Reference Values for Water-Specific T1 of the Liver at 3 T: T2*-Compensation and the Confounding Effects of Fat.

BACKGROUND: T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water ), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown. PURPOSE: Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability. STUDY TYPE: Prospective observational; phantoms. POPULATIONS: One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years). FIELD STRENGTH/SEQUENCE: 2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI. ASSESSMENT: SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility. STATISTICAL TESTS: Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters. DATA CONCLUSION: Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Dynamic changes in lung water density and volume following supine body positioning.

PURPOSE: Measure the changes in relative lung water density (rLWD), lung volume, and total lung water content as a function of time after supine body positioning. METHODS: An efficient ultrashort-TE pulse sequence with a yarnball k-space trajectory was used to measure water density-weighted lung images for 25 min following supine body positioning (free breathing, 74-s acquisitions, 3D images at functional residual capacity, 18 time points) in 9 healthy volunteers. Global and regional (10 chest-to-back positions) rLWD, lung volume, and total lung water volume were measured in all subjects at all time points. Volume changes were validated with a nitrogen washout study in 3 participants. RESULTS: Global rLWD increased significantly (p = 0.001) from 31.8 ± 5.5% to 34.8 ± 6.8%, while lung volumes decreased significantly (p < 0.001) from 2390 ± 620 mL to 2130 ± 630 mL over the same 25-min interval. Total lung water volume decreased slightly from 730 ± 125 mL to 706 ± 126 mL (p = 0.028). There was a significant chest-to-back gradient in rLWD (20.7 ± 4.6% to 39.9 ± 6.1%) at all time points with absolute increases of 1.8 ± 1.2% at the chest and 5.4 ± 1.9% at the back. Nitrogen washout studies yielded a similar reduction in lung volume (12.5 ± 0.9%) and time course following supine positioning. CONCLUSION: Lung volumes during tidal breathing decrease significantly over tens of minutes following supine body positioning, with corresponding increases in lung water density (9.2 ± 4.4% relative increase). The total volume of lung water is slightly reduced over this interval (3.3 ± 4.0% relative change). Evaluation of rLWD should take time after supine positioning, and more generally, all sources of lung volume changes should be taken into consideration to avoid significant bias.

Simultaneous time-of-flight MR angiography and quantitative susceptibility mapping with key time-of-flight features.

A technique for combined time-of-flight (TOF) MR angiography (MRA) and quantitative susceptibility mapping (QSM) was developed with key features of standard three-dimensional (3D) TOF acquisitions, including multiple overlapping thin slab acquisition (MOTSA), ramped RF excitation, and venous saturation. The developed triple-echo 3D TOF-QSM sequence enabled TOF-MRA, susceptibility-weighted imaging (SWI), QSM, and R2* mapping. The effects of ramped RF, resolution, flip angle, venous saturation, and MOTSA were studied on QSM. Six volunteers were scanned at 3 T with the developed sequence, conventional TOF-MRA, and conventional SWI. Quantitative comparison of susceptibility values on QSM and normalized arterial and venous vessel-to-background contrasts on TOF and SWI were performed. The ramped RF excitation created an inherent phase variation in the raw phase. A generic correction factor was computed to remove the phase variation to obtain QSM without artifacts from the TOF-QSM sequence. No statistically significant difference was observed between the developed and standard QSM sequence for susceptibility values. However, maintaining standard TOF features led to compromises in signal-to-noise ratio for QSM and SWI, arising from the use of MOTSA rather than one large 3D slab, higher TOF spatial resolution, increased TOF background suppression due to larger flip angles, and reduced venous signal from venous saturation. In terms of vessel contrast, veins showed higher normalized contrast on SWI derived from TOF-QSM than the standard SWI sequence. While fast flowing arteries had reduced contrast compared with standard TOF-MRA, no statistical difference was observed for slow flowing arteries. Arterial contrast differences largely arise from the longer TR used in TOF-QSM over standard TOF-MRA to accommodate additional later echoes for SWI. In conclusion, although the sequence has a longer TR and slightly lower arterial contrast, provided an adequate correction is made for ramped RF excitation effects on phase, QSM may be performed from a multiecho sequence that includes all key TOF features, thus enabling simultaneous TOF-MRA, SWI, QSM, and R2* map computation.

