancy Trimester, Third ,Internal Medicine ,Humans ,Female ,Heart ,Obesity - Abstract
Background- Gestational diabetes mellitus (GDM) is the most prevalent metabolic disorder during pregnancy and is associated with increased risks of cardiovascular morbidity and mortality in later life. Compromised cardiac energy production is an important contributor to most forms of heart disease. The changes in myocardial energetics in GDM have not been characterized previously. Objective- We investigated if women with GDM in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function or tissue characteristics. Methods- Thirty-eight healthy pregnant (HP) women and thirty women with GDM were recruited. Participants underwent phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine to ATP ratio (PCr/ATP)), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS) and mitral in-flow E/A ratio. Results- Participants were matched for age, gestational age and ethnicity. The women with GDM had higher body-mass index (27±4 versus 33±5kg/m2; p=0.0001), systolic (115±11 versus 121±13mmHg; p=0.04) and diastolic (72±7 versus 76±9mmHg; p=0.04) blood pressure. There was no difference in NTproBNP concentrations between the groups. The women with GDM had lower myocardial PCr/ATP ratio (2.2±0.3 versus 1.9±0.4; p Conclusions- Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared to lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM.
- Published
- 2023
26. 29 Role of cardiac energetics in aortic stenosis disease progression: identifying the high-risk metabolic phenotype
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Shveta Monga, Ladislav Valkovič, Masliza Mahmod, Saul G Myerson, Stefan Neubauer, and Oliver J Rider
- Published
- 2023
27. 30 A randomised double-blind placebo-controlled study of fenofibrate as a metabolic modulator to augment cardiac physiology in moderate-severe aortic stenosis
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Shveta Monga, Ladislav Valkovič, Saul G Myerson, Stefan Neubauer, Masliza Mahmod, and Oliver J Rider
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- 2023
28. Efficacy and Tolerability of AXA1125 (Endogenous Metabolic Modulator) in Fatigue-Predominant Long COVID: A Randomized, Double-Blind, Controlled Study
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Lucy Elizabeth Mary Finnigan, Mark Philip Cassar, Margaret James Koziel, Joel Pradines, Hanan Lamlum, Karim Azer, Dan Kirby, Hugh Montgomery, Stefan Neubauer, Ladislav Valkovič, and Betty Raman
- Published
- 2023
29. Compartment-based reconstruction of 3D acquisition-weighted 31P cardiac magnetic resonance spectroscopic imaging at 7 T:A reproducibility study
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Andrew Tyler, Jane Ellis, Justin Y. C. Lau, Jack J. Miller, Paul A. Bottomley, Christopher T. Rodgers, Damian J. Tyler, and Ladislav Valkovič
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spectroscopy ,cardiac ,7 T ,SLAM ,Molecular Medicine ,Radiology, Nuclear Medicine and imaging ,Spectroscopy ,SLIM - Abstract
Even at 7 T, cardiac 31P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T. Twelve healthy volunteers were scanned twice. Each scan session consisted of a 6.5-min 3D acquisition-weighted (AW) cardiac 31P phase encode-based MRSI acquisition and two 6.5-min truncated k-space acquisitions with increased averaging (4 × 4 × 4 central k-space phase encodes and fractional SLAM [fSLAM] optimized k-space phase encodes). Spectra were reconstructed using (i) AW Fourier reconstruction; (ii) AW SLAM; (iii) AW SLIM; (iv) 4 × 4 × 4 SLAM; (v) 4 × 4 × 4 SLIM; and (vi) fSLAM acquisition–reconstruction combinations. The phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio, the PCr SNR, and spatial response functions were computed, in addition to coefficients of reproducibility and variability. Using the compartment-based reconstruction algorithms with the AW 31P acquisition resulted in a significant increase in SNR compared with previously published Fourier-based MRSI reconstruction methods while maintaining the measured PCr/ATP ratio and improving interscan reproducibility. The alternative acquisition strategies with truncated k-space performed no better than the common AW approach. Compartment-based spectroscopy approaches provide an attractive reconstruction method for cardiac 31P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k-space sampling strategy.
