Rapidity of responding to a hypoxic challenge during exercise

The ability to modify power output (PO) in response to a changing stimulus during exercise is crucial for optimizing performance involving an integration system involving a performance template and feedback from peripheral receptors. The rapidity with which PO is modified has not been established, but would be of interest relative to understanding how PO is regulated. The objective is to determine the rapidity of changes in PO in response to a hypoxic challenge, and if change in PO is linked to changes in arterial O₂ saturation (S _aO₂). Well-trained cyclists performed randomly ordered 5-km time trials. Subjects began the trials breathing room air and switched to hypoxic (HYPOXIC, F_IO₂ = 0.15) or room (CONTROL, F_IO₂ = 0.21) air at 2 km, then to room air at 4 km. The time delay to begin decreasing S _aO₂ and PO and to recover S _aO₂ and PO on to room air was compared, along with the half time (t _1/2) during the HYPOXIC trial. Mean S _aO₂ and PO between 2 and 4 km were significantly different between CONTROL and HYPOXIC (94 ± 2 vs. 83 ± 2% and 285 ± 16 vs. 245 ± 19 W, respectively). There was no difference between the time delay for S _aO₂ (31.5 ± 12.8 s) and in PO (25.8 ± 14.4 s) or the recovery of S _aO₂ (29.0 ± 7.7 s) and PO (21.5 ± 12.4 s). The half time for decreases in S _aO₂ (56.6 ± 14.4 s) and in PO (62.7 ± 20.8 s) was not significantly different. Modifications of PO due to the abrupt administration of hypoxic air are related to the development of arterial hypoxemia, and begin within ~30 s.     

Diaphragm degeneration and cardiac structure in mdx mouse: potential clinical implications for Duchenne muscular dystrophy

We examined the effects of exercise on diaphragm degeneration and cardiomyopathy in dystrophin‐deficient mdx mice. Mdx mice (11 months of age) were exercised (swimming) for 2 months to worsen diaphragm degeneration. Control mdx mice were kept sedentary. Morphological evaluation demonstrated increased fibrosis in the diaphragm of exercised mdx mice (33.3 ± 6.0% area of fibrosis) compared with control mdx mice (20.9 ± 1.7% area of fibrosis). Increased (26%) activity of MMP‐2, a marker of fibrosis, was detected in the diaphragms from exercised mdx mice. Morphological evaluation of the heart demonstrated a 45% increase in fibrosis in the right ventricle (8.3 ± 0.6% in sedentary vs. 12.0 ± 0.6% of fibrosis in exercised) and in the left ventricle (35% increase) in the exercised mdx mice. The density of inflammatory cells–degenerating cardiomyocytes increased 95% in the right ventricle (2.3 ± 0.6 in sedentary vs. 4.5 ± 0.8 in exercised) and 71% in the left ventricle (1.4 ± 0.6 sedentary vs. 2.4 ± 0.5 exercised). The levels of both active MMP‐2 and the pro‐fibrotic factor transforming growth factor beta were elevated in the hearts of exercised compared with sedentary mdx mice. The wall thickness to lumen diameter ratio of the pulmonary trunk was significantly increased in the exercised mdx mice (0.11 ± 0.04 in sedentary vs. 0.28 ± 0.12 in exercised), as was the thickness of the right ventricle wall, which suggests the occurrence of pulmonary hypertension in those animals. It is suggested that diaphragm degeneration is a main contributor to right ventricle dystrophic pathology. These findings may be relevant for future interventional studies for Duchenne muscular dystrophy‐associated cardiomyopathy.     

Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor‐deficient mice

Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of focal lesions caused by inflammation and fibrosis is challenging. We propose that quantitative susceptibility mapping (QSM) may be particularly sensitive for the identification of inflammation and fibrosis. In this study, we applied QSM in a mouse model deficient for angiotensin receptor type 1 (AT₁). This model is known for graded pathologies, including focal interstitial fibrosis, cortical inflammation, glomerulocysts and inner medullary hypoplasia. We acquired high‐resolution MRI on kidneys from AT₁‐deficient mice that were perfusion fixed with contrast agent. Two MR sequences were used (three‐dimensional spin echo and gradient echo) to produce three image contrasts: T₁, T₂* (magnitude) and QSM. T₁ and T₂* (magnitude) images were acquired to segment major renal structures and to provide landmarks for the focal lesions of inflammation and fibrosis in the three‐dimensional space. The volumes of major renal structures were measured to determine the relationship of the volumes to the degree of renal abnormalities and magnetic susceptibility values. Focal lesions were segmented from QSM images and were found to be closely associated with the major vessels. Susceptibilities were relatively more paramagnetic in wild‐type mice: 1.46 ± 0.36 in the cortex, 2.14 ± 0.94 in the outer medulla and 2.10 ± 2.80 in the inner medulla (10^–2 ppm). Susceptibilities were more diamagnetic in knockout mice: –7.68 ± 4.22 in the cortex, –11.46 ± 2.13 in the outer medulla and –7.57 ± 5.58 in the inner medulla (10^–2 ppm). This result was consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. QSM was very sensitive in detecting pathology caused by small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney. Copyright © 2013 John Wiley & Sons, Ltd.     

Single breath‐hold 3D cardiac T1 mapping using through‐time spiral GRAPPA

The quantification of cardiac T₁ relaxation time holds great potential for the detection of various cardiac diseases. However, as a result of both cardiac and respiratory motion, only one two‐dimensional T₁ map can be acquired in one breath‐hold with most current techniques, which limits its application for whole heart evaluation in routine clinical practice. In this study, an electrocardiogram (ECG)‐triggered three‐dimensional Look–Locker method was developed for cardiac T₁ measurement. Fast three‐dimensional data acquisition was achieved with a spoiled gradient‐echo sequence in combination with a stack‐of‐spirals trajectory and through‐time non‐Cartesian generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration. The effects of different magnetic resonance parameters on T₁ quantification with the proposed technique were first examined by simulating data acquisition and T₁ map reconstruction using Bloch equation simulations. Accuracy was evaluated in studies with both phantoms and healthy subjects. These results showed that there was close agreement between the proposed technique and the reference method for a large range of T₁ values in phantom experiments. In vivo studies further demonstrated that rapid cardiac T₁ mapping for 12 three‐dimensional partitions (spatial resolution, 2 × 2 × 8 mm³) could be achieved in a single breath‐hold of ~12 s. The mean T₁ values of myocardial tissue and blood obtained from normal volunteers at 3 T were 1311 ± 66 and 1890 ± 159 ms, respectively. In conclusion, a three‐dimensional T₁ mapping technique was developed using a non‐Cartesian parallel imaging method, which enables fast and accurate T₁ mapping of cardiac tissues in a single short breath‐hold.     

Aerobically trained individuals have greater increases in rectal temperature than untrained ones during exercise in the heat at similar relative intensities

To determine if the increases in rectal temperature (T _REC) during exercise in the heat at a given percent of [(V)\dot]O_2 \textpeak \dot{V}\hbox{O}_{{2\,{\text{peak}}}} depend on a subject’s aerobic fitness level. On three occasions, 10 endurance-trained (Tr) and 10 untrained (UTr) subjects ([(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} : 60 ± 6 vs. 44 ± 3 mL kg⁻¹ min⁻¹, P < 0.05) cycled in a hot-dry environment (36 ± 1°C; 25 ± 2% humidity, airflow 2.5 m s⁻¹) at three workloads (40, 60, and 80% [(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} ). At the same percent of [(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} , on average, Tr had 28 ± 5% higher heat production but also higher skin blood flow (29 ± 3%) and sweat rate (20 ± 7%; P = 0.07) and lower skin temperature (0.5°C; P < 0.05). Pre-exercise T _REC was lower in the Tr subjects (37.4 ± 0.2 vs. 37.6 ± 0.2; P < 0.05) but similar to the UTr at the end of 40 and 60% [(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} trials. Thus, exercise T _REC increased more in the Tr group than in the UTr group (0.6 ± 0.1 vs. 0.3 ± 0.1°C at 40% [(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} and 1.0 ± 0.1 vs. 0.6 ± 0.3°C at 60% [(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} ; P < 0.05). At 80% [(V)\dot]O_2 peak \dot{V}\hbox{O}_{2\,{\rm peak}} not only the increase in T _REC (1.7 ± 0.1 vs. 1.3 ± 0.3°C) but also the final T _REC was larger in Tr than in UTr subjects (39.15 ± 0.1 vs. 38.85 ± 0.1°C; P < 0.05). During exercise in the heat at the same relative intensity, aerobically trained individuals have a larger rise in T _REC than do the untrained ones which renders them more hyperthermic after high-intensity exercise.     

