The SASHA sequence is a simple and fast approach to in vivo T1 mapping with good accuracy in simulations and phantom experiments.

To compare accuracy, precision, and reproducibility of four commonly used myocardial T1 mapping sequences: modified Look-Locker inversion recovery (MOLLI), shortened MOLLI (ShMOLLI), saturation recovery single-shot acquisition (SASHA), and saturation pulse prepared heart rate independent inversion recovery (SAPPHIRE). Materials andMethods:This HIPAA-compliant study was approved by the institutional review board. All subjects provided written informed consent. Accuracy, precision, and reproducibility of the four T1 mapping sequences were first compared in phantom experiments. In vivo analysis was performed in seven healthy subjects (mean age 6 standard deviation, 38 years 6 19; four men, three women) who were imaged twice on two separate days. In vivo reproducibility of native T1 mapping and extracellular volume (ECV) were measured. Differences between the sequences were assessed by using Kruskal-Wallis and Wilcoxon rank sum tests (phantom data) and mixed-effect models (in vivo data). Results:T1 mapping accuracy in phantoms was lower with ShMOLLI (62 msec) and MOLLI (44 msec) than with SASHA (13 msec; P , .05) and SAPPHIRE (12 msec; P , .05). MOLLI had similar precision to ShMOLLI (4.0 msec vs 5.6 msec; P = .07) but higher precision than SAPPHIRE (6.8 msec; P = .002) and SASHA (8.7 msec; P , .001). All sequences had similar reproducibility in phantoms (P = .1). The four sequences had similar in vivo reproducibility for native T1 mapping (~25-50 msec; P . .05) and ECV quantification (~0.01-0.02; P . .05). Conclusion:SASHA and SAPPHIRE yield higher accuracy, lower precision, and similar reproducibility compared with MOLLI and ShMOLLI for T1 measurement. Different sequences yield different ECV values; however, all sequences have similar reproducibility for ECV quantification.q RSNA, 2014

Purpose The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2-overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity. Patients and Methods In this double-blinded, placebo-controlled trial, patients with HER2-positive early breast cancer were randomly assigned to receive treatment with perindopril, bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy. Patients underwent cardiac magnetic resonance imaging at baseline and post-cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF. Results Thirty-three patients received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline demographic, cancer, and cardiovascular profiles were similar between groups. Study drugs were well tolerated with no serious adverse events. After 17 cycles of trastuzumab, indexed left ventricular end diastolic volume increased in patients treated with perindopril (+7 ± 14 mL/m), bisoprolol (+8 mL ± 9 mL/m), and placebo (+4 ± 11 mL/m; P = .36). In secondary analyses, trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients (-1 ± 5%) relative to the perindopril (-3 ± 4%) and placebo (-5 ± 5%) groups ( P = .001). Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis. Conclusion Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy-related declines in LVEF; however, trastuzumab-mediated left ventricular remodeling-the primary outcome-was not prevented by these pharmacotherapies.

Pulmonary arterial hypertension (PAH) is a progressive vascular disease with a high mortality rate. It is characterized by an occlusive vascular remodeling due to a pro-proliferative and antiapoptotic environment in the wall of resistance pulmonary arteries (PAs). Proliferating cells exhibit a cancer-like metabolic switch where mitochondrial glucose oxidation is suppressed, whereas glycolysis is up-regulated as the major source of adenosine triphosphate production. This multifactorial mitochondrial suppression leads to inhibition of apoptosis and downstream signaling promoting proliferation. We report an increase in pyruvate dehydrogenase kinase (PDK), an inhibitor of the mitochondrial enzyme pyruvate dehydrogenase (PDH, the gatekeeping enzyme of glucose oxidation) in the PAs of human PAH compared to healthy lungs. Treatment of explanted human PAH lungs with the PDK inhibitor dichloroacetate (DCA) ex vivo activated PDH and increased mitochondrial respiration. In a 4-month, open-label study, DCA (3 to 6.25 mg/kg b.i.d.) administered to patients with idiopathic PAH (iPAH) already on approved iPAH therapies led to reduction in mean PA pressure and pulmonary vascular resistance and improvement in functional capacity, but with a range of individual responses. Lack of ex vivo and clinical response was associated with the presence of functional variants of and that predict reduced protein function. Impaired function of these proteins causes PDK-independent mitochondrial suppression and pulmonary hypertension in mice. This first-in-human trial of a mitochondria-targeting drug in iPAH demonstrates that PDK is a druggable target and offers hemodynamic improvement in genetically susceptible patients, paving the way for novel precision medicine approaches in this disease.

