Blood flow specific assessment of ventricular function : Visualization and quantification using 4D flow CMR

The spectrum of cardiovascular diseases is the leading cause of morbidity and mortality globally. Early assessment and treatment of these conditions, acquired as well as congenital, is therefore of paramount importance.   The human heart has a great ability to adapt to various hemodynamic conditions by cardiac remodeling. Pathologic cardiac remodeling can occur as a result of cardiovascular disease in an effort to maintain satisfactory cardiac function. With time, cardiac function diminishes leading to disease progression and subsequent heart failure, the end-point of many heart diseases, associated with very poor prognosis.   Within the normal cardiac ventricles blood flows in highly organized patterns, and changes in cardiac configuration or function will affect these flow patterns. Conversely, altered flows and pressures can bring about cardiac remodeling. In congenital heart disease, even after corrective surgery, cardiac anatomy and thereby intracardiac blood flow patterns are inherently altered. The clinically most available imaging technique, ultrasound with Doppler, allows only for one-directional flow assessment and is limited by the need of clear examination windows, thus failing to fully assess the complex three-dimensional blood flow within the beating heart. Cardiovascular magnetic resonance imaging (CMR) with phase-contrast has the ability to acquire three-dimensional (3D), three-directional time resolved velocity data (3D + time = 4D flow data) from which visualization and quantification of blood flow patterns over the complete cardiac cycle can be performed. Four functional blood flow components have previously been defined based on the blood route and distribution through the ventricle, where the inflowing blood that passes directly to the outflow is called Direct flow. From these components, various quantitative measures can be derived, such as component volumes and kinetic energy (KE) throughout the cardiac cycle. In addition, the 4D flow technique has the ability to quantify and visualize turbulent flow with increased velocity fluctuations in the heart and vessels, turbulent kinetic energy (TKE).   The technique has been developed and evaluated for assessment of left ventricular (LV) blood flow in healthy subjects and in patients with dilated dysfunctional left ventricles, showing significant changes in blood flow patterns and energetics with disease. There is however still no study addressing the gap in the spectrum from the healthy cohorts to patients with moderate to severe left ventricular remodeling. In Paper III, 4D flow CMR was utilized to assess LV blood flow in patients with subtle LV dysfunction, and a shift in blood flow component volumes and KE was seen from the Direct flow to the non-ejecting blood flow components.   In patients with both left- and right-sided acquired and congenital heart disease, right ventricular (RV) function is of great prognostic significance, however this ventricle has historically been somewhat overseen. With its complex geometry, advanced physiology and retrosternal location, assessment of the RV is still challenging and the right ventricular blood flow is still incompletely described. In Paper I, the RV blood flow in healthy subjects was assessed, and the proportionally larger Direct flow component was located in the most basal region of the ventricle and possessed higher levels of KE at end-diastole than the other flow components suggesting that this portion of blood was prepared for efficient systolic ejection. In Paper II, the blood flow was assessed in the RV of patients with subtle primary LV disease, and even if conventional echocardiographic or CMR RV parameters did not show any RV dysfunction, alterations of flow patterns suggestive of RV impairment were found in the patients with the more remodeled LVs.   With improvements of the cardiovascular health care, including the surgical techniques, the number of adult patients with surgically corrected complex congenital heart diseases increases, one of which is tetralogy of Fallot (ToF). Surgical repair of ToF involves widening of the pulmonary stenosis, which postoperatively may cause pulmonary insufficiency and regurgitation (PR). Disturbed or turbulent flow patterns are rare in the healthy cardiovascular system. With pathological changes, such as valvular insufficiency, increased amounts of TKE have been demonstrated. Turbulence is known to be harmful to organic tissues and could be significant in the development of ventricular remodeling, such as dilation and other complications seen in Fallot patients. In Paper IV, the RV intraventricular TKE levels were assessed in relation to conventional measures of PR. Results showed that RV TKE was increased in ToF patients with PR compared to healthy controls, and that these 4D flow-specific measures related slightly stronger to indices of RV remodeling than the conventional measures of PR.   4D flow CMR analysis of the intracardiac blood flow has the potential of adding to pathophysiological understanding, and thereby provide useful diagnostic information and contribute to optimization of treatment of heart disease at earlier stages before irreversible and clinically noticeable changes occur. The flow specific measures used in this thesis could be utilized to detect these alterations of intracardiac blood flow and could thus act as potential markers of progressing ventricular dysfunction, pathological remodeling or used for risk stratification in adults with early repair tetralogy of Fallot. Visualizations of intracardiac flow patterns could provide useful information to cardiac/thoracic surgeons pre- and post-operatively

Är hårdare straff det rätta vapnet? En studie om skärpningarna i vapenlagens brottspreventiva verkan

Due to the fact that Sweden during the past five years has seen an increase of gun related crimes we find it necessary to further explore this area. The public´s trust regarding the legal system has started to decline as an effect of this negative trend. We are currently experiencing a shift within the criminal policy regarding the tendency by politicians to ignore scientifically research and choose to get tough on crime. This is done in order to show the public that the state is capable of action. The state has chosen to strengthen the current law regarding possession and use of illegal firearms. The aim of this paper is to evaluate if the current changes regarding the law of possession and use of illegal firearms will achieve its intended effect. This will be conducted by gathering adequate data which consists of previous research, legal cases and interviews with members representing the legal system as well as past convicted criminals in order to provide the reader with a holistic perspective. The analysis will be conducted by the use of Jürgen Habermas and Travis Hirschis theoretical framework in order to examine how law as a medium can be used to reduce the friction between society and the system

Turbulent kinetic energy in the right ventricle : Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot

Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling. Materials and Methods: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (11%) and one higher PR fraction group (&gt;11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. Assessment: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC). Results: The higher PR fraction group had more remodeled RVs (140 6 25 vs. 107 6 22 [lower PR fraction, P &lt; 0.01] and 93 6 15 ml/m2[healthy, P &lt; 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 6 3.15 vs. 2.23 6 0.81 [lower PR fraction, P &lt; 0.01] and 1.91 6 0.78 mJ [healthy, P &lt; 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R25 0.47, P 5 0.002). Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair.Funding agencies:  European Research Council [310612]; Swedish Heart and Lung Foundation [20140398]; County Council of Ostergotland; Medical Research Council of Southeast Sweden (FORSS); Swedish Research Council [2013-6077, 2014-6191]</p

Correlation plots.

<p>A. Direct flow (DF) volume ratio (in relation to LVEDV) versus LVEDV index (LVEDVI). B. DF Kinetic energy (KE) ratio at ED versus LVEDVI. C. Non-ejecting (NE) volume ratio versus LVEDVI. D. NE KE ratio at ED versus LVEDVI.</p

The 4D flow components as proportions of total LV EDV (percent ± SD) in the three sub-groups stratified by LVEDVI.

<p>Non-ejecting volume is comprised of the Retained inflow (yellow) and Residual volume (red) flow components (yellow + red = orange). * P<0.05 vs Control group; † P<0.05 vs Lower LVEDVI group.</p