Voluntary exercise during puberty promotes spatial memory and hippocampal DG/CA3 synaptic transmission in mice.

Physical exercise has been shown to have an impact on memory and hippocampal function across different age groups. Nevertheless, the influence and mechanisms underlying how voluntary exercise during puberty affects memory are still inadequately comprehended. This research aims to examine the impacts of self-initiated physical activity throughout adolescence on spatial memory. Developing mice were exposed to a 4-wk voluntary wheel running exercise protocol, commencing at the age of 30 d. After engaging in voluntary wheel running exercise during development, there was an enhancement in spatial memory. Moreover, hippocampal dentate gyrus and CA3 neurons rather than CA1 neurons exhibited an increase in the miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents. In addition, there was an increase in the expression of NR2A/NR2B subunits of N-methyl-D-aspartate receptors and α1GABAA subunit of gamma-aminobutyric acid type A receptors, as well as dendritic spine density, specifically within dentate gyrus and CA3 regions rather than CA1 region. The findings suggest that voluntary exercise during development can enhance spatial memory in mice by increasing synapse numbers and improving synaptic transmission in hippocampal dentate gyrus and CA3 regions, but not in CA1 region. This study sheds light on the neural mechanisms underlying how early-life exercise improves cognitive function.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

Brain mechanisms discriminating enactive mental simulations of running and plogging.

Enactive cognition emphasizes co-constructive roles of humans and their environment in shaping cognitive processes. It is specifically engaged in the mental simulation of behaviors, enhancing the connection between perception and action. Here we investigated the core network of brain regions involved in enactive cognition as applied to mental simulations of physical exercise. We used a neuroimaging paradigm in which participants (N = 103) were required to project themselves running or plogging (running while picking-up litter) along an image-guided naturalistic trail. Using both univariate and multivariate brain imaging analyses, we find that a broad spectrum of brain activation discriminates between the mental simulation of plogging versus running. Critically, we show that self-reported ratings of daily life running engagement and the quality of mental simulation (how well participants were able to imagine themselves running) modulate the brain reactivity to plogging versus running. Finally, we undertook functional connectivity analyses centered on the insular cortex, which is a key region in the dynamic interplay between neurocognitive processes. This analysis revealed increased positive and negative patterns of insular-centered functional connectivity in the plogging condition (as compared to the running condition), thereby confirming the key role of the insular cortex in action simulation involving complex sets of mental mechanisms. Taken together, the present findings provide new insights into the brain networks involved in the enactive mental simulation of physical exercise.

Effects of long-term voluntary wheel running and selective breeding for wheel running on femoral nutrient canals.

The nutrient artery provides ~50%-70% of the total blood volume to long bones in mammals. Studying the functional characteristics of this artery in vivo can be difficult and expensive, so most researchers have measured the nutrient foramen, an opening on the outer surface of the bone that served as the entry point for the nutrient artery during development and bone ossification. Others have measured the nutrient canal (i.e., the passage which the nutrient artery once occupied), given that the external dimensions of the foramen do not necessarily remain uniform from the periosteal surface to the medullary cavity. The nutrient canal, as an indicator of blood flow to long bones, has been proposed to provide a link to studying organismal activity (e.g., locomotor behavior) from skeletal morphology. However, although external loading from movement and activity causes skeletal remodeling, it is unclear whether it affects the size or configuration of nutrient canals. To investigate whether nutrient canals can exhibit phenotypic plasticity in response to physical activity, we studied a mouse model in which four replicate high runner (HR) lines have been selectively bred for high voluntary wheel-running behavior. The selection criterion is the average number of wheel revolutions on days 5 and 6 of a 6-day period of wheel access as young adults (~6-8 weeks old). An additional four lines are bred without selection to serve as controls (C). For this study, 100 female mice (half HR, half C) from generation 57 were split into an active group housed with wheels and a sedentary group housed without wheels for 12 weeks starting at ~24 days of age. Femurs were collected, soft tissues were removed, and femora were micro-computed tomography scanned at a resolution of 12 µm. We then imported these scans into AMIRA and created 3D models of femoral nutrient canals. We tested for evolved differences in various nutrient canal traits between HR and C mice, plastic changes resulting from chronic exercise, and the selection history-by-exercise interaction. We found few differences between the nutrient canals of HR versus C mice, or between the active and sedentary groups. We did find an interaction between selection history and voluntary exercise for the total number of nutrient canals per femur, in which wheel access increased the number of canals in C mice but decreased it in HR mice. Our results do not match those from an earlier study, conducted at generation 11, which was prior to the HR lines reaching selection limits for wheel running. The previous study found that mice from the HR lines had significantly larger total canal cross-sectional areas compared to those from C lines. However, this discrepancy is consistent with studies of other skeletal traits, which have found differences between HR and C mice to be somewhat inconsistent across generations, including the loss of some apparent adaptations with continued selective breeding after reaching a selection limit for wheel-running behavior.

