|
1
|
Rizwan S, Ayubcha C, Al-Daoud O, Al-Atout M, Amiruddin R, Werner TJ, Alavi A. PET imaging of atherosclerosis: artificial intelligence applications and recent advancements. Nucl Med Commun 2025; 46:503-514. [PMID: 40143664 DOI: 10.1097/mnm.0000000000001973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
PET imaging has become a valuable tool for assessing atherosclerosis by targeting key processes such as inflammation and microcalcification. Among available tracers, 18F-sodium fluoride has demonstrated superior performance compared to 18F-fluorodeoxyglucose, particularly in detecting coronary artery disease. However, the role of other tracers remains underexplored, requiring further validation. Emerging technologies such as artificial intelligence show potential in enhancing diagnostic speed and accuracy. Furthermore, the integration of the Alavi-Carlsen Calcification Score offers a novel approach to evaluating global disease burden, presenting a more clinically applicable method for predicting outcomes. Techniques such as total-body PET provide faster and more comprehensive imaging of the entire vascular system with reduced radiation exposure, representing a significant advancement in early detection and intervention. The combination of molecular imaging and advanced computational tools may revolutionize the management of atherosclerosis, facilitating earlier identification of at-risk individuals and improving long-term cardiovascular outcomes.
Collapse
Affiliation(s)
- Shaheer Rizwan
- Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Cyrus Ayubcha
- Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Omar Al-Daoud
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Mamdouh Al-Atout
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Raisa Amiruddin
- Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Thomas J Werner
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Abass Alavi
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| |
Collapse
|
|
2
|
Fanta O, Patil S, Werner T, Torigian DA, Alavi A. Reproducibility of 18F-Sodium Fluoride Positron Emission Tomography for Assessing Microcalcification in Coronary Arterial and Thoracic Aortic Atherosclerosis: Is the Signal below the Resolution of PET? Curr Cardiol Rep 2025; 27:88. [PMID: 40369378 PMCID: PMC12078425 DOI: 10.1007/s11886-025-02240-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/17/2025] [Indexed: 05/16/2025]
Abstract
PURPOSE OF REVIEW The rising prevalence of atherosclerosis has prompted the development of novel diagnostic methods capable of identifying early-stage disease when therapeutic interventions may be most effective. 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) is a molecular imaging technique that can quantify subclinical microcalcification in arterial plaque. The focus of this review article is to discuss the utility of 18F-NaF PET/CT in assessing atherosclerotic disease of major susceptible blood vessels, particularly the coronary arteries and thoracic aorta. RECENT FINDINGS 18F-NaF uptake observed on PET imaging demonstrates promising potential as a marker of atherosclerotic burden in individual coronary arteries, whole heart segmentations, and the thoracic aorta. Global versus focal assessment of 18F-NaF uptake in small arteries is a significant source of methodological heterogeneity among studies. The accuracy and reproducibility of 18F-NaF PET/CT may be improved by standardized quantification methods in light of the limited spatial resolution of PET, particularly through the use of techniques to evaluate global atherosclerotic burden.
Collapse
Affiliation(s)
- Ondrej Fanta
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19107, USA
| | - Shiv Patil
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19107, USA
| | - Thomas Werner
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19107, USA
| | - Drew A Torigian
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19107, USA
| | - Abass Alavi
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19107, USA.
| |
Collapse
|
|
3
|
Kwiecinski J, Wang KL, Tzolos E, Moss A, Daghem M, Adamson PD, Dey D, Molek-Dziadosz P, Dawson D, Arumugam P, Sabharwal N, Greenwood JP, Townend JN, Calvert PA, Rudd JH, Berman D, Verjans JW, Williams MC, Slomka P, Dweck MR, Newby DE. Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography. Eur J Nucl Med Mol Imaging 2024; 51:3934-3943. [PMID: 38926161 PMCID: PMC11774508 DOI: 10.1007/s00259-024-06810-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024]
Abstract
INTRODUCTION There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.
Collapse
Affiliation(s)
- Jacek Kwiecinski
- Department of Interventional Cardiology and Angiology, Institute of Cardiology, Alpejska 42, Warsaw, 04-628, Poland.
| | - Kang-Ling Wang
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Evangelos Tzolos
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Alastair Moss
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Marwa Daghem
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Philip D Adamson
- Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
| | - Damini Dey
- Departments of Medicine (Artificial Intelligence in Medicine), Imaging, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | | | - Dana Dawson
- Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Aberdeen, United Kingdom
| | | | - Nikant Sabharwal
- Oxford University Hospitals, NHS Foundation Trust, Oxford, United Kingdom
| | - John P Greenwood
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, and Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - John N Townend
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Patrick A Calvert
- Royal Papworth Hospital, University of Cambridge, Cambridge, United Kingdom
| | - James Hf Rudd
- Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Daniel Berman
- Departments of Medicine (Artificial Intelligence in Medicine), Imaging, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | - Johan W Verjans
- Australian Institute for Machine Learning, The University of Adelaide, Adelaide, Australia
- Royal Adelaide Hospital, Adelaide, Australia
| | - Michelle C Williams
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Piotr Slomka
- Departments of Medicine (Artificial Intelligence in Medicine), Imaging, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | - Marc R Dweck
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - David E Newby
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| |
Collapse
|
|
4
|
Gao M, Wen W, Li H, Zheng Y, Yun M, Meng J, Wang S, Wang B, Hu B, Mou T, Yu Y, Zhang X, Li X. Coronary sodium [ 18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics. Eur J Nucl Med Mol Imaging 2024; 51:3235-3251. [PMID: 38730084 DOI: 10.1007/s00259-024-06736-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/26/2024] [Indexed: 05/12/2024]
Abstract
PURPOSE The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).
Collapse
Affiliation(s)
- Mingxin Gao
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Wanwan Wen
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China
| | - Haiyang Li
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Yaqi Zheng
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Mingkai Yun
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China
| | - Jingjing Meng
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China
| | - Shipan Wang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Bolin Wang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Biao Hu
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China
| | - Tiantian Mou
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China
| | - Yang Yu
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China.
| | - Xiaoli Zhang
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, No.2, Anzhen Road, Chaoyang District, Beijing, 10029, China.
| | - Xiang Li
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
5
|
Ruddy TD, Kadoya Y, Small GR. Targeting atherosclerosis with antihypertensive therapy. J Nucl Cardiol 2023; 30:1627-1629. [PMID: 37138176 DOI: 10.1007/s12350-023-03272-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 03/31/2023] [Indexed: 05/05/2023]
Affiliation(s)
- Terrence D Ruddy
- Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada.
| | - Yoshito Kadoya
- Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada
| | - Gary R Small
- Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada
| |
Collapse
|
|
6
|
Singh SB, Ng SJ, Lau HC, Khanal K, Bhattarai S, Paudyal P, Shrestha BB, Naseer R, Sandhu S, Gokhale S, Raynor WY. Emerging PET Tracers in Cardiac Molecular Imaging. Cardiol Ther 2023; 12:85-99. [PMID: 36593382 PMCID: PMC9986170 DOI: 10.1007/s40119-022-00295-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/26/2022] [Indexed: 01/04/2023] Open
Abstract
18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) represent emerging PET tracers used to assess atherosclerosis-related inflammation and molecular calcification, respectively. By localizing to sites with high glucose utilization, FDG has been used to assess myocardial viability for decades, and its role in evaluating cardiac sarcoidosis has come to represent a major application. In addition to determining late-stage changes such as loss of perfusion or viability, by targeting mechanisms present in atherosclerosis, PET-based techniques have the ability to characterize atherogenesis in the early stages to guide intervention. Although it was once thought that FDG would be a reliable indicator of ongoing plaque formation, micro-calcification as portrayed by NaF-PET/CT appears to be a superior method of monitoring disease progression. PET imaging with NaF has the additional advantage of being able to determine abnormal uptake due to coronary artery disease, which is obscured by physiologic myocardial activity on FDG-PET/CT. In this review, we discuss the evolving roles of FDG, NaF, and other PET tracers in cardiac molecular imaging.
