Imperial College London

ProfessorDudleyPennell

Faculty of MedicineNational Heart & Lung Institute

Professor of Cardiology
 
 
 
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Contact

 

+44 (0)20 7351 8810d.pennell

 
 
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Location

 

CMR UnitRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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1024 results found

Huo Z, Wen K, Luo Y, Neji R, Kunze KP, Ferreira PF, Pennell DJ, Scott AD, Nielles-Vallespin Set al., 2024, Referenceless Nyquist ghost correction outperforms standard navigator-based method and improves efficiency of in vivo diffusion tensor cardiovascular magnetic resonance, Magnetic Resonance in Medicine, Vol: 91, Pages: 2403-2416, ISSN: 0740-3194

PURPOSE: The study aims to assess the potential of referenceless methods of EPI ghost correction to accelerate the acquisition of in vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) data using both computational simulations and data from in vivo experiments. METHODS: Three referenceless EPI ghost correction methods were evaluated on mid-ventricular short axis DT-CMR spin echo and STEAM datasets from 20 healthy subjects at 3T. The reduced field of view excitation technique was used to automatically quantify the Nyquist ghosts, and DT-CMR images were fit to a linear ghost model for correction. RESULTS: Numerical simulation showed the singular value decomposition (SVD) method is the least sensitive to noise, followed by Ghost/Object method and entropy-based method. In vivo experiments showed significant ghost reduction for all correction methods, with referenceless methods outperforming navigator methods for both spin echo and STEAM sequences at b = 32, 150, 450, and 600   smm - 2 $$ {\mathrm{smm}}^{-2} $$ . It is worth noting that as the strength of the diffusion encoding increases, the performance gap between the referenceless method and the navigator-based method diminishes. CONCLUSION: Referenceless ghost correction effectively reduces Nyquist ghost in DT-CMR data, showing promise for enhancing the accuracy and efficiency of measurements in clinical practice without the need for any additional reference scans.

Journal article

Gatehouse PD, Captur G, Nielles-Vallespin S, Pennell DJet al., 2024, Field camera input to virtual phantom (ViP) scanner acquisitions for quality assurance of derived MRI quantities: first implementation and proof-of-principle., MAGMA, Vol: 37, Pages: 199-213

INTRODUCTION: Quality assurance (QA) of measurements derived from MRI can require complicated test phantoms. This work introduces a new QA concept using gradient and transmit RF recordings by a limited field camera (FC) to govern the previous Virtual Phantom (ViP) method. The purpose is to describe the first technical implementation of combined FC+ViP, and illustrate its performance in examples, including quantitative first-pass myocardial perfusion. MATERIALS AND METHODS: The new QA concept starts with a synthetic test object (STO) representing some arbitrary test input. Using recordings of the unmodified standard sequence by a gradient and RF waveform camera (FC), ViP calculates by Bloch simulation the continuous RF signal emitted by the STO during this sequence (hence FC+ViP). During nominally identical repetition of the sequence acquisition, ViP transmits the RF signal for scanner reception, reconstruction and any further parametric derivations by the unmodified standard scanner image reconstruction and analysis software. RESULTS: The scanner outputs were compared against the input STOs. CONCLUSION: First proof-of-principle was discussed and supported by correlation between scanner outputs and the input STO. The work makes no claim that its examples are valid QA methods. It concludes by proposing a new industrial standard for QA without the FC.

Journal article

Owen R, Buchan R, Frenneaux M, Jarman JWE, Baruah R, Lota AS, Halliday BP, Roberts AM, Izgi C, Van Spall H, Michos ED, McMurray J, Januzzi JL, Pennell DJ, Cook SA, Ware JS, Barton PJ, Gregson J, Prasad SK, Tayal Uet al., 2024, Sex differences in the clinical presentation and natural history of dilated cardiomyopathy, JACC: Heart Failure, Vol: 12, Pages: 352-363, ISSN: 2213-1787