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- 2023
30. Design and rationale of the EMPA‐VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure
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Eleanor Wicks, Hanan Lamlum, Jyothis T. George, Olorunsola F. Agbaje, Christopher T. Rodgers, Rury R. Holman, Oliver J Rider, Ladislav Valkovič, Heiko G. Niessen, Rolf Grempler, Stefan Neubauer, Moritz Hundertmark, Joanne E. Milton, Jisoo Lee, Ruth L. Coleman, Masliza Mahmod, Rodgers, Christopher [0000-0003-1275-1197], and Apollo - University of Cambridge Repository
- Subjects
31P-MRS ,Trial design ,medicine.medical_specialty ,Study Designs ,Empagliflozin ,Heart failure ,Placebo ,31P‐MRS ,Glucosides ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Benzhydryl Compounds ,Study Design ,Ejection fraction ,business.industry ,Diabetes ,Type 2 Diabetes Mellitus ,medicine.disease ,Clinical trial ,Diabetes Mellitus, Type 2 ,RC666-701 ,Cohort ,Cardiology ,Quality of Life ,Cardiology and Cardiovascular Medicine ,business ,SGLT2 inhibitors - Abstract
Aims Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium-glucose co-transporter-2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR-Reduced trial and cardiovascular mortality in the EMPA-REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR). Methods and results The EMPA-VISION trial is a double-blind, randomized, placebo-controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine-to-adenosine triphosphate ratio, as measured by 31Phosphorus-MRS. Conclusions EMPA-VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR-Reduced and EMPEROR-Preserved).
- Published
- 2021
31. Detection and alterations of acetylcarnitine (AC) in human liver by
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Dragana, Savic, Ferenc E, Mózes, Peregrine G, Green, Matthew K, Burrage, Mette Skalshøi, Kjaer, Leanne, Hodson, Stefan, Neubauer, Michael, Pavlides, and Ladislav, Valkovič
- Abstract
Acetylcarnitine can be assessed in vivo using proton MRS (Baseline acetylcarnitine levels were quantified using a STEAM sequence with prolonged TE in 15 healthy adults. Using STEAM with four different TEs was evaluated in phantoms. To assess reproducibility of the measurements, five of the participants had repeatedThere was good separation between the acetylcarnitine and fat in the phantoms using TE = 100 ms. Hepatic acetylcarnitine levels were reproducible (coefficient of reproducibility = 0.049%) and there was a significant (p 0.001) increase in the relative abundance after a single supplementation of l-carnitine. Hepatic allylic, methyl, and methylene peaks were not altered by l-carnitine supplementation in healthy volunteers.Our results demonstrate that our
- Published
- 2022
32. OP2 A randomised double-blind placebo-controlled study of fenofibrate as a metabolic modulator to augment cardiac physiology in moderate-severe aortic stenosis
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Shveta Monga, Ladislav Valkovič, Saul G Myerson, Stefan Neubauer, Masliza Mahmod, and Oliver J Rider
- Published
- 2022
33. Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy
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John Farrant, Susanna Dodd, Carly Vaughan, Anna Reid, Matthias Schmitt, Clifford Garratt, Mohammed Akhtar, Masliza Mahmod, Stefan Neubauer, Robert M Cooper, Sanjay K Prasad, Anvesha Singh, Ladislav Valkovič, Betty Raman, Zakariye Ashkir, Dannii Clayton, Olatz Baroja, Beatriz Duran, Catherine Spowart, Emma Bedson, Josephine H Naish, Chris Harrington, and Christopher A Miller
- Subjects
Cardiology and Cardiovascular Medicine - Abstract
AimsHypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.MethodsThe Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I–III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.ConclusionTEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.Trial registration numbersNCT04706429andISRCTN57145331.
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- 2023
34. Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study
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Lucy E.M. Finnigan, Mark Philip Cassar, Margaret James Koziel, Joel Pradines, Hanan Lamlum, Karim Azer, Dan Kirby, Hugh Montgomery, Stefan Neubauer, Ladislav Valkovič, and Betty Raman
- Subjects
General Medicine - Published
- 2023
35. Rapid, ‐insensitive, dual‐band quasi‐adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux
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A Tyler, Jack J. Miller, Paul A. Bottomley, Ladislav Valkovič, Christopher T. Rodgers, William Watson, Lisa C. Heather, Damian J. Tyler, Kerstin N. Timm, Matthew Kerr, and Lau Jyc.
