Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping [Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively] and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis.

Introduction: Dysregulated myocardial calcium handling may be a precursor for heart failure in type 1 (T1D) and type 2 diabetes (T2D). Manganese-enhanced magnetic resonance imaging (MEMRI) is a novel non-invasive method of assessing in vivo myocardial calcium handling. Hypothesis Myocardial calcium handling is impaired in patients with either T1D or T2D, despite normal left ventricular (LV) systolic function. Methods Prospective, multicentre, study in patients with T1D (n=19), T2D (n=30), and healthy volunteers (n=28), all of whom were free of known cardiovascular disease. Cardiac MRI was performed including MEMRI, during which T1 mapping was performed at baseline and every 2.5 min for 30 min after manganese infusion (Figure 1a). The rate of myocardial manganese uptake, determined by Patlak modelling [1]. Results No difference in LV systolic function was observed between groups, but those with T2D had more concentric LV remodelling compared to T1Ds and healthy volunteers (LV mass:volume 0.90±0.16 vs. 0.75±0.09 vs. 0.74±0.10 g/mL, respectively; p=0.001, Table 1). Mean myocardial manganese uptake was significantly lower in both T1Ds (6.47±0.99 mL/100g/min) and T2Ds (6.43±0.77 mL/100g/min) compared with healthy volunteers (8.33±0.77 mL/100g/min; p<0.001 for both, Figure 1b). Conclusion For the first time, we have demonstrated that myocardial calcium handling is impaired in patients with either T1D or T2D despite apparently normal LV systolic function. This may be a precursor to the development of diabetic cardiomyopathy and has implications for developing novel therapeutic targets for its prevention and treatment. [1] Skjold, A et al. J Magn Reson Imag 2006;24:1047-1055 graphic_{ECFA3EC4-96D0-4ADC-8599-3D854C84F04F}graphic_{F1770AC6-718C-4C39-B107-4A5DD60957A8}

Abstract Background There is a high prevalence of subclinical cardiac dysfunction in people with type 2 diabetes (T2D) which is associated with subsequent development of heart failure. Dysregulated myocardial calcium handling has been demonstrated in animal models of T2D and may be a key mechanism driving the development of heart failure. Manganese-enhanced cardiac magnetic resonance imaging (MEMRI) provides a unique method to assess in vivo myocardial calcium handling. Purpose To determine whether myocardial calcium handling is perturbed in people with T2D with no history of cardiovascular disease. We hypothesised that myocardial manganese uptake would be reduced in people with T2D compared with healthy volunteers. Methods Cross-sectional case-control study, adults with (n=20) and without (n=9) T2D underwent both gadolinium-enhanced MRI and MEMRI. Standard gadolinium-enhanced MRI was used to assess cardiac structure, function and tissue characteristics. MEMRI scans were performed within two weeks of the initial scan. Native T1 maps were obtained in the mid-short axis slice position using a Modified Look-Locker Inversion recovery sequence. An intravenous infusion of manganese dipyridoxyl diphosphate (5 μmol/kg (0.1 mL/kg) at 1 mL/min) was administered and T1 maps at the same location were repetitively acquired every 2.5 min for 30 min. Regions of interest were drawn in the inferoseptal segment and blood pool for all T1 maps from 0 to 30 min by a single observer. The primary outcome was the rate of manganese uptake which was assessed by Patlak modelling as a measure of myocardial calcium handling. Manganese uptake constants were compared using analysis of co-variance, with age, sex and body mass index as co-variates. Results Subjects with T2D were older (62±7 vs. 57±5 years, p=0.046) but body mass index (29.0±4.5 vs. 26.2±3.4 kg/m2, p=0.106), systolic (135±16 vs. 134±17 mmHg, p=0.809) and diastolic (81±10 vs. 83±9 mmHg, p=0.736) blood pressures were similar. Compared to control subjects, participants with T2D had normal systolic function but more concentric left ventricular remodelling (mass/volume ratio 0.90±0.14 vs. 0.71±0.06 g/mL, p<0.001) and reduced peak early diastolic strain rate (0.64±0.17 vs. 0.91±0.26 s–1, p=0.002). Myocardial manganese uptake was substantially reduced in people with T2D compared with controls (6.51±1.46 vs. 8.45±2.52 ml/100 g of tissue/min, p=0.003) (Figure 1). Conclusions For the first time, we have demonstrated in vivo that despite no history of cardiovascular disease and normal systolic function, patients with T2D have marked impairment of myocardial calcium handling. This has potential major implications for the pathogenesis, diagnosis and treatment of diabetic cardiomyopathy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and National Institute for Health Research