Dynamic alteration in myocardium creatine during acute infarction using MR CEST imaging

Creatine (Cr) is an essential metabolite in the creatine kinase reaction, which plays a critical role in maintaining normal cardiac function. Chemical exchange saturation transfer (CEST) MRI offers a novel way to map myocardium Cr. This study aims to investigate the dynamic alteration in myocardium Cr during acute infarction using CEST MRI, which may facilitate understanding of the heart remodeling mechanism at the molecular level. Seven adult Bama pigs underwent cardiac cine, Cr CEST, and late gadolinium-enhanced (LGE) T₁-weighted (T₁w) imaging three and 14 days after myocardial infarction induction on a 3 T scanner. Cardiac structural and functional indices, including myocardium mass (MM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF), were measured from cines. Infarct angle was determined from LGE T₁w images, based on which myocardium was classified into infarct, adjacent, and remote regions. Cr-weighted CEST signal was quantified from a three-pool Lorentzian fitting model and measured within each region and the entire myocardium. Student's t-test was conducted to evaluate any significant differences in measurements between the two time points. Correlation was assessed with Pearson correlation. P values less than 0.05 were considered statistically significant. Over the studied period, MM, EDV, and ESV did not alter significantly (P > 0.05), whereas significant increases of SV and EF and decrease of infarct angle were observed (P < 0.05). Meanwhile, the Cr-weighted CEST signal elevated significantly on Day 14 compared with Day 3 in the infarct (10.00 ± 1.28% versus 6.91 ± 1.54%, P < 0.01), adjacent (11.17 ± 2.00% versus 8.01 ± 1.58%, P = 0.01), and entire myocardium (11.03 ± 1.36% versus 8.19 ± 1.28%, P < 0.01). Moderate negative correlations were shown between the infarct angle and Cr-weighted CEST signals in the infarct (r = −0.80, P < 0.001), adjacent (r = −0.58, P = 0.03), and entire myocardium (r = −0.76, P < 0.01). In conclusion, the dynamic increase of myocardium Cr during acute infarction may interact with cardiac structural and functional recovery. The study provides supplementary insights into the heart remodeling process from the metabolic viewpoint.     

Feasibility of quantitative ultrashort echo time (UTE)‐based methods for MRI of peripheral nerve

Peripheral nerves are a composite tissue consisting of neurovascular elements packaged within a well‐organized extracellular matrix. Their composition, size, and anatomy render nerves a challenging medical imaging target. In contrast to morphological MRI, which represents the predominant approach to nerve imaging, quantitative MRI sequences can provide information regarding tissue composition. Here, we applied standard clinical Carr‐Purcell‐Meiboom‐Gill (CPMG) and experimental three‐dimensional (3D) ultrashort echo time (UTE) Cones sequences for quantitative nerve imaging including T₂ measurement with single‐component analysis, T₂* measurement with single‐component and bi‐component analyses, and magnetization transfer ratio (MTR) analysis. We demonstrated the feasibility and the high quality of single‐component T₂*, bi‐component T₂*, and MTR approaches to analyze nerves imaged with clinically deployed 3D UTE Cones pulse sequences. For 24 single fascicles from eight nerves, we measured a mean single‐component T₂* of 22.6 ±8.9 ms, and a short T₂* component (STC) with a mean T₂* of 1.7 ±1.0 ms and a mean fraction of (6.74 ±4.31)% in bi‐component analysis. For eight whole nerves, we measured a mean single‐component T₂* of 16.7 ±2.2 ms, and an STC with a mean T₂* of 3.0 ±1.0 ms and a mean fraction of (15.56 ±7.07)% in bi‐component analysis. For nine fascicles from three healthy nerves, we measured a mean MTR of (25.2 ±1.9)% for single fascicles and a mean MTR of (23.6 ±0.9)% for whole nerves. No statistically significant correlation was observed between any MRI parameter and routine histological outcomes, perhaps due to the small sample size and lack of apparent sample pathology. Overall, we have successfully demonstrated the feasibility of measuring quantitative MR outcomes ex vivo, which might reflect features of nerve structure and macromolecular content. These methods should be validated comprehensively on a larger and more diverse set of nerve samples, towards the interpretation of in vivo outcomes. These approaches have new and broad implications for the management of nerve disease, injury, and repair.     