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Work (thermodynamics) ,Materials science ,biology ,Pulse (signal processing) ,Analytical chemistry ,Signal ,030218 nuclear medicine & medical imaging ,Phosphocreatine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Bloch equations ,biology.protein ,Degradation (geology) ,Radiology, Nuclear Medicine and imaging ,Creatine kinase ,Saturation (chemistry) ,030217 neurology & neurosurgery - Abstract
PURPOSE Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through the creatine kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification of total ATP utilization is currently underexplored, as it requires simultaneous saturation of inorganic phosphate ( Pi ) and PCr. This is challenging, as currently available saturation pulses reduce the already-low γ-ATP signal present. METHODS Using a hybrid optimal-control and Shinnar-Le Roux method, a quasi-adiabatic RF pulse was designed for the dual saturation of PCr and Pi to enable determination of total ATP utilization. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before being applied to perfused rat hearts at 11.7 T. RESULTS The quasi-adiabatic pulse was insensitive to a >2.5-fold variation in B1 , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective B1 . This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux (4.24 ± 0.8 mM/s, SEM) was not significantly different from degradation flux (6.88 ± 2 mM/s, P = .06) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi -to-ATP measurement that may explain a trend suggesting a possible imbalance. CONCLUSIONS This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.
- Published
- 2021
36. Evaluation of acute supplementation with the ketone ester (R)-3-Hydroxybutyl-(R)-3-hydroxybutyrate (deltaG) in healthy volunteers by cardiac and skeletal muscle P-31 magnetic resonance spectroscopy
- Author
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Donnie Cameron, Adrian Soto-Mota, David R. Willis, Jane Ellis, Nathan E. K. Procter, Richard Greenwood, Neil Saunders, Rolf F. Schulte, Vassilios S. Vassiliou, Damian J. Tyler, Albrecht Ingo Schmid, Christopher T. Rodgers, Paul N. Malcolm, Kieran Clarke, Michael P. Frenneaux, Ladislav Valkovič, Rodgers, Christopher [0000-0003-1275-1197], and Apollo - University of Cambridge Repository
- Subjects
31P-MRS ,P-31-MRS ,7T ,Physiology ,Physiology (medical) ,ketone bodies ,phosphorus MRS ,QP1-981 ,heart ,ketone monoester ,skeletal muscle ,3T - Abstract
In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23-70 years for cardiac 31P-MRS, and 16 aged 60-75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (-28.8%, p ≪ 0.001; -28.2%, p = 0.02; and -49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in 31P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function., This study was funded by a combination of seed funding awarded to D.C. by Norwich Medical School, University of East Anglia, and funding from TdeltaS., Ltd. L.V is a Sir Henry Dale Fellow supported jointly by the Wellcome Trust and the Royal Academy (#221805/Z/20/Z), and he also acknowledges the support of the Slovak Grant Agencies VEGA (#2/0003/20) and APVV (#19-0032). A.I.S. was supported by The Austrian Science Fund (FWF) Schrödinger Fellowship (J 4043). C.T.R. is funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (#098436/Z/12/B) and acknowledges support from the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. J.E. was funded by the Medical Research Council.