Background: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved.Objective: To investigate sex-specific differences in DCM presentation, natural history, and prognostic factors.Methods We conducted a prospective observational cohort study of DCM patients, assessing baseline characteristics, CMR-imaging, biomarkers and genotype. The composite outcome was cardiovascular mortality or major heart-failure (HF) events. Results: Overall, 206 females and 398 males with DCM were followed for a median of 3.9 years. At baseline female patients had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less prevalent mid-wall myocardial fibrosis (23% vs 42%) and lower high sensitivity cardiac troponin (hs-cTnI) than males (all p<0.05), with no difference in time from diagnosis, age at enrollment, NT-proBNP levels, pathogenic DCM genetic variants, myocardial fibrosis extent or medications used for HF. Despite a more favourable profile, the risk of the primary outcome at 2 years was higher in females than males (8.6% vs 4.4%, adjusted hazard ratio 3.14, 95% CI 1.55 to 6.35, p=0.001). Between 2-5 years, the effect of sex as a prognostic modifier attenuated. Age, mid-wall myocardial fibrosis, LVEF, left atrial volume, NT-proBNP, hs-cTnI, left bundle branch block and NYHA class were not sex specific prognostic factors. Conclusions: We identify a novel paradox in prognosis for females with DCM. Female DCM patients have a paradoxical early increase in major HF events despite less prevalent myocardial fibrosis and a milder phenotype at presentation. Future studies should interrogate the mechanistic basis for these sex differences.

Journal article

Pan Y, Varghese J, Tong MS, Yildiz VO, Azzu A, Gatehouse P, Wage R, Nielles-Vallespin S, Pennell DJ, Jin N, Bacher M, Hayes C, Speier P, Simonetti OPet al., 2024, Two-center validation of Pilot Tone based cardiac triggering of a comprehensive cardiovascular magnetic resonance examination., Int J Cardiovasc Imaging, Vol: 40, Pages: 261-273

The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. To evaluate the performance of PTC triggering in a comprehensive CMR exam. Fifteen volunteers and 20 patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.

Journal article

Nazir MS, Okafor J, Murphy T, Andres MS, Ramalingham S, Rosen SD, Chiribiri A, Plein S, Prasad S, Mohiaddin R, Pennell DJ, Baksi AJ, Khattar R, Lyon ARet al., 2024, Echocardiography versus Cardiac MRI for Measurement of Left Ventricular Ejection Fraction in Individuals with Cancer and Suspected Cardiotoxicity., Radiol Cardiothorac Imaging, Vol: 6

Purpose To compare left ventricular ejection fraction (LVEF) measured with echocardiography and cardiac MRI in individuals with cancer and suspected cardiotoxicity and assess the potential effect on downstream clinical decision-making. Materials and Methods In this prospective, single-center observational cohort study, participants underwent same-day two-dimensional (2D) echocardiography and cardiac MRI between 2011 and 2021. Participants with suboptimal image quality were excluded. A subset of 74 participants also underwent three-dimensional (3D) echocardiography. The agreement of LVEF derived from each modality was assessed using Bland-Altman analysis and at relevant thresholds for cardiotoxicity. Results A total of 745 participants (mean age, 60 years ± 5 [SD]; 460 [61.7%] female participants) underwent same-day echocardiography and cardiac MRI. According to Bland-Altman analysis, the mean bias was -3.7% ± 7.6 (95% limits of agreement [LOA]: -18.5% to 11.1%) for 2D echocardiography versus cardiac MRI. In 74 participants who underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, the mean LVEFs were 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (P < .001). At the 50% LVEF threshold for detection of cardiotoxicity, there was disagreement for 9.3% of participants with 2D echocardiography and cardiac MRI. Agreement was better with 3D echocardiography and cardiac MRI (mean bias, -1.6% ± 6.3 [95% LOA: -13.9% to 10.7%]) compared with 2D echocardiography and cardiac MRI (mean bias, -2.8% ± 6.3 [95% LOA: -15.2% to 9.6%]; P = .016). Conclusion Two-dimensional echocardiography had variations of ±15% for LVEF measurement compared with cardiac MRI in participants with cancer and led to misclassification of approximately 10% of participants for cardiotoxicity detection. Three-dimensional echocardiography had better agreement with cardiac MRI and should be used as first-line imaging. Keywords: Ec

Journal article

Roehl M, Conway M, Ghonim S, Ferreira P, Nielles-Vallespin S, Babu-Narayan S, Pennell D, Gatehouse P, Scott Aet al., 2024, STEAM-SASHA: A novel approach for blood and fat suppressed native T1 measurement in the right ventricular myocardium, Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN: 0968-5243