Collapse
Affiliation(s)
- Shashi Bhushan Singh
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - Sze Jia Ng
- Department of Medicine, Crozer-Chester Medical Center, 1 Medical Center Boulevard, Upland, PA, 19013, USA
| | - Hui Chong Lau
- Department of Medicine, Crozer-Chester Medical Center, 1 Medical Center Boulevard, Upland, PA, 19013, USA
| | - Kishor Khanal
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
- Division of Cardiology, Memorial Healthcare System, 3501 Johnson Street, Hollywood, FL, 33021, USA
| | - Sanket Bhattarai
- Department of Medicine, KIST Medical College, Mahalaxmi 01, Lalitpur, Bagmati, Nepal
| | - Pranita Paudyal
- West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Bimash Babu Shrestha
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - Rizwan Naseer
- Department of Medicine, Crozer-Chester Medical Center, 1 Medical Center Boulevard, Upland, PA, 19013, USA
| | - Simran Sandhu
- College of Health and Human Development, Pennsylvania State University, 10 East College Avenue, University Park, PA, 16802, USA
| | - Saket Gokhale
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | - William Y Raynor
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
- Department of Radiology, Rutgers Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, MEB #404, New Brunswick, NJ, 08901, USA.
| |
Collapse
|
|
7
|
Advances in the Assessment of Coronary Artery Disease Activity with PET/CT and CTA. Tomography 2023; 9:328-341. [PMID: 36828378 PMCID: PMC9962109 DOI: 10.3390/tomography9010026] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 01/30/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Non-invasive testing plays a pivotal role in the diagnosis, assessment of progression, response to therapy, and risk stratification of coronary artery disease. Although anatomical plaque imaging by computed tomography angiography (CTA) and ischemia detection with myocardial perfusion imaging studies are current standards of care, there is a growing body of evidence that imaging of the processes which drive atherosclerotic plaque progression and rupture has the potential to further enhance risk stratification. In particular, non-invasive imaging of coronary plaque inflammation and active calcification has shown promise in this regard. Positron emission tomography (PET) with newly-adopted radiotracers provides unique insights into atheroma activity acting as a powerful independent predictor of myocardial infarctions. Similarly, by providing a quantitative measure of coronary inflammation, the pericoronary adipose tissue density (PCAT) derived from standard coronary CTA enhances cardiac risk prediction and allows re-stratification over and above current state-of-the-art assessments. In this review, we shall discuss the recent advances in the non-invasive methods of assessment of disease activity by PET and CTA, highlighting how these methods could improve risk stratification and ultimately benefit patients with coronary artery disease.
Collapse
|
|
8
|
Kwiecinski J. Novel PET Applications and Radiotracers for Imaging Cardiovascular Pathophysiology. Cardiol Clin 2023; 41:129-139. [PMID: 37003671 DOI: 10.1016/j.ccl.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
PET allows the assessment of cardiovascular pathophysiology across a wide range of cardiovascular conditions. By imaging processes directly involved in disease progression and adverse events, such as inflammation and developing calcifications (microcalcifications), PET can not only enhance our understanding of cardiovascular disease, but also, as shown for 18F-sodium fluoride, has the potential to predict hard endpoints. In this review, the recent advances in disease activity assessment with cardiovascular PET, which provide hope that this promising technology could be leveraged in the clinical setting, shall be discussed.
Collapse
Affiliation(s)
- Jacek Kwiecinski
- Department of Interventional Cardiology and Angiology, KKiAI, Institute of Cardiology, Alpejska 42, Warsaw 04-628, Poland.
| |
Collapse
|
|
9
|
Ng SJ, Lau HC, Naseer R, Sandhu S, Raynor WY, Werner TJ, Alavi A. Atherosclerosis Imaging. PET Clin 2023; 18:71-80. [DOI: 10.1016/j.cpet.2022.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
10
|
Assessing Agreement When Agreement Is Hard to Assess-The Agatston Score for Coronary Calcification. Diagnostics (Basel) 2022; 12:diagnostics12122993. [PMID: 36553000 PMCID: PMC9777110 DOI: 10.3390/diagnostics12122993] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Method comparison studies comprised simple scatterplots of paired measurements, a 45-degree line as benchmark, and correlation coefficients up to the advent of Bland-Altman analysis in the 1980s. The Agatston score for coronary calcification is based on computed tomography of the heart, and it originated in 1990. A peculiarity of the Agatston score is the often-observed skewed distribution in screening populations. As the Agatston score has manifested itself in preventive cardiology, it is of interest to investigate how reproducibility of the Agatston score has been established. This review is based on literature findings indexed in MEDLINE/PubMed before 20 November 2021. Out of 503 identified articles, 49 papers were included in this review. Sample sizes were highly variable (10-9761), the main focus comprised intra- and interrater as well as intra- and interscanner variability assessments. Simple analysis tools such as scatterplots and correlation coefficients were successively supplemented by first difference, later Bland-Altman plots; however, only very few publications were capable of deriving Limits of Agreement that fit the observed data visually in a convincing way. Moreover, several attempts have been made in the recent past to improve the analysis and reporting of method comparison studies. These warrant increased attention in the future.
Collapse
|
|
11
|
Alavi A, Werner TJ, Høilund-Carlsen PF, Revheim ME. Can Target-to-Background Ratio Measurement Lead to Detection and Accurate Quantification of Atherosclerosis With FDG PET? Likely Not. Clin Nucl Med 2022; 47:532-536. [PMID: 35384906 PMCID: PMC9071036 DOI: 10.1097/rlu.0000000000004131] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 01/19/2022] [Indexed: 12/02/2022]
Abstract
ABSTRACT The introduction of FDG in 1976 started a new discipline and enhanced the role of molecular imaging in medicine. While the initial intent with this tracer was to determine brain function in a variety of neuropsychiatric disorders, over time, this powerful approach has made a major impact on managing many other diseases and disorders. During the past 2 decades, FDG PET has been used to detect inflammatory lesions in the atherosclerotic plaques and in other settings. However, the suboptimal spatial resolution of PET limits its ability to visualize plaques that are very small in size. Furthermore, this tracer remains in the blood for an extended period and therefore provides suboptimal results. Target-to-background ratio (TBR) has been suggested to correct for this source of error. Unfortunately, TBR values vary substantially, depending on the timing of image acquisition. Delayed imaging at later time points (3-4 hours) may obviate the need for TBR measurement, but it is impractical with conventional PET instruments. Recently, 18F-sodium fluoride (NaF) has been used for detection and quantification of molecular calcification in the plaques. This tracer is highly specific for calcification and is rapidly cleared from the circulation. In addition, global atherosclerotic burden as measured by NaF PET can be determined accurately either in the heart or major arteries throughout the body. Therefore, the role of FDG PET-based TBR measurement for detection and quantification of atherosclerotic plaques is questionable at this time.