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- 2022
37. MR Spectroscopy of the Liver
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Ladislav Valkovič, Martin Gajdošík, Marek Chmelík, and Martin Krššák
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- 2022
38. Evaluation of Acute Supplementation With the Ketone Ester (
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Donnie, Cameron, Adrian, Soto-Mota, David R, Willis, Jane, Ellis, Nathan E K, Procter, Richard, Greenwood, Neil, Saunders, Rolf F, Schulte, Vassilios S, Vassiliou, Damian J, Tyler, Albrecht Ingo, Schmid, Christopher T, Rodgers, Paul N, Malcolm, Kieran, Clarke, Michael P, Frenneaux, and Ladislav, Valkovič
- Abstract
In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (
- Published
- 2021
39. Impaired myocardial energetics limits cardiac functional reserve and leads to exercise-induced pulmonary congestion in heart failure with preserved ejection fraction
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Jack J. Miller, Moritz Hundertmark, Matthew K. Burrage, William Watson, Oliver J Rider, Andrew Lewis, V Ferreira, Ladislav Valkovič, Nikant Sabharwal, S Neubauer, and Jennifer J Rayner
- Subjects
Myocardial energetics ,medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,Medicine ,Pulmonary congestion ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business - Abstract
Background Abnormal cardiac mitochondrial function and energetics may be a unifying feature in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity and symptoms in patients with HFpEF. Purpose We sought to determine if impaired myocardial energetics limits cardiac exercise reserve and leads to exercise-induced pulmonary congestion in HFpEF. Methods 42 patients across the spectrum of diastolic dysfunction and HFpEF (controls n=10; type 2 diabetes (T2DM) n=9; HFpEF n=14; severe diastolic dysfunction due to cardiac amyloid n=9) (Fig. 1a) underwent assessment of cardiac energetics (myocardial phosphocreatine to adenosine triphosphate ratio, PCr/ATP) and function using cardiovascular magnetic resonance (CMR) imaging and echocardiography, and lung-water using a novel pulmonary proton-density MR sequence. Studies were performed at rest and during exercise (20W for 6 minutes) using a CMR-ergometer. Results Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio, p The novel pulmonary proton-density sequence provided images that scaled linearly with water content (validated using a water-doped sponge phantom; r 0.98, p Conclusion A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. This energetic deficit is related to markedly abnormal cardiac exercise responses, which leads to transient pulmonary congestion. The findings support an energetic basis for impaired cardiac reserve and exercise-induced pulmonary congestion in HFpEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Baseline clinical and CMR parametersExercise cardiopulmonary parameters
- Published
- 2021
40. Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI
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Christopher T. Rodgers, Jane Ellis, Peter J. Friend, Richard Colling, Ladislav Valkovič, Carlo D L Ceresa, Ferenc E. Mózes, Liam A J Young, Constantin C. Coussios, Young, Liam AJ [0000-0003-0720-421X], Valkovič, Ladislav [0000-0003-2567-3642], Rodgers, Christopher T [0000-0003-1275-1197], and Apollo - University of Cambridge Repository
- Subjects
temperature sensitivity ,Relaxometry ,medicine.medical_treatment ,MOLLI T1 ,Cold storage ,Liver transplantation ,static cold storage ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Machine perfusion ,liver transplantation ,proton density fat fraction ,business.industry ,Chemistry ,medicine.disease ,Magnetic Resonance Imaging ,Transplantation ,Fatty Liver ,Perfusion ,Liver ,normothermic machine perfusion ,Liver function ,Steatosis ,Nuclear medicine ,business ,Ex vivo - Abstract
Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265, Funder: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Funder: Royal Society, PURPOSE: A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool. Therefore, better noninvasive tests are required to determine which livers will function following implantation and hence can be safely transplanted. This study assesses the temperature sensitivity of proton density fat fraction and relaxometry parameters and examines their potential for assessment of liver function ex vivo. METHODS: Six ex vivo human livers were scanned during static cold storage following normothermic machine perfusion. Proton density fat fraction, T1 , T2 , and T2∗ were measured repeatedly during cooling on ice. Temperature corrections were derived from these measurements for the parameters that showed significant variation with temperature. RESULTS: Strong linear temperature sensitivities were observed for proton density fat fraction (R2 = 0.61, P < .001) and T1 (R2 = 0.78, P < .001). Temperature correction according to a linear model reduced the coefficient of repeatability in these measurements by 41% and 36%, respectively. No temperature dependence was observed in T2 or T2∗ measurements. Comparing livers deemed functional and nonfunctional during normothermic machine perfusion by hemodynamic and biochemical criteria, T1 differed significantly: 516 ± 50 ms for functional versus 679 ± 60 ms for nonfunctional, P = .02. CONCLUSION: Temperature correction is essential for robust measurement of proton density fat fraction and T1 in cold-stored human livers. These parameters may provide a noninvasive measure of viability for transplantation.