ObjectivesTo determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19.MethodsIn a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis.ResultsIn 52 patients (median age: 54 (IQR 51–57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms.ConclusionsPatients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities.Trial registration numberNCT04625075.

AIMS:The aim of this study is to quantify altered myocardial calcium handling in non-ischaemic cardiomyopathy using magnetic resonance imaging. METHODS AND RESULTS:Patients with dilated cardiomyopathy (n = 10) or hypertrophic cardiomyopathy (n = 17) underwent both gadolinium and manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers (n = 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model. Compared with healthy volunteers, reduction in T1 with manganese-enhanced magnetic resonance imaging was lower in patients with dilated cardiomyopathy [mean reduction 257 ± 45 (21%) vs. 288 ± 34 (26%) ms, P < 0.001], with higher T1 at 40 min (948 ± 57 vs. 834 ± 28 ms, P < 0.0001). In patients with hypertrophic cardiomyopathy, reductions in T1 were less than healthy volunteers [mean reduction 251 ± 86 (18%) and 277 ± 34 (23%) vs. 288 ± 34 (26%) ms, with and without fibrosis respectively, P < 0.001]. Myocardial manganese uptake was modelled, rate of uptake was reduced in both dilated and hypertrophic cardiomyopathy in comparison with healthy volunteers (mean Ki 19 ± 4, 19 ± 3, and 23 ± 4 mL/100 g/min, respectively; P = 0.0068). In patients with dilated cardiomyopathy, manganese uptake rate correlated with left ventricular ejection fraction (r2 = 0.61, P = 0.009). Rate of myocardial manganese uptake demonstrated stepwise reductions across healthy myocardium, hypertrophic cardiomyopathy without fibrosis and hypertrophic cardiomyopathy with fibrosis providing absolute discrimination between the healthy myocardium and fibrosed myocardium (mean Ki 23 ± 4, 19 ± 3, and 13 ± 4 mL/100 g/min, respectively; P < 0.0001). CONCLUSION:The rate of manganese uptake in both dilated and hypertrophic cardiomyopathy provides a measure of altered myocardial calcium handling. This holds major promise for the detection and monitoring of dysfunctional myocardium, with the potential for early intervention and prognostication.

First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89–0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure–function analysis.

ObjectiveIn a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.MethodsHealthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model.ResultsAfter manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r2=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium.ConclusionsThrough visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases.Trial registration numbersNCT03607669; EudraCT number 2016-003782-25.