Inline dual-echo T2 quantification in brain using a fast mapping reconstruction technique.

T2 mapping from 2D proton density and T2-weighted images (PD-T2) using Bloch equation simulations can be time consuming and introduces a latency between image acquisition and T2 map production. A fast T2 mapping reconstruction method is investigated and compared with a previous modeling approach to reduce computation time and allow inline T2 maps on the MRI console. Brain PD-T2 images from five multiple sclerosis patients were used to compare T2 map reconstruction times between the new subtraction method and the Euclidean norm minimization technique. Bloch equation simulations were used to create the lookup table for decay curve matching in both cases. Agreement of the two techniques used Bland-Altman analysis for investigating individual subsets of data and all image points in the five volumes (meta-analysis). The subtraction method resulted in an average reduction of computation time for single slices from 134 s (minimization method) to 0.44 s. Comparing T2 values between the subtraction and minimization methods resulted in a confidence interval ranging from -0.06 to 0.06 ms (95% of values were within ± 0.06 ms between the techniques). Using identical reconstruction code based on the subtraction method, inline T2 maps were produced from PD-T2 images directly on the scanner console. The excellent agreement between the two methods permits the subtraction technique to be interchanged with the previous method, reducing computation time and allowing inline T2 map reconstruction based on Bloch simulations directly on the scanner.

Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans.

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.

Longitudinal Changes in Skeletal Muscle Metabolism, Oxygen Uptake, and Myosteatosis During Cardiotoxic Treatment for Early-Stage Breast Cancer.

BACKGROUND: While cardiotoxic chemotherapy is known to negatively impact cardiac function and hemoglobin levels, the impact on skeletal muscle has been understudied among patients. The purpose was to longitudinally characterize myosteatosis (muscle fat), skeletal muscle metabolism, and oxygen (O2) consumption during cardiotoxic chemotherapy for breast cancer. PATIENTS AND METHODS: Thirty-four patients with stage I-III breast cancer were enrolled before trastuzumab-containing and/or anthracycline-containing chemotherapy. We used magnetic resonance imaging to non-invasively quantify thigh myosteatosis (fat-water imaging), and lower leg metabolism (31P spectroscopy), O2 consumption (custom techniques), and peak power output during single-leg plantarflexion exercise at pre-, mid-, end-chemotherapy, and 1-year. We also measured pulmonary VO2peak and maximal leg press strength. RESULTS: During chemotherapy, VO2peak and leg press strength decreased while peak plantarflexion power output was maintained. At mid-chemotherapy, hemoglobin decreased (16%) and lower leg blood flow increased (37%) to maintain lower leg O2 delivery; exercise Pi:PCr and myosteatosis increased. Between mid- and end-chemotherapy, lower leg O2 extraction (28%) and O2 consumption (21%) increased, while plantarflexion exercise efficiency (watts/O2 consumed) decreased. At one year, VO2peak and leg press strength returned to pre-chemotherapy levels, but lower leg exercise O2 extraction, consumption and Pi:PCr, and myosteatosis remained elevated. CONCLUSION: Lower leg skeletal muscle blood flow and O2 extraction adapt to compensate for chemotherapy-related hemoglobin reduction for small muscle mass exercise but are insufficient to maintain large muscle mass exercise (pulmonary VO2peak, leg press strength). The excess O2 required to perform work, increased Pi:PCr ratio and myosteatosis together suggest suppressed fat oxidation during chemotherapy.

Cardiac and skeletal muscle predictors of impaired cardiorespiratory fitness post-anthracycline chemotherapy for breast cancer.

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.

Tricuspid Valve Tethering Is Associated with Residual Regurgitation after Valve Repair in Hypoplastic Left Heart Syndrome: A Three-Dimensional Echocardiographic Study.