Treadmill Running Regulates Adult Neurogenesis, Spatial and Non-spatial Learning, Parvalbumin Neuron Activity by ErbB4 Signaling.

Exercise can promote adult neurogenesis and improve symptoms associated with schizophrenia and other mental disorders via parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus ErbB4 is the receptor of neurotrophic factor neuregulin 1, expressed mostly in PV-positive interneurons. Whether ErbB4 in PV-positive neurons mediates the beneficial effect of exercise and adult neurogenesis on mental disorder needs to be further investigation. Here, we first conducted a four-week study on the effects of AG1478, an ErbB4 inhibitor, on memory and neurogenesis. AG1478 significantly impaired the performance in several memory tasks, including the T-maze, Morris water maze, and contextual fear conditioning, downregulated the expression of total ErbB4 (T-ErbB4) and the ratio of phosphate-ErbB4 (p-ErbB4) to T-ErbB4, and associated with neurogenesis impairment. Interestingly, AG1478 also appeared to decrease intracellular calcium levels in PV neurons, which could be reversed by exercise. These results suggest exercise may regulate adult neurogenesis and PV neuron activity through ErbB4 signaling. Overall, these findings provide further evidence of the importance of exercise for neurogenesis and suggest that targeting ErbB4 may be a promising strategy for improving memory and other cognitive functions in individuals with mental disorders.

The fatigue-inducing effects of cancer and its therapy are characterized by decreased physical activity in the absence of any motivational deficit.

Although cancer and its therapy are well known to be associated with fatigue, the exact nature of cancer-related fatigue remains ill-defined. We previously reported that fatigue-like behavior induced independently by tumor growth and by the chemotherapeutic agent cisplatin is characterized by reduced voluntary wheel running and an intact motivation to expand effort for food rewards. The present set of experiments was initiated to characterize the functional consequences of fatigue induced by chemoradiotherapy in tumor-bearing mice and relate them to changes in the expression of genes coding for inflammation, mitochondria dynamics and metabolism. Two syngeneic murine models of cancer were selected for this purpose, a model of human papilloma virus-related head and neck cancer and a model of lung cancer. In both models, tumor-bearing mice were submitted to chemoradiotherapy to limit tumor progression. Two dimensions of fatigue were assessed, the physical dimension by changes in physical activity in mice trained to run in wheels and the motivational dimension by changes in the performance of mice trained to nose poke to obtain a food reward in a progressive ratio schedule of food reinforcement. Chemoradiotherapy reliably decreased wheel running activity but had no effect on performance in the progressive ratio in both murine models of cancer. These effects were the same for the two murine models of cancer and did not differ according to sex. Livers and brains were collected at the end of the experiments for qRT-PCR analysis of expression of genes coding for inflammation, mitochondria dynamics, and metabolism. The observed changes were mainly apparent in the liver and typical of activation of type I interferon and NF-κB-dependent signaling, with alterations in mitochondrial dynamics and a shift toward glycolysis. Although the importance of these alterations for the pathophysiology of cancer-related fatigue remains to be explored, the present findings indicate that fatigue brought on by cancer therapy in tumor-bearing mice is more physical than motivational.

Wheel Running During Pregnancy Alleviates Anxiety-and Depression-Like Behaviors During the Postpartum Period in Mice: The Roles of NLRP3 Neuroinflammasome Activation, Prolactin, and the Prolactin Receptor in the Hippocampus.

Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1 h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.

Maximum velocity and leg-specific ground reaction force production change with radius during flat curve sprinting.