Objective:The excellent blood and fat suppression of stimulated echo acquisition mode (STEAM) can be combined with saturation recovery single-shot acquisition (SASHA) in a novel STEAM-SASHA sequence for right ventricular (RV) native T1 mapping.Materials and methods:STEAM-SASHA splits magnetization preparation over two cardiac cycles, nulling blood signal and allowing fat signal to decay. Breath-hold T1 mapping was performed in a T1 phantom and twice in 10 volunteers using STEAM-SASHA and a modified Look-Locker sequence at peak systole at 3T. T1 was measured in 3 RV regions, the septum and left ventricle (LV).Results:In phantoms, MOLLI under-estimated while STEAM-SASHA over-estimated T1, on average by 3.0% and 7.0% respectively, although at typical 3T myocardial T1 (T1 > 1200 ms) STEAM-SASHA was more accurate. In volunteers, T1 was higher using STEAM-SASHA than MOLLI in the LV and septum (p = 0.03, p = 0.006, respectively), but lower in RV regions (p > 0.05). Inter-study, inter-observer and intra-observer coefficients of variation in all regions were < 15%. Blood suppression was excellent with STEAM-SASHA and noise floor effects were minimal.Discussion:STEAM-SASHA provides accurate and reproducible T1 in the RV with excellent blood and fat suppression. STEAM-SASHA has potential to provide new insights into pathological changes in the RV in future studies.

Journal article

Jones RE, Hammersley DJ, Zheng S, McGurk KA, de Marvao A, Theotokis PI, Owen R, Tayal U, Rea G, Hatipoglu S, Buchan RJ, Mach L, Curran L, Lota AS, Simard F, Reddy RK, Talukder S, Yoon WY, Vazir A, Pennell DJ, O'Regan DP, Baksi AJ, Halliday BP, Ware JS, Prasad SKet al., 2024, Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease, European Journal of Heart Failure, Vol: 26, Pages: 46-55, ISSN: 1388-9842

AimsTo examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD).Methods and resultsThis study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22–2.01, p < 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%, p < 0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%, p < 0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4–4.3, p = 0.4). NI-LGE was not independently associated with adverse clinical outcomes.ConclusionRare pathogenic variants in DCM-associated genes impact left ventricular remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.

Journal article

Tänzer M, Ferreira P, Scott A, Khalique Z, Dwornik M, Rajakulasingam R, de Silva R, Pennell D, Yang G, Rueckert D, Nielles-Vallespin Set al., 2024, Correction to: Faster Diffusion Cardiac MRI with Deep Learning-Based Breath Hold Reduction, Medical Image Understanding and Analysis, Publisher: Springer International Publishing, Pages: C1-C1, ISBN: 9783031120527

Book chapter

Curran L, Simoes Monteiro de Marvao A, Inglese P, McGurk K, Schiratti P-R, Clement A, Zheng S, Li S, Pua CJ, Shah M, Jafari M, Theotokis P, Buchan R, Jurgens S, Raphael C, Baksi A, Pantazis A, Halliday B, Pennell D, Bai W, Chin C, Tadros R, Bezzina C, Watkins H, Cook S, Prasad S, Ware J, O'Regan Det al., 2023, Genotype-phenotype taxonomy of hypertrophic cardiomyopathy, Circulation: Genomic and Precision Medicine, Vol: 16, Pages: 559-570, ISSN: 2574-8300

Background:Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes but there is no systematic framework for classifying morphology or assessing associated risks. Here we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.Methods:We enrolled 436 HCM patients (median age 60 years; 28.8% women) with clinical, genetic and imaging data. Anindependent cohort of 60 HCM patients from Singapore (median age 59 years; 11% women) and a reference population from UK Biobank (n = 16,691, mean age 55 years; 52.5% women) were also recruited. We used machine learning to analyse the three-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.Results:Carriers of pathogenic or likely pathogenic variants (P/LP) for HCM had lower left ventricular mass, but greater basalseptal hypertrophy, with reduced lifespan (mean follow-up 9.9 years) compared to genotype negative individuals(hazard ratio: 2.66; 95% confidence interval [CI]: 1.42-4.96; P < 0.002). Four main phenotypic branches were identified using unsupervised learning of three-dimensional shape: 1) non-sarcomeric hypertrophy with co-existing hypertension; 2) diffuse and basal asymmetric hypertrophy associated with outflow tract obstruction; 3) isolated basal hypertrophy; 4) milder non-obstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for P/LP variants: 2.18 [95% CI: 1.93-2.28, P = 0.0001]). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalisable to an independent cohort (trustworthiness M1: 0.86-0.88).Conclusions:We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severi