Background Widespread abnormalities of the myocardium have been reported in patients with COVID-19. However, these patients often have substantial co-morbidities and it is essential to understand whether cardiac abnormalities represent pre-existing disease or are the consequence of COVID-19. Objective To determine the contribution and cardiac impact of co-morbidities in patients who have recovered from COVID-19. Methods In a prospective observational study, adult patients hospitalized with confirmed COVID-19 were recruited from the Edinburgh Heart Centre between May and November 2020 and compared to healthy and co-morbidity-matched volunteers. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging and coronary computed tomography angiography. Results Twenty-three patients (54±11 years, 20 male) who recovered from COVID-19 were recruited. Half (n=11, 48%) required admission to the intensive care unit and a third (n=7, 31%) received non-invasive or invasive ventilation. Patients had a high prevalence of known cardiovascular disease (n=18, 78%), associated risk factors (n=11, 45%) and coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), myocardial native T1 values (1202±25 versus 1162±27 ms, P=0.008, figure 1) and extracellular volume fraction (31.9±1.7 versus 29.8±0.5 %, P=0.001, figure 1) were higher with no differences in manganese uptake. Compared to co-morbidity-matched volunteers (n=20), there were no differences in native T1 values (1202±25 versus 1196±39 ms, P=0.61, figure 1), extracellular volume fraction (31.9±1.7 versus 31.0±0.5 %, P=0.11), presence of late gadolinium enhancement or manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of concomitant myocardial injury or coronary artery disease. Conclusions Patients who have recovered following hospitalization with COVID-19 have no evidence of a major excess in myocardial injury or dysfunction compared to co-morbidity-matched volunteers. The presence of co-morbidities likely explains many of the previously reported myocardial abnormalities. Conflict of Interest None

We assessed myocardial calcium handling in patients with acute and established myocardial withmanganese-enhanced magnetic resonance imaging (MEMRI). Patients (n=20) with acute myocardial infarction and healthy volunteers (n=20) underwent gadolinium delayed enhanced MRI (DEMRI) and MEMRI (

Background: Previous studies suggest an association between short-term exposure to carbon monoxide and myocardial infarction. We performed a systematic review and meta-analysis to assess current evidence on this association to support the update of the World Health Organization (WHO) Global Air Quality Guidelines. Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials to update the evidence published in a previous systematic review up to 30th September 2018 for studies investigating the association between short-term exposure to ambient carbon monoxide (up to lag of seven days) and emergency department visits or hospital admissions and mortality due to myocardial infarction. Two reviewers assessed potentially eligible studies and performed data extraction independently. Random-effects meta-analysis was used to derive the pooled risk estimate per 1 mg/m(3) increase in ambient carbon monoxide concentration. Risk of bias in individual studies was assessed using a domain-based assessment tool. The overall certainty of the body of evidence was evaluated using an adapted certainty of evidence assessment framework Results: We evaluated 1,038 articles from the previous review and our updated literature search, of which, 26 satisfied our inclusion criteria. Overall, myocardial infarction was associated with exposure to ambient carbon monoxide concentration (risk ratio of 1.052, 95% confidence interval 1.017-1.089 per 1 mg/m(3) increase). A third of studies were assessed to be at high risk of bias (RoB) due to inadequate adjustment for confounding. Using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, the overall evidence was assessed to be of moderate certainty. Conclusions: This review demonstrated that the pooled risk ratio for myocardial infarction was 1.052 (95% CI 1.017-1.089) per 1 mg/m(3) increase in ambient carbon monoxide concentration. However, very few studies originated from lowand middle-income countries.

