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1.  Regionally accentuated reversible brain grey matter reduction in ultra marathon runners detected by voxel-based morphometry 
During the 4,487 km ultra marathon TransEurope-FootRace 2009 (TEFR09), runners showed catabolism with considerable reduction of body weight as well as reversible brain volume reduction. We hypothesized that ultra marathon athletes might have developed changes to grey matter (GM) brain morphology due to the burden of extreme physical training. Using voxel-based morphometry (VBM) we undertook a cross sectional study and two longitudinal studies.
Prior to the start of the race 13 runners volunteered to participate in this study of planned brain scans before, twice during, and 8 months after the race. A group of matched controls was recruited for comparison. Twelve runners were able to participate in the scan before the start of the race and were taken into account for comparison with control persons. Because of drop-outs during the race, VBM could be performed in 10 runners covering the first 3 time points, and in 7 runners who also had the follow-up scan after 8 months. Volumetric 3D datasets were acquired using an MPRAGE sequence. A level of p < 0.05, family-wise corrected for multiple comparisons was the a priori set statistical threshold to infer significant effects from VBM.
Baseline comparison of TEFR09 participants and controls revealed no significant differences regarding GM brain volume. During the race however, VBM revealed GM volume decreases in regionally distributed brain regions. These included the bilateral posterior temporal and occipitoparietal cortices as well as the anterior cingulate and caudate nucleus. After eight months, GM normalized.
Contrary to our hypothesis, we did not observe significant differences between TEFR09 athletes and controls at baseline. If this missing difference is not due to small sample size, extreme physical training obviously does not chronically alter GM.
However, during the race GM volume decreased in brain regions normally associated with visuospatial and language tasks. The reduction of the energy intensive default mode network as a means to conserve energy during catabolism is discussed. The changes were reversible after 8 months.
Despite substantial changes to brain composition during the catabolic stress of an ultra marathon, the observed differences seem to be reversible and adaptive.
PMCID: PMC3896776  PMID: 24438692
Voxel based morphometry; VBM; Catabolism; Plasticity; Brain; Default mode network; MRI; Ultra marathon
2.  Characteristics, changes and influence of body composition during a 4486 km transcontinental ultramarathon: results from the Transeurope Footrace mobile whole body MRI-project 
BMC Medicine  2013;11:122.
Almost nothing is known about the medical aspects of runners doing a transcontinental ultramarathon over several weeks. The results of differentiated measurements of changes in body composition during the Transeurope Footrace 2009 using a mobile whole body magnetic resonance (MR) imager are presented and the proposed influence of visceral and somatic adipose and lean tissue distribution on performance tested.
22 participants were randomly selected for the repeated MR measurements (intervals: 800 km) with a 1.5 Tesla MR scanner mounted on a mobile unit during the 64-stage 4,486 km ultramarathon. A standardized and validated MRI protocol was used: T1 weighted turbo spin echo sequence, echo time 12 ms, repetition time 490 ms, slice thickness 10 mm, slice distance 10 mm (breath holding examinations). For topographic tissue segmentation and mapping a modified fuzzy c-means algorithm was used. A semi-automatic post-processing of whole body MRI data sets allows reliable analysis of the following body tissue compartments: Total body volume (TV), total somatic (TSV) and total visceral volume (TVV), total adipose (TAT) and total lean tissue (TLT), somatic (SLT) and visceral lean tissue (VLT), somatic (SAT) and visceral adipose tissue (VAT) and somatic adipose soft tissue (SAST). Specific volume changes were tested on significance. Tests on difference and relationship regarding prerace and race performance and non-finishing were done using statistical software SPSS.
Total, somatic and visceral volumes showed a significant decrease throughout the race. Adipose tissue showed a significant decrease compared to the start at all measurement times for TAT, SAST and VAT. Lean adipose tissues decreased until the end of the race, but not significantly. The mean relative volume changes of the different tissue compartments at the last measurement compared to the start were: TV −9.5% (SE 1.5%), TSV −9.4% (SE 1.5%), TVV −10.0% (SE 1.4%), TAT −41.3% (SE 2.3%), SAST −48.7% (SE 2.8%), VAT −64.5% (SE 4.6%), intraabdominal adipose tissue (IAAT) −67.3% (SE 4.3%), mediastinal adopose tissue (MAT) −41.5% (SE 7.1%), TLT −1.2% (SE 1.0%), SLT −1.4% (SE 1.1%). Before the start and during the early phase of the Transeurope Footrace 2009, the non-finisher group had a significantly higher percentage volume of TVV, TAT, SAST and VAT compared to the finisher group. VAT correlates significantly with prerace training volume and intensity one year before the race and with 50 km- and 24 hour-race records. Neither prerace body composition nor specific tissue compartment volume changes showed a significant relationship to performance in the last two thirds of the Transeurope Footrace 2009.
