Publications by authors named "Edwin J R van Beek"

175 Publications

Quantifying microcalcification activity in the thoracic aorta.

J Nucl Cardiol 2021 Jan 20. Epub 2021 Jan 20.

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

Background: Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying F-sodium fluoride (18F-NaF) uptake in the thoracic aorta.

Methods: Twenty patients underwent two hybrid F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each F-NaF quantification method was compared to validated cardiovascular risk scores.

Results: Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease.

Conclusions: AMA is a simple, rapid and reproducible method of quantifying global F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.
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http://dx.doi.org/10.1007/s12350-020-02458-wDOI Listing
January 2021

Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society.

Eur Respir J 2021 Jan 5;57(1). Epub 2021 Jan 5.

Université Paris Saclay, Inserm UMR S999, Dept of Pneumology, AP-HP, Pulmonary Hypertension Reference Center, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: Is noninvasive imaging capable of identifying PH? What is the role of imaging in establishing the cause of PH? How does imaging determine the severity and complications of PH? How should imaging be used to assess chronic thromboembolic PH before treatment? Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH.
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http://dx.doi.org/10.1183/13993003.04455-2020DOI Listing
January 2021

Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society.

Radiology 2021 Mar 5;298(3):531-549. Epub 2021 Jan 5.

From the Department of Thoracic Imaging, Hôpital Calmette, Boulevard Jules Leclercq, 59037 Lille, France (M.R.J.); Department of Medicine, University of British Columbia and Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, Canada (C.J.R.); Department of Radiology, UW-Madison School of Medicine and Public Health, Madison, Wis (M.L.S.); Department of Radiology, Stanford University Medical Center, Stanford, Calif (A.N.C.L.); Division of Imaging, Department of Infection Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, England (J.M.W.); Department of Respiratory Medicine, Hannover Medical School and German Centre of Lung Research (DZL), Hannover, Germany (M.M.H.); Department of Radiology, Saint Louis University School of Medicine, St Louis, Mo (P.O.A.); Department of Radiology, Medical College of Wisconsin, Milwaukee, Wis (L.R.G.); Department of Radiology, Vancouver General Hospital, Vancouver, Canada (J.M.); Department of Radiology and Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY (L.B.H.); Department of Radiology, Fujita Health University School of Medicine, Toyoake, Japan (Y.O.); Division of Cardiothoracic Surgery, University of California, San Diego, La Jolla, Calif (P.T.); Edinburgh Imaging, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland (E.J.R.v.B.); Department of Library and Knowledge Services (S.L.K.) and Department of Radiology (D.A.L.), National Jewish Health, Denver, Colo; Department of Radiology, Duke University School of Medicine, Durham, NC (G.D.R.); and Université Paris Saclay, Inserm UMR S999, Department of Pneumology, AP-HP, Pulmonary Hypertension Reference Center, Hôpital de Bicêtre, Le Kremlin Bicêtre, France (M.H.).

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: Is noninvasive imaging capable of identifying PH? What is the role of imaging in establishing the cause of PH? How does imaging determine the severity and complications of PH? How should imaging be used to assess chronic thromboembolic PH before treatment? Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in and . The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society.
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http://dx.doi.org/10.1148/radiol.2020203108DOI Listing
March 2021

Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography.

Eur Heart J Cardiovasc Imaging 2021 Feb;22(3):262-270

University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Chancellor's Building, 49 Little France Crescent, Edinburgh EH164SB, UK.

Aims: Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes.

Methods And Results: In 1769 patients (58 ± 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60-5.17; P < 0.001] or mitral (HR 3.50; 95% CI 1.47-8.07; P = 0.004) valve calcification, but this was not independent of coronary artery calcification or obstructive coronary artery disease.

Conclusion: Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease.
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http://dx.doi.org/10.1093/ehjci/jeaa263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899264PMC
February 2021

Coronary F-Fluoride Uptake and Progression of Coronary Artery Calcification.

Circ Cardiovasc Imaging 2020 12 10;13(12):e011438. Epub 2020 Dec 10.