Collapse
Affiliation(s)
- Abass Alavi
- From the Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Thomas J. Werner
- From the Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Poul Flemming. Høilund-Carlsen
- Department of Nuclear Medicine, Odense University Hospital
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Mona-Elisabeth Revheim
- Division of Radiology and Nuclear Medicine, Oslo University Hospital
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| |
Collapse
|
|
12
|
Kwiecinski J, Tzolos E, Fletcher AJ, Nash J, Meah MN, Cadet S, Adamson PD, Grodecki K, Joshi N, Williams MC, van Beek EJR, Lai C, Tavares AAS, MacAskill MG, Dey D, Baker AH, Leipsic J, Berman DS, Sellers SL, Newby DE, Dweck MR, Slomka PJ. Bypass Grafting and Native Coronary Artery Disease Activity. JACC Cardiovasc Imaging 2022; 15:875-887. [PMID: 35216930 PMCID: PMC9246289 DOI: 10.1016/j.jcmg.2021.11.030] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 11/01/2021] [Accepted: 11/15/2021] [Indexed: 11/18/2022]
Abstract
OBJECTIVES The aim of this study was to describe the potential of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression. BACKGROUND As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis. METHODS Patients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery. RESULTS Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting. CONCLUSIONS Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.
Collapse
Affiliation(s)
- Jacek Kwiecinski
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland
| | - Evangelos Tzolos
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California, USA; BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Alexander J Fletcher
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Jennifer Nash
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Mohammed N Meah
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Sebastien Cadet
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Philip D Adamson
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Kajetan Grodecki
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Nikhil Joshi
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Michelle C Williams
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Edwin J R van Beek
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Edinburgh Imaging, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Chi Lai
- Department of Radiology, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
| | - Adriana A S Tavares
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Mark G MacAskill
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Damini Dey
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Andrew H Baker
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Jonathon Leipsic
- Department of Radiology, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
| | - Daniel S Berman
- Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Stephanie L Sellers
- Department of Radiology, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
| | - David E Newby
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Edinburgh Imaging, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Marc R Dweck
- BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Piotr J Slomka
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
| |
Collapse
|
|
13
|
Wen W, Gao M, Yun M, Meng J, Yu W, Zhu Z, Tian Y, Mou T, Zhang Y, Hacker M, Li S, Yu Y, Li X, Zhang X. In Vivo Coronary 18F-Sodium Fluoride Activity: Correlations With Coronary Plaque Histological Vulnerability and Physiological Environment. JACC. CARDIOVASCULAR IMAGING 2022; 16:508-520. [PMID: 36648038 DOI: 10.1016/j.jcmg.2022.03.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 03/01/2022] [Accepted: 03/04/2022] [Indexed: 01/18/2023]
Abstract
OBJECTIVES This prospective study aimed to evaluate the associations between in vivo coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET)/computed tomography (CT) activity and ex vivo histological characteristics, to determine whether coronary 18F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of 18F-NaF adsorption to vascular microcalcification. BACKGROUND 18F-NaF PET/CT is a promising new approach for assessing microcalcification in vascular plaque. METHODS Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and 18F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary 18F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor-α, interleukin-1β), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High- and low- to medium-risk plaques were defined by standard pathological classification. RESULTS A total of 55 specimens were obtained from 42 CAD patients. Coronary 18F-NaF activity of high-risk specimens was significantly higher than low- to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary 18F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histologically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor-α expression, and interleukin-1β expression correlated with coronary 18F-NaF activity (all P < 0.05). No significant association between coronary 18F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05). CONCLUSIONS Coronary 18F-NaF activity was associated with histological vulnerability, CD68 expression, inflammatory cytokines expression, but not with osteogenic differentiation cytokines expression. 18F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients.
Collapse
Affiliation(s)
- Wanwan Wen
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Mingxin Gao
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Mingkai Yun
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jingjing Meng
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Wenyuan Yu
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ziwei Zhu
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yi Tian
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Tiantian Mou
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yandong Zhang
- Department of Pathology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Marcus Hacker
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Sijin Li
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yang Yu
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Xiang Li
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
| | - Xiaoli Zhang
- Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| |
Collapse
|
|
14
|
Badin JK, Eggenberger C, Rodenbeck SD, Hashmi ZA, Wang IW, Garcia JP, Alloosh M, Sturek M. Intracellular Ca 2+ Dysregulation in Coronary Smooth Muscle Is Similar in Coronary Disease of Humans and Ossabaw Miniature Swine. J Cardiovasc Transl Res 2022; 15:167-178. [PMID: 34286469 PMCID: PMC10620470 DOI: 10.1007/s12265-021-10153-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 07/02/2021] [Indexed: 12/31/2022]
Abstract
Intracellular free Ca2+ ([Ca2+]i) dysregulation occurs in coronary smooth muscle (CSM) in atherosclerotic coronary artery disease (CAD) of metabolic syndrome (MetS) swine. Our goal was to determine how CAD severity, arterial structure, and MetS risk factors associate with [Ca2+]i dysregulation in human CAD compared to changes in Ossabaw miniature swine. CSM cells were dispersed from coronary arteries of explanted hearts from transplant recipients and from lean and MetS swine with CAD. CSM [Ca2+]i elicited by Ca2+ influx and sarcoplasmic reticulum (SR) Ca2+ release and sequestration was measured with fura-2. Increased [Ca2+]i signaling was associated with advanced age and a greater media area in human CAD. Decreased [Ca2+]i signaling was associated with a greater number of risk factors and a higher plaque burden in human and swine CAD. Similar [Ca2+]i dysregulation exhibited in human and Ossabaw swine CSM provides strong evidence for the translational relevance of this large animal model.
Collapse
Affiliation(s)
- Jill K Badin
- Department of Anatomy, Cell Biology, & Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Sciences, Room 385, Indianapolis, IN, 46202, USA
| | - Caleb Eggenberger
- Department of Anatomy, Cell Biology, & Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Sciences, Room 385, Indianapolis, IN, 46202, USA
- Marian University College of Osteopathic Medicine, Indianapolis, IN, 46222, USA
| | - Stacey Dineen Rodenbeck
- Department of Anatomy, Cell Biology, & Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Sciences, Room 385, Indianapolis, IN, 46202, USA
- Department of Biology, Harding University, Searcy, AR, 72149, USA
| | - Zubair A Hashmi
- Cardiothoracic Transplantation Surgery, Indiana University - Methodist Hospital, Indianapolis, IN, 46202, USA
| | - I-Wen Wang
- Cardiothoracic Transplantation Surgery, Indiana University - Methodist Hospital, Indianapolis, IN, 46202, USA
| | - Jose P Garcia
- Cardiothoracic Transplantation Surgery, Indiana University - Methodist Hospital, Indianapolis, IN, 46202, USA
| | - Mouhamad Alloosh
- Department of Anatomy, Cell Biology, & Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Sciences, Room 385, Indianapolis, IN, 46202, USA
| | - Michael Sturek
- Department of Anatomy, Cell Biology, & Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Sciences, Room 385, Indianapolis, IN, 46202, USA.
| |
Collapse
|
|
15
|
Raynor WY, Borja AJ, Rojulpote C, Høilund-Carlsen PF, Alavi A. 18F-sodium fluoride: An emerging tracer to assess active vascular microcalcification. J Nucl Cardiol 2021; 28:2706-2711. [PMID: 32390112 DOI: 10.1007/s12350-020-02138-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 12/21/2022]
Affiliation(s)
- William Y Raynor
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
- Drexel University College of Medicine, Philadelphia, PA, USA.
| | - Austin J Borja
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Chaitanya Rojulpote
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
- Department of Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, PA, USA
| | - Poul Flemming Høilund-Carlsen
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Abass Alavi
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| |
Collapse
|
|
16
|
Raynor WY, Park PSU, Borja AJ, Sun Y, Werner TJ, Ng SJ, Lau HC, Høilund-Carlsen PF, Alavi A, Revheim ME. PET-Based Imaging with 18F-FDG and 18F-NaF to Assess Inflammation and Microcalcification in Atherosclerosis and Other Vascular and Thrombotic Disorders. Diagnostics (Basel) 2021; 11:diagnostics11122234. [PMID: 34943473 PMCID: PMC8700072 DOI: 10.3390/diagnostics11122234] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/19/2021] [Accepted: 11/23/2021] [Indexed: 01/13/2023] Open
Abstract
Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) represents a method of detecting and characterizing arterial wall inflammation, with potential applications in the early assessment of vascular disorders such as atherosclerosis. By portraying early-stage molecular changes, FDG-PET findings have previously been shown to correlate with atherosclerosis progression. In addition, recent studies have suggested that microcalcification revealed by 18F-sodium fluoride (NaF) may be more sensitive at detecting atherogenic changes compared to FDG-PET. In this review, we summarize the roles of FDG and NaF in the assessment of atherosclerosis and discuss the role of global assessment in quantification of the vascular disease burden. Furthermore, we will review the emerging applications of FDG-PET in various vascular disorders, including pulmonary embolism, as well as inflammatory and infectious vascular diseases.