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- 2021
41. Energetic basis for exercise-induced pulmonary congestion in heart failure with preserved ejection fraction
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Jack J. Miller, William Watson, Andrew Lewis, Moritz Hundertmark, Ladislav Valkovič, Jennifer J Rayner, Vanessa M Ferreira, Matthew K. Burrage, Nikant Sabharwal, Stefan Neubauer, and Oliver J Rider
- Subjects
Male ,medicine.medical_specialty ,Pulmonary Circulation ,Heart Failure, Diastolic/diagnosis ,heart failure ,Hyperemia ,Pulmonary Edema ,Cardiac energetics ,Severity of Illness Index ,Exercise/adverse effects ,Ventricular Function, Left ,Original Research Articles ,Physiology (medical) ,Internal medicine ,Medicine ,magnetic resonance imaging ,Humans ,Pulmonary Edema/diagnosis ,Hyperemia/complications ,Exercise ,Aged ,Heart Failure ,Heart Failure, Diastolic ,medicine.diagnostic_test ,exercise ,business.industry ,Magnetic resonance imaging ,Stroke Volume ,Exercise capacity ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Lung water ,Echocardiography ,Heart failure ,Heart Function Tests ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Cardiology ,Exercise Test ,Female ,Pulmonary congestion ,Disease Susceptibility ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business ,Biomarkers - Abstract
Supplemental Digital Content is available in the text., Background: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. Methods: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. Results: Paralleling the stepwise decline in diastolic function across the groups (E/e′ ratio; P
- Published
- 2021
42. MR compatible ergometers for dynamic 31P MRS
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Petr Sedivy, Ladislav Valkovič, Monika Dezortova, Miloslav Drobny, Milan Hájek, Jan Rydlo, and Martin Krššák
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Health, Toxicology and Mutagenesis ,Intracellular pH ,Biomedical Engineering ,Context (language use) ,Oxidative phosphorylation ,General Biochemistry, Genetics and Molecular Biology ,Phosphocreatine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Nuclear magnetic resonance ,Artificial Intelligence ,medicine ,General Pharmacology, Toxicology and Pharmaceutics ,General Immunology and Microbiology ,medicine.diagnostic_test ,Muscle fatigue ,General Neuroscience ,Magnetic resonance imaging ,General Medicine ,030205 complementary & alternative medicine ,chemistry ,Anaerobic glycolysis ,030220 oncology & carcinogenesis ,General Agricultural and Biological Sciences ,Flux (metabolism) - Abstract
Magnetic Resonance (MR) compatible ergometers are specialized ergometers used inside the MR scanners for the characterization of tissue metabolism changes during physical stress. They are most commonly used for dynamic phosphorous magnetic resonance spectroscopy (31P MRS), but can also be used for lactate production measurements, perfusion studies using arterial spin labelling or muscle oxygenation measurements by blood oxygen dependent contrast sequences. We will primarily discuss the importance of ergometers in the context of dynamic 31P MRS. Dynamic 31P MRS can monitor muscle fatigue and energy reserve during muscle contractions as well as the dynamics of recuperation of skeletal muscle tissue during the following recovery through signal changes of phosphocreatine (PCr), inorganic phosphate and adenosine triphosphate (ATP). Based on the measured data it is possible to calculate intracellular pH, metabolic flux of ATP through creatine-kinase reaction, anaerobic glycolysis and oxidative phosphorylation and other metabolic parameters as mitochondrial capacity. This review primarily focuses on describing various technical designs of MR compatible ergometers for dynamic 31P MRS that must be constructed with respect to the presence of magnetic field. It is also expected that the construction of ergometers will be easy for the handling and well accepted by examined subjects.