British Heart Foundation Centre for Cardiovascular Science (M.K.D., M.N.M., A.J.M., J.P.M.A., R.B., M.S., M.D., A.S., M.C.W., E.J.R.v.B., M.R.D., D.E.N., P.D.A.), University of Edinburgh, United Kingdom.

Background Positron emission tomography (PET) using F-sodium fluoride (F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease. Methods Patients with established multivessel coronary atherosclerosis underwent F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume. Results In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased F-fluoride uptake in at least one vessel. Individuals with increased F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39-166] versus 35 [7-93] AU; <0.0001). Indeed, the calcium score only increased in coronary segments with F-fluoride uptake (from 95 [30-209] to 148 [61-289] AU; <0.001) and remained unchanged in segments without F-fluoride uptake (from 46 [16-113] to 49 [20-115] AU; =0.329). Baseline coronary F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively; <0.0001 for all). At the segmental level, baseline F-fluoride activity was an independent predictor of calcium score at 12 months (<0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score (=0.50). Conclusions Coronary F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02110303.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771641PMC
December 2020

Pharmacokinetic modelling for the simultaneous assessment of perfusion and F-flutemetamol uptake in cerebral amyloid angiopathy using a reduced PET-MR acquisition time: Proof of concept.

Neuroimage 2021 01 4;225:117482. Epub 2020 Nov 4.

Edinburgh Imaging Facility, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.

Purpose: Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease associated with perivascular β-amyloid deposition. CAA is also associated with strokes due to lobar intracerebral haemorrhage (ICH). F-flutemetamol amyloid ligand PET may improve the early detection of CAA. We performed pharmacokinetic modelling using both full (0-30, 90-120 min) and reduced (30 min) F-flutemetamol PET-MR acquisitions, to investigate regional cerebral perfusion and amyloid deposition in ICH patients.

Methods: DynamicF-flutemetamol PET-MR was performed in a pilot cohort of sixteen ICH participants; eight lobar ICH cases with probable CAA and eight deep ICH patients. A model-based input function (mIF) method was developed for compartmental modelling. mIF 1-tissue (1-TC) and 2-tissue (2-TC) compartmental modelling, reference tissue models and standardized uptake value ratios were assessed in the setting of probable CAA detection.

Results: The mIF 1-TC model detected perfusion deficits and F-flutemetamol uptake in cases with probable CAA versus deep ICH patients, in both full and reduced PET acquisition time (all P < 0.05). In the reduced PET acquisition, mIF 1-TC modelling reached the highest sensitivity and specificity in detecting perfusion deficits (0.87, 0.77) and F-flutemetamol uptake (0.83, 0.71) in cases with probable CAA. Overall, 52 and 48 out of the 64 brain areas with F-flutemetamol-determined amyloid deposition showed reduced perfusion for 1-TC and 2-TC models, respectively.

Conclusion: Pharmacokinetic (1-TC) modelling using a 30 min PET-MR time frame detected impaired haemodynamics and increased amyloid load in probable CAA. Perfusion deficits and amyloid burden co-existed within cases with CAA, demonstrating a distinct imaging pattern which may have merit in elucidating the pathophysiological process of CAA.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117482DOI Listing
January 2021

d-Dimer and COVID-19.

Radiology 2020 12 13;297(3):E343-E344. Epub 2020 Oct 13.

Edinburgh Imaging, Queens Medical Research Institute, University of Edinburgh, Scotland.

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http://dx.doi.org/10.1148/radiol.2020203481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556118PMC
December 2020

18F-fluoride PET/MR in cardiac amyloid: A comparison study with aortic stenosis and age- and sex-matched controls.

J Nucl Cardiol 2020 Sep 30. Epub 2020 Sep 30.

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK.

Objectives: Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls.

Methods: In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBR) after correction for blood pool activity in the right atrium.

Results: 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBR values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBR values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBR threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004).