Background 3 billion people worldwide rely on polluting fuels and technologies for domestic cooking and heating. We estimate the global, regional, and national health burden associated with exposure to household air pollution. Methods For the systematic review and meta-analysis, we systematically searched four databases for studies published from database inception to April 2, 2020, that evaluated the risk of adverse cardiorespiratory, paediatric, and maternal outcomes from exposure to household air pollution, compared with no exposure. We used a random-effects model to calculate disease-specific relative risk (RR) meta-estimates. Household air pollution exposure was defined as use of polluting fuels (coal, wood, charcoal, agricultural wastes, animal dung, or kerosene) for household cooking or heating. Temporal trends in mortality and disease burden associated with household air pollution, as measured by disability-adjusted life-years (DALYs), were estimated from 2000 to 2017 using exposure prevalence data from 183 of 193 UN member states. 95% CIs were estimated by propagating uncertainty from the RR meta-estimates, prevalence of household air pollution exposure, and disease-specific mortality and burden estimates using a simulation-based approach. This study is registered with PROSPERO, CRD42019125060. Findings 476 studies (15.5 million participants) from 123 nations (99[80%]of which were classified as low-income and middle-income) met the inclusion criteria. Household air pollution was positively associated with asthma (RR 1.23, 95% CI 1.11-1-36), acute respiratory infection in both adults (1-53, 1- 22-1.93) and children (1.39, 1. 29-1- 49), chronic obstructive pulmonary disease (1.70, 1.47-1.97), lung cancer (1.69, 1. 44-1.98), and tuberculosis (1.26, 1.08-1.48); cerebrovascular disease (1.09, 1.04-1.14) and ischaeinic heart disease (1.10, 1.09-1-11); and low birthweight (1.36, 1-19-1.55) and stillbirth (1- 22, 1. 06-1. 41); as well as with under-5 (1- 25, 1.18-1-33), respiratory (1-19, 1.18-1- 20), and cardiovascular (1.07, 1.04-1.11) mortality. Household air pollution was associated with 1.8 million (95% CI 1.1-2- 7) deaths and 60.9 million (34.6-93.3) DALYs in 2017, with the burden overwhelmingly experienced in low-income and middle-income countries (LMICs; 60.8 million [34. 6-92. 9] DALYs) compared with high-income countries (0.09 million [0.01-0.40] DALYs). From 2000, mortality associated with household air pollution had reduced by 36% (95% CI 29-43) and disease burden by 30% (25-36), with the greatest reductions observed in higher-income nations. Interpretation The burden of cardiorespiratory, paediatric, and maternal diseases associated with household air pollution has declined worldwide but remains high in the world's poorest regions. Urgent integrated health and energy strategies are needed to reduce the adverse health impact of household air pollution, especially in LMICs. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.

Manganese-enhanced MRI (MEMRI) holds promise in myocardial viability assessment, quantifying infarct and detecting altered calcium-handling. We aimed to validate MEMRI against 18F-FDG positron emission/computed tomography (PET/CT). Male Sprague-Dawley rats (180-300g) underwent coronary artery

Visual Abstract Myocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, 18F-LW223, are suitable for clinical translation; and validate whether 18F-LW223 can detect macrophage-driven inflammation in a rat MI model. Methods: Fifty-one human brain and 29 human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3H-PK11195 and the following ligands: PK11195, PBR28, and our novel compounds (AB5186 and LW223). Naïve rats and mice were used for in vivo PET kinetic studies, radiometabolite studies, and dosimetry experiments. Rats underwent permanent coronary artery ligation and were scanned using PET/CT with an invasive input function at 7 d after MI. For quantification of PET signal in the hypoperfused myocardium, K1 (rate constant for transfer from arterial plasma to tissues) was used as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue (BPTC). Results: LW223 binding to TSPO was not susceptible to the rs6971 genetic polymorphism in human brain and heart samples. In rodents, 18F-LW223 displayed a specific uptake consistent with TSPO expression, a slow metabolism in blood (69% of parent at 120 min), a high plasma free fraction of 38.5%, and a suitable dosimetry profile (effective dose of 20.5–24.5 μSv/MBq). 18F-LW223 BPTC was significantly higher in the MI cohort within the infarct territory of the anterior wall relative to the anterior wall of naïve animals (32.7 ± 5.0 vs. 10.0 ± 2.4 cm3/mL/min, P ≤ 0.001). Ex vivo immunofluorescent staining for TSPO and CD68 (macrophage marker) resulted in the same pattern seen with in vivo BPTC analysis. Conclusion: 18F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics, and is able to accurately map macrophage-driven inflammation after MI.