Collapse
Affiliation(s)
- William Y. Raynor
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; (W.Y.R.); (P.S.U.P.); (A.J.B.); (T.J.W.); (A.A.)
| | - Peter Sang Uk Park
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; (W.Y.R.); (P.S.U.P.); (A.J.B.); (T.J.W.); (A.A.)
- Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA;
| | - Austin J. Borja
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; (W.Y.R.); (P.S.U.P.); (A.J.B.); (T.J.W.); (A.A.)
- Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA;
| | - Yusha Sun
- Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA;
| | - Thomas J. Werner
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; (W.Y.R.); (P.S.U.P.); (A.J.B.); (T.J.W.); (A.A.)
| | - Sze Jia Ng
- Department of Medicine, Crozer-Chester Medical Center, Upland, PA 19013, USA; (S.J.N.); (H.C.L.)
| | - Hui Chong Lau
- Department of Medicine, Crozer-Chester Medical Center, Upland, PA 19013, USA; (S.J.N.); (H.C.L.)
| | - Poul Flemming Høilund-Carlsen
- Department of Nuclear Medicine, Odense University Hospital, 5000 Odense C, Denmark;
- Department of Clinical Research, University of Southern Denmark, 5000 Odense C, Denmark
| | - Abass Alavi
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; (W.Y.R.); (P.S.U.P.); (A.J.B.); (T.J.W.); (A.A.)
| | - Mona-Elisabeth Revheim
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA; (W.Y.R.); (P.S.U.P.); (A.J.B.); (T.J.W.); (A.A.)
- Division of Radiology and Nuclear Medicine, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Problemveien 7, 0315 Oslo, Norway
- Correspondence: or
| |
Collapse
|
|
17
|
AlJaroudi WA, Hage FG. Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2020: positron emission tomography, computed tomography, and magnetic resonance. J Nucl Cardiol 2021; 28:2100-2111. [PMID: 34105040 PMCID: PMC8186871 DOI: 10.1007/s12350-021-02685-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 05/19/2021] [Indexed: 11/13/2022]
Abstract
Although the year 2020 was different from other years in many respects, the Journal of Nuclear Cardiology published excellent articles pertaining to imaging in patients with cardiovascular disease due to the dedication of the investigators in our field all over the world. In this review, we will summarize a selection of these articles to provide a concise review of the main advancements that have recently occurred in the field and provide the reader with an opportunity to review a wide selection of articles. We will focus on publications dealing with positron emission tomography, computed tomography, and magnetic resonance and hope that you will find this review helpful.
Collapse
Affiliation(s)
- Wael A AlJaroudi
- Division of Cardiovascular Medicine, Augusta University, Augusta, GA, USA
| | - Fadi G Hage
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Lyons Harrison Research Building 306, 1900 University BLVD, Birmingham, AL, 35294, USA.
- Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.
| |
Collapse
|
|
18
|
Mayer J, Wurster TH, Schaeffter T, Landmesser U, Morguet A, Bigalke B, Hamm B, Brenner W, Makowski MR, Kolbitsch C. Imaging coronary plaques using 3D motion-compensated [ 18F]NaF PET/MR. Eur J Nucl Med Mol Imaging 2021; 48:2455-2465. [PMID: 33474584 PMCID: PMC8241750 DOI: 10.1007/s00259-020-05180-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 12/26/2020] [Indexed: 12/19/2022]
Abstract
Background Cardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images. Methods Free-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter. Results MR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by −22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions. Conclusions The MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-020-05180-4.
Collapse
Affiliation(s)
- Johannes Mayer
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Berlin, Germany.
| | - Thomas-Heinrich Wurster
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany.,Berlin Institute of Health, Berlin, Germany
| | - Tobias Schaeffter
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Berlin, Germany.,School of Biomedical Imaging Sciences, King's College London, London, UK.,Department of Medical Engineering, Technische Universität Berlin, Berlin, Germany
| | - Ulf Landmesser
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Morguet
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Boris Bigalke
- Klinik für Kardiologie, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Bernd Hamm
- Department of Radiology, Charité, Universitätsmedizin Berlin, Berlin, Germany
| | - Winfried Brenner
- Department of Nuclear Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany
| | - Marcus R Makowski
- Department of Medical Engineering, Technische Universität Berlin, Berlin, Germany.,Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, München, Germany
| | - Christoph Kolbitsch
- Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Berlin, Germany.,School of Biomedical Imaging Sciences, King's College London, London, UK
| |
Collapse
|
|
19
|
Advances in Quantitative Analysis of 18F-Sodium Fluoride Coronary Imaging. Mol Imaging 2021; 2021:8849429. [PMID: 33746631 PMCID: PMC7953548 DOI: 10.1155/2021/8849429] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 12/05/2020] [Indexed: 11/22/2022] Open
Abstract
18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has emerged as a promising noninvasive imaging tool for the assessment of active calcification processes in coronary artery disease. 18F-NaF uptake colocalizes to high-risk and ruptured atherosclerotic plaques. Most recently, 18F-NaF coronary uptake was shown to be a robust and independent predictor of myocardial infarction in patients with advanced coronary artery disease. In this review, we provide an overview of the advances in coronary 18F-NaF imaging. In particular, we discuss the recently developed and validated motion correction techniques which address heart contractions, tidal breathing, and patient repositioning during the prolonged PET acquisitions. Additionally, we discuss a novel quantification approach—the coronary microcalcification activity (which has been inspired by the widely employed method in oncology total active tumor volume measurement). This new method provides a single number encompassing 18F-NaF activity within the entire coronary vasculature rather than just information regarding a single area of most intense tracer uptake.
Collapse
|
|
20
|
Massera D, Doris MK, Cadet S, Kwiecinski J, Pawade TA, Peeters FECM, Dey D, Newby DE, Dweck MR, Slomka PJ. Analytical quantification of aortic valve 18F-sodium fluoride PET uptake. J Nucl Cardiol 2020; 27:962-972. [PMID: 30499069 PMCID: PMC6541558 DOI: 10.1007/s12350-018-01542-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 11/07/2018] [Indexed: 11/24/2022]
Abstract
BACKGROUND Challenges to cardiac PET-CT include patient motion, prolonged image acquisition and a reduction of counts due to gating. We compared two analytical tools, FusionQuant and OsiriX, for quantification of gated cardiac 18F-sodium fluoride (18F-fluoride) PET-CT imaging. METHODS Twenty-seven patients with aortic stenosis were included, 15 of whom underwent repeated imaging 4 weeks apart. Agreement between analytical tools and scan-rescan reproducibility was determined using the Bland-Altman method and Lin's concordance correlation coefficients (CCC). RESULTS Image analysis was faster with FusionQuant [median time (IQR) 7:10 (6:40-8:20) minutes] compared with OsiriX [8:30 (8:00-10:10) minutes, p = .002]. Agreement of uptake measurements between programs was excellent, CCC = 0.972 (95% CI 0.949-0.995) for mean tissue-to-background ratio (TBRmean) and 0.981 (95% CI 0.965-0.997) for maximum tissue-to-background ratio (TBRmax). Mean noise decreased from 11.7% in the diastolic gate to 6.7% in motion-corrected images (p = .002); SNR increased from 25.41 to 41.13 (p = .0001). Aortic valve scan-rescan reproducibility for TBRmax was improved with FusionQuant using motion correction compared to OsiriX (error ± 36% vs ± 13%, p < .001) while reproducibility for TBRmean was similar (± 10% vs ± 8% p = .252). CONCLUSION 18F-fluoride PET quantification with FusionQuant and OsiriX is comparable. FusionQuant with motion correction offers advantages with respect to analysis time and reproducibility of TBRmax values.