Conclusion: Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition.
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http://dx.doi.org/10.1007/s12350-020-02356-1DOI Listing
September 2020

Consensus Recommendations on the Use of F-FDG PET/CT in Lung Disease.

J Nucl Med 2020 12 18;61(12):1701-1707. Epub 2020 Sep 18.

Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

PET with F-FDG has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and to monitor disease progression and treatment outcomes in lung diseases that interfere with gas exchange through alterations of the pulmonary parenchyma, airways, or vasculature. To date, however, there are no widely accepted standard acquisition protocols or imaging data analysis methods for pulmonary F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging. To help harmonize the acquisition and analysis and promote reproducibility, we collated details of acquisition protocols and analysis methods from 7 PET centers. From this information and our discussions, we reached the consensus recommendations given here on patient preparation, choice of dynamic versus static imaging, image reconstruction, and image analysis reporting.
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http://dx.doi.org/10.2967/jnumed.120.244780DOI Listing
December 2020

Coronary Artery Calcification on Thoracic Computed Tomography Is an Independent Predictor of Mortality in Patients With Bronchiectasis.

J Thorac Imaging 2020 Sep 2. Epub 2020 Sep 2.

Edinburgh Imaging facility QMRI.

Purpose: Coronary artery calcification (CAC) on thoracic computed tomography (CT) can identify patients at risk of coronary artery disease (CAD) mortality. However, the overlap between bronchiectasis and CAC severity for predicting subsequent outcomes is unknown.

Materials And Methods: CT images from 362 patients (mean age 66±14 y, 38% male) with known bronchiectasis were assessed. Bronchiectasis severity was assessed using the Bronchiectasis Severity Index (0 to 4, mild; 5 to 8, moderate; and ≥9, severe). CAC was assessed with a visual ordinal score (0, none; 1, mild; 2, moderate; 3, severe) in each of the left main stem, left anterior descending, left circumflex, and right coronary arteries. Vessel CAC scores were summed and categorized as none (0), mild (1 to 3), moderate (4 to 8), and severe (9 to 12).

Results: Patients with severe bronchiectasis were older (P<0.001), but were not more likely to have a history of CAD, hypertension, or smoking. CAC was present in 196 (54%). Over a mean of 6±2 years, 59 (16%) patients died. Patients with moderate or severe CAC were 5 times more likely to die than patients without CAC (hazard ratio: 5.49, 95% confidence interval: 2.82-10.70, P<0.001). Patients with severe bronchiectasis were 10 times more likely to die than patients with mild bronchiectasis (hazard ratio: 10.11, 95% confidence interval: 4.22-24.27, P<0.001). CAC and bronchiectasis severity were independent predictors of mortality, but age, sex, smoking, and history of CAD or cerebrovascular disease were not.

Conclusions: CAC is common in patients with bronchiectasis, and both CAC and bronchiectasis severity are independent predictors of mortality.
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http://dx.doi.org/10.1097/RTI.0000000000000553DOI Listing
September 2020

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders: Fleischner Society Position Paper.

Radiology 2020 Nov 1;297(2):286-301. Epub 2020 Sep 1.

From the Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115 (H.H.); Department of Radiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Department of Radiology, Penn Medicine, University of Pennsylvania, Philadelphia, Pa (W.B.G.); Department of Medical Biophysics, Western University, London, Canada (G.P.); Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (B.M.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, Korea (K.S.L.); Department of Radiology, University of Missouri, Columbia, Mo (T.A.A.); Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.); Department of Radiology, Vancouver General Hospital and University of British Colombia, Vancouver, Canada (J.R.M.); Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (J.B.S.); Section of Academic Radiology, University of Sheffield, Sheffield, England, United Kingdom (J.M.W.); Edinburgh Imaging, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom (E.J.R.v.B.); Department of Radiology, UW Madison School of Medicine and Public Health, Madison, Wis (M.L.S.); and Diagnostic and Interventional Radiology, University Hospital Heidelberg, Translational Lung Research Center Heidelberg, member of the German Center of Lung Research, Heidelberg, Germany (H.U.K.).