Simultaneous bilateral T1, T2, and T1ρ relaxation mapping of the hip joint with magnetic resonance fingerprinting

Quantitative MRI can detect early biochemical changes in cartilage, but its bilateral use in clinical routines is challenging. The aim of this prospective study was to demonstrate the feasibility of magnetic resonance fingerprinting for bilateral simultaneous T₁, T₂, and T_1ρ mapping of the hip joint. The study population consisted of six healthy volunteers with no known trauma or pain in the hip. Monoexponential T₁, T₂, and T_1ρ relaxation components were assessed in femoral lateral, superolateral, and superomedial, and inferior, as well as acetabular, superolateral, and superomedial subregions in left and right hip cartilage. Aligned ranked nonparametric factorial analysis was used to assess the side's impact on the subregions. Kruskal–Wallis and Wilcoxon tests were used to compare subregions, and coefficient of variation to assess repeatability. Global averages of T₁ (676.0 ± 45.4 and 687.6 ± 44.5 ms), T₂ (22.5 ± 2.6 and 22.1 ± 2.5 ms), and T_1ρ (38.2 ± 5.5 and 38.2 ± 5.5 ms) were measured in the left and right hip, and articular cartilage, respectively. The Kruskal–Wallis test showed a significant difference between different subregions’ relaxation times regardless of the hip side (p < 0.001 for T₁, p = 0.012 for T₂, and p < 0.001 for T_1ρ). The Wilcoxon test showed that T₁ of femoral layers was significantly (p < 0.003) higher than that for acetabular cartilage. The experiments showed excellent repeatability with CV_rms of 1%, 2%, and 4% for T₁, T₂, and T_1ρ, respectively. It was concluded that bilateral T₁, T₂, and T_1ρ relaxation times, as well as B₁⁺ maps, can be acquired simultaneously from hip joints using the proposed MRF sequence.     

Cardiac function and arteriovenous oxygen difference during exercise in obese adults

The purpose of this study was to assess cardiac function and arteriovenous oxygen difference (a-vO₂ difference) at rest and during exercise in young, normal-weight (n = 20), and obese (n = 12) men and women who were matched for age and fitness level. Participants were assessed for body composition, peak oxygen consumption (VO_2peak), and cardiac variables (thoracic bioimpedance)—cardiac index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection fraction (EF)—at rest and during cycling exercise at 65% of VO_2peak. Differences between groups were assessed with multivariate ANOVA and mixed-model ANOVA with repeated measures controlling for sex. Absolute VO_2peak and VO_2peak relative to fat-free mass (FFM) were similar between normal-weight and obese groups (Mean ± SEE 2.7 ± 0.2 vs. 3.3 ± 0.3 l min⁻¹, p = 0.084 and 52.4 ± 1.5 vs. 50.9 ± 2.3 ml kg FFM⁻¹ min⁻¹, p = 0.583, respectively). In the obese group, resting Q and SV were higher (6.7 ± 0.4 vs. 4.9 ± 0.1 l min⁻¹, p < 0.001 and 86.8 ± 4.3 vs. 65.8 ± 1.9 ml min⁻¹, p < 0.001, respectively) and EF lower (56.4 ± 2.2 vs. 65.5 ± 2.2%, p = 0.003, respectively) when compared with the normal-weight group. During submaximal exercise, the obese group demonstrated higher mean CI (8.8 ± 0.3 vs. 7.7 ± 0.2 l min⁻¹ m⁻², p = 0.007, respectively), Q (19.2 ± 0.9 vs. 13.1 ± 0.3 l min⁻¹, p < 0.001, respectively), and SV (123.0 ± 5.6 vs. 88.9 ± 4.1 ml min⁻¹, p < 0.001, respectively) and a lower a-vO₂ difference (10.4 ± 1.0 vs. 14.0 ± 0.7 ml l00 ml⁻¹, p = 0.002, respectively) compared with controls. Our study suggests that the ability to extract oxygen during exercise may be impaired in obese individuals.     