Journal article

Arai AE, Schulz-Menger J, Shah DJ, Han Y, Bandettini WP, Abraham A, Woodard PK, Selvanayagam JB, Hamilton-Craig C, Tan R-S, Carr J, Teo L, Kramer CM, Wintersperger BJ, Harisinghani MG, Flamm SD, Friedrich MG, Klem I, Raman SV, Haverstock D, Liu Z, Brueggenwerth G, Santiuste M, Berman DS, Pennell DJet al., 2023, Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease., J Am Coll Cardiol, Vol: 82, Pages: 1828-1838

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagno

Journal article

Hammersley D, Jones R, Owen R, Mach L, Lota A, Khalique Z, de Marvao A, Androulakis E, Hatipoglu S, Gulati A, Reddy R, Yoon WY, Talukder S, Shah R, Baruah R, Guha K, Pantazis A, Baksi J, Gregson J, Cleland J, Tayal U, Pennell D, Ware J, Halliday B, Prasad Set al., 2023, Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy, European Journal of Heart Failure, Vol: 25, Pages: 2050-2059, ISSN: 1388-9842

AimsTo characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM).Methods and resultsWe conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H−/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D−), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36–58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52–59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H−/D+, higher in early-NICM H+/D− and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5–10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36–11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73–8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73–15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11–34) months.ConclusionEarly-NICM is not benign. Fibrosis develops early in the phenot

Journal article

Jones RE, Gruszczyk AV, Schmidt C, Hammersley DJ, Mach L, Lee M, Wong J, Yang M, Hatipoglu S, Lota AS, Barnett SN, Toscano-Rivalta R, Owen R, Raja S, De Robertis F, Smail H, De-Souza A, Stock U, Kellman P, Griffin J, Dumas M-E, Martin JL, Saeb-Parsy K, Vazir A, Cleland JGF, Pennell DJ, Bhudia SK, Halliday BP, Noseda M, Frezza C, Murphy MP, Prasad SKet al., 2023, Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease, Nature Cardiovascular Research, Vol: 2, Pages: 733-745, ISSN: 2731-0590

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

Journal article

Alemany I, Rose JN, Ferreira PF, Pennell DJ, Nielles-Vallespin S, Scott AD, Doorly DJet al., 2023, Realistic numerical simulations of diffusion tensor cardiovascular magnetic resonance: the effects of perfusion and membrane permeability, Magnetic Resonance in Medicine, Vol: 90, Pages: 1641-1656, ISSN: 0740-3194

PurposeTo study the sensitivity of diffusion tensor cardiovascular magnetic resonance (DT-CMR) to microvascular perfusion and changes in cell permeability.MethodsMonte Carlo (MC) random walk simulations in the myocardium have been performed to simulate self-diffusion of water molecules in histology-based media with varying extracellular volume fraction (ECV) and permeable membranes. The effect of microvascular perfusion on simulations of the DT-CMR signal has been incorporated by adding the contribution of particles traveling through an anisotropic capillary network to the diffusion signal. The simulations have been performed considering three pulse sequences with clinical gradient strengths: monopolar stimulated echo acquisition mode (STEAM), monopolar pulsed-gradient spin echo (PGSE), and second-order motion-compensated spin echo (MCSE).ResultsReducing ECV intensifies the diffusion restriction and incorporating membrane permeability reduces the anisotropy of the diffusion tensor. Widening the intercapillary velocity distribution results in increased measured diffusion along the cardiomyocytes long axis when the capillary networks are anisotropic. Perfusion amplifies the mean diffusivity for STEAM while the opposite is observed for short diffusion encoding time sequences (PGSE and MCSE).ConclusionThe effect of perfusion on the measured diffusion tensor is reduced using an increased reference b-value. Our results pave the way for characterization of the response of DT-CMR to microstructural changes underlying cardiac pathology and highlight the higher sensitivity of STEAM to permeability and microvascular circulation due to its longer diffusion encoding time.