Pulmonary MRI provides structural and quantitative functional images of the lungs without ionizing radiation, but it has had limited clinical use due to low signal intensity from the lung parenchyma. The lack of radiation makes pulmonary MRI an ideal modality for pediatric examinations, pregnant women, and patients requiring serial and longitudinal follow-up. Fortunately, recent MRI techniques, including ultrashort echo time and zero echo time, are expanding clinical opportunities for pulmonary MRI. With the use of multicoil parallel acquisitions and acceleration methods, these techniques make pulmonary MRI practical for evaluating lung parenchymal and pulmonary vascular diseases. The purpose of this Fleischner Society position paper is to familiarize radiologists and other interested clinicians with these advances in pulmonary MRI and to stratify the Society recommendations for the clinical use of pulmonary MRI into three categories: suggested for current clinical use, promising but requiring further validation or regulatory approval, and appropriate for research investigations. This position paper also provides recommendations for vendors and infrastructure, identifies methods for hypothesis-driven research, and suggests opportunities for prospective, randomized multicenter trials to investigate and validate lung MRI methods.
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http://dx.doi.org/10.1148/radiol.2020201138DOI Listing
November 2020

What Do We Really Know About Pulmonary Thrombosis in COVID-19 Infection?

J Thorac Imaging 2020 Jun 29. Epub 2020 Jun 29.

Edinburgh Imaging, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.

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http://dx.doi.org/10.1097/RTI.0000000000000545DOI Listing
June 2020

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis.

Nat Commun 2020 06 18;11(1):3097. Epub 2020 Jun 18.

University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.

Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype.
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http://dx.doi.org/10.1038/s41467-020-16878-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303125PMC
June 2020

Coronary F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease.

J Am Coll Cardiol 2020 06;75(24):3061-3074

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.

Background: Reliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary F-sodium fluoride (F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.

Objectives: This study assessed whether F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.

Methods: Patients with known coronary artery disease underwent F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary F-NaF uptake was determined by the coronary microcalcification activity (CMA).

Results: In a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p < 0.001). On receiver operator curve analysis, fatal or nonfatal myocardial infarction prediction was highest for F-NaF CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index and Reduction of Atherothrombosis for Continued Health (REACH) and Secondary Manifestations of Arterial Disease (SMART) risk scores (area under the curve: 0.76 vs. 0.54, 0.62, 0.52, and 0.54, respectively; p < 0.001 for all). Patients with CMA >1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.

Conclusions: In patients with established coronary artery disease, F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.
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http://dx.doi.org/10.1016/j.jacc.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380446PMC
June 2020

Observer repeatability and interscan reproducibility of 18F-sodium fluoride coronary microcalcification activity.

J Nucl Cardiol 2020 Jun 11. Epub 2020 Jun 11.

Department of Imaging (Division of Nuclear Medicine), Medicine, and Biomedical Sciences, Artificial Intelligence in Medicine Program, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Ste A047N, Los Angeles, CA, 90048, USA.

Background: We aimed to establish the observer repeatability and interscan reproducibility of coronary F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA).

Methods: Patients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level.

Results: In 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronaryF-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively.

Conclusions: CMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.
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http://dx.doi.org/10.1007/s12350-020-02221-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728624PMC
June 2020

Exercise Electrocardiography and Computed Tomography Coronary Angiography for Patients With Suspected Stable Angina Pectoris: A Post Hoc Analysis of the Randomized SCOT-HEART Trial.

JAMA Cardiol 2020 06 3. Epub 2020 Jun 3.

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.

Importance: Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina.

Objective: To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing.

Design, Setting, And Participants: This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019.

Interventions: Patients were randomized in a 1:1 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alone. The present analysis was limited to the 3283 patients who underwent exercise ECG alone or in combination with coronary CT angiography.

Main Outcomes And Measures: The primary clinical end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years.