In a hot–dry environment racewalking increases the risk of hyperthermia in comparison to when running at a similar velocity

The purpose of this study was to determine if in a hot–dry environment, racewalking increases intestinal temperature (T_int) above the levels observed when running either at the same velocity or at a similar rate of heat production. Nine trained racewalkers exercised for 60 min in a hot–dry environment (30.0 ± 1.4°C; 33 ± 8% relative humidity; 2.4 m s⁻¹ air speed) on three separate occasions: (1) racewalking at 10.9 ± 1.0 km h⁻¹ (Walk), (2) running at the same velocity (RunVel) and (3) running at 13 ± 1.8 km h⁻¹ to obtain a similar [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} than during Walk (Run [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} ). As designed, energy expenditure rate was similar during Walk and Run [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} , but lower during RunVel (842 ± 78 and 827 ± 75 vs. 713 ± 55 W; p < 0.01). Final T_int was lower during RunVel than during both Walk and Run [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} (38.4 ± 0.3 vs. 39.2 ± 0.4 and 39.0 ± 0.4°C; p < 0.01). Heart rate and sweat rate were also lower during RunVel than during Walk and Run [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} (i.e. heart rate 159 ± 13 vs. 179 ± 11 and 181 ± 11 beats min⁻¹ and sweat rate 0.8 ± 0.3 vs. 1.1 ± 0.3 and 1.1 ± 0.3 L h⁻¹; p < 0.01). However, we could not detect differences in skin temperature among trials. In conclusion, our data indicate that in a hot–dry environment racewalking increases the risk of hyperthermia in comparison with when running at a similar velocity. However, exercise mode (walking vs. running) had no measurable impact on T_INT or heat dissipation when matched for energy expenditure.     

SAturation-recovery and Variable-flip-Angle–based three-dimensional free-breathing cardiovascular magnetic resonance T1 mapping at 3 T

The purpose of the current study was to develop and validate a three-dimensional (3D) free-breathing cardiac T₁-mapping sequence using SAturation-recovery and Variable-flip-Angle (SAVA). SAVA sequentially acquires multiple electrocardiogram-triggered volumes using a multishot spoiled gradient-echo sequence. The first volume samples the equilibrium signal of the longitudinal magnetization, where a flip angle of 2° is used to reduce the time for the magnetization to return to equilibrium. The succeeding three volumes are saturation prepared with variable delays, and are acquired using a 15° flip angle to maintain the signal-to-noise ratio. A diaphragmatic navigator is used to compensate the respiratory motion. T₁ is calculated using a saturation-recovery model that accounts for the flip angle. We validated SAVA by simulations, phantom, and human subject experiments at 3 T. SAVA was compared with modified Look-Locker inversion recovery (MOLLI) and saturation-recovery single-shot acquisition (SASHA) in vivo. In phantoms, T₁ by SAVA had good agreement with the reference (R² = 0.99). In vivo 3D T₁ mapping by SAVA could achieve an imaging resolution of 1.25 × 1.25 × 8 mm³. Both global and septal T₁ values by SAVA (1347 ± 37 and 1332 ± 42 ms) were in between those by SASHA (1612 ± 63 and 1618 ± 51 ms) and MOLLI (1143 ± 59 and 1188 ± 65 ms). According to the standard deviation (SD) and coefficient of variation (CV), T₁ precision measured by SAVA (SD: 99 ± 14 and 60 ± 8 ms; CV: 7.4% ± 0.9% and 4.5% ± 0.6%) was comparable with MOLLI (SD: 99 ± 25 and 46 ± 12 ms; CV: 8.8% ± 2.5% and 3.9% ± 1.1%) and superior to SASHA (SD: 222 ± 89 and 132 ± 33 ms; CV: 13.8% ± 5.5% and 8.1% ± 2.0%). It was concluded that the proposed free-breathing SAVA sequence enables more efficient 3D whole-heart T₁ estimation with good accuracy and precision.     

Evaluation of normal cadaveric Achilles tendon and enthesis with ultrashort echo time (UTE) magnetic resonance imaging and indentation testing

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T₂), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three‐dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T₂*, T₁, and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (<50 years) were investigated. On average, tendons and entheses respectively had T₂* values of 0.93 ± 0.48 ms and 2.77 ± 0.79 ms, T₁ values of 644 ± 22 ms and 780 ± 55 ms, MTRs of 0.373 ± 0.03 and 0.244 ± 0.009 with an MT power of 1000° and frequency offset of 2 kHz, and macromolecular proton fractions of 18.0 ± 2.2% and 13.9 ± 1.9%. Compared with the tendon, the enthesis generally had a longer T₂*, a longer T₁, a lower MTR, and a lower macromolecular proton fraction as well as both a higher Young's modulus and stiffness. Results from this study are likely to provide a useful baseline for identifying deviations from the normal in seronegative arthritis and other disease of the entheses.     