With this mobile MRI field study the complex changes in body composition during a multistage ultramarathon could be demonstrated in detail in a new and differentiated way. Participants lost more than half of their adipose tissue. Even lean tissue volume (mainly skeletal muscle tissue) decreased due to the unpreventable chronic negative energy balance during the race. VAT has the fastest and highest decrease compared to SAST and lean tissue compartments during the race. It seems to be the most sensitive morphometric parameter regarding the risk of non-finishing a transcontinental footrace and shows a direct relationship to prerace-performance. However, body volume or body mass and, therefore, fat volume has no correlation with total race performances of ultra-athletes finishing a 4,500 km multistage race.
PMCID: PMC3668188  PMID: 23657091
Magnetic resonance imaging; MRI; Body mass; Body volume; Body composition; Running; Marathon; Ultramarathon; Performance; Adipose tissue; Body fat; Lean tissue; Visceral; Somatic; Topography; Segmentation; Mapping
3.  Association of Mediterranean diet, dietary supplements and alcohol consumption with breast density among women in South Germany: a cross-sectional study 
BMC Public Health  2013;13:203.
Effects of dietary factors, such as adherence to Mediterranean diet, multivitamin-multimineral supplements use and alcohol consumption on mammographic breast density, an important biomarker of breast cancer risk, are not sufficiently consistent to elaborate preventive recommendations. This study aims to investigate the association between current diet and mammographic density.
We performed a cross-sectional study in 424 pre- and post-menopausal women aged 21 to 84 years. Current Mediterranean dietary pattern, multivitamin-multimineral supplements use, alcohol consumption and potential confounders were assessed with a self-administered questionnaire in the University Hospital Ulm (2007–2008). Radiologists evaluated mammographic density according to the American College of Radiology (ACR) classification, which was summarized in low = ACR1/2 and high = ACR3/4 mammographic density. Logistic regression models were used to assess the association between current diet and mammographic density.
Adherance to Mediterranean dietary pattern was inversely associated with mammographic density in the models adjusted for age and BMI (per 1 unit increase of score OR 0.95; 95%CI 0.90–0.997). Current use of multivitamin-multimineral supplements was also inversely associated with mammographic density (OR 0.53; 95%CI 0.34–0.83). Further adjustment revealed similar point estimates but the associations were no longer statistically significant. Compared to non-drinkers, excessive alcohol consumption (<10 g/d) was positively associated with mammographic density (OR 1.47; 95%CI 0.82-2.63).
Our results show that dietary factors are associated with mammographic density. Adherence to Mediterranean diet and current use of multivitamin-multimineral supplements could be inversely associated with mammographic density and may suggest a protective effect against breast cancer, whereas high alcohol consumption was associated with increased mammographic density.
PMCID: PMC3599490  PMID: 23497280
Mammographic breast density; Diet; Supplements; Alcohol; Breast cancer
4.  Substantial and reversible brain gray matter reduction but no acute brain lesions in ultramarathon runners: experience from the TransEurope-FootRace Project 
BMC Medicine  2012;10:170.
During the extremely challenging 4,487 km ultramarathon TransEurope-FootRace 2009, runners showed considerable reduction of body weight. The effects of this endurance run on brain volume changes but also possible formation of brain edema or new lesions were explored by repeated magnetic resonance imaging (MRI) studies.
A total of 15 runners signed an informed consent to participate in this study of planned brain scans before, twice during, and about 8 months after the race. Because of dropouts, global gray matter volume analysis could only be performed in ten runners covering three timepoints, and in seven runners who also had a follow-up scan. Scanning was performed on three identical 1.5 T Siemens MAGNETOM Avanto scanners, two of them located at our university. The third MRI scanner with identical sequence parameters was a mobile MRI unit escorting the runners. Volumetric 3D datasets were acquired using a magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. Additionally, diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR) imaging was performed.
Average global gray matter volume as well as body weight significantly decreased by 6% during the race. After 8 months, gray matter volume returned to baseline as well as body weight. No new brain lesions were detected by DWI or FLAIR imaging.
Physiological brain volume reduction during aging is less than 0.2% per year. Therefore a volume reduction of about 6% during the 2 months of extreme running appears to be substantial. The reconstitution in global volume measures after 8 months shows the process to be reversible. As possible mechanisms we discuss loss of protein, hypercortisolism and hyponatremia to account for both substantiality and reversibility of gray matter volume reductions. Reversible brain volume reduction during an ultramarathon suggests that extreme running might serve as a model to investigate possible mechanisms of transient brain volume changes. However, despite massive metabolic load, we found no new lesions in trained athletes participating in a multistage ultramarathon.
See related commentary
PMCID: PMC3566943  PMID: 23259507
body weight; brain volume; catabolism; DWI; lesion; MRI; ultramarathon
5.  The Transeurope Footrace Project: longitudinal data acquisition in a cluster randomized mobile MRI observational cohort study on 44 endurance runners at a 64-stage 4,486km transcontinental ultramarathon 
BMC Medicine  2012;10:78.