BACKGROUND: Tricuspid valve regurgitation (TR) is a risk factor for morbidity and mortality in children with hypoplastic left heart syndrome (HLHS). Surgical tricuspid valve (TV) repair is common, but durable repair remains challenging. The aim of this study was to examine mechanisms of TR requiring surgery, features associated with unsuccessful repair, and TV changes after surgical repair. METHODS: Thirty-six patients with HLHS requiring TV repair (TVR) and 36 matched control subjects with HLHS were assessed using two-dimensional and three-dimensional echocardiography. Using three-dimensional echocardiography, TV coordinates from the annulus, leaflet, and ventricle were used to measure annular, leaflet, prolapse, and tethering values and anterior papillary muscle angle. TR grade and ventricular size, function, and shape were assessed using two-dimensional echocardiography. RESULTS: Patients requiring TVR had greater total leaflet prolapse, larger TV annular and leaflet areas, and flatter annuli, with no difference in tethering, coaptation index, or anterior papillary muscle angle. In patients with HLHS, successful TVR at follow-up (58%) was associated with preoperative total leaflet prolapse (especially posterior). Unsuccessful repair was associated with preoperative tethering of the septal leaflet. TVR in patients with HLHS caused a reduction of total annular and leaflet size and reduced prolapse and tethering of the posterior leaflet but did not affect anterior leaflet prolapse or septal leaflet tethering. CONCLUSIONS: Features associated with TVR include a flattened and dilated TV annulus with leaflet prolapse. The additional presence of a tethered septal leaflet before TVR is associated with significant postoperative TR. Current surgical techniques, predominantly posterior annuloplasty and commissuroplasty, adequately address annular size and posterior leaflet pathology, but not septal leaflet tethering. Individualized and innovative surgical techniques are vital to improve surgical repair success.

Quantification of lung water density with UTE Yarnball MRI.

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.

Reliability and reproducibility of cardiac MRI quantification of peak exercise function with long-axis views.

The conventional approach to cardiac magnetic resonance (CMR) involving breath holds, electrocardiography-gating, and acquisition of a short-axis (SAX) image stack, introduces technical and logistical challenges for assessing exercise left ventricular (LV) function. Real-time, free-breathing CMR acquisition of long-axis (LAX) images overcomes these issues and also enables assessment of global longitudinal strain (GLS). We evaluated the reliability of a free-breathing LAX approach compared to the standard SAX approach and the reproducibility of free-breathing LAX. LV SAX (contiguous stack) and LAX (two-chamber and four-chamber) 3T CMR cine images were acquired four times within one scan in 32 women with cardiovascular risk factors (56±10 years, 28±4 kg/m2) as follows: 1) resting, gated-segmented, end-expiration breath-hold; 2) resting, real-time, free-breathing; 3) test-retest set of resting, real-time, free-breathing; 4) peak exercise (incremental-to-maximum, in-magnet, stepper test), real-time, free-breathing. A second scan was performed within one week in a subset (n = 5) to determine reproducibility of peak exercise measures. Reliability and agreement of the free-breathing LAX approach with the conventional SAX approach were assessed by intraclass correlation coefficient (ICC) and Bland-Altman plots, respectively. Normal control GLS reserve was also acquired in a separate set of 12 young, healthy control women (25±4 years, 22±2 kg/m2) for comparison. Comparisons of LV volumes and function among all techniques at rest had good-to-excellent reliability (ICC = 0.80-0.96), and excellent reliability between peak exercise free-breathing LAX and SAX evaluations (ICC = 0.92-0.96). Higher resting heart rates with free-breathing acquisitions compared to breath-hold (mean difference, limits of agreement: 5, 1-12 beats per minute) reduced reliability for cardiac output (ICC = 0.67-0.79). Reproducibility of the free-breathing LAX approach was good-to-excellent at rest and peak exercise (ICC = 0.74-0.99). GLS exercise reserve was impaired in older women at cardiovascular risk compared to young healthy women (-4.7±2.3% vs -7.4±2.1%, p = 0.001). Real-time, free-breathing CMR with LAX evaluation provides a reliable and reproducible method to assess rest and peak exercise cardiac function, including GLS.