- Published
- 2019
43. Letter regarding the article ‘Cardiac energetics in patients with chronic heart failure and iron deficiency: an in‐vivo <scp> 31 P </scp> magnetic resonance spectroscopy study’
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Matthew K. Burrage, Ladislav Valkovič, and Oliver Rider
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Cardiology and Cardiovascular Medicine - Published
- 2022
44. Water‐suppression cycling 3‐T cardiac 1 H‐MRS detects altered creatine and choline in patients with aortic or mitral stenosis
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Christopher T. Rodgers, M A Peterzan, Ferenc E. Mózes, Oliver J Rider, Ladislav Valkovič, and Belinda Ding
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Adult ,Male ,1H‐MRS ,PRESS ,medicine.medical_specialty ,cardiac ,Proton Magnetic Resonance Spectroscopy ,Metabolite ,heart ,Signal-To-Noise Ratio ,Creatine ,Choline ,Cohort Studies ,Young Adult ,chemistry.chemical_compound ,Internal medicine ,Mole ,medicine ,Humans ,Mitral Valve Stenosis ,Radiology, Nuclear Medicine and imaging ,3 T ,human ,Research Articles ,Spectroscopy ,Aged ,STEAM ,Reproducibility ,Phantoms, Imaging ,Myocardium ,Reproducibility of Results ,Water ,Aortic Valve Stenosis ,Repeatability ,Middle Aged ,medicine.disease ,Healthy Volunteers ,Stenosis ,Endocrinology ,chemistry ,water‐suppression cycling ,Metabolome ,Molecular Medicine ,Female ,Body mass index ,Research Article - Abstract
Cardiac proton spectroscopy (1H‐MRS) is widely used to quantify lipids. Other metabolites (e.g. creatine and choline) are clinically relevant but more challenging to quantify because of their low concentrations (approximately 10 mmol/L) and because of cardiac motion. To quantify cardiac creatine and choline, we added water‐suppression cycling (WSC) to two single‐voxel spectroscopy sequences (STEAM and PRESS). WSC introduces controlled residual water signals that alternate between positive and negative phases from transient to transient, enabling robust phase and frequency correction. Moreover, a particular weighted sum of transients eliminates residual water signals without baseline distortion. We compared WSC and the vendor's standard ‘WET’ water suppression in phantoms. Next, we tested repeatability in 10 volunteers (seven males, three females; age 29.3 ± 4.0 years; body mass index [BMI] 23.7 ± 4.1 kg/m2). Fat fraction, creatine concentration and choline concentration when quantified by STEAM‐WET were 0.30% ± 0.11%, 29.6 ± 7.0 μmol/g and 7.9 ± 6.7 μmol/g, respectively; and when quantified by PRESS‐WSC they were 0.30% ± 0.15%, 31.5 ± 3.1 μmol/g and 8.3 ± 4.4 μmol/g, respectively. Compared with STEAM‐WET, PRESS‐WSC gave spectra whose fitting quality expressed by Cramér‐Rao lower bounds improved by 26% for creatine and 32% for choline. Repeatability of metabolite concentration measurements improved by 72% for creatine and 40% for choline. We also compared STEAM‐WET and PRESS‐WSC in 13 patients with severe symptomatic aortic or mitral stenosis indicated for valve replacement surgery (10 males, three females; age 75.9 ± 6.3 years; BMI 27.4 ± 4.3 kg/m2). Spectra were of analysable quality in eight patients for STEAM‐WET, and in nine for PRESS‐WSC. We observed comparable lipid concentrations with those in healthy volunteers, significantly reduced creatine concentrations, and a trend towards decreased choline concentrations. We conclude that PRESS‐WSC offers improved performance and reproducibility for the quantification of cardiac lipids, creatine and choline concentrations in healthy volunteers at 3 T. It also offers improved performance compared with STEAM‐WET for detecting altered creatine and choline concentrations in patients with valve disease., A water‐suppression cycling (WSC) module was added to STEAM and PRESS single‐voxel spectroscopy pulse sequences. We report an improvement in the accuracy and repeatability in the quantification of low concentration metabolites like creatine and choline in the myocardium using WSC compared with the vendor's standard WET water suppression. This allowed us to detect a significant decrease in creatine levels in patients with symptomatic aortic stenosis in less than half the scan time compared with the vendor's standard WET water suppression.