Overshoot phenomenon of oxygen uptake during recovery from maximal exercise in patients with previous myocardial infarction

The overshoot in oxygen uptake ([(V)\dot] \dot{\rm{V}} O₂ overshoot) during recovery from maximal exercise is thought to reflect an overshoot in cardiac output. We investigated whether this phenomenon is related to cardiopulmonary function during exercise in cardiac patients. A total of 201 consecutive patients with previous myocardial infarction underwent cardiopulmonary exercise testing (CPX). An apparent [(V)\dot] \dot{\rm{V}} O₂ overshoot during the recovery from CPX (6.5 ± 8.1% increase relative to the peak [(V)\dot] \dot{\rm{V}} O₂) was observed in ten patients. A comparison of patients with the [(V)\dot] \dot{\rm{V}} O₂ overshoot to those without the [(V)\dot] \dot{\rm{V}} O₂ overshoot revealed that the former had a significantly lower left ventricular ejection fraction (40.1 ± 19.1 vs. 55. 2 ± 14.9%, respectively, p = 0.002) and larger left ventricular diastolic and systolic dimensions. Patients with the [(V)\dot] \dot{\rm{V}} O₂ overshoot also had a significantly lower peak [(V)\dot] \dot{\rm{V}} O₂ (13.1 ± 6.1 vs. 18.1 ± 4.5 ml/min/kg, p < 0.001), lower Δ[(V)\dot] \dot{\rm{V}} O₂/ΔWR (work rate) (6.6 ± 3.8 vs. 9.5 ± 1.7 mL/min/W, p < 0.0001), and a higher [(V)\dot] \dot{\rm{V}} E (minute ventilation)/[(V)\dot] \dot{\rm{V}} CO₂ (carbon dioxide output) slope (45.0 ± 18.6 vs. 32.6 ± 6.6, p < 0.0001) than those without the overshoot. A [(V)\dot] \dot{\rm{V}} O₂ overshoot during recovery from maximal exercise was found in 5% of patients with previous myocardial infarction. This condition, which suggests a transient mismatch between cardiac contractility and afterload reduction, was found to be related to impaired cardiopulmonary function during exercise.     

Effects of low and high cadence interval training on power output in flat and uphill cycling time-trials

This study tested the effects of low-cadence (60 rev min⁻¹) uphill (Int₆₀) or high-cadence (100 rev min⁻¹) level-ground (Int₁₀₀) interval training on power output (PO) during 20-min uphill (TT_up) and flat (TT_flat) time-trials. Eighteen male cyclists ( [(V)\dot]\textO_2max \dot{V}{\text{O}}_{2\max } : 58.6 ± 5.4 mL min⁻¹ kg⁻¹) were randomly assigned to Int₆₀, Int₁₀₀ or a control group (Con). The interval training comprised two training sessions per week over 4 weeks, which consisted of six bouts of 5 min at the PO corresponding to the respiratory compensation point (RCP). For the control group, no interval training was conducted. A two-factor ANOVA revealed significant increases on performance measures obtained from a laboratory-graded exercise test (GXT) (P _max: 2.8 ± 3.0%; p < 0.01; PO and [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} at RCP: 3.6 ± 6.3% and 4.7 ± 8.2%, respectively; p < 0.05; and [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} at ventilatory threshold: 4.9 ± 5.6%; p < 0.01), with no significant group effects. Significant interactions between group and uphill and flat time-trial, pre- versus post-training on PO were observed (p < 0.05). Int₆₀ increased PO during both TT_up (4.4 ± 5.3%) and TT_flat (1.5 ± 4.5%). The changes were −1.3 ± 3.6, 2.6 ± 6.0% for Int₁₀₀ and 4.0 ± 4.6%, −3.5 ± 5.4% for Con during TT_up and TT_flat, respectively. PO was significantly higher during TT_up than TT_flat (4.4 ± 6.0; 6.3 ± 5.6%; pre and post-training, respectively; p < 0.001). These findings suggest that higher forces during the low-cadence intervals are potentially beneficial to improve performance. In contrast to the GXT, the time-trials are ecologically valid to detect specific performance adaptations.     