BackgroundThe late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors.MethodsThirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO2). CMR measured ventricular function, mass, T1 and T2 values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography.ResultsPatients had normal LVEF (59 ± 7%) but peak VO2 was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = −0.49). Increased ECV correlated with decreased mass/volume ratio (r = −0.64), decreased LV wall thickness/height ratio (r = −0.72), lower peak VO2(r = −0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO2 or cumulative dose.ConclusionsMyocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.

Background-Fabry disease (FD) is an X-linked disorder of lysosomal metabolism affecting multiple organs with cardiac disease being the leading cause of death. Current imaging evaluations of the heart are suboptimal.

Purpose To evaluate the accuracy and feasibility of a free‐breathing 4D flow technique using compressed sensing (CS), where 4D flow imaging of the thoracic aorta is performed in 2 min with inline image reconstruction on the MRI scanner in less than 5 min. Methods The 10 in vitro 4D flow MRI scans were performed with different acceleration rates on a pulsatile flow phantom (9 CS acceleration factors [R = 5.4–14.1], 1 generalized autocalibrating partially parallel acquisition [GRAPPA] R = 2). Based on in vitro results, CS‐accelerated 4D flow of the thoracic aorta was acquired in 20 healthy volunteers (38.3 ± 15.2 years old) and 11 patients with aortic disease (61.3 ± 15.1 years) with R = 7.7. A conventional 4D flow scan was acquired with matched spatial coverage and temporal resolution. Results CS depicted similar hemodynamics to conventional 4D flow in vitro, and in vivo, with >70% reduction in scan time (volunteers: 1:52 ± 0:25 versus 7:25 ± 2:35 min). Net flow values were within 3.5% in healthy volunteers, and voxel‐by‐voxel comparison demonstrated good agreement. CS significantly underestimated peak velocities (vmax) and peak flow (Qmax) in both volunteers and patients (volunteers: vmax, −16.2% to −9.4%, Qmax: −11.6% to −2.9%, patients: vmax, −11.2% to −4.0%; Qmax, −10.2% to −5.8%). Conclusion Aortic 4D flow with CS is feasible in a two minute scan with less than 5 min for inline reconstruction. While net flow agreement was excellent, CS with R = 7.7 produced underestimation of Qmax and vmax; however, these were generally within 13% of conventional 4D flow‐derived values. This approach allows 4D flow to be feasible in clinical practice for comprehensive assessment of hemodynamics.

AimsTo determine how native myocardial T1 and extracellular volume (ECV) change with age, both to understand aging and to inform on normal reference ranges.Methods and resultsNinety-four healthy volunteers with no a history or symptoms of cardiovascular disease or diabetes underwent cardiovascular magnetic resonance at 1.5 T. Mid-ventricular short axis native and post-contrast T1 maps by Shortened MOdified Look-Locker Inversion-recovery (ShMOLLI), MOdified Look-Locker Inversion Recovery (MOLLI) [pre-contrast: 5s(3s)3s, post-contrast: 4s(1s)3s(1s)2s] and saturation recovery single-shot acquisition (SASHA) were acquired and ECV by these three techniques were derived for the mid anteroseptum. Mean age was 50 ± 14 years (range 20–76), male 52%, with no age difference between genders (males 51 ± 14 years; females 49 ± 15 years, P = 0.55). Quoting respectively ShMOLLI, MOLLI, SASHA throughout, mean myocardial T1 was 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms (P < 0.0001) and ECV 28.4 ± 3.0% [95% confidence interval (CI) 27.8–29.0], 27.3 ± 2.7 (95% CI 26.8–27.9), 24.1 ± 2.9% (95% CI 23.5–24.7) (P < 0.0001), with all values higher in females for all techniques (T1 +18 ms, +35 ms, +51 ms; ECV +2.7%, +2.6%, +3.4%). Native myocardial T1 reduced slightly with age (R2 = 0.042, P = 0.048; R2 = 0.131, P < 0.0001—on average by 8–11 ms/decade—but not for SASHA (R2 = 0.033 and P = 0.083). ECV did not change with age (R2 = 0.003, P = 0.582; R2 = 0.002, P = 0.689; R2 = 0.003, P = 0.615). Heart rate decreased slightly with age (R2 = 0.075, coefficient = −0.273, P = 0.008), but there was no relationship between age and other blood T1 influences (haematocrit, iron, high density lipoprotein-cholesterol).ConclusionGender influences native T1 and ECV with women having a higher native T1 and ECV. Native T1 measured by MOLLI and ShMOLLI was slightly lower with increasing age but not with SASHA and ECV was independent of age for all techniques.