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- 2021
45. Effects of contrast agents on relaxation properties of 31P metabolites
- Author
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Jack J. Miller, Oliver J Rider, Ivan Frollo, Ladislav Valkovič, Christopher T. Rodgers, Ines Abdesselam, Justin Y. C. Lau, Damian J. Tyler, Valkovič, Ladislav [0000-0003-2567-3642], Lau, Justin YC [0000-0001-7316-811X], Rider, Oliver J [0000-0003-1295-7769], Tyler, Damian J [0000-0002-0780-8905], Rodgers, Christopher T [0000-0003-1275-1197], Miller, Jack JJ [0000-0002-6258-1299], and Apollo - University of Cambridge Repository
- Subjects
In vivo magnetic resonance spectroscopy ,Gadolinium ,Spin–lattice relaxation ,chemistry.chemical_element ,contrast agent ,magnetic resonance spectroscopy ,Iopamidol ,Ferumoxytol ,chemistry.chemical_compound ,Nuclear magnetic resonance ,Gadopentetic acid ,chemistry ,In vivo ,medicine ,phosphorus‐31 ,Radiology, Nuclear Medicine and imaging ,Chelation ,phosphorus-31 ,medicine.drug - Abstract
Purpose Phosphorous MR spectroscopy (31P‐MRS) forms a powerful, non‐invasive research tool to quantify the energetics of the heart in diverse patient populations. 31P‐MRS is frequently applied alongside other radiological examinations, many of which use various contrast agents that shorten relaxation times of water in conventional proton MR, for a better characterisation of cardiac function, or following prior computed tomography (CT). It is, however, unknown whether these agents confound 31P‐MRS signals, for example, 2,3‐diphosphoglycerate (2,3‐DPG). Methods In this work, we quantitatively assess the impact of non‐ionic, low osmolar iodinated CT contrast agent (iopamidol/Niopam), gadolinium chelates (linear gadopentetic acid dimeglumine/Magnevist and macrocyclic gadoterate meglumine/Dotarem) and superparamagnetic iron oxide nanoparticles (ferumoxytol/Feraheme) on the nuclear T1 and T2 of 31P metabolites (ie, 2,3‐DPG), and 1H in water in live human blood and saline phantoms at 11.7 T. Results Addition of all contrast agents led to significant shortening of all relaxation times in both 1H and 31P saline phantoms. On the contrary, the T1 relaxation time of 2,3‐DPG in blood was significantly shortened only by Magnevist (P = .03). Similarly, the only contrast agent that influenced the T2 relaxation times of 2,3‐DPG in blood samples was ferumoxytol (P = .02). Conclusion Our results show that, unlike conventional proton MR, phosphorus MRS is unconfounded in patients who have had prior CT with contrast, not all gadolinium‐based contrast agents influence 31P‐MRS data in vivo, and that ferumoxytol is a promising contrast agent for the reduction in 31P‐MRS blood‐pool signal.
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- 2021
46. Hydration and glycogen affect T
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Ferenc E, Mózes, Ladislav, Valkovič, Michael, Pavlides, Matthew D, Robson, and Elizabeth M, Tunnicliffe
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Adult ,Male ,Time Factors ,Phantoms, Imaging ,Water ,Middle Aged ,Magnetic Resonance Imaging ,Young Adult ,Liver ,Linear Models ,Humans ,Computer Simulation ,Female ,Glycogen - Abstract
T
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- 2020
47. Quantifying the effect of dobutamine stress on myocardial Pi and pH in healthy volunteers: A 31 P MRS study at 7T
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Stefan Neubauer, Moritz Hundertmark, William T. Clarke, Elizabeth M. Tunnicliffe, Albrecht Ingo Schmid, Andrew Apps, M A Peterzan, Christopher T. Rodgers, Oliver J Rider, Jane Ellis, Lau Jyc., Damian J. Tyler, Ladislav Valkovič, Apps, Andrew [0000-0003-0478-8918], Valkovič, Ladislav [0000-0003-2567-3642], Lau, Justin YC [0000-0001-7316-811X], Clarke, William [0000-0001-7159-7025], Rodgers, Christopher T [0000-0003-1275-1197], Schmid, Albrecht Ingo [0000-0002-5196-151X], and Apollo - University of Cambridge Repository
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medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,7T ,Phosphocreatine ,Cardiomyopathy ,030218 nuclear medicine & medical imaging ,Phosphates ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adenosine Triphosphate ,Internal medicine ,Dobutamine ,medicine ,Pi ,Humans ,Radiology, Nuclear Medicine and imaging ,STEAM ,Chemistry ,Myocardium ,myocardial pH ,Repeatability ,Dobutamine stress ,Hydrogen-Ion Concentration ,medicine.disease ,Endocrinology ,31P MRS ,Catecholamine ,Adenosine triphosphate ,cardiac energetics ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Purpose Phosphorus spectroscopy (31P-MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3-diphosphoglycerate (2,3-DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3-DPG. Methods Using a 31P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3-DPG, the Pi peak was cleanly resolved. Resting state UTE-chemical shift imaging (PCr/ATP) and STEAM 31P-MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion. Results We achieved a clean Pi signal both at rest and stress with good 2,3-DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P = .95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P = .81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy. Conclusion We introduced a method that can resolve Pi using 7 Tesla STEAM 31P-MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics.