Humans attain slower maximum velocity (vmax) on curves versus straight paths, potentially due to centripetal ground reaction force (GRF) production, and this depends on curve radius. Previous studies found GRF production differences between an athlete's inside versus outside leg relative to the center of the curve. Further, sprinting clockwise (CW) versus counterclockwise (CCW) slows vmax. We determined vmax, step kinematics and individual leg GRF on a straight path and on curves with 17.2 and 36.5 m radii for nine (8 male, 1 female) competitive sprinters running CW and CCW and compared vmax with three predictive models. We combined CW and CCW directions and found that vmax slowed by 10.0±2.4% and 4.1±1.6% (P<0.001) for the 17.2 and 36.5 m radius curves versus the straight path, respectively. vmax values from the predictive models were up to 3.5% faster than the experimental data. Contact length was 0.02 m shorter and stance average resultant GRF was 0.10 body weights (BW) greater for the 36.5 versus 17.2 m radius curves (P<0.001). Stance average centripetal GRF was 0.10 BW greater for the inside versus outside leg (P<0.001) on the 36.5 m radius curve. Stance average vertical GRF was 0.21 BW (P<0.001) and 0.10 BW (P=0.001) lower for the inside versus outside leg for the 17.2 and 36.5 m radius curves, respectively. For a given curve radius, vmax was 1.6% faster in the CCW compared with CW direction (P=0.003). Overall, we found that sprinters change contact length and modulate GRFs produced by their inside and outside legs as curve radius decreases, potentially limiting vmax.

Tibial strains are sensitive to speed perturbations, but not grade perturbations, during running.

A fatigue-failure process is hypothesized to govern the development of tibial stress fractures, where bone damage is highly dependent on the peak strain magnitude. To date, much of the work examining tibial strain during running has ignored uphill and downhill running despite the prevalence of this terrain. This study examined the sensitivity of tibial strain to changes in running grade and speed using a combined musculoskeletal-finite element modelling routine. Seventeen participants ran on a treadmill at ±10, ±5 and 0 deg; at each grade, participants ran at 3.33 m s-1 and at a grade-adjusted speed of 2.50 and 4.17 m s-1 for uphill and downhill grades, respectively. Force and motion data were recorded in each grade and speed combination. Muscle and joint contact forces were estimated using inverse-dynamics-based static optimization. These forces were applied to a participant-adjusted finite element model of the tibia. None of the strain variables (50th and 95th percentile strain and strained volume ≥4000 µÎµ) differed as a function of running grade; however, all strain variables were sensitive to running speed (F1≥9.59, P≤0.03). In particular, a 1 m s-1 increase in speed resulted in a 9% (∼260 µÎµ) and 155% (∼600 mm3) increase in peak strain and strained volume, respectively. Overall, these findings suggest that faster running speeds, but not changes in running grade, may be more deleterious to the tibia.

Regulation of muscle pyruvate dehydrogenase activity and fuel use during exercise in high-altitude deer mice.

Adult, lab-reared, highland deer mice acclimate to hypoxia by increasing reliance on carbohydrates to fuel exercise. Yet neither the underlying mechanisms for this shift in fuel use nor the impact of lifetime hypoxia exposure experienced in high alpine conditions, are fully understood. Thus, we assessed the use of fuel during exercise in wild highland deer mice running in their native environment. We examined a key step in muscle carbohydrate oxidation - the regulation of pyruvate dehydrogenase (PDH) - during exercise at altitude in wild highlanders and in first generation (G1) lab-born and -raised highlanders acclimated to normoxia or hypoxia. PDH activity was also determined in the gastrocnemius of G1 highlanders using an in situ muscle preparation. We found that wild highlanders had a high reliance on carbohydrates while running in their native environment, consistent with data from hypoxia-acclimated G1 highlanders. PDH activity in the gastrocnemius was similar post exercise between G1 and wild highlanders. However, when the gastrocnemius was stimulated at a light work rate in situ, PDH activity was higher in hypoxia-acclimated G1 highlanders and was associated with lower intramuscular lactate levels. These findings were supported by lower PDH kinase 2 protein production in hypoxia-acclimated G1 mice. Our findings indicate that adult phenotypic plasticity in response to low oxygen is sufficient to increase carbohydrate reliance during exercise in highland deer mice. Additionally, variation in PDH regulation with hypoxia acclimation contributes to shifts in whole-animal patterns of fuel use and is likely to improve exercise performance via elevated energy yield per mole of O2. .

A meta-analysis of whole-body and heart mass effect sizes from a long-term artificial selection experiment for high voluntary exercise.

