Magnetic Resonance Investigation of the Human Brain after 6 Days of Acclimatization to 4554 m - Preliminary Results of the EFA study -

Objective: Hypoxia is the main trigger of acute mountain sickness (AMS). However it is not the cause of the actual symptoms of AMS. The biochemical mechanisms underlying the AMS development are not well understood what leads to a high uncertainty regarding the likeliness of AMS development in astronauts living in future moderate hypobaric hypoxic habitats on Mars or moon. The hypothesis of the EFA study (Edema Formation in the High Alps) was that hypoxia triggered inflammatory processes lead to a breakdown of the capillary barrier and edema formation in vulnerable tissues as the brain. Methods: 11 subjects (5 women) ascended within 48 h from 1154 m to the Capanna Regina Margherita in 4554 m. Brain magnetic resonance imaging (MRI) was performed at sea level before the altitude exposure and within the first 12 h after descent. MRI included amongst others an anatomical 3D volumetric T1-weighted MPRAGE (magnetization-prepared rapid acquisition of gradient echo) scan, a susceptibility weighted gradient echo sequence, T2 weighted spin echo sequences and a diffusion weighted sequence to gain an apparent diffusion coefficient mapping and a trace image to test for volume changes of the different brain compartments, for hypoxic triggered brain edema and for micro-bleedings. Baseline measurements were performed at the DLR MRI lab in Cologne (77 m) whereas post line measurements were performed at the MRI department of the German Air Force in Fürstenfeldbruck (517 m) by applying identical sequences at both centers. Results: Neither mean global intracranial volume (p=7.97) nor mean volumes of the particular brain compartments grey (p=0.279) and white matter (p=0.758) or cerebrospinal fluid (p=0.586) showed any significant differences after the altitude exposure with respect to baseline. However 6 days of altitude exposure lead to the exacerbation of pre-existing white matter lesions in one subject and the occurrence of a local hypoxic edema in the splenium of a second subjects in the sense of a reversible splenial lesion syndrome (RESLES) (1, 2). Conclusion: Contradictory to the current literature (3) we were not able to show a general volume gain of the intracranial compartments after high altitude adaptation. However our findings of white matter lesions (4) and RESLES in two subjects not presenting any symptoms of a high altitude cerebral edema (HACE) have, as far as we know, not been described before (5)

AI-based Evaluation of cardiac real-time MRI with congenital heart disease

Cardiac MRI scans are an important tool used by cardiologists. It can be utilized for diagnoses and assessment of vital parameters like the stroke volume or blood flow. The significant reduction in acquisition time that is achievable nowadays allows the recording of realtime 3D videos of the human heart. Such high frame rates yield very large amounts of data. To evaluate this data highly efficiently and with as little manual intervention as possible, it must be processed and interpreted automatically. We introduce the key challenges in such automated evaluations of realtime cardiac MRI. As patients are able breath freely during the examination, the effect of respiration on parameters such as blood flow and stroke volume can be investigated. However, this leads to the challenge of respiratory synchronization. Also, as the 3D representation of the heart is acquired slice by slice, the cardiac cycles in those slices must be synchronized. Another challenge is the physiological segmentation of the images. Especially for pathological hearts (e.g. univentricular hearts) this is a great challenge as high accuracy and automation are demanded. Furthermore, we present our workflow to tackle those challenges and show and discuss first results. One result is a breath- and cardiac cycle synchronized segmented univentricular heart in 4D (3D+time)

Cardiovascular deconditioning and impact of artificial gravity during 60-day head-down bed rest-Insights from 4D flow cardiac MRI

: Microgravity has deleterious effects on the cardiovascular system. We evaluated some parameters of blood flow and vascular stiffness during 60 days of simulated microgravity in head-down tilt (HDT) bed rest. We also tested the hypothesis that daily exposure to 30 min of artificial gravity (1 g) would mitigate these adaptations. 24 healthy subjects (8 women) were evenly distributed in three groups: continuous artificial gravity, intermittent artificial gravity, or control. 4D flow cardiac MRI was acquired in horizontal position before (-9 days), during (5, 21, and 56 days), and after (+4 days) the HDT period. The false discovery rate was set at 0.05. The results are presented as median (first quartile; third quartile). No group or group × time differences were observed so the groups were combined. At the end of the HDT phase, we reported a decrease in the stroke volume allocated to the lower body (-30% [-35%; -22%]) and the upper body (-20% [-30%; +11%]), but in different proportions, reflected by an increased share of blood flow towards the upper body. The aortic pulse wave velocity increased (+16% [+9%; +25%]), and so did other markers of arterial stiffness ( CAVI ; CAVI0 ). In males, the time-averaged wall shear stress decreased (-13% [-17%; -5%]) and the relative residence time increased (+14% [+5%; +21%]), while these changes were not observed among females. Most of these parameters tended to or returned to baseline after 4 days of recovery. The effects of the artificial gravity countermeasure were not visible. We recommend increasing the load factor, the time of exposure, or combining it with physical exercise. The changes in blood flow confirmed the different adaptations occurring in the upper and lower body, with a larger share of blood volume dedicated to the upper body during (simulated) microgravity. The aorta appeared stiffer during the HDT phase, however all the changes remained subclinical and probably the sole consequence of reversible functional changes caused by reduced blood flow. Interestingly, some wall shear stress markers were more stable in females than in males. No permanent cardiovascular adaptations following 60 days of HDT bed rest were observed

Cardiac adaptations to 60 day head-down-tilt bed rest deconditioning. Findings from the AGBRESA study