We assessed myocardial calcium handling in patients with non-ischaemic cardiomyopathy usingmanganese-enhanced magnetic resonance imaging (MEMRI). Healthy volunteers (HV; n=20, 13 male, 42±11 yr), patients with hypertrophic (HCM; n=17, 10 male, 57±10 yr) or dilated (DCM; n=10, 6 male, 54±10 yr)

Gadolinium chelates are widely used in cardiovascular magnetic resonance imaging (MRI) as passive intravascular and extracellular space markers. Manganese, a biologically active paramagnetic calcium analogue, provides novel intracellular myocardial tissue characterisation. We previously showed manganese-enhanced MRI (MEMRI) more accurately quantifies myocardial infarction than gadolinium delayed-enhancement MRI (DEMRI). Here, we evaluated the potential of MEMRI to assess myocardial viability compared to gold-standard 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) viability. Coronary artery ligation surgery was performed in male Sprague-Dawley rats (n = 13) followed by dual MEMRI and 18F-FDG PET imaging at 10–12 weeks. MEMRI was achieved with unchelated (EVP1001-1) or chelated (mangafodipir) manganese. T1 mapping MRI was followed by 18F-FDG micro-PET, with tissue taken for histological correlation. MEMRI and PET demonstrated good agreement with histology but native T1 underestimated infarct size. Quantification of viability by MEMRI, PET and MTC were similar, irrespective of manganese agent. MEMRI showed superior agreement with PET than native T1. MEMRI showed excellent agreement with PET and MTC viability. Myocardial MEMRI T1 correlated with 18F-FDG standard uptake values and influx constant but not native T1. Our findings indicate that MEMRI identifies and quantifies myocardial viability and has major potential for clinical application in myocardial disease and regenerative therapies.

Background Fibrosis is a fundamental process involved in healing and remodelling post myocardial infarction (MI) and during heart failure (HF). Positron emission tomography (PET) is a potential tool for investigating active collagen biosynthesis in the myocardium with fluoroprolines. We hypothesised that 18F-fluoroprolines can identify either triple helix collagen (trans-4-18F-fluoro-L-proline, e.g.scar tissue) or single-chain polypeptide abnormal collagen (cis 4 18F fluoro L proline, e.g.interstitial fibrosis) by directly targeting collagen biosynthesis. Methods Adult male Sprague-Dawley rats underwent total left coronary artery occlusion to induce MI. Seven days after MI, animals underwent magnetic resonance imaging (MRI) and were injected with trans- or cis-4-18F-fluoro-L-prolines for PET imaging. Hearts collected after in vivo imaging were stained with Picrosirius red (PSR) to assess myocardial fibrosis. Another set of rats underwent 4-week angiotensin-II (AngII) treatment (250 ng/kg/min or 500 ng/kg/min), to induce left ventricular hypertrophy and diffuse fibrosis, with blood pressure checks and ex vivo assessment of myocardial collagen content (PSR stain; hydroxyproline (HP) assay), to develop a model of interstitial fibrosis for future PET imaging studies. Results Uptake of trans-fluoroproline was strongest in the infarct area and cis-fluoroproline was strongest in the remote myocardium (mean standard uptake value ratio of 1.3 vs 0.7). The trans-fluoroproline SUVr strongly, and inversely correlated with ventricular ejection fraction (r2=0.93) and scar tissue size, as determined by MRI, and areas of fibrosis determined by PSR staining. Following AngII treatment, blood pressure significantly increased in both treatment groups by week 2 and stayed high until the end of the study in the high dose group compared to baseline. PSR analysis of heart tissue (AngII study-arm) showed a trend towards increased% fibrosis in the myocardium in the high dose group compared to controls. HP levels were significantly increased with high dose treatment compared to controls (mean: 0.7 vs 0.37 µg/mg; ANOVA p<0.01). PSR values significantly correlated with HP measurements (global heart: p=0.0016). Conclusions Fluoroproline PET imaging could identify and quantify fibrosis activity in vivo following MI and the results validated with histological markers of fibrosis. Based on the results so far, the development of the diffuse fibrosis model to mimic hypertensive HF is promising. Future PET imaging studies with 18F-fluoroprolines and the model of hypertensive heart failure are ongoing.