Results: Among the 3283 patients (1889 men; median age, 57.0 years [interquartile range, 50.0-64.0 years]), exercise ECG had a sensitivity of 39% and a specificity of 91% for detecting any obstructive coronary artery disease in those who underwent subsequent invasive angiography. Abnormal results of exercise ECG were associated with a 14.47-fold (95% CI, 10.00-20.41; P < .001) increase in coronary revascularization at 1 year and a 2.57-fold (95% CI, 1.38-4.63; P < .001) increase in mortality from coronary heart disease death at 5 years or in cases of nonfatal myocardial infarction at 5 years. Compared with exercise ECG alone, results of coronary CT angiography had a stronger association with 5-year coronary heart disease death or nonfatal myocardial infarction (hazard ratio, 10.63; 95% CI, 2.32-48.70; P = .002). The greatest numerical difference in outcome with CT angiography compared with exercise ECG alone was observed for those with inconclusive results of exercise ECG (5 of 285 [2%] vs 13 of 283 [5%]), although this was not statistically significant (log-rank P = .05).

Conclusions And Relevance: This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG.

Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.
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http://dx.doi.org/10.1001/jamacardio.2020.1567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271417PMC
June 2020

Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands.

Radiology 2020 10 23;297(1):E216-E222. Epub 2020 Apr 23.

From the Faculty of Medical Sciences, State University of Groningen, Groningen, the Netherlands (M.O.); Institute for Diagnostic Accuracy, Groningen, the Netherlands (M.O.); Department of Vascular Medicine, Amsterdam University Medical Centre, Amsterdam, the Netherlands (H.R.B., N.v.E.); Department of Radiology, Haaglanden Medical Centre, The Hague, the Netherlands (D.K.); Department of Radiology, Nederlands Kanker Instituut, Amsterdam, the Netherlands (S.F.O.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (T.M.); Department of Intensive Care Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands (D.G.); National Institute of Public Health, Ministry of Health, Bilthoven, the Netherlands (J.v.D.); Department of Vascular Medicine, Maastricht University, Maastricht, the Netherlands (H.t.C.); and Edinburgh Imaging, CO.19, Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland (E.J.R.v.B.).

A potential link between mortality, d-dimer values, and a prothrombotic syndrome has been reported in patients with coronavirus disease 2019 (COVID-19) infection. The National Institute for Public Health of the Netherlands asked a group of radiology and vascular medicine experts to provide guidance for the imaging work-up and treatment of these important complications. This report summarizes evidence for thromboembolic disease, potential diagnostic and preventive actions, and recommendations for prophylaxis and treatment of patients with COVID-19 infection.
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http://dx.doi.org/10.1148/radiol.2020201629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233406PMC
October 2020

Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial (Scottish Computed Tomography of the HEART).

Circulation 2020 May 16;141(18):1452-1462. Epub 2020 Mar 16.

Cedars-Sinai Medical Centre, Los Angeles, CA (P.M., S.C., P.J.S., D.S.B., D.D.).

Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction.

Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses.

Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0-5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score (=0.34; <0.001), strongly with coronary artery calcium score (=0.62; <0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, =0.83; <0.001). Low-attenuation plaque burden (7.5% [4.8-9.2] versus 4.1% [0-6.8]; <0.001), coronary artery calcium score (336 [62-1064] versus 19 [0-217] Agatston units; <0.001), and the presence of obstructive coronary artery disease (54% versus 25%; <0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10-2.34) per doubling; =0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06-10.5; <0.001).

Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01149590.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195857PMC
May 2020

"Screening for lung cancer: Does MRI have a role?' [European Journal of Radiology 86 (2017) 353-360].

Eur J Radiol 2020 04 20;125:108896. Epub 2020 Feb 20.

Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC), Member of the German Lung ResearchCenter (DZL), Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.

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http://dx.doi.org/10.1016/j.ejrad.2020.108896DOI Listing
April 2020

Association between hypertension and retinal vascular features in ultra-widefield fundus imaging.

Open Heart 2020 8;7(1):e001124. Epub 2020 Jan 8.