Collapse
Affiliation(s)
- Daniele Massera
- Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA
| | - Mhairi K Doris
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, Scotland, UK
| | - Sebastien Cadet
- Department of Imaging, Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Ste A047 N, Los Angeles, CA, 90048, USA
| | - Jacek Kwiecinski
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, Scotland, UK
- Department of Imaging, Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Ste A047 N, Los Angeles, CA, 90048, USA
| | - Tania A Pawade
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, Scotland, UK
| | | | - Damini Dey
- Department of Imaging, Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Ste A047 N, Los Angeles, CA, 90048, USA
| | - David E Newby
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, Scotland, UK
| | - Marc R Dweck
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, Scotland, UK
| | - Piotr J Slomka
- Department of Imaging, Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Ste A047 N, Los Angeles, CA, 90048, USA.
| |
Collapse
|
|
21
|
Abstract
Swine disease models are essential for mimicry of human metabolic and vascular pathophysiology, thereby enabling high-fidelity translation to human medicine. The worldwide epidemic of obesity, metabolic disease, and diabetes has prompted the focus on these diseases in this review. We highlight the remarkable similarity between Ossabaw miniature swine and humans with metabolic syndrome and atherosclerosis. Although the evidence is strongest for swine models of coronary artery disease, findings are generally applicable to any vascular bed. We discuss the major strengths and weaknesses of swine models. The development of vascular imaging is an example of optimal vascular engineering in swine. Although challenges regarding infrastructure and training of engineers in the use of swine models exist, opportunities are ripe for gene editing, studies of molecular mechanisms, and use of swine in coronary artery imaging and testing of devices that can move quickly to human clinical studies.
Collapse
Affiliation(s)
- Michael Sturek
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA; .,Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 46907, USA
| | - Mouhamad Alloosh
- Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA;
| | - Frank W Sellke
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA
| |
Collapse
|
|
22
|
|
|
23
|
Kwiecinski J, Slomka PJ, Dweck MR, Newby DE, Berman DS. Vulnerable plaque imaging using 18F-sodium fluoride positron emission tomography. Br J Radiol 2019; 93:20190797. [PMID: 31804143 DOI: 10.1259/bjr.20190797] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Positron emission tomography (PET) with 18F-sodium fluoride (18F-NaF) has emerged as a promising non-invasive imaging modality to identify high-risk and ruptured atherosclerotic plaques. By visualizing microcalcification, 18F-NaF PET holds clinical promise in refining how we evaluate coronary artery disease, shifting our focus from assessing disease burden to atherosclerosis activity. In this review, we provide an overview of studies that have utilized 18F-NaF PET for imaging atherosclerosis. We discuss the associations between traditional coronary artery disease measures (risk factors) and 18F-NaF plaque activity. We also present the data on the histological validation as well as show how 18F-NaF uptake is associated with plaque morphology on intravascular and CT imaging. Finally, we discuss the technical challenges associated with 18F-NaF coronary PET highlighting recent advances in this area.
Collapse
Affiliation(s)
- Jacek Kwiecinski
- Department of Imaging (Division of Nuclear Medicine), Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, USA.,Department of Interventional Cardiology and Angiology, Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland
| | - Piotr J Slomka
- Department of Imaging (Division of Nuclear Medicine), Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, USA
| | - Marc R Dweck
- BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK
| | - David E Newby
- BHF Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK
| | - Daniel S Berman
- Department of Imaging (Division of Nuclear Medicine), Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, USA
| |
Collapse
|
|
24
|
MacAskill MG, Newby DE, Tavares AAS. Frontiers in positron emission tomography imaging of the vulnerable atherosclerotic plaque. Cardiovasc Res 2019; 115:1952-1962. [PMID: 31233100 PMCID: PMC6872971 DOI: 10.1093/cvr/cvz162] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 04/16/2019] [Accepted: 06/19/2019] [Indexed: 02/07/2023] Open
Abstract
Rupture of vulnerable atherosclerotic plaques leading to an atherothrombotic event is the primary driver of myocardial infarction and stroke. The ability to detect non-invasively the presence and evolution of vulnerable plaques could have a huge impact on the future identification and management of atherosclerotic cardiovascular disease. Positron emission tomography (PET) imaging with an appropriate radiotracer has the potential to achieve this goal. This review will discuss the biological hallmarks of plaque vulnerability before going on to evaluate and to present PET imaging approaches which target these processes. The focus of this review will be on techniques beyond [18F]FDG imaging, some of which are clinically advanced, and others which are on the horizon. As inflammation is the primary driving force behind atherosclerotic plaque development, we will predominantly focus on approaches which either directly, or indirectly, target this process.
Collapse
Affiliation(s)
- Mark G MacAskill
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
- Edinburgh Imaging, University of Edinburgh, Edinburgh, UK
| | - David E Newby
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Adriana A S Tavares
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
- Edinburgh Imaging, University of Edinburgh, Edinburgh, UK
| |
Collapse
|
|
25
|
Sorci O, Batzdorf AS, Mayer M, Rhodes S, Peng M, Jankelovits AR, Hornyak JN, Gerke O, Høilund-Carlsen PF, Alavi A, Rajapakse CS. 18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification. Eur J Nucl Med Mol Imaging 2019; 47:1678-1687. [DOI: 10.1007/s00259-019-04590-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 10/22/2019] [Indexed: 11/25/2022]
|
|
26
|
Salarian M, Sadeghi MM. Hype or Hope 18F-NaF Positron Emission Tomography for Vulnerable Coronary Plaque Imaging. Circ Cardiovasc Imaging 2019; 12:e009591. [PMID: 31382767 DOI: 10.1161/circimaging.119.009591] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Mani Salarian
- Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (M.S., M.M.S.).,VA Connecticut Healthcare System, West Haven (M.S., M.M.S.)
| | - Mehran M Sadeghi
- Section of Cardiovascular Medicine and Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (M.S., M.M.S.).,VA Connecticut Healthcare System, West Haven (M.S., M.M.S.)
| |
Collapse
|
|
27
|
Høilund-Carlsen PF, Moghbel MC, Gerke O, Alavi A. Evolving Role of PET in Detecting and Characterizing Atherosclerosis. PET Clin 2019; 14:197-209. [DOI: 10.1016/j.cpet.2018.12.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
|
28
|
Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques. JACC Cardiovasc Imaging 2019; 12:2000-2010. [PMID: 30772226 DOI: 10.1016/j.jcmg.2018.11.032] [Citation(s) in RCA: 135] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/12/2018] [Accepted: 11/15/2018] [Indexed: 12/27/2022]
Abstract
OBJECTIVES This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA). BACKGROUND Coronary 18F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized. METHODS Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm3). Patients with HRPs were recruited to undergo 18F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion-corrected 18F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured. RESULTS Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18F-NaF activity. Lesions with 18F-NaF uptake had higher surrounding PCAT density than those without 18F-NaF uptake (-73 HU; interquartile range -79 to -68 HU vs. -86 HU; interquartile range -94 to -80 HU; p < 0.001). 18F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP). CONCLUSIONS In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by 18F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.