Aerobic Fitness Is Related to Myocardial Fibrosis Post-Anthracycline Therapy.

PURPOSE: We evaluated the impact of anthracyclines on left ventricular function and myocardial tissue characteristics using cardiovascular magnetic resonance (CMR) imaging to determine their relationship with V˙O2peak. METHODS: Women with breast cancer who had not yet received treatment (No-AT, n = 16) and had received anthracycline treatment ~1 yr earlier (Post-AT, n = 16) and controls without cancer (CON, n = 16) performed a maximal exercise test and a comprehensive 3T CMR examination, including native myocardial T1 mapping, where elevated T1 times are indicative of myocardial fibrosis. ANOVA and linear regression were used to compare CMR variables between groups and to determine associations with V˙O2peak. Subgroup analysis was performed by categorizing participants as "fit" or "unfit" based on whether their V˙O2peak value was greater or less than 100% of reference value for age, respectively. RESULTS: Left ventricular end-diastolic volume, ejection fraction, and mass were similar between groups. Post-AT, T1 times were elevated (1534 ± 32 vs 1503 ± 28 ms, P < 0.01), and V˙O2peak was reduced (23.1 ± 7.5 vs 29.5 ± 7.7 mL·kg-1⋅min-1, P = 0.02) compared with CON. In No-AT, T1 times and V˙O2peak were similar to CON. In the Post-AT group, T1 time was associated with V˙O2peak (R2 = 64%), whereas in the absence of anthracyclines (i.e., No-AT and CON groups), T1 time was not associated with V˙O2peak. Regardless of group, all fit women had similar T1 times, whereas unfit women Post-AT had higher T1 than unfit CON (1546 ± 22 vs 1500 ± 33 ms, P < 0.01). CONCLUSIONS: After anthracycline chemotherapy, an elevated T1 time suggesting greater extent of myocardial fibrosis, was associated with lower V˙O2peak. However, those who were fit did not have evidence of myocardial fibrosis after anthracycline treatment.

Simultaneous proton density fat-fraction and R2∗ imaging with water-specific T1 mapping (PROFIT1 ): application in liver.

PURPOSE: To describe and validate a simultaneous proton density fat-fraction (PDFF) imaging and water-specific T1 mapping (T1(Water) ) approach for the liver (PROFIT1 ) with R2∗ mapping and low sensitivity to B1+ calibration or inhomogeneity. METHODS: A multiecho gradient-echo sequence, with and without saturation preparation, was designed for simultaneous imaging of liver PDFF, R2∗ , and T1(Water) (three slices in ~13 seconds). Chemical-shift-encoded MRI processing yielded fat-water separated images and R2∗ maps. T1(Water)  calculation utilized saturation and nonsaturation-recovery water-separated images. Several variable flip angle schemes across k-space (increasing flip angles in sequential RF pulses) were evaluated for minimization of T1 weighting, to reduce the B1+ dependence of T1(Water)  and PDFF (reduced flip angle dependence). T1(Water)  accuracy was validated in mixed fat-water phantoms, with various PDFF and T1 values (3T). In vivo application was illustrated in five volunteers and five patients with nonalcoholic fatty liver disease (PDFF, T1(Water) , R2∗ ). RESULTS: A sin3 (θ) flip angle pattern (0 < Î¸ < π/2 over k-space) yielded the largest PROFIT1 signal yield with negligible B1+ dependence for both T1(Water) and PDFF. Mixed fat-water phantom experiments illustrated excellent agreement between PROFIT1 and gold-standard spectroscopic evaluation of PDFF and T1(Water)  (<1% T1 error). In vivo PDFF, T1(Water) , and R2∗ maps illustrated independence of the PROFIT1 values from B1+ inhomogeneity and significant differences between volunteers and patients with nonalcoholic fatty liver disease for T1(Water) (927 ± 56 ms vs. 1033 ± 23 ms; P < .05) and PDFF (2.0% ± 0.8% vs. 13.4% ± 5.0%, P < .05).  R2∗ was similar between groups. CONCLUSION: The PROFIT1 pulse sequence provides fast simultaneous quantification of PDFF, T1(Water) , and R2∗ with minimal sensitivity to B1+ miscalibration or inhomogeneity.