Edinburgh Imaging Facility QMRI, University of Edinburgh, Edinburgh, UK.

Objective: Changes to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.

Methods: We retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal-annular arteriole:venule ratio (NA-AVR), a novel combined parameter.

Results: Left and right eyes were analysed from 440 participants (aged 50-59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).

Conclusions: Semiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.
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http://dx.doi.org/10.1136/openhrt-2019-001124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999694PMC
June 2020

Mechanical property alterations across the cerebral cortex due to Alzheimer's disease.

Brain Commun 2020 17;2(1):fcz049. Epub 2019 Dec 17.

Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh EH8 9JZ, UK.

Alzheimer's disease is a personally devastating neurodegenerative disorder and a major public health concern. There is an urgent need for medical imaging techniques that better characterize the early stages and monitor the progression of the disease. Magnetic resonance elastography (MRE) is a relatively new and highly sensitive MRI technique that can non-invasively assess tissue microstructural integrity via measurement of brain viscoelastic mechanical properties. For the first time, we use high-resolution MRE methods to conduct a voxel-wise MRE investigation and state-of-the-art region of interest analysis of the viscoelastic properties of the cerebral cortex in patients with Alzheimer's disease ( = 11) compared with cognitively healthy older adults ( = 12). We replicated previous findings that have reported significant volume and stiffness reductions at the whole-brain level. Significant reductions in volume were also observed in Alzheimer's disease when white matter, cortical grey matter and subcortical grey matter compartments were considered separately; lower stiffness was also observed in white matter and cortical grey matter, but not in subcortical grey matter. Voxel-based morphometry of both cortical and subcortical grey matter revealed localized reductions in volume due to Alzheimer's disease in the hippocampus, fusiform, middle, superior temporal gyri and precuneus. Similarly, voxel-based MRE identified lower stiffness in the middle and superior temporal gyri and precuneus, although the spatial distribution of these effects was not identical to the pattern of volume reduction. Notably, MRE additionally identified stiffness deficits in the operculum and precentral gyrus located within the frontal lobe; regions that did not undergo volume loss identified through voxel-based morphometry. Voxel-based-morphometry and voxel-based MRE results were confirmed by a complementary region-of-interest approach in native space where the viscoelastic changes remained significant even after statistically controlling for regional volumes. The pattern of reduction in cortical stiffness observed in Alzheimer's disease patients raises the possibility that MRE may provide unique insights regarding the neural mechanisms which underlie the development and progression of the disease. The measured mechanical property changes that we have observed warrant further exploration to investigate the diagnostic usefulness of MRE in cases of Alzheimer's disease and other dementias.
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http://dx.doi.org/10.1093/braincomms/fcz049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976617PMC
December 2019

Sex associations and computed tomography coronary angiography-guided management in patients with stable chest pain.

Eur Heart J 2020 04;41(13):1337-1345

British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, University of Glasgow, Glasgow G12 8TA, UK.

Aims: The relative benefits of computed tomography coronary angiography (CTCA)-guided management in women and men with suspected angina due to coronary heart disease (CHD) are uncertain.

Methods And Results: In this post hoc analysis of an open-label parallel-group multicentre trial, we recruited 4146 patients referred for assessment of suspected angina from 12 cardiology clinics across the UK. We randomly assigned (1:1) participants to standard care alone or standard care plus CTCA. Fewer women had typical chest pain symptoms (n = 582, 32.0%) when compared with men (n = 880, 37.9%; P < 0.001). Amongst the CTCA-guided group, more women had normal coronary arteries [386 (49.6%) vs. 263 (26.2%)] and less obstructive CHD [105 (11.5%) vs. 347 (29.8%)]. A CTCA-guided strategy resulted in more women than men being reclassified as not having CHD {19.2% vs. 13.1%; absolute risk difference, 5.7 [95% confidence interval (CI): 2.7-8.7, P < 0.001]} or having angina due to CHD [15.0% vs. 9.0%; absolute risk difference, 5.6 (2.3-8.9, P = 0.001)]. After a median of 4.8 years follow-up, CTCA-guided management was associated with similar reductions in the risk of CHD death or non-fatal myocardial infarction in women [hazard ratio (HR) 0.50, 95% CI 0.24-1.04], and men (HR 0.63, 95% CI 0.42-0.95; Pinteraction = 0.572).