Aims: Reduced physical activity increases the risk of heart failure; however, non-invasive methodologies detecting subclinical changes in myocardial function are not available. We hypothesized that myocardial, left ventricular, systolic strain measurements could capture subtle abnormalities in myocardial function secondary to physical inactivity. Methods and results: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (eight women) were submitted to 60 day strict -6° head-down-tilt bed rest. Participants were assigned to three groups of eight subjects: a control group, continuous artificial gravity training on a short-arm centrifuge (30 min/day), or intermittent centrifugation (6 × 5 min/day). We assessed cardiac morphology, function, strain, and haemodynamics by cardiac magnetic resonance imaging (MRI) and echocardiography. We observed no differences between groups and, therefore, conducted a pooled analysis. Consistent with deconditioning, resting heart rate (∆8.3 ± 6.3 b.p.m., P < 0.0001), orthostatic heart rate responses (∆22.8 ± 19.7 b.p.m., P < 0.0001), and diastolic blood pressure (∆8.8 ± 6.6 mmHg, P < 0.0001) increased, whereas cardiac output (∆-0.56 ± 0.94 L/min, P = 0.0096) decreased during bed rest. Left ventricular mass index obtained by MRI did not change. Echocardiographic left ventricular, systolic, global longitudinal strain (∆1.8 ± 1.83%, P < 0.0001) decreased, whereas left ventricular, systolic, global MRI circumferential strain increased not significantly (∆-0.68 ± 1.85%, P = 0.0843). MRI values rapidly returned to baseline during recovery. Conclusion: Prolonged head-down-tilt bed rest provokes changes in cardiac function, particularly strain measurements, that appear functional rather than mediated through cardiac remodelling. Thus, strain measurements are of limited utility in assessing influences of physical deconditioning or exercise interventions on cardiac function

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

Automated Cardiac Realtime MRI Evaluation

We introduce our workflow to tackle automated evaluation of cardiac realtime MRI. The key approach is inspired by Active Learning and consists of N steps. First a limited amount of Training Data is annotated by staff with expert knowledge in the domain of pediatric cardiology. With this data we train a UNet using nnU-Net (Isensee, et. al). We then predict semantic labels with the trained model and use various techniques to judge the quality of each prediction. With that we are able to label each predicted segmentation with high or low quality. Predictions judged as low quality ones, are then presented to the domain experts and are manually corrected by them. Then, we can add those high quality labels to the training data set and start a new iteration by training the model. When the quality of predictions of an entire data set to be analyzed is high enough, we go on to synchronize the data set by assembling volumes of specific cardiac-respiration combinations based on the semantic segmentations. Finally, we are able to compute the stroke volume at different respiratory phases and compare them. The workflow explained above is deployed as a Plugin for the Software "3D Slicer"

Glucose-sensitive hypothalamic nuclei traced through functional magnetic resonance imaging

IntroductionHypothalamic glucose-sensitive neural circuits, which regulate energy metabolism and can contribute to diseases such as obesity and type 2 diabetes, have been difficult to study in humans. We developed an approach to assess hypothalamic functional connectivity changes during glucose loading using functional magnetic resonance imaging (fMRI).MethodsTo do so, we conducted oral glucose tolerance tests while acquiring functional images before, and 10 and 45 min after glucose ingestion in a healthy male and cross-sectionally in 20 healthy participants on two different diets.ResultsAt group level, 39 fMRI sessions were not sufficient to detect glucose-mediated connectivity changes. However, 10 repeated sessions in a single subject revealed significant intrinsic functional connectivity increases 45 min after glucose intake in the arcuate, paraventricular, and dorsomedial nuclei, as well as in the posterior hypothalamic area, median eminence, and mammillary bodies.DiscussionOur methodology allowed to outline glucose-sensitive hypothalamic pathways in a single human being and holds promise in delineating individual pathophysiology mechanisms in patients with dysglycemia

Using the Hephaistos orthotic device to study countermeasure effectiveness of neuromuscular electrical stimulation and dietary lupin protein supplementation, a randomised controlled trial

Purpose The present study investigated whether neuromuscular electrical stimulation for 20 min twice a day with an electrode placed over the soleus muscle and nutritional supplementation with 19 g of protein rich lupin seeds can reduce the loss in volume and strength of the human calf musculature during long term unloading by wearing an orthotic unloading device. Methods Thirteen healthy male subjects (age of 26.4 ± 3.7 years) wore a Hephaistos orthosis one leg for 60 days during all habitual activities. The leg side was randomly chosen for every subject. Six subjects only wore the orthosis as control group, and 7 subjects additionally received the countermeasure consisting of neuromuscular electrical stimulation of the soleus and lateral gastrocnemius muscles and lupin protein supplementation. Twenty-eight days before and on the penultimate day of the intervention cross-sectional images of the calf muscles were taken by magnetic resonance imaging (controls n = 5), and maximum voluntary torque (controls n = 6) of foot plantar flexion was estimated under isometric (extended knee, 90Ê knee flexion) and isokinetic conditions (extended knee), respectively. Results After 58 days of wearing the orthosis the percentage loss of volume in the entire triceps surae muscle of the control subjects (-11.9 ± 4.4%, mean ± standard deviation) was reduced by the countermeasure (-3.5 ± 7.2%, p = 0.032). Wearing the orthosis generally reduced plantar flexion torques values, however, only when testing isometric contraction at 90Ê knee ankle the countermeasure effected a significantly lower percentage decrease of torque (-9.7 ± 7.2%, mean ± SD) in comparison with controls (-22.3 ± 11.2%, p = 0.032). Conclusion Unloading of calf musculature by an orthotic device resulted in the expected loss of muscle volume and maximum of plantar flexion torque. Neuromuscular electrical muscle stimulation and lupin protein supplementation could significantly reduce the process of atrophy