Purpose An efficient Yarnball ultrashort‐TE k‐space trajectory, in combination with an optimized pulse sequence design and automated image‐processing approach, is proposed for fast and quantitative imaging of water density in the lung parenchyma. Methods Three‐dimensional Yarnball k‐space trajectories (TE = 0.07 ms) were designed at 3 T for breath‐hold and free‐breathing navigator acquisitions targeting the lung parenchyma (full torso spatial coverage) with minimal T1 and T2∗ weighting. A composite of all solid tissues surrounding the lungs (muscle, liver, heart, blood pool) was used for user‐independent lung water density signal referencing and B1‐inhomogeneity correction needed for the calculation of relative lung water density images. Sponge phantom experiments were used to validate absolute water density quantification, and relative lung water density was evaluated in 10 healthy volunteers. Results Phantom experiments showed excellent agreement between sponge wet weight and imaging‐derived water density. Breath‐hold (13 seconds) and free‐breathing (~2 minutes) Yarnball acquisitions in volunteers (2.5‐mm isotropic resolution) had negligible artifacts and good lung parenchyma SNR (>10). Whole‐lung average relative lung water density values with fully automated analysis were 28.2 ± 1.9% and 28.6 ± 1.8% for breath‐hold and free‐breathing acquisitions, respectively, with good test–retest reproducibility (intraclass correlation coefficient = 0.86 and 0.95, respectively). Conclusions Quantitative lung water density imaging with an optimized Yarnball k‐space acquisition approach is possible in a breath‐hold or short free‐breathing study with automated signal referencing and segmentation.

Background. Peak oxygen consumption (VO 2 ) is reduced in women with a history of breast cancer (BC). We measured leg blood flow, oxygenation, bioenergetics, and muscle composition in women with BC treated with anthracycline chemotherapy (n = 16, mean age: 56 years) and age-and body mass index-matched controls (n = 16). Materials and Methods. Whole-body peak VO 2 was measured during cycle exercise. 31 Phosphorus magnetic resonance (MR) spectroscopy was used to measure muscle bioenergetics during and after incremental to maximal plantar flexion exercise (PFE). MR imaging was used to measure lower leg blood flow, venous oxygen saturation (S v O 2 ), and VO 2 during submaximal PFE, and abdominal, thigh, and lower leg intermuscular fat (IMF) and skeletal muscle (SM). Results. Whole-body peak VO 2 was significantly lower in BC survivors versus controls (23.1 AE 7.5 vs. 29.5 AE 7.7 mL/kg/minute).Muscle bioenergetics and mitochondrial oxidative capacity were not different between groups. No group differences were found during submaximal PFE for lower leg blood flow, S v O 2 , or VO 2 . The IMF-to-SM ratio was higher in the thigh and lower leg in BC survivors (0.36 AE 0.19 vs. 0.22 AE 0.07, p = .01; 0.10 AE 0.06 vs. 0.06 AE 0.02, p = .03, respectively) and were inversely related to whole-body peak VO 2 (r = −0.71, p = .002; r = −0.68, p = .003, respectively) . In the lower leg, IMF-to-SM ratio was inversely related to VO 2 and O 2 extraction during PFE. Conclusion. SM bioenergetics and oxidative capacity in response to PFE are not impaired following anthracycline treatment. Abnormal SM composition (increased thigh and lower leg IMF-to-SM ratio) may be an important contributor to reduced peak VO 2 during whole-body exercise among anthracycline-treated BC survivors. The Oncologist 2020;25:e852-e860 Implications for Practice: Peak oxygen consumption (peak VO 2 ) is reduced in breast cancer (BC) survivors and is prognostic of increased risk of cardiovascular disease-related and all-cause mortality. Results of this study demonstrated that in the presence of deficits in peak VO 2 1 year after anthracycline therapy, skeletal muscle bioenergetics and oxygenation are not impaired. Rather, body composition deterioration (e.g., increased ratio of intermuscular fat to skeletal muscle) may contribute to reduced exercise tolerance in anthracycline BC survivors. This finding points to the importance of lifestyle interventions including caloric restriction and exercise training to restore body composition and cardiovascular health in the BC survivorship setting.

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (− 30.4 ± 2.2 vs − 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.

Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non‐invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non‐failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1–150.3] versus 137.4 [109.2–165.9] μg/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1 μg/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF‐MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF‐MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron‐deficient hearts. Mechanistically, iron uptake pathways were impeded in HF‐MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts. Conclusions MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non‐invasively monitor MID.