Selection experiments play an increasingly important role in comparative and evolutionary physiology. However, selection experiments can be limited by relatively low statistical power, in part because replicate line is the experimental unit for analyses of direct or correlated responses (rather than number of individuals measured). One way to increase the ability to detect correlated responses is through a meta-analysis of studies for a given trait across multiple generations. To demonstrate this, we applied meta-analytic techniques to two traits (body mass and heart ventricle mass, with body mass as a covariate) from a long-term artificial selection experiment for high voluntary wheel-running behavior. In this experiment, all four replicate High Runner (HR) lines reached apparent selection limits around generations 17-27, running approximately 2.5- to 3-fold more revolutions per day than the four non-selected Control (C) lines. Although both traits would also be expected to change in HR lines (relative heart size expected to increase, expected direction for body mass is less clear), their statistical significance has varied, despite repeated measurements. We compiled information from 33 unique studies and calculated a measure of effect size (Pearson's R). Our results indicate that, despite a lack of statistical significance in most generations, HR mice have evolved larger hearts and smaller bodies relative to controls. Moreover, plateaus in effect sizes for both traits coincide with the generational range during which the selection limit for wheel-running behavior was reached. Finally, since reaching the selection limit, absolute effect sizes for body mass and heart ventricle mass have become smaller (i.e. closer to 0).

An approximate solution of the SLIP model under the regime of linear angular dynamics during stance and the stability of symmetric periodic running gaits.

Terrestrial locomotion is a complex phenomenon that is often linked to the survival of an individual and of an animal species. Mathematical models seek to express in quantitative terms how animals move, but this is challenging because the ways in which the nervous and musculoskeletal systems interact to produce body movement is not completely understood. Models with many variables tend to lack biological interpretability and describe the motion of an animal with too many independent degrees of freedom. Instead, reductionist models aim to describe the essential features of a gait with the smallest number of variables, often concentrating on the center of mass dynamics. In particular, spring-mass models have been successful in extracting and describing important characteristics of running. In this paper, we consider the spring loaded inverted pendulum model under the regime of constant angular velocity, small compression, and small angle swept during stance. We provide conditions for the asymptotic stability of periodic trajectories for the full range of parameters. The hypothesis of linear angular dynamics during stance is successfully tested on publicly available human data of individuals running on a treadmill at different velocities. Our analysis highlights a novel bifurcation phenomenon for varying Froude number: there are periodic trajectories of the spring loaded inverted pendulum model that are stable only in a restricted range of Froude numbers, while they become unstable for smaller or larger Froude numbers.

Effects of morning and evening physical exercise on subjective and objective sleep quality: an ecological study.

To optimise the relationship between exercise and sleep quality, the intensity of exercise and its proximity to sleep are key factors to manage. Although low-to-moderate exercises promote sleep quality, late-evening vigorous exercise instead of morning should still be avoided. It potentially impacts the objective and subjective markers of sleep quality. In the present study, we investigated the effects of vigorous morning and evening exercise on objective and subjective sleep features in an ecological context. A total of 13 recreational runners (mean [SD] age 27.7 [7.2] years, four females) performed a 45-60 min run (70% maximal aerobic velocity) either in the MORNING (30 min to 2 h after waking-up) or in the EVENING (2 h to 30 min before sleep). The two exercise conditions were separated by a REST day. After each condition, sleep was objectively assessed using an electroencephalographic headband and subjectively using the Spiegel Sleep Inventory. Compared with REST, both MORNING and EVENING exercise increased the time spent in non-rapid eye movement (NREM, +24.9 min and +22.7 min; p = 0.01, η2 = 0.11, respectively). Longer NREM duration was mainly due to sleep stage 2 extension after both MORNING (+20.8 min) and EVENING (+22.8 min) exercise relative to REST (p = 0.02, η2 = 0.12). No other effect of exercise on either objective or subjective sleep could be observed. Exercise, independently of the time at which it takes place, leads to extended NREM sleep without other effects on sleep quality. Considering the crucial role of exercise in achieving good health, sleep hygiene guidelines should be updated to promote exercise at any time of the day.

Dietary restriction plus exercise change gene expression of Cxcl12 abundant reticular cells in female mice.

