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Introduction | 3

               both men and woman globally.  Mainly due to the increasing prevalence of known
               cardiovascular  risk  factors,  such  as  obesity,  diabetes,  and  metabolic  syndrome,  the
               incidence  of  CAD  is  increasing.   Although  CAD  mortality  is  falling  globally,   an
               increasing number of individuals with non-fatal CAD live with chronic disabilities and
               impaired quality of life.  The associated financial impact on the health care system is
               tremendous, with cardiovascular diseases alone already exceeding 11% of the total
               healthcare costs in the Netherlands,  and even larger numbers in other parts of the
               Western world. Therefore, effective and timely strategies are required to address CAD.
               Among such strategies is revascularization therapy, which aims to re-establish blood
               supply  to  myocardial  tissue  with  reduced  function  and  blood  flow.  Although
               revascularization therapy can be highly effective, its success rate is highly dependent
               on whether the targeted myocardial tissue is still viable with the potential to contribute
               to systolic function again.  Myocardial viability therefore acts as a key parameter for
               making CAD related patient management decisions.

               Late gadolinium enhancement

               Late  gadolinium  enhancement  (LGE)  is  a  widely  used  cardiovascular  magnetic
               resonance imaging (MRI) technique for assessing myocardial viability. Since its initial
               validation  against  histology  approximately  two  decades  ago, 10,11   its  ability  to
               distinguish areas of MI from normal myocardium has gained wide acceptance. Over
               the years, the clinical utility of LGE has widened considerably, including detection of
               non-ischemic  scar  patterns, 12,13   pre-procedural  assessment  of  arrhythmogenic
               substrate, 14,15   and  visualization  of  induced  ablation  lesions. 16,17   More  recently,  LGE
               emerged as a promising tool for guiding subsequent electrophysiology procedures to
               treat  cardiac  arrhythmias. 18,19   Nowadays,  LGE  is  used  to  diagnose  a  broad  range  of
               ischemic  and  non-ischemic  cardiomyopathies  in  everyday  clinical  practice  and
               considered  the  reference  standard  for  the  non-invasive  assessment  of  myocardial

               Contrast agent pharmacokinetics
               Gadolinium-based contrast agents (CAs) are routinely used for MRI examinations based
               on their strong T 1-shortening effect and local distribution within the body. For LGE MRI
               in particular, the time required for the CA to reach the various tissue compartments
               after an intravenous injection plays a major role in the contrast of the acquired image.
               As various compartments within the myocardium have different wash-in and wash-out
               kinetics, the CA concentration in these individual compartments will constantly vary
               after contrast injection.  While the CA reaches the normal myocardium already soon
               after injection, areas of MI are reached on a much slower rate (Figure 1.2). A similar
               effect is observed for the clearance of the CA. While the CA is cleared quickly after
               reaching its peak concentration in the normal myocardium, it resides in areas of MI for
               a much longer time.
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