Journal article

Pan Y, Varghese J, Tong MS, Yildiz VO, Azzu A, Gatehouse P, Wage R, Nielles-Vallespin S, Pennell D, Jin N, Bacher M, Hayes C, Speier P, Simonetti OPet al., 2023, Two-center validation of Pilot Tone Based Cardiac Triggering of a Comprehensive Cardiovascular Magnetic Resonance Examination., Res Sq

BACKGROUND: The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. PURPOSE: To evaluate the performance of PTC triggering in a comprehensive CMR exam. METHODS: Fifteen volunteers and twenty patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. RESULTS: Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. CONCLUSION: PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.

Journal article

Kwan CT, Ching OHS, Yap PM, Fung SY, Tang HS, Tse WWV, Kwan CNF, Chow YHP, Yiu NC, Lee YP, Lau JWK, Fong AHT, Ren Q-W, Wu M-Z, Wan EYF, Lee KCK, Leung CY, Li A, Montero D, Vardhanabhuti V, Hai JSH, Siu C-W, Tse H-F, Zingan V, Zhao X, Wang H, Pennell DJ, Mohiaddin R, Senior R, Yiu K-H, Ng M-Yet al., 2023, Intraventricular 4D flow cardiovascular magnetic resonance for assessing patients with heart failure with preserved ejection fraction: a pilot study, INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, ISSN: 1569-5794

Journal article

Jones RE, Zaidi HA, Hammersley DJ, Hatipoglu S, Owen R, Balaban G, de Marvao A, Simard F, Lota AS, Mahon C, Almogheer B, Mach L, Musella F, Chen X, Gregson J, Lazzari L, Ravendren A, Leyva F, Zhao S, Vazir A, Lamata P, Halliday BP, Pennell DJ, Bishop MJ, Prasad SKet al., 2023, Comprehensive phenotypic characterization of late gadolinium enhancement predicts sudden cardiac death in coronary artery disease, JACC: Cardiovascular Imaging, Vol: 16, Pages: 628-638, ISSN: 1936-878X

BackgroundLate gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD).ObjectivesThe authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD).MethodsPatients with stable CAD were prospectively recruited into a CMR registry. LGE quantification of core infarction and the peri-infarct zone (PIZ) was performed alongside computational image analysis to extract morphologic and texture scar microstructure features. The primary outcome was SCD or aborted SCD.ResultsOf 437 patients (mean age: 64 years; mean left ventricular ejection fraction [LVEF]: 47%) followed for a median of 6.3 years, 49 patients (11.2%) experienced the primary outcome. On multivariable analysis, PIZ mass and core infarct mass were independently associated with the primary outcome (per gram: HR: 1.07 [95% CI: 1.02-1.12]; P = 0.002 and HR: 1.03 [95% CI: 1.01-1.05]; P = 0.01, respectively), and the addition of both parameters improved discrimination of the model (Harrell’s C-statistic: 0.64-0.79). PIZ mass, however, did not provide incremental prognostic value over core infarct mass based on Harrell’s C-statistic or risk reclassification analysis. Severely reduced LVEF did not predict the primary endpoint after adjustment for scar mass. On scar microstructure analysis, the number of LGE islands in addition to scar transmurality, radiality, interface area, and entropy were all associated with the primary outcome after adjustment for severely reduced LVEF and New York Heart Association functional class of >1. No scar microstructure feature remained associated with the primary endpoint when PIZ mass and core infarct mass were added to the regression models.ConclusionsComprehensive LGE characterization independently predicted SCD risk beyond conventional predictors used in im

Journal article

Krupickova S, Voges I, Mohiaddin R, Bautista C, Li W, Herberg J, Daubeney PEF, Pennell DJ, Fraisse Aet al., 2023, Short-term outcome of late gadolinium changes detected on cardiovascular magnetic resonance imaging following coronavirus disease 2019 Pfizer/BioNTech vaccine-related myocarditis in adolescents, PEDIATRIC RADIOLOGY, Vol: 53, Pages: 892-899, ISSN: 0301-0449

Journal article

Allen JJ, Keegan J, Mathew G, Conway M, Jenkins S, Pennell DJ, Nielles-Vallespin S, Gatehouse P, Babu-Narayan SVet al., 2023, Fully-modelled blood-focused variable inversion times for 3D late gadolinium-enhanced imaging, Magnetic Resonance Imaging, Vol: 98, Pages: 44-54, ISSN: 0730-725X