INTRODUCTION: Low energy availability due to excessive exercise lowers bone mass and impairs various physiological functions, including immunity and hematopoiesis. We focused on Cxcl12 abundant reticular (CAR) cells, which are bone marrow mesenchymal stem cells and are essential for the maintenance of hematopoietic and immune cells in bone marrow. We examine the functional changes in CAR cells resulting from dietary restriction combined with exercise. MATERIALS AND METHODS: Five-week-old wild-type female mice were divided into an ad libitum group (CON), a 60% dietary restriction group (DR), an ad libitum with exercise group (CON + ex), and a 60% dietary restriction with exercise group (DR + ex). Blood parameters, bone structure parameters, and bone marrow fat volume were evaluated after 5 weeks. In addition, bone marrow CAR cells were isolated by cell sorting and analyzed for gene expression by RT-qPCR. RESULTS: Bone mineral density (BMD) was significantly decreased in DR and DR + ex compared to CON and CON + ex. Especially, cortical bone mass and thickness were significantly decreased in DR and DR + ex groups, whereas trabecular bone mass was significantly increased. Bone marrow fat volume was significantly increased in DR and DR + ex groups compared to CON and CON + ex. The number of leukocytes in the blood was significantly decreased in the DR + ex group compared to the other three groups. RT-qPCR showed a significant decrease in gene expression of both Foxc1 and Runx2 in CAR cells of the DR + ex group compared to CON. CONCLUSION: Dietary restriction combined with exercise promotes CAR cell differentiation into bone marrow adipocyte and suppresses osteoblast differentiation.

Seroma formation after mastectomy: A systematic review and network meta-analysis of different flap fixation techniques.

Flap fixation is the most promising solution to prevent seroma formation after mastectomy. In this systematic review with network meta-analysis (NMA), three different techniques were compared. The NMA included 25 articles, comprising 3423 patients, and revealed that sutures are superior to tissue glue in preventing clinically significant seroma. In addition, running sutures seemed to be superior to interrupted sutures. An RCT comparing these suture techniques seems necessary, given the quality and nature of existing literature.

Intra-bin correction and inter-bin compensation of respiratory motion in free-running five-dimensional whole-heart magnetic resonance imaging.

BACKGROUND: Free-running cardiac and respiratory motion-resolved whole-heart five-dimensional (5D) cardiovascular magnetic resonance (CMR) can reduce scan planning and provide a means of evaluating respiratory-driven changes in clinical parameters of interest. However, respiratory-resolved imaging can be limited by user-defined parameters which create trade-offs between residual artifact and motion blur. In this work, we develop and validate strategies for both correction of intra-bin and compensation of inter-bin respiratory motion to improve the quality of 5D CMR. METHODS: Each component of the reconstruction framework was systematically validated and compared to the previously established 5D approach using simulated free-running data (N = 50) and a cohort of 32 patients with congenital heart disease. The impact of intra-bin respiratory motion correction was evaluated in terms of image sharpness while inter-bin respiratory motion compensation was evaluated in terms of reconstruction error, compression of respiratory motion, and image sharpness. The full reconstruction framework (intra-acquisition correction and inter-acquisition compensation of respiratory motion [IIMC] 5D) was evaluated in terms of image sharpness and scoring of image quality by expert reviewers. RESULTS: Intra-bin motion correction provides significantly (p < 0.001) sharper images for both simulated and patient data. Inter-bin motion compensation results in significant (p < 0.001) lower reconstruction error, lower motion compression, and higher sharpness in both simulated (10/11) and patient (9/11) data. The combined framework resulted in significantly (p < 0.001) sharper IIMC 5D reconstructions (End-expiration (End-Exp): 0.45 ± 0.09, End-inspiration (End-Ins): 0.46 ± 0.10) relative to the previously established 5D implementation (End-Exp: 0.43 ± 0.08, End-Ins: 0.39 ± 0.09). Similarly, image scoring by three expert reviewers was significantly (p < 0.001) higher using IIMC 5D (End-Exp: 3.39 ± 0.44, End-Ins: 3.32 ± 0.45) relative to 5D images (End-Exp: 3.02 ± 0.54, End-Ins: 2.45 ± 0.52). CONCLUSION: The proposed IIMC reconstruction significantly improves the quality of 5D whole-heart MRI. This may be exploited for higher resolution or abbreviated scanning. Further investigation of the diagnostic impact of this framework and comparison to gold standards is needed to understand its full clinical utility, including exploration of respiratory-driven changes in physiological measurements of interest.

Combined free-running four-dimensional anatomical and flow magnetic resonance imaging with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals.