Optimized AIR and investigational MOLLI cardiac T1 mapping pulse sequences produce similar intra‐scan repeatability in patients at 3T

This study was conducted to improve the precision of arrhythmia‐insensitive rapid (AIR) cardiac T₁ mapping through pulse sequence optimization and then evaluate the intra‐scan repeatability in patients at 3T against investigational modified Look–Locker inversion recovery (MOLLI) T₁ mapping. In the first development phase (five human subjects), we implemented and tested centric‐pair k‐space ordering to suppress image artifacts associated with eddy currents. In the second development phase (15 human subjects), we determined optimal flip angles to reduce the measurement variation in T₁ maps. In the validation phase (35 patients), we compared the intra‐scan repeatability between investigational MOLLI and optimized AIR. In 23 cardiac planes, conventional centric k‐space ordering (3.7%) produced significantly (p < 0.05) more outliers as a fraction of left ventricular cavity area than optimal centric k‐space ordering (1.4%). In 15 human subjects, for each of four types of measurement (native myocardial T₁, native blood T₁, post‐contrast myocardial T₁, post‐contrast blood T₁), flip angles of 55–65° produced lower measurement variation while producing results that are not significantly different from those produced with the previously used flip angle of 35° (p > 0.89, intra‐class correlation coefficient ≥ 0.95 for all four measurement types). Compared with investigational MOLLI (coefficient of repeatability, CR = 40.0, 77.2, 26.5, and 25.9 ms for native myocardial, native blood, post‐contrast myocardial, and post‐contrast blood T₁, and 2.0% for extracellular volume (ECV) measurements, respectively), optimized AIR (CR = 54.3, 89.7, 30.5, and 14.7 ms for native myocardial, native blood, post‐contrast myocardial, and post‐contrast blood T₁, and 1.6% for ECV measurements, respectively) produced similar absolute intra‐scan repeatability in all 35 patients in the validation phase. High repeatability is critically important for longitudinal studies, where the goal is to monitor physiologic/pathologic changes, not measurement variation. Optimized AIR cardiac T₁ mapping is likely to yield high scan–retest repeatability for pre‐clinical and clinical applications.     

Bi‐exponential 23Na T2* component analysis in the human brain

The purpose of this study was to measure the sodium transverse relaxation time T₂* in the healthy human brain. Five healthy subjects were scanned with 18 echo times (TEs) as short as 0.17 ms. T₂* values were fitted on a voxel‐by‐voxel basis using a bi‐exponential model. Data were also analysed using a continuous distribution fit with a region of interest‐based inverse Laplace transform. Average T₂* values were 3.4 ± 0.2 ms and 23.5 ± 1.8 ms in white matter (WM) for the short and long components, respectively, and 3.9 ± 0.5 ms and 26.3 ± 2.6 ms in grey matter (GM) for the short and long components, respectively, using the bi‐exponential model. Continuous distribution fits yielded results of 3.1 ± 0.3 ms and 18.8 ± 3.2 ms in WM for the short and long components, respectively, and 2.9 ± 0.4 ms and 17.2 ± 2 ms in GM for the short and long components, respectively. ²³Na T₂* values of the brain for the short and long components for various anatomical locations using ultra‐short TEs are presented for the first time.     

Characterization of the ultrashort‐TE (UTE) MR collagen signal

Although current cardiovascular MR (CMR) techniques for the detection of myocardial fibrosis have shown promise, they nevertheless depend on gadolinium‐based contrast agents and are not specific to collagen. In particular, the diagnosis of diffuse myocardial fibrosis, a precursor of heart failure, would benefit from a non‐invasive imaging technique that can detect collagen directly. Such a method could potentially replace the need for endomyocardial biopsy, the gold standard for the diagnosis of the disease. The objective of this study was to measure the MR properties of collagen using ultrashort TE (UTE), a technique that can detect short T₂* species. Experiments were performed in collagen solutions. Via a model of bi‐exponential T₂* with oscillation, a linear relationship (slope = 0.40 ± 0.01, R² = 0.99696) was determined between the UTE collagen signal fraction associated with these properties and the measured collagen concentration in solution. The UTE signal of protons in the collagen molecule was characterized as having a mean T₂* of 0.75 ± 0.05 ms and a mean chemical shift of ?3.56 ± 0.01 ppm relative to water at 7 T. The results indicated that collagen can be detected and quantified using UTE. A knowledge of the collagen signal properties could potentially be beneficial for the endogenous detection of myocardial fibrosis. Copyright © 2015 John Wiley & Sons, Ltd.     