Exercise Intolerance in Anthracycline-Treated Breast Cancer Survivors: The Role of Skeletal Muscle Bioenergetics, Oxygenation, and Composition.

BACKGROUND: Peak oxygen consumption (VO2 ) 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 VO2 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 (Sv O2 ), and VO2 during submaximal PFE, and abdominal, thigh, and lower leg intermuscular fat (IMF) and skeletal muscle (SM). RESULTS: Whole-body peak VO2 was significantly lower in BC survivors versus controls (23.1 ± 7.5 vs. 29.5 ± 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, Sv O2 , or VO2 . The IMF-to-SM ratio was higher in the thigh and lower leg in BC survivors (0.36 ± 0.19 vs. 0.22 ± 0.07, p = .01; 0.10 ± 0.06 vs. 0.06 ± 0.02, p = .03, respectively) and were inversely related to whole-body peak VO2 (r = -0.71, p = .002; r = -0.68, p = .003, respectively). In the lower leg, IMF-to-SM ratio was inversely related to VO2 and O2 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 VO2 during whole-body exercise among anthracycline-treated BC survivors. IMPLICATIONS FOR PRACTICE: Peak oxygen consumption (peak VO2 ) 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 VO2 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.

Modeling and simulation of hypothermia effects on cardiac electrical dynamics.

Previous experimental evidence has shown the effect of temperature on the action potential duration (APD). It has also been demonstrated that regional cooling of the heart can prolong the APD and promote the termination of ventricular tachycardia. The aim of this study is to demonstrate the effect of hypothermia in suppressing cardiac arrhythmias using numerical modeling. For this purpose, we developed a mathematical model that couples Pennes' bioheat equation and the bidomain model to simulate the effect of heat on the cardiac action potential. The simplification of the proposed heat-bidomain model to the heat-monodomain model is provided. A suitable numerical scheme for this coupling, based on a time adaptive mesh finite element method, is also presented. First, we performed two-dimensional numerical simulations to study the effect of heat on a regular electrophysiological wave, with the comparison of the calculated and experimental values of Q10. Then, we demonstrated the effect of global hypothermia in suppressing single and multiple spiral waves.

Measurement and correction of the bulk magnetic susceptibility effects of fat: application in venous oxygen saturation imaging.

PURPOSE: To develop a correction method for the effects of the magnetic susceptibility of fat (χFat ) on the calculation of venous oxygen saturation (SvO2 ). THEORY: The magnetic field shifts associated with the magnetic susceptibility of deoxyhemoglobin can be used to estimate SvO2 , a measure of oxygen extraction and metabolism. However, the distinct magnetic susceptibility of fat surrounding targeted veins will give rise to magnetic field perturbations that will extend into the vein and surrounding tissues, potentially confounding the calculation of SvO2 . METHODS: Multi-echo modified Dixon fat-water separated imaging was used to quantify fat-water distributions around the superficial femoral vein (venous return from the lower leg). Fat fraction images were used to generate χFat images, to calculate and remove the associated fat-susceptibility-induced magnetic field shifts before the estimation of SvO2 . This approach was evaluated at rest and with plantar flexion exercise to evaluate calf muscle oxygen extraction in 10 healthy subjects. RESULTS: The presence of fat around the vein resulted in complex magnetic field shifts and errors in estimated SvO2 . Corrected resting SvO2 values were significantly larger than those measured with conventional methods, at rest (72.6 ± 11.0% vs. 65.2 ± 12.2%, P < 0.05) and post-exercise (37.4 ± 12.3% vs. 31.7 ± 12.7%, P < 0.05), with larger errors in individuals and/or regions with increased fat volumes. Estimation and removal of the field-effects from χFat enabled the use of fat tissues for the measurement and removal of the background magnetic field. CONCLUSIONS: The magnetic susceptibility effects of fat can confound SvO2 estimation, but the susceptibility field effects can estimated and removed with the use of modified Dixon fat-water separated imaging.