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Introduction | 9

               additional  magnetization  preparation.  The  simplicity  and  ease  of  use  of  this  novel
               method should thereby accelerate its adaptation into clinical routine settings.

               The  entire  development  process  from  ‘bench-to-bedside’  was  divided  using  the
               following sub aims:

                   1.  To  create  an  overview  of  published  dark-blood  LGE  methods  that  aim  for
                      improved subendocardial scar conspicuity.

                   2.  To develop a novel LGE method that increases scar-to-blood contrast while
                      being readily available and easy to implement in every clinical routine setting.

                   3.  To histologically validate this novel LGE method in an animal model.

                   4.  To  evaluate  ischemic  scar  detection  of  this  novel  LGE  method  in  a  large,
                      unselected cohort of patients.

                   5.  To  translate  this  novel  LGE  approach  to  3D  imaging  methods  with  high
                      isotropic resolution, while maintaining superior scar-to-blood contrast.

                   6.  To study the effect of this novel LGE method on the detection and assessment
                      of papillary muscle scar in patients with mitral valve prolapse.

                   7.  To  investigate  the  impact  of  this  novel  LGE  method  on  the  myocardial
                      ischemic burden (MIB) required for making patient management decisions.

               This  thesis  follows  the  development  progress  around  these  sub  aims.  Chapter  2
               provides a review of previous efforts that were made to increase scar-to-blood contrast
               in  LGE  MRI.  The  used  contrast  mechanisms  are  described,  (pre)clinical  results  are
               discussed, and perspectives on future research are provided. Following this overview,
               the development and feasibility of a novel dark-blood LGE method without additional
               magnetization  preparation  are  described  in  Chapter  3.  Computer  simulations  were
               performed, and contrast-to-noise ratios were obtained from a small number of patients
               as a proof of principle. This novel method was then validated against histopathology
               in a porcine animal model, of which the results are presented in Chapter 4. MI was
               induced using catheter balloon inflation and assessed by both novel dark-blood LGE
               and conventional bright-blood LGE MRI, using histopathology as reference standard.
               Chapter 5 describes the clinical value of the novel LGE method as assessed in a large,
               unselected cohort of patients using MR systems running at both 1.5 T and 3 T from
               multiple  vendors.  Ischemic  scar  detection,  among  others,  was  assessed  using  novel
               dark-blood LGE and compared to conventional bright-blood LGE. Chapter 6 focuses
               on the translation of the dark-blood contrast mechanism to high resolution 3D imaging
               methods. A novel dynamic TI mechanism is presented to ensure optimal blood pool
               nulling  and  thereby  obtain  reliable  dark-blood  contrast  throughout  the  entire  3D
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