PurposeVariable heart rate during single-cycle inversion-recovery Late Gadolinium-Enhanced (LGE) scanning degrades image quality, which can be mitigated using Variable Inversion Times (VTIs) in real-time response to R-R interval changes. We investigate in vivo and in simulations an extension of a single-cycle VTI method previously applied in 3D LGE imaging, that now fully models the longitudinal magnetisation (fmVTI).MethodsThe VTI and fmVTI methods were used to perform 3D LGE scans for 28 3D LGE patients, with qualitative image quality scores assigned for left atrial wall clarity and total ghosting. Accompanying simulations of numerical phantom images were assessed in terms of ghosting of normal myocardium, blood, and myocardial scar.ResultsThe numerical simulations for fmVTI showed a significant decrease in blood ghosting (VTI: 410 ± 710, fmVTI: 68 ± 40, p < 0.0005) and scar ghosting (VTI: 830 ± 1300, fmVTI: 510 ± 730, p < 0.02). Despite this, there was no significant change in qualitative image quality scores, either for left atrial wall clarity (VTI: 2.0 ± 1.0, fmVTI: 1.8 ± 1.0, p > 0.1) or for total ghosting (VTI: 1.9 ± 1.0, fmVTI: 2.0 ± 1.0, p > 0.7).ConclusionsSimulations indicated reduced ghosting with the fmVTI method, due to reduced Mz variability in the blood signal. However, other sources of phase-encode ghosting and blurring appeared to dominate and obscure this finding in the patient studies available.

Journal article

Mohiaddin R, Hatipoglu S, 2023, Diagnosis of cardiac sarcoidosis in patients presenting with cardiac arrest or life-threatening arrhythmias, Heart, Vol: 109, Pages: 748-755, ISSN: 1355-6037

Objective Cardiac sarcoidosis (CS) may present with cardiac arrest or life-threatening arrhythmias. There are limited data on this subgroup of patients with CS. Advanced imaging including cardiovascular magnetic resonance (CMR) and cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) are used for diagnosis. This study aimed to describe advanced imaging patterns suggestive of CS among patients presenting with cardiac arrest or life-threatening arrhythmias.Methods An imaging database of a CS referral centre (Royal Brompton Hospital, London) was screened for patients presenting with cardiac arrest or life-threatening arrhythmias and having imaging features of suspected CS. Patients diagnosed with definite or probable/possible CS were included.Results Study population included 60 patients (median age 49 years) with male predominance (76.7%). The left ventricle was usually non-dilated with mildly reduced ejection fraction (53.4±14.8%). CMR studies showed extensive late gadolinium enhancement (LGE) with 5 (4–8) myocardial segments per patient affected; the right ventricular (RV) side of the septum (28/45) and basal anteroseptum (28/45) were most frequently involved. Myocardial inflammation by FDG-PET was detected in 45 out of 58 patients vs 11 out of 33 patients with oedema imaging available on CMR. When PET was treated as reference to detect myocardial inflammation, CMR oedema imaging was 33.3% sensitive and 77% specific.Conclusions In patients with CS presenting with cardiac arrest or life-threatening arrhythmias, LGE was located in areas where the cardiac conduction system travels (basal anteroseptal wall and RV side of the septum). While CMR was the imaging technique that raised possibility of cardiac scarring, oedema imaging had low sensitivity to detect myocardial inflammation compared with FDG-PET.

Journal article

Tang HS, Kwan CT, He J, Ng PP, Hai SHJ, Kwok FYJ, Sze HF, So MH, Lo HY, Fong HTA, Wan EYF, Lee C-H, Yu EYT, Lai YTA, Lee CYJ, Leung ST, Chan HL, Tse HF, Pennell DJ, Mohiaddin RH, Senior R, Yan AT, Yiu K-H, Ng M-Yet al., 2023, Prognostic Utility of Cardiac MRI Myocardial Strain Parameters in Patients With Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study, AMERICAN JOURNAL OF ROENTGENOLOGY, Vol: 220, Pages: 524-538, ISSN: 0361-803X