BACKGROUND: Four-dimensional (4D) flow magnetic resonance imaging (MRI) often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses pilot tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running three-dimensional radial acquisitions, to create co-registered anatomy and flow images. METHODS: Thirteen volunteers and two Marfan syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional two-dimensional (2D) flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation. RESULTS: Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5 ± 0.3) was significantly higher than for Native 4D flow (0.7 ± 0.1, p < 0.01) and was comparable to 2D flow (2.3 ± 0.9, p = 0.02). Image quality scores of SyNAPS 4D flow from the experts (M.P.: 1.9 ± 0.3, E.T.: 2.5 ± 0.5) were overall significantly higher than the scores from Native 4D flow (M.P.: 1.6 ± 0.6, p = 0.03, E.T.: 0.8 ± 0.4, p < 0.01) but still significantly lower than the scores from the reference 2D flow datasets (M.P.: 2.8 ± 0.4, p < 0.01, E.T.: 3.5 ± 0.7, p < 0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69 ± 0.24 for the AAo and 0.83 ± 0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12 ± 0.48 for the AAo and 0.08 ± 0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r2 = 0.83) and peak flow (r2 = 0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r2 = 0.79) and peak flow (r2 = 0.76). CONCLUSION: The feasibility and utility of SyNAPS were demonstrated for joint whole-heart anatomical and flow MRI without requiring electrocardiography gating, respiratory navigators, or contrast agents. Using SyNAPS, a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents.

Trajectory correction enables free-running chemical shift encoded imaging for accurate cardiac proton-density fat fraction quantification at 3T.

BACKGROUND: Metabolic diseases can negatively alter epicardial fat accumulation and composition, which can be probed using quantitative cardiac chemical shift encoded (CSE) cardiovascular magnetic resonance (CMR) by mapping proton-density fat fraction (PDFF). To obtain motion-resolved high-resolution PDFF maps, we proposed a free-running cardiac CSE-CMR framework at 3T. To employ faster bipolar readout gradients, a correction for gradient imperfections was added using the gradient impulse response function (GIRF) and evaluated on intermediate images and PDFF quantification. METHODS: Ten minutes free-running cardiac 3D radial CSE-CMR acquisitions were compared in vitro and in vivo at 3T. Monopolar and bipolar readout gradient schemes provided 8 echoes (TE1/ΔTE = 1.16/1.96 ms) and 13 echoes (TE1/ΔTE = 1.12/1.07 ms), respectively. Bipolar-gradient free-running cardiac fat and water images and PDFF maps were reconstructed with or without GIRF correction. PDFF values were evaluated in silico, in vitro on a fat/water phantom, and in vivo in 10 healthy volunteers and 3 diabetic patients. RESULTS: In monopolar mode, fat-water swaps were demonstrated in silico and confirmed in vitro. Using bipolar readout gradients, PDFF quantification was reliable and accurate with GIRF correction with a mean bias of 0.03% in silico and 0.36% in vitro while it suffered from artifacts without correction, leading to a PDFF bias of 4.9% in vitro and swaps in vivo. Using bipolar readout gradients, in vivo PDFF of epicardial adipose tissue was significantly lower compared to subcutaneous fat (80.4 ± 7.1% vs 92.5 ± 4.3%, P < 0.0001). CONCLUSIONS: Aiming for an accurate PDFF quantification, high-resolution free-running cardiac CSE-MRI imaging proved to benefit from bipolar echoes with k-space trajectory correction at 3T. This free-breathing acquisition framework enables to investigate epicardial adipose tissue PDFF in metabolic diseases.

Aesthetic outcome of running subcuticular suture versus running horizontal mattress suture in closure of linear wounds of the trunk and extremities: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Both running horizontal mattress (HM) and running subcuticular (SQ) suturing techniques have been suggested to be superior to other running cuticular suturing techniques. These 2 techniques have not been directly compared. OBJECTIVE: To compare cosmetic outcomes between a running HM and a running SQ technique in a split scar model following linear closure of trunk and extremity defects. METHODS: Fifty patients were enrolled in a randomized, evaluator-blinded, split-scar study. One side of the surgical wound was randomized to receive one intervention (HM vs SQ) with the other side receiving the alternate intervention. The primary outcome was the Patient and Observer Scar Assessment Scale (POSAS) score at a minimum of 3 months postoperatively. RESULTS: Observer POSAS sum of components was 19.49 and 17.76 for HM and SQ, respectively (P = .14). The mean score for patient overall opinion was 4.71 for HM and 3.50 for the SQ technique (P = .02). Overall opinion scores of evaluators were 3.87 and 3.29 for HM and SQ, respectively (P = .03). LIMITATIONS: Single-center study of a relatively homogenous population. CONCLUSION: Although there was no significant difference in the sum of POSAS components between HM and SQ (P = .14), both patients and evaluators had a superior overall opinion of the SQ-treated side (patient P = .02, evaluator P = .03).