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- 2020
- Full Text
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48. Use of cardiac magnetic resonance to detect changes in metabolism in heart failure
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Oliver J Rider, Jack J. Miller, Ladislav Valkovič, Andrew Lewis, Damian J. Tyler, Stefan Neubauer, and William Watson
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medicine.diagnostic_test ,business.industry ,fungi ,Cardiomyopathy ,food and beverages ,Magnetic resonance imaging ,Metabolism ,Nuclear magnetic resonance spectroscopy ,Review Article on The Use of Advanced Cardiac MRI in Heart Failure and Cardiac Hypertrophy ,030204 cardiovascular system & hematology ,medicine.disease ,030218 nuclear medicine & medical imaging ,Phosphocreatine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Nuclear magnetic resonance ,chemistry ,Heart failure ,medicine ,Cardiology and Cardiovascular Medicine ,Spectroscopy ,business ,Adenosine triphosphate - Abstract
The heart has a massive adenosine triphosphate (ATP) requirement, produced from the oxidation of metabolic substrates such as fat and glucose. Magnetic resonance spectroscopy offers a unique opportunity to probe this biochemistry: (31)Phosphorus spectroscopy can demonstrate the production of ATP and quantify levels of the transport molecule phosphocreatine while 13Carbon spectroscopy can demonstrate the metabolic fates of glucose in real time. These techniques allow the metabolic deficits in heart failure to be interrogated and can be a potential future clinical tool.
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- 2020
49. Effects of contrast agents on relaxation properties of
- Author
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Ladislav, Valkovič, Justin Y C, Lau, Ines, Abdesselam, Oliver J, Rider, Ivan, Frollo, Damian J, Tyler, Christopher T, Rodgers, and Jack J J, Miller
- Abstract
Phosphorous MR spectroscopy (In this work, we quantitatively assess the impact of non-ionic, low osmolar iodinated CT contrast agent (iopamidol/Niopam), gadolinium chelates (linear gadopentetic acid dimeglumine/Magnevist and macrocyclic gadoterate meglumine/Dotarem) and superparamagnetic iron oxide nanoparticles (ferumoxytol/Feraheme) on the nuclear TAddition of all contrast agents led to significant shortening of all relaxation times in bothOur results show that, unlike conventional proton MR, phosphorus MRS is unconfounded in patients who have had prior CT with contrast, not all gadolinium-based contrast agents influence
- Published
- 2020
50. Quantifying the effect of dobutamine stress on myocardial Pi and pH in healthy volunteers: A
- Author
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Andrew, Apps, Ladislav, Valkovič, Mark, Peterzan, Justin Y C, Lau, Moritz, Hundertmark, William, Clarke, Elizabeth M, Tunnicliffe, Jane, Ellis, Damian J, Tyler, Stefan, Neubauer, Oliver J, Rider, Christopher T, Rodgers, and Albrecht Ingo, Schmid
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STEAM ,Full Papers—Spectroscopic Methodology ,Magnetic Resonance Spectroscopy ,Phosphocreatine ,Full Paper ,7T ,Myocardium ,myocardial pH ,Hydrogen-Ion Concentration ,Phosphates ,Adenosine Triphosphate ,31P MRS ,Dobutamine ,Humans ,cardiac energetics - Abstract
Purpose Phosphorus spectroscopy (31P‐MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3‐diphosphoglycerate (2,3‐DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3‐DPG. Methods Using a 31P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3‐DPG, the Pi peak was cleanly resolved. Resting state UTE‐chemical shift imaging (PCr/ATP) and STEAM 31P‐MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion. Results We achieved a clean Pi signal both at rest and stress with good 2,3‐DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P = .95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P = .81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy. Conclusion We introduced a method that can resolve Pi using 7 Tesla STEAM 31P‐MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics.
- Published
- 2019
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