CEST MRI reveals a correlation between visceral fat mass and reduced myocardial creatine in obese individuals despite preserved ventricular structure and function

Systolic cardiac function is typically preserved in obese adults, potentially masking underlying declines in cardiomyocyte metabolism that may contribute to heart failure. We used chemical exchange saturation transfer (CEST) MRI, a sensitive method for measurement of myocardial creatine, to examine whether myocardial creatine levels correlate with cardiac structure, contractile function, or visceral fat mass in obese adults. In this study, obese (body mass index, BMI > 30, n = 20) and healthy (BMI < 25, n = 11) adults were examined with dual‐energy x‐ray absorptiometry to quantify fat masses. Cine MRI and myocardial tagging were performed at 1.5 T to measure ventricular structure and global function. CEST imaging with offsets in the range of ±10 parts per million (ppm) were performed in one mid‐ventricular slice, where creatine CEST contrast was calculated at 1.8 ppm following field homogeneity correction. Ventricular structure, global function (ejection fraction 69.4 ± 4.3% healthy versus 69.6 ± 9.3% obese, NS), and circumferential strain (?17.0 ± 2.3% healthy versus ?16.5 ± 1.5% obese, NS) and strain rate were preserved in obese adults. However, creatine CEST contrast was significantly reduced in obese adults (6.8 ± 1.3% healthy versus 4.1 ± 2.7% obese, p = 0.001). Creatine CEST contrast was inversely correlated with total body fat% (ρ = ?0.45, p = 0.011), visceral fat mass (ρ = ?0.58, p = 0.001), and septal wall thickness (ρ = ?0.44, p = 0.013), but uncorrelated to ventricular function or contractile function. In conclusion, creatine CEST‐MRI reveals a strong correlation between heightened body and visceral fat masses and reduced myocardial metabolic function that is independent of ventricular structure and global function in obese adults.     

No effect of skin temperature on human ventilation response to hypercapnia during light exercise with a normothermic core temperature

Hyperthermia potentiates the influence of CO₂ on pulmonary ventilation ( [(V)\dot]_\textE \dot{V}_{\text{E}} ). It remains to be resolved how skin and core temperatures contribute to the elevated exercise ventilation response to CO₂. This study was conducted to assess the influences of mean skin temperature ( [`(T)]<sub>\textSK</sub> \overline{T}_{\text{SK}} ) and end-tidal PCO<sub>2</sub> (P<sub>ET</sub>CO<sub>2</sub>) on [(V)\dot]<sub>\textE</sub> \dot{V}_{\text{E}} during submaximal exercise with a normothermic esophageal temperature (T <sub>ES</sub>). Five males and three females who were 1.76 ± 0.11 m tall (mean ± SD), 75.8 ± 15.6 kg in weight and 22.0 ± 2.2 years of age performed three 1 h exercise trials in a climatic chamber with the relative humidity (RH) held at 31.5 ± 9.5% and the ambient temperature (T <sub>AMB</sub>) maintained at one of 25, 30, or 35°C. In each trial, the volunteer breathed eucapnic air for 5 min during a rest period and subsequently cycle ergometer exercised at 50 W until T <sub>ES</sub> stabilized at ~37.1 ± 0.4°C. Once T <sub>ES</sub> stabilized in each trial, the volunteer breathed hypercapnic air twice for ~5 min with P<sub>ET</sub>CO<sub>2</sub> elevated by approximately +4 or +7.5 mmHg. The significantly (P < 0.05) different increases of P<sub>ET</sub>CO<sub>2</sub> of +4.20 ± 0.49 and +7.40 ± 0.51 mmHg gave proportionately larger increases in [(V)\dot]<sub>\textE</sub> \dot{V}_{\text{E}} of 10.9 ± 3.6 and 15.2 ± 3.6 L min<sup>−1</sup> (P = 0.001). This hypercapnia-induced hyperventilation was uninfluenced by varying the [`(T)]_\textSK \overline{T}_{\text{SK}} to three significantly different levels (P < 0.001) of 33.2 ± 1.2°C, to 34.5 ± 0.8°C to 36.4 ± 0.5°C. In conclusion, the results support that skin temperature between ~33 and ~36°C has neither effect on pulmonary ventilation nor on hypercapnia-induced hyperventilation during a light exercise with a normothermic core temperature.