Journal article

Barbaroux H, Kunze KP, Neji R, Nazir MS, Pennell DJ, Nielles-Vallespin S, Scott AD, Young AAet al., 2023, Automated segmentation of long and short axis DENSE cardiovascular magnetic resonance for myocardial strain analysis using spatio-temporal convolutional neural networks, Journal of Cardiovascular Magnetic Resonance, Vol: 25, Pages: 1-17, ISSN: 1097-6647

BACKGROUND: Cine Displacement Encoding with Stimulated Echoes (DENSE) facilitates the quantification of myocardial deformation, by encoding tissue displacements in the cardiovascular magnetic resonance (CMR) image phase, from which myocardial strain can be estimated with high accuracy and reproducibility. Current methods for analyzing DENSE images still heavily rely on user input, making this process time-consuming and subject to inter-observer variability. The present study sought to develop a spatio-temporal deep learning model for segmentation of the left-ventricular (LV) myocardium, as spatial networks often fail due to contrast-related properties of DENSE images. METHODS: 2D + time nnU-Net-based models have been trained to segment the LV myocardium from DENSE magnitude data in short- and long-axis images. A dataset of 360 short-axis and 124 long-axis slices was used to train the networks, from a combination of healthy subjects and patients with various conditions (hypertrophic and dilated cardiomyopathy, myocardial infarction, myocarditis). Segmentation performance was evaluated using ground-truth manual labels, and a strain analysis using conventional methods was performed to assess strain agreement with manual segmentation. Additional validation was performed using an externally acquired dataset to compare the inter- and intra-scanner reproducibility with respect to conventional methods. RESULTS: Spatio-temporal models gave consistent segmentation performance throughout the cine sequence, while 2D architectures often failed to segment end-diastolic frames due to the limited blood-to-myocardium contrast. Our models achieved a DICE score of 0.83 ± 0.05 and a Hausdorff distance of 4.0 ± 1.1 mm for short-axis segmentation, and 0.82 ± 0.03 and 7.9 ± 3.9 mm respectively for long-axis segmentations. Strain measurements obtained from automatically estimated myo

Journal article

Azzu A, Antonopoulos AS, Krupickova S, Mohiaddin Z, Almogheer B, Vlachopoulos C, Pantazis A, Pennell DJ, Mohiaddin RHet al., 2023, Myocardial strain analysis by cardiac magnetic resonance 3D feature-tracking identifies subclinical abnormalities in patients with neuromuscular disease and no overt cardiac involvement, EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING, Vol: 24, Pages: 503-511, ISSN: 2047-2404

Journal article

Ng M-Y, Kwan CT, Yap PM, Fung SY, Tang HS, Tse WWV, Kwan CNF, Chow YHP, Yiu NC, Lee YP, Fong AHT, Hwang S, Fong ZFW, Ren Q-W, Wu M-Z, Wan EYF, Lee KCK, Leung CY, Li A, Montero D, Vardhanabhuti V, Hai J, Siu C-W, Tse H-F, Pennell DJ, Mohiaddin R, Senior R, Yiu K-Het al., 2023, Diagnostic accuracy of cardiovascular magnetic resonance strain analysis and atrial size to identify heart failure with preserved ejection fraction., Eur Heart J Open, Vol: 3

AIMS: Heart failure with preserved ejection fraction (HFpEF) continues to be a diagnostic challenge. Cardiac magnetic resonance atrial measurement, feature tracking (CMR-FT), tagging has long been suggested to diagnose HFpEF and potentially complement echocardiography especially when echocardiography is indeterminate. Data supporting the use of CMR atrial measurements, CMR-FT or tagging, are absent. Our aim is to conduct a prospective case-control study assessing the diagnostic accuracy of CMR atrial volume/area, CMR-FT, and tagging to diagnose HFpEF amongst patients suspected of having HFpEF. METHODS AND RESULTS: One hundred and twenty-one suspected HFpEF patients were prospectively recruited from four centres. Patients underwent echocardiography, CMR, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements within 24 h to diagnose HFpEF. Patients without HFpEF diagnosis underwent catheter pressure measurements or stress echocardiography to confirm HFpEF or non-HFpEF. Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Fifty-three HFpEF (median age 78 years, interquartile range 74-82 years) and thirty-eight non-HFpEF (median age 70 years, interquartile range 64-76 years) were recruited. Cardiac magnetic resonance left atrial (LA) reservoir strain (ResS), LA area index (LAAi), and LA volume index (LAVi) had the highest diagnostic accuracy (AUCs 0.803, 0.815, and 0.776, respectively). Left atrial ResS, LAAi, and LAVi had significantly better diagnostic accuracy than CMR-FT left ventricle (LV)/right ventricle (RV) parameters and tagging (P < 0.01). Tagging circumferential and radial strain had poor diagnostic accuracy (AUC 0.644 and 0.541, respectively). CONCLUSION: Cardiac magnetic resonance LA ResS, LAAi, and LAVi have the highest diagnostic accuracy to identify HFpEF patients from non-HFpEF patients amongst clinically suspected HFpEF patients. Cardiac magnetic resonance feature tracking LV/RV parameters and tagging

