Background-Diffuse myocardial fibrosis is a final end point in most cardiac diseases. It is missed by the cardiovascular magnetic resonance (CMR) late gadolinium enhancement technique. Currently, quantifying diffuse myocardial fibrosis requires invasive biopsy, with inherent risk and sampling error. We have developed a robust and noninvasive technique, equilibrium contrast CMR (EQ-CMR) to quantify diffuse fibrosis and have validated it against the current gold standard of surgical myocardial biopsy. Methods and Results-The 3 principles of EQ-CMR are a bolus of extracellular gadolinium contrast followed by continuous infusion to achieve equilibrium; a blood sample to measure blood volume of distribution (1Ϫhematocrit); and CMR to measure pre-and postequilibrium T1 (with heart rate correction). The myocardial volume of distribution is calculated, reflecting diffuse myocardial fibrosis. Clinical validation occurred in patients undergoing aortic valve replacement for aortic stenosis or myectomy in hypertrophic cardiomyopathy (nϭ18 and nϭ8, respectively). Surgical biopsies were analyzed for picrosirius red fibrosis quantification on histology. Key Words: magnetic resonance imaging Ⅲ cardiomyopathy Ⅲ imaging Ⅲ endomyocardial fibrosis Ⅲ collagen F ibrosis is a final common end point in virtually all pathological processes in human organs and tissues. In the heart, focal fibrosis (scar) as a result of myocardial infarction is the leading cause of death and heart failure in the world. 1 Cardiovascular magnetic resonance (CMR) using the late gadolinium enhancement (LGE) contrast technique is the gold standard method for its assessment. 2,3 Focal fibrosis also occurs in other diseases, including cardiomyopathy, 4 myocarditis, 5 and infiltrative diseases. 6 Scar leads to an increased volume of distribution for gadolinium and slower contrast kinetics, 7 leading to late enhancement of scar by CMR. Clinical Perspective on p 144Diffuse myocardial fibrosis is a covert process that occurs as a part of normal aging. 8 -10 It is accelerated in diseases such as hypertension, aortic stenosis, and cardiomyopathy, 11Ϫ13 where it contributes to breathlessness, heart failure, and arrhythmia. 14 -16 Unlike scar, however, it may be reversible and is a treatment target. 17,18 Currently, the only method to quantify diffuse fibrosis is invasive biopsy, which carries significant morbidity and is prone to sampling error. 19 The LGE technique cannot be used to visualize diffuse fibrosis because "normal" myocardium with diffuse fibrosis is "nulled" to highlight focal scar, thereby losing all information of any background interstitial expansion. Recently, attempts to quantify diffuse fibrosis with CMR have been made, but they have required complex kinetic modeling and have not definitively excluded confounding factors such as heart rate, body composition, and renal clearance variability. Histological validation, where present, has In this study, we describe a potentially clinically applicable, robust, noninvasive method to quantify diffuse myo...

Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms “radiation” AND “heart” AND “disease,” OR “radiation” AND “stroke,” OR “radiation” AND “circulatory” AND “disease.” Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.Results: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.Conclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).

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