Conclusion: Following the addition of CTCA, women were more likely to be found to have normal coronary arteries than men. This led to more women being reclassified as not having CHD, resulting in more downstream tests and treatments being cancelled. There were similar prognostic benefits of CTCA for women and men.
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http://dx.doi.org/10.1093/eurheartj/ehz903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109601PMC
April 2020

Magnetic resonance elastography (MRE) shows significant reduction of thigh muscle stiffness in healthy older adults.

Geroscience 2020 02 21;42(1):311-321. Epub 2019 Dec 21.

School of Sport, Exercise and Rehabilitation Sciences, MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, NIHR Birmingham BRC, The University of Birmingham, B15 2TT, Birmingham, UK.

Determining the effect of ageing on thigh muscle stiffness using magnetic resonance elastography (MRE) and investigate whether fat fraction and muscle cross-sectional area (CSA) are related to stiffness. Six healthy older adults in their eighth and ninth decade and eight healthy young men were recruited and underwent a 3 T MRI protocol including MRE and Dixon fat fraction imaging. Muscle stiffness, fat fraction and muscle CSA were calculated in ROIs corresponding to the four quadriceps muscles (i.e. vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), rectus femoris (RF)), combined quadriceps, combined hamstrings and adductors and whole thigh. Muscle stiffness was significantly reduced (p < 0.05) in the older group in all measured ROIs except the VI (p = 0.573) and RF (p = 0.081). Similarly, mean fat fraction was significantly increased (p < 0.05) in the older group over all ROIs with the exception of the VI (p = 0.059) and VL muscle groups (p = 0.142). Muscle CSA was significantly reduced in older participants in the VM (p = 0.003) and the combined quadriceps (p = 0.001), hamstrings and adductors (p = 0.008) and whole thigh (p = 0.003). Over the whole thigh, stiffness was significantly negatively correlated with fat fraction (r = - 0.560, p = 0.037) and positively correlated with CSA (r = 0.749, p = 0.002). Stepwise regression analysis revealed that age was the most significant predictor of muscle stiffness (p = 0.001). These results suggest that muscle stiffness is significantly decreased in healthy older adults. Muscle fat fraction and muscle CSA are also significantly changed in older adults; however, age is the most significant predictor of muscle stiffness.
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http://dx.doi.org/10.1007/s11357-019-00147-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031192PMC
February 2020

Current state of the art MRI for the longitudinal assessment of cystic fibrosis.

J Magn Reson Imaging 2020 11 17;52(5):1306-1320. Epub 2019 Dec 17.

Department of Radiology, University of Missouri, Columbia, Missouri, USA.

Pulmonary MRI can now provide high-resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T /T contrast images can be obtained within a single breath-hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo-time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized-gas MRI, increasingly using Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure-function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center. Level of Evidence: 4 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019.
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http://dx.doi.org/10.1002/jmri.27030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297663PMC
November 2020

Cardiovascular F-fluoride positron emission tomography-magnetic resonance imaging: A comparison study.

J Nucl Cardiol 2019 Dec 2. Epub 2019 Dec 2.

British Heart Foundation Centre of Cardiovascular Sciences, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, University of Edinburgh, Edinburgh, EH16 4SB, UK.

Background: F-Fluoride uptake denotes calcification activity in aortic stenosis and atherosclerosis. While PET/MR has several advantages over PET/CT, attenuation correction of PET/MR data is challenging, limiting cardiovascular application. We compared PET/MR and PET/CT assessments of F-fluoride uptake in the aortic valve and coronary arteries.