Collapse
|
|
29
|
Alavi A, Werner TJ, Høilund-Carlsen PF. What can be and what cannot be accomplished with PET to detect and characterize atherosclerotic plaques. J Nucl Cardiol 2018; 25:2012-2015. [PMID: 28695405 DOI: 10.1007/s12350-017-0977-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 06/06/2017] [Indexed: 01/09/2023]
Affiliation(s)
- Abass Alavi
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
| | - Thomas J Werner
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
| | | |
Collapse
|
|
30
|
Moghbel M, Al-Zaghal A, Werner TJ, Constantinescu CM, Høilund-Carlsen PF, Alavi A. The Role of PET in Evaluating Atherosclerosis: A Critical Review. Semin Nucl Med 2018; 48:488-497. [DOI: 10.1053/j.semnuclmed.2018.07.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
31
|
Bellinge JW, Francis RJ, Majeed K, Watts GF, Schultz CJ. In search of the vulnerable patient or the vulnerable plaque: 18F-sodium fluoride positron emission tomography for cardiovascular risk stratification. J Nucl Cardiol 2018; 25:1774-1783. [PMID: 29992525 DOI: 10.1007/s12350-018-1360-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 06/18/2018] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease (CVD) remains a leading cause of death. Preventative therapies that reduce CVD are most effective when targeted to individuals at high risk. Current risk stratification tools have only modest prognostic capabilities, resulting in over-treatment of low-risk individuals and under-treatment of high-risk individuals. Improved methods of CVD risk stratification are required. Molecular imaging offers a novel approach to CVD risk stratification. In particular, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has shown promise in the detection of both high-risk atherosclerotic plaque features and vascular calcification activity, which predicts future development of new vascular calcium deposits. The rate of change of coronary calcium scores, measured by serial computed tomography scans over a 2-year period, is a strong predictor of CVD risk. Vascular calcification activity, as measured with 18F-NaF PET, has the potential to provide prognostic information similar to consecutive coronary calcium scoring, with a single-time-point convenience. However, owing to the rapid motion and small size of the coronary arteries, new solutions are required to address the traditional limitations of PET imaging. Two different methods of coronary PET analysis have been independently proposed and here we compare their respective strengths, weaknesses, and the potential for clinical translation.
Collapse
Affiliation(s)
- Jamie W Bellinge
- Department of Cardiology, Royal Perth Hospital, 197 Wellington St, Perth, WA, 6000, Australia.
- School of Medicine, University of Western Australia, Perth, Australia.
| | - Roslyn J Francis
- School of Medicine, University of Western Australia, Perth, Australia
- Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, Australia
| | - Kamran Majeed
- Department of Cardiology, Royal Perth Hospital, 197 Wellington St, Perth, WA, 6000, Australia
- School of Medicine, University of Western Australia, Perth, Australia
| | - Gerald F Watts
- Department of Cardiology, Royal Perth Hospital, 197 Wellington St, Perth, WA, 6000, Australia
- School of Medicine, University of Western Australia, Perth, Australia
| | - Carl J Schultz
- Department of Cardiology, Royal Perth Hospital, 197 Wellington St, Perth, WA, 6000, Australia
- School of Medicine, University of Western Australia, Perth, Australia
| |
Collapse
|
|
32
|
Kwiecinski J, Berman DS, Lee SE, Dey D, Cadet S, Lassen ML, Germano G, Jansen MA, Dweck MR, Newby DE, Chang HJ, Yun M, Slomka PJ. Three-Hour Delayed Imaging Improves Assessment of Coronary 18F-Sodium Fluoride PET. J Nucl Med 2018; 60:530-535. [PMID: 30213848 DOI: 10.2967/jnumed.118.217885] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 09/05/2018] [Indexed: 01/26/2023] Open
Abstract
Coronary 18F-sodium fluoride (18F-NaF) PET identifies ruptured plaques in patients with recent myocardial infarction and localizes to atherosclerotic lesions with active calcification. Most studies to date have performed the PET acquisition 1 h after injection. Although qualitative and semiquantitative analysis is feasible with 1-h images, residual blood-pool activity often makes it difficult to discriminate plaques with 18F-NaF uptake from noise. We aimed to assess whether delayed PET performed 3 h after injection improves image quality and uptake measurements. Methods: Twenty patients (67 ± 7 y old, 55% male) with stable coronary artery disease underwent coronary CT angiography (CTA) and PET/CT both 1 h and 3 h after the injection of 266.2 ± 13.3 MBq of 18F-NaF. We compared the visual pattern of coronary uptake, maximal background (blood pool) activity, noise, SUVmax, corrected SUVmax (cSUVmax), and target-to-background (TBR) ratio in lesions defined by CTA on 1-h versus 3-h 18F-NaF PET. Results: On 1-h PET, 26 CTA lesions with 18F-NaF PET uptake were identified in 12 (60%) patients. On 3-h PET, we detected 18F-NaF PET uptake in 7 lesions that were not identified on 1-h PET. The median cSUVmax and TBRs of these lesions were 0.48 (interquartile range [IQR], 0.44-0.51) and 1.45 (IQR, 1.39-1.52), respectively, compared with -0.01 (IQR, -0.03-0.001) and 0.95 (IQR, 0.90-0.98), respectively, on 1-h PET (both P < 0.001). Across the entire cohort, 3-h PET SUVmax was similar to 1-h PET measurements (1.63 [IQR, 1.37-1.98] vs. 1.55 [IQR, 1.43-1.89], P = 0.30), and the background activity was lower (0.71 [IQR, 0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], P < 0.001). On 3-h PET, TBR, cSUVmax, and noise were significantly higher (respectively: 2.30 [IQR, 1.70-2.68] vs. 1.28 [IQR, 0.98-1.56], P < 0.001; 0.38 [IQR, 0.27-0.70] vs. 0.90 [IQR, 0.64-1.17], P < 0.001; and 0.10 [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], P = 0.02). Median cSUVmax and TBR increased by 92% (range, 33%-225%) and 80% (range, 20%-177%), respectively. Conclusion: Blood-pool activity decreases on delayed imaging, facilitating the assessment of 18F-NaF uptake in coronary plaques. Median TBR increases by 80%, leading to the detection of more plaques with significant uptake than are detected using the standard 1-h protocol. A greater than 1-h delay may improve the detection of 18F-NaF uptake in coronary artery plaques.