The TransEurope FootRace 2009 (TEFR09) was one of the longest transcontinental ultramarathons with an extreme endurance physical load of running nearly 4,500 km in 64 days. The aim of this study was to assess the wide spectrum of adaptive responses in humans regarding the different tissues, organs and functional systems being exposed to such chronic physical endurance load with limited time for regeneration and resulting negative energy balance. A detailed description of the TEFR project and its implemented measuring methods in relation to the hypotheses are presented.
The most important research tool was a 1.5 Tesla magnetic resonance imaging (MRI) scanner mounted on a mobile unit following the ultra runners from stage to stage each day. Forty-four study volunteers (67% of the participants) were cluster randomized into two groups for MRI measurements (22 subjects each) according to the project protocol with its different research modules: musculoskeletal system, brain and pain perception, cardiovascular system, body composition, and oxidative stress and inflammation. Complementary to the diverse daily mobile MR-measurements on different topics (muscle and joint MRI, T2*-mapping of cartilage, MR-spectroscopy of muscles, functional MRI of the brain, cardiac and vascular cine MRI, whole body MRI) other methods were also used: ice-water pain test, psychometric questionnaires, bioelectrical impedance analysis (BIA), skinfold thickness and limb circumference measurements, daily urine samples, periodic blood samples and electrocardiograms (ECG).
Thirty volunteers (68%) reached the finish line at North Cape. The mean total race speed was 8.35 km/hour. Finishers invested 552 hours in total. The completion rate for planned MRI investigations was more than 95%: 741 MR-examinations with 2,637 MRI sequences (more than 200,000 picture data), 5,720 urine samples, 244 blood samples, 205 ECG, 1,018 BIA, 539 anthropological measurements and 150 psychological questionnaires.
This study demonstrates the feasibility of conducting a trial based centrally on mobile MR-measurements which were performed during ten weeks while crossing an entire continent. This article is the reference for contemporary result reports on the different scientific topics of the TEFR project, which may reveal additional new knowledge on the physiological and pathological processes of the functional systems on the organ, cellular and sub-cellular level at the limits of stress and strain of the human body.
Please see related articles: and
PMCID: PMC3409063  PMID: 22812450
6.  The foot in multistage ultra-marathon runners: experience in a cohort study of 22 participants of the Trans Europe Footrace Project with mobile MRI 
BMJ Open  2012;2(3):e001118.
67 runners participated in the Trans Europe FootRace 2009 (TEFR09), a 4487 km (2789 mi) multistage ultra-marathon covering the south of Europe (Bari, Italy) to the North Cape. Reports on ultra-marathons are lacking, but the literature reports overuse injuries in athletes, especially to the Achilles tendon (AT), ankle or hind foot. Bone oedema may be related to exposure and is present in fatigue fractures. Therefore, the aim of this study was to determine prospectively if sustained maximal load during an ultra-marathon leads to damage to the foot.
Design and participants
In a cohort study, repeated scanning of the 22 athletes participating in the study was performed before and during (approximately every 1000 km) the race. Using the obtained fat saturated inversion recovery sequence, two experienced readers blinded to the clinical data rated the images regarding foot lesions. Statistical analysis included regression analysis and computation of the inter-rater reliability.
The TEFR09 course. MRI scanning was performed according to prearranged schedules for every participant, using a mobile 1.5 Tesla MRI unit on a trailer following the race.
Primary outcome measures
MRI data such as AT diameter, bone or tendon lesions, subcutaneous, plantar fascia or intraosseous oedema.
The 22 study participants did not differ significantly from the total of the 67 TEFR09 runners regarding height, weight and age. The AT diameter increased significantly from 6.8 to 7.8 mm as did intraosseous signal, bone lesions and subcutaneous oedema. However, finishers differed only regarding plantar aponeurosis and subcutaneous oedema from participants aborting the TEFR09. Inter-rater reliability was 0.88–0.98.
Under the extreme stress of the TEFR09, an increase of the AT diameter as well as bone signal are thought to be adaptive since only subcutaneous oedema and plantar fascia oedema were related to abortion of the race.
Trial registration number
University of Ulm, Germany Ethics Committee Number 78/08-UBB/se.
Article summary
Article focus
A study on effects of ultra-marathon running, in this case, the multistage Trans Europe FootRace covering a distance of 4487 km from Bari (Italy) to the North Cape.
Observational cohort study using MRI to look for possible lesions to the foot.
Key messages
During sustained maximal load, AT diameter and bone MRI short τ inversion recovery signal (hinting at subtle oedema) increases. This is thought to be adaptive.
Subcutaneous oedema and plantar fascia signal were related to abortion of the race. These measurements seem to be related to relevant changes leading to discontinuation of the run.
No relevant new foot joint or tendon lesions were detected during the race over 4487 km.
