Diagnostic precision and sex differences in quantitative cardiovascular magnetic resonance

Correct medical treatment necessitates a correct diagnosis. Cardiac imaging aims to establish an accurate diagnosis without performing unnecessary invasive procedures. Cardiovascular magnetic resonance (CMR) has emerged as a valuable diagnostic tool in clinical cardiology because of its inherently good soft-tissue contrast, dynamic visualizations and the possibility to perform quantitative tissue characterization. However, diagnostic precision may be affected in quantitative imaging by several factors such as the presence of sex differences, or measurements errors. Therefore, the aim of this thesis was to identify parameters and sex differences that affect precision and accuracy, and to evaluate post-processing methods to increase diagnostic precision. We found that intramyocardial blood affects native myocardial T" values in patients without focal abnormalities, and that native myocardial T" values differ between the sexes. We developed a blood correction model that maintained an increase in diagnostic precision by 13% when applied to an independent patient cohort, which furthermore also eliminated sex differences in healthy volunteers in Study I. In Study II, we evaluated a post-processing method called stationary tissue background correction for increasing diagnostic precision in clinical blood flow measurements. We found that the number of patients with a pulmonaryto-systemic blood flow ratio (Qp/Qs) outside of the normal range decreased following stationary tissue background correction. In Study III, we investigated the presence of sex differences in a newly developed myocardial perfusion imaging sequence in healthy volunteers. We found that women have higher myocardial blood volume, myocardial perfusion and myocardial extracellular volume compared to men both at rest and during adenosine stress, which provide mechanistic insight into myocardial physiology. In Study IV, we investigated the clinical accuracy and precision of synthetic scar images (SynLGE) from post-contrast T" maps compared to conventional scar images (LGE) for diagnosing focal myocardial fibrosis of any etiology. Compared to LGE, SynLGE yielded a sensitivity of 77%, a specificity of 98%, a positive predictive value of 97% and a negative predictive value of 86%. In conclusion, there are sex differences in several aspects of clinical quantitative CMR imaging that may affect diagnostic precision. Post-processing is a powerful tool to improve diagnostic precision both by increasing precision in native myocardial T" values via blood correction, and in Qp/Qs via stationary tissue background correction. SynLGE can provide complementary confidence in the assessment of focal myocardial fibrosis in complement to conventional LGE, and thereby increase diagnostic accuracy and precision. LIST OF SCIENTIFIC PAPERS I. Nickander J, Lundin M, Abdula G, Sorensson P, Rosmini S, Moon JC, Kellman P, Sigfridsson A, and Ugander M. Blood correction reduces variability and gender differences in native myocardial T1 values at 1.5 T cardiovascular magnetic resonance a derivation/validation approach. J Cardiovasc Magn Reson. 2017;19(1):41 II. Nickander J, Lundin M, Abdula G, Jenner J, Maret E, Sorensson P, Heiberg E, Sigfridsson A, Ugander M. Stationary tissue background correction improves precision of the pulmonary-to-systemic blood flow ratio by phase contrast velocity encoded cardiovascular magnetic resonance. Submitted III. Nickander J, Themudo R, Sigfridsson A, Xue H, Kellman P and Ugander M. Females have higher myocardial blood volume, myocardial perfusion and myocardial extracellular volume compared to males – both at rest and during adenosine stress cardiovascular magnetic resonance. Submitted IV. Abdula G, Nickander J, Sorensson P, Lundin M, Kellman P, Sigfridsson A and Ugander M. Synthetic late gadolinium enhancement cardiac magnetic resonance for diagnosing myocardial scar. Scand Cardiovas J, 2018, In press. DOI:10.1080/14017431.2018. 1449960. CONTENTS