Collapse
Affiliation(s)
- Jacek Kwiecinski
- Cedars-Sinai Medical Center, Los Angeles, California.,BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, United Kingdom; and
| | | | - Sang-Eun Lee
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Damini Dey
- Cedars-Sinai Medical Center, Los Angeles, California
| | | | | | - Guido Germano
- Cedars-Sinai Medical Center, Los Angeles, California
| | - Maurits A Jansen
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, United Kingdom; and
| | - Marc R Dweck
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, United Kingdom; and
| | - David E Newby
- BHF Centre for Cardiovascular Science, Clinical Research Imaging Centre, Edinburgh Heart Centre, University of Edinburgh, Edinburgh, United Kingdom; and
| | - Hyuk-Jae Chang
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Mijin Yun
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | | |
Collapse
|
|
33
|
18F-NaF and 18F-FDG as molecular probes in the evaluation of atherosclerosis. Eur J Nucl Med Mol Imaging 2018; 45:2190-2200. [PMID: 29978245 PMCID: PMC6182398 DOI: 10.1007/s00259-018-4078-0] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 06/21/2018] [Indexed: 12/12/2022]
Abstract
The early detection of atherosclerotic disease is vital to the effective prevention and management of life-threatening cardiovascular events such as myocardial infarctions and cerebrovascular accidents. Given the potential for positron emission tomography (PET) to visualize atherosclerosis earlier in the disease process than anatomic imaging modalities such as computed tomography (CT), this application of PET imaging has been the focus of intense scientific inquiry. Although 18F-FDG has historically been the most widely studied PET radiotracer in this domain, there is a growing body of evidence that 18F-NaF holds significant diagnostic and prognostic value as well. In this article, we review the existing literature on the application of 18F-FDG and 18F-NaF as PET probes in atherosclerosis and present the findings of original animal and human studies that have examined how well 18F-NaF uptake correlates with vascular calcification and cardiovascular risk.
Collapse
|
|
34
|
Badin JK, Bruning RS, Sturek M. Effect of metabolic syndrome and aging on Ca 2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine. Exp Gerontol 2018; 108:247-255. [PMID: 29730333 DOI: 10.1016/j.exger.2018.04.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 03/19/2018] [Accepted: 04/29/2018] [Indexed: 12/30/2022]
Abstract
BACKGROUND Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. METHODS Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura-2 imaging. RESULTS CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca2+]i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca2+ store release, increased Ca2+ influx through voltage-gated Ca2+ channels, and attenuated sarco-endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation. CONCLUSIONS Ca2+ dysregulation, mainly the SR Ca2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca2+ handling dysfunction in CAD.
Collapse
Affiliation(s)
- Jill K Badin
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, United States
| | - Rebecca S Bruning
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, United States; RTI International, Global Health Technologies, Research Triangle Park, NC 27709, United States
| | - Michael Sturek
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, United States.
| |
Collapse
|
|
35
|
Abstract
PURPOSE OF REVIEW This short review summarizes the recent development in clinical and experimental imaging techniques for coronary atherosclerosis. RECENT FINDINGS Coronary atherosclerosis is the underlying disease of myocardial infarction, the leading cause of death in the industrialized world. Conventional ways of risk assessment, including evaluation of traditional risk factors and interrogation of luminal stenosis, have proven imprecise for the prediction of major events. Rapid advances in noninvasive imaging techniques including MRI, CT, and PET, as well as catheter-based methods, have opened the doors to more in-depth interrogation of plaque burden, composition, and many crucial pathological processes such as inflammation and hemorrhage. These emerging imaging modalities and methodologies, combined with conventional imaging evidences of anatomy and ischemia, offer the promises to provide comprehensive information of the disease status. There is tremendous clinical potential for imaging to improve the current management of coronary atherosclerosis, including the identification of high-risk patients for aggressive therapies and guiding personalized treatment. In this review, we provide an overview of the state-of-the-art coronary plaque imaging techniques focusing on their respective strengths and weaknesses, as well as their clinical outlook.
Collapse
Affiliation(s)
- Yibin Xie
- Biomedical Imaging Research Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd., PACT Suite 400, Los Angeles, CA, 90048, USA
| | - Hang Jin
- Biomedical Imaging Research Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd., PACT Suite 400, Los Angeles, CA, 90048, USA
- Department of Radiology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, China
| | - Debiao Li
- Biomedical Imaging Research Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd., PACT Suite 400, Los Angeles, CA, 90048, USA.
- Department of Bioengineering, University of California, Los Angeles, CA, USA.
| |
Collapse
|
|
36
|
Badin JK, Kole A, Stivers B, Progar V, Pareddy A, Alloosh M, Sturek M. Alloxan-induced diabetes exacerbates coronary atherosclerosis and calcification in Ossabaw miniature swine with metabolic syndrome. J Transl Med 2018. [PMID: 29523165 PMCID: PMC5845376 DOI: 10.1186/s12967-018-1431-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background There is a preponderance of evidence implicating diabetes with increased coronary artery disease (CAD) and calcification (CAC) in human patients with metabolic syndrome (MetS), but the effect of diabetes on CAD severity in animal models remains controversial. We investigated whether diabetes exacerbates CAD/CAC and intracellular free calcium ([Ca2+]i) dysregulation in the clinically relevant Ossabaw miniature swine model of MetS. Methods Sixteen swine, eight with alloxan-induced diabetes, were fed a hypercaloric, atherogenic diet for 6 months. Alloxan-induced pancreatic beta cell damage was examined by immunohistochemical staining of insulin. The metabolic profile was confirmed by body weight, complete blood panel, intravenous glucose tolerance test (IVGTT), and meal tolerance test. CAD severity was assessed with intravascular ultrasound and histology. [Ca2+]i handling in coronary smooth muscle (CSM) cells was assessed with fura-2 ratiometric imaging. Results Fasting and post-prandial blood glucose, total cholesterol, and serum triglycerides were elevated in MetS-diabetic swine. This group also exhibited hypoinsulinemia during IVGTT and less pancreatic beta cell mass when compared to lean and MetS-nondiabetic swine. IVUS analysis revealed that MetS-diabetic swine had greater percent wall coverage, percent plaque burden, and calcium index when compared to lean and MetS-nondiabetic swine. Fura-2 imaging of CSM [Ca2+]i revealed that MetS-nondiabetic swine exhibited increased sarcoplasmic reticulum Ca2+ store release and Ca2+ influx through voltage-gated Ca2+ channels compared to lean swine. MetS-diabetic swine exhibited impaired Ca2+ efflux. Conclusions Diabetes exacerbates coronary atherosclerosis and calcification in Ossabaw miniature swine with MetS, accompanied by progression of [Ca2+]i dysregulation in advanced CAD/CAC. These results recapitulate increased CAD in humans with diabetes and establish Ossabaw miniature swine as an animal model for future MetS/diabetes comorbidity studies.
Collapse
Affiliation(s)
- Jill K Badin
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA
| | - Ayeeshik Kole
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA.,Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Dr, West Lafayette, IN, 47907, USA
| | - Benjamin Stivers
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA
| | - Victor Progar
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA
| | - Anisha Pareddy
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA
| | - Mouhamad Alloosh
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA
| | - Michael Sturek
- Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 385, Indianapolis, IN, 46202-5120, USA. .,Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Dr, West Lafayette, IN, 47907, USA.
| |
Collapse
|
|
37
|
Reimann C, Brangsch J, Colletini F, Walter T, Hamm B, Botnar RM, Makowski MR. Molecular imaging of the extracellular matrix in the context of atherosclerosis. Adv Drug Deliv Rev 2017; 113:49-60. [PMID: 27639968 DOI: 10.1016/j.addr.2016.09.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/01/2016] [Accepted: 09/07/2016] [Indexed: 12/25/2022]
Abstract
This review summarizes the current status of molecular imaging of the extracellular matrix (ECM) in the context of atherosclerosis. Apart from cellular components, the ECM of the atherosclerotic plaque plays a relevant role during the initiation of atherosclerosis and its' subsequent progression. Important structural and signaling components of the ECM include elastin, collagen and fibrin. However, the ECM not only plays a structural role in the arterial wall but also interacts with different cell types and has important biological signaling functions. Molecular imaging of the ECM has emerged as a new diagnostic tool to characterize biological aspects of atherosclerotic plaques, which cannot be characterized by current clinically established imaging techniques, such as X-ray angiography. Different types of molecular probes can be detected in vivo by imaging modalities such as magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT). The modality specific signaling component of the molecular probe provides information about its spatial location and local concentration. The successful introduction of molecular imaging into clinical practice and guidelines could open new pathways for an earlier detection of disease processes and a better understanding of the disease state on a biological level. Quantitative in vivo molecular parameters could also contribute to the development and evaluation of novel cardiovascular therapeutic interventions and the assessment of response to treatment.
