Tryggve H. Storås

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.

Prostate magnetic resonance imaging: Multiexponential T2 decay in prostate tissue

To investigate the T2 decay in prostate tissue for multiexponentiality and to assess how the biexponential model relates to established T2W contrast.

Visualization of deep veins and detection of deep vein thrombosis (DVT) with balanced turbo field echo (b-TFE) and contrast-enhanced T1 fast field echo (CE-FFE) using a blood pool agent (BPA).

To assess image quality, vessel visualization, preliminary diagnostic properties, and interobserver variability of a novel balanced turbo field echo (b‐TFE) sequence and contrast‐enhanced T1 fast field echo (CE‐FFE) sequence with blood pool agent (BPA).

Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention

Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12‐week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real‐time PCR of mRNA of lipid droplet‐associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large‐scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training.

Insulin sensitivity, body composition and adipose depots following 12 w combined endurance and strength training in dysglycemic and normoglycemic sedentary men

Abstract Context: Insulin resistance and dysglycemia are associated with physical inactivity and adiposity, and may be improved by exercise. Objective: Investigate the effect of exercise on insulin sensitivity, body composition and adipose depots in sedentary men with (n = 11) or without (n = 11) overweight and dysglycemia. Material and methods: Euglycemic-hyperinsulinemic clamp, ankle-to-neck MRI, MRS, muscle and adipose tissue biopsies before and after 12 weeks combined strength and endurance exercise. Results: Insulin sensitivity, VO2max, strength, whole-body and muscle fat content, and abdominal adipose depots were improved without obvious differences between normo- and dysglycemic men. Hepatic fat, waist circumference and subcutaneous adipose tissue were reduced in the dysglycemic group. For both groups plasma adiponectin was reduced, whereas IL-6 was unchanged. Visceral fat was preferentially lost compared with other adipose depots. Discussion and conclusion: Body composition, fat distribution and insulin sensitivity improved following training in sedentary middle-aged men with and without dysglycemia.

Split dynamic MRI: Single bolus high spatial–temporal resolution and multi contrast evaluation of breast lesions

To test the feasibility of a novel “split dynamic” method in which high temporal and high spatial resolution dynamic MR images are acquired during a single bolus injection.

Three-dimensional balanced steady state free precession imaging of the prostate: flip angle dependency of the signal based on a two component T2-decay model.

To investigate the contrast of three‐dimensional balanced steady state free precession (3D bSSFP) in the two component T2 model and to apply the results to optimize 3D bSSFP for prostate imaging at 1.5 Tesla.

Single bolus split dynamic MRI: Is the combination of high spatial and dual‐echo high temporal resolution interleaved sequences useful in the differential diagnosis of breast masses?

To test the split dynamic magnetic resonance imaging (MRI) technique in the assessment of breast masses in which high spatial resolution and dual‐echo high temporal resolution data are acquired during a single bolus injection.

Effect of candesartan and metoprolol on myocardial tissue composition during anthracycline treatment: the PRADA trial

Aims Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003). Conclusions Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume.

Dynamic multi‐echo DCE‐ and DSC‐MRI in rectal cancer: Low primary tumor Ktrans and ΔR2* peak are significantly associated with lymph node metastasis

To implement a dynamic contrast‐based multi‐echo MRI sequence in assessment of rectal cancer and evaluate associations between histopathologic data and the acquired dynamic contrast‐enhanced (DCE) and dynamic susceptibility contrast (DSC) ‐MRI parameters.