Journal article

Voges I, Caliebe A, Hinz S, Boroni Grazioli S, Gabbert DD, Daubeney PEF, Uebing AS, Pennell DJ, Krupickova Set al., 2023, Pediatric Cardiac Magnetic Resonance Reference Values for Biventricular Volumes Derived From Different Contouring Techniques, JOURNAL OF MAGNETIC RESONANCE IMAGING, Vol: 57, Pages: 774-788, ISSN: 1053-1807

Journal article

Hammersley DJ, Zaidi HA, Jones RE, Hatipoglu S, Androulakis E, Mach L, Lota AS, Tayal U, Khalique Z, De Marvao A, Baruah R, Guha K, Pennell DJ, Halliday BP, Bishop MJ, Prasad SKet al., 2023, 13 Myocardial fibrosis entropy is associated with life-threatening arrhythmia in non-ischaemic cardiomyopathy, Publisher: BMJ PUBLISHING GROUP, Pages: A10-A10, ISSN: 1355-6037

Conference paper

Conway M, Vallespin SN, Ferreira P, Scott A, Roehl M, McCarthy K, Smith GC, Ho SY, Li W, Pennell DJ, Babu-Narayan Set al., 2023, IN-VIVO DIFFUSION TENSOR CARDIOVASCULAR MAGNETIC RESONANCE DETECTS THE ARRANGEMENT AND DYNAMIC NATURE OF RIGHT VENTRICULAR MICROSTRUCTURE IN HEALTH AND DISEASE, 17th Annual Congress of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A2-A3, ISSN: 1355-6037

Conference paper

Tsoumani Z, Nakou E, Alpendurada F, Pennell DJ, Lota Aet al., 2023, COMPARISON OF NATIVE MYOCARDIAL T1 AND T2 MAPPING AT 1.5T AND 3T IN HEALTHY VOLUNTEERS FOLLOWING INSTALLATION OF NEW SCANNERS, 17th Annual Congress of the British-Society-of-Cardiovascular-Magnetic-Resonance (BSCMR), Publisher: BMJ PUBLISHING GROUP, Pages: A17-A18, ISSN: 1355-6037

Conference paper

Ferreira PF, Banerjee A, Scott AD, Khalique Z, Yang G, Rajakulasingam R, Dwornik M, De Silva R, Pennell DJ, Firmin DN, Nielles-Vallespin Set al., 2022, Accelerating Cardiac Diffusion Tensor Imaging With a U-Net Based Model: Toward Single Breath-Hold, JOURNAL OF MAGNETIC RESONANCE IMAGING, Vol: 56, Pages: 1691-1704, ISSN: 1053-1807

Journal article

Fong LCW, Lee NHC, Poon JWL, Chin CWL, He B, Luo L, Chen C, Wan EYF, Pennell DJ, Mohiaddin R, Ng M-Yet al., 2022, Prognostic value of cardiac magnetic resonance derived global longitudinal strain analysis in patients with ischaemic and non-ischaemic dilated cardiomyopathy: a systematic review and meta-analysis, INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, Vol: 38, Pages: 2707-2721, ISSN: 1569-5794

Journal article

Hammersley DJ, Jones RE, Mach L, Owen R, Lota AS, Khalique Z, de Marvao A, Gulati A, Baruah R, Guha K, Ware JS, Cleland JG, Pennell DJ, Halliday BP, Tayal U, Prasad SKet al., 2022, Effect of Diabetes Mellitus on Clinical Phenotype and Cardiovascular Mortality in Non-Ischaemic Dilated Cardiomyopathy, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

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