Collapse
Affiliation(s)
| | | | | | - Thula Walter
- Department of Radiology, Charité, Berlin, Germany
| | - Bernd Hamm
- Department of Radiology, Charité, Berlin, Germany
| | - Rene M Botnar
- King's College London, Division of Imaging Sciences, United Kingdom; Wellcome Trust and EPSRC Medical Engineering Center, United Kingdom; BHF Centre of Excellence, King's College London, London, United Kingdom; NIHR Biomedical Research Centre, King's College London, London, United Kingdom
| | - Marcus R Makowski
- Department of Radiology, Charité, Berlin, Germany; King's College London, Division of Imaging Sciences, United Kingdom.
| |
Collapse
|
|
38
|
Patel K, Tarkin J, Serruys PW, Tenekecioglu E, Foin N, Zhang YJ, Crake T, Moon J, Mathur A, Bourantas CV. Invasive or non-invasive imaging for detecting high-risk coronary lesions? Expert Rev Cardiovasc Ther 2017; 15:165-179. [PMID: 28256179 DOI: 10.1080/14779072.2017.1297231] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Advances in our understanding about atherosclerotic evolution have enabled us to identify specific plaque characteristics that are associated with coronary plaque vulnerability and cardiovascular events. With constant improvements in signal and image processing an arsenal of invasive and non-invasive imaging modalities have been developed that are capable of identifying these features allowing in vivo assessment of plaque vulnerability. Areas covered: This review article presents the available and emerging imaging modalities introduced to assess plaque morphology and biology, describes the evidence from the first large scale studies that evaluated the efficacy of invasive and non-invasive imaging in detecting lesions that are likely to progress and cause cardiovascular events and discusses the potential implications of the in vivo assessment of coronary artery pathology in the clinical setting. Expert commentary: Invasive imaging, with its high resolution, and in particular hybrid intravascular imaging appears as the ideal approach to study the mechanisms regulating atherosclerotic disease progression; whereas non-invasive imaging is expected to enable complete assessment of coronary tree pathology, detection of high-risk lesions, more accurate risk stratification and thus to allow a personalized treatment of vulnerable patients.
Collapse
Affiliation(s)
- Kush Patel
- a Barts Heart Centre, Barts Health NHS Trust , London , UK
| | - Jason Tarkin
- a Barts Heart Centre, Barts Health NHS Trust , London , UK.,b Division of Cardiovascular Medicine , University of Cambridge , Cambridge , UK
| | - Patrick W Serruys
- c Thoraxcenter , Erasmus Medical Centre , Rotterdam , The Netherlands.,d Faculty of Medicine , National Heart & Lung Institute, Imperial College , London , UK
| | | | - Nicolas Foin
- e National Heart Centre Singapore , Duke-NUS Medical School , Singapore
| | - Yao-Jun Zhang
- f Nanjing First Hospital , Nanjing Medical University , Nanjing , China
| | - Tom Crake
- a Barts Heart Centre, Barts Health NHS Trust , London , UK
| | - James Moon
- a Barts Heart Centre, Barts Health NHS Trust , London , UK
| | - Anthony Mathur
- a Barts Heart Centre, Barts Health NHS Trust , London , UK
| | - Christos V Bourantas
- a Barts Heart Centre, Barts Health NHS Trust , London , UK.,g Institute of Cardiovascular Sciences , University College London , London , UK
| |
Collapse
|
|
39
|
Stabley JN, Towler DA. Arterial Calcification in Diabetes Mellitus: Preclinical Models and Translational Implications. Arterioscler Thromb Vasc Biol 2017; 37:205-217. [PMID: 28062508 PMCID: PMC5480317 DOI: 10.1161/atvbaha.116.306258] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Accepted: 12/12/2016] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus increasingly afflicts our aging and dysmetabolic population. Type 2 diabetes mellitus and the antecedent metabolic syndrome represent the vast majority of the disease burden-increasingly prevalent in children and older adults. However, type 1 diabetes mellitus is also advancing in preadolescent children. As such, a crushing wave of cardiometabolic disease burden now faces our society. Arteriosclerotic calcification is increased in metabolic syndrome, type 2 diabetes mellitus, and type 1 diabetes mellitus-impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency, and lower extremity amputation. Preclinical models of these dysmetabolic settings have provided insights into the pathobiology of arterial calcification. Osteochondrogenic morphogens in the BMP-Wnt signaling relay and transcriptional regulatory programs driven by Msx and Runx gene families are entrained to innate immune responses-responses activated by the dysmetabolic state-to direct arterial matrix deposition and mineralization. Recent studies implicate the endothelial-mesenchymal transition in contributing to the phenotypic drift of mineralizing vascular progenitors. In this brief overview, we discuss preclinical disease models that provide mechanistic insights-and point to challenges and opportunities to translate these insights into new therapeutic strategies for our patients afflicted with diabetes mellitus and its arteriosclerotic complications.
Collapse
MESH Headings
- Animals
- Animals, Genetically Modified
- Arteries/metabolism
- Arteries/pathology
- Atherosclerosis/etiology
- Atherosclerosis/metabolism
- Atherosclerosis/pathology
- Diabetes Mellitus, Experimental/complications
- Diabetes Mellitus, Experimental/genetics
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Type 1/complications
- Diabetes Mellitus, Type 1/genetics
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/genetics
- Diabetes Mellitus, Type 2/metabolism
- Diabetic Angiopathies/etiology
- Diabetic Angiopathies/metabolism
- Diabetic Angiopathies/pathology
- Diet, High-Fat
- Disease Models, Animal
- Female
- Genetic Predisposition to Disease
- Humans
- Hyperlipidemias/complications
- Hyperlipidemias/genetics
- Male
- Phenotype
- Plaque, Atherosclerotic
- Rats
- Signal Transduction
- Translational Research, Biomedical
- Vascular Calcification/etiology
- Vascular Calcification/metabolism
- Vascular Calcification/pathology
Collapse
Affiliation(s)
- John N Stabley
- From the Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
| | - Dwight A Towler
- From the Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.
| |
Collapse
|
|
40
|
Abstract
Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.
Collapse
Affiliation(s)
- Jason M Tarkin
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - Marc R Dweck
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - Nicholas R Evans
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - Richard A P Takx
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - Adam J Brown
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - Ahmed Tawakol
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - Zahi A Fayad
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.)
| | - James H F Rudd
- From the Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK (J.M.T., A.J.B., J.H.F.R.); Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK (N.R.E.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom (M.R.D); Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA (R.A.P.T., A.T.); Imaging Sciences Laboratories, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F., M.R.D.); and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (Z.A.F.).
| |
Collapse
|
|
41
|
Fiz F, Morbelli S, Bauckneht M, Piccardo A, Ferrarazzo G, Nieri A, Artom N, Cabria M, Marini C, Canepa M, Sambuceti G. Correlation between thoracic aorta 18F-natrium fluoride uptake and cardiovascular risk. World J Radiol 2016; 8:82-89. [PMID: 26834946 PMCID: PMC4731351 DOI: 10.4329/wjr.v8.i1.82] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 11/24/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigating the relationship between thoracic and cardiac 18F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors.
METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F-NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to-background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta.
RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 ± 0.76 vs 1.07 ± 0.3, P < 0.001), but also between MR and HR-LR (1.4 ± 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively).
CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients’ risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination.
Collapse
|