Methods And Results: 18 patients with aortic stenosis or recent myocardial infarction underwent F-fluoride PET/CT followed immediately by PET/MR. Valve and coronary F-fluoride uptake were evaluated independently. Both standard (Dixon) and novel radial GRE) MR attenuation correction (AC) maps were validated against PET/CT with results expressed as tissue-to-background ratios (TBRs). Visually, aortic valve F-fluoride uptake was similar on PET/CT and PET/MR. TBR values were comparable with radial GRE AC (PET/CT 1.55±0.33 vs. PET/MR 1.58 ± 0.34, P = 0.66; 95% limits of agreement - 27% to + 25%) but performed less well with Dixon AC (1.38 ± 0.44, P = 0.06; bias (-)14%; 95% limits of agreement - 25% to + 53%). In native coronaries, F-fluoride uptake was similar on PET/MR to PET/CT regardless of AC approach. PET/MR identified 28/29 plaques identified on PET/CT; however, stents caused artifact on PET/MR making assessment of F-fluoride uptake challenging.

Conclusion: Cardiovascular PET/MR demonstrates good visual and quantitative agreement with PET/CT. However, PET/MR is hampered by stent-related artifacts currently limiting clinical application.
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http://dx.doi.org/10.1007/s12350-019-01962-yDOI Listing
December 2019

Guiding Therapy by Coronary CT Angiography Improves Outcomes in Patients With Stable Chest Pain.

J Am Coll Cardiol 2019 10;74(16):2058-2070

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

Background: Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint).

Objectives: This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint.

Methods: In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies.

Results: Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size.

Conclusions: The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).
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http://dx.doi.org/10.1016/j.jacc.2019.07.085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899446PMC
October 2019

A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography.

Eur Heart J 2019 11;40(43):3529-3543

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, UK.

Background: Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction.

Methods And Results: We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62-0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOT-HEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (Δ[C-statistic] = 0.126, P < 0.001). In Study 3, FRP was significantly higher in 44 patients presenting with acute myocardial infarction compared with 44 matched controls, but unlike FAI, remained unchanged 6 months after the index event, confirming that FRP detects persistent PVAT changes not captured by FAI.

Conclusion: The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art.
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http://dx.doi.org/10.1093/eurheartj/ehz592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855141PMC
November 2019

Validated imaging biomarkers as decision-making tools in clinical trials and routine practice: current status and recommendations from the EIBALL* subcommittee of the European Society of Radiology (ESR).

Insights Imaging 2019 Aug 29;10(1):87. Epub 2019 Aug 29.

University Hospital Basel, Radiology and Nuclear Medicine, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.

Observer-driven pattern recognition is the standard for interpretation of medical images. To achieve global parity in interpretation, semi-quantitative scoring systems have been developed based on observer assessments; these are widely used in scoring coronary artery disease, the arthritides and neurological conditions and for indicating the likelihood of malignancy. However, in an era of machine learning and artificial intelligence, it is increasingly desirable that we extract quantitative biomarkers from medical images that inform on disease detection, characterisation, monitoring and assessment of response to treatment. Quantitation has the potential to provide objective decision-support tools in the management pathway of patients. Despite this, the quantitative potential of imaging remains under-exploited because of variability of the measurement, lack of harmonised systems for data acquisition and analysis, and crucially, a paucity of evidence on how such quantitation potentially affects clinical decision-making and patient outcome. This article reviews the current evidence for the use of semi-quantitative and quantitative biomarkers in clinical settings at various stages of the disease pathway including diagnosis, staging and prognosis, as well as predicting and detecting treatment response. It critically appraises current practice and sets out recommendations for using imaging objectively to drive patient management decisions.
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http://dx.doi.org/10.1186/s13244-019-0764-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715762PMC
August 2019

Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque.

JACC Cardiovasc Imaging 2020 07 14;13(7):1549-1560. Epub 2019 Aug 14.

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.

Objectives: The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque.

Background: High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy.

Methods: In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary F-fluoride uptake.

Results: In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33).

Conclusions: Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303).
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http://dx.doi.org/10.1016/j.jcmg.2019.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342015PMC
July 2020