Purpose T\(_{1P}\) dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T\(_{1P}\) mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T\(_{1P}\) mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals. Methods A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T\(_{1P}\) quantification accuracy. The in vivo validation of T\(_{1P}\) mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal. Results The Bloch simulation-based sampling shows considerably higher image quality as well as improved T\(_{1P}\) quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of - 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T\(_{1P}\) mapping. The mean T\(_{1P}\) in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T\(_{1P}\) dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz. Conclusion This new and fast T\(_{1P}\) quantification technique enables high-resolution myocardial T\(_{1P}\) mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.

A rising percentage of women with risk factors for cardiovascular disease (CVD) reach menopause and experience postmenopausal symptoms. In consequence they require assessment concerning the appropriate combination and safety of a hormone replacement therapy. Clinical trials using the combination of equine estrogens and medroxyprogesterone acetate (MPA) reported an increased risk of thromboembolic events and no cardiovascular protective effects in women receiving this type of hormone replacement therapy. However unopposed estradiol and different regimes estrogens/progestins in vitro and in animal studies have proved to be beneficial for the cardiovascular system. Thus it is possible that the negative outcomes of the clinical trials are an exclusive feature of the regime equine estrogens plus MPA. The present study was initiated to evaluate the cardiovascular effects and possible mechanism of damage of the regime MPA plus 17ß-estradiol in comparison to unopposed 17ß-estradiol during cardiac disease. The role of 17ß-estradiol and MPA during left ventricular dysfunction and chronic heart failure was studied in female Wistar rats that received myocardial infarction. After 8 weeks of treatment the combination of MPA plus estradiol aggravated left ventricular remodelling and dysfunction as judged by increased heart weight, elevated left ventricular end diastolic pressure and decreased left ventricular fractional shortening, effects that were accompanied by increase left ventricular oxidative stress and expression of rac 1 and p67phox regulatory subunits of the NADPH oxidase. In contrast ovariectomy as well as 17ß- estradiol supplementation conferred neutral effects on cardiac function and remodelling post myocardial infarction. Suggesting that the aggravating symptoms of the regime MPA plus 17ß –estradiol are inherent to this pharmacological regime and are not a class effect of the progesterone receptor ligands and are neither due to inhibition of estradiol beneficial effects. Considering that aldosterone plays an important role in the development and aggravation of cardiovascular disease the cardiovascular effects of MPA plus 17ß –estradiol was studied in a model of mineralocorticoid receptor activation and compared to the effects of regimes based in drospirenone, a new progestin with antimineralocorticoid properties. The complex pattern of cardiovascular injury in ovariectomized Wistar rats induced by 8 weeks of continuous chronic aldosterone infusion and high-salt diet was significantly attenuated in sham-ovariectomized rats and by coadministration of 17 ß-estradiol in ovariectomized animals. The beneficial role of 17 ß-estradiol on blood pressure, cardiac hypertrophy, vascular osteopontin expression and perivascular fibrosis was completely abrogated by coadministration of MPA. In contrast, drospirenone was either neutral or additive to 17 ß-estradiol in protecting against aldosterone salt-induced cardiovascular injury and inflammation. Taking into account that the kidney plays a major role for the development and aggravation of hypertension a further characterization of fluid balance, renal morphology and renal gene expression in the aldosterone salt treated rats was conducted. Aldo-salt treatment resulted in remnant kidney hypertrophy without structural damage, effects that were not modified by 17 ß-estradiol. However combination of MPA with 17 ß-estradiol enhanced kidney hypertrophy, fluid turnover, renal sodium retention and potassium excretion and was associated with increased renal ENaC expression, extensive renal lesions, tubular damage and enhanced p67phox expression and protein tyrosin nitrosylation. Different to the protective effects of drospirenone that included a complete blockade of kidney hypertrophy and sodium retention and enhanced renal expression of angiotensin II type-2 receptors. Therefore the loss of 17 ß-estradiol cardiovascular beneficial effects and the renal harmful effects in the aldosterone salt treated rats receiving MPA can not be extrapolated to other progestins. Indeed drospirenone conferred protective effects due to its antimineralocorticoid properties. In conclusion, the choice of specific synthetic progestins has profound implications on the development of cardiovascular and renal injury; MPA aggravated cardiac disease, which contributes to explain the adverse outcomes of clinical trials on the prevention of cardiovascular disease by combined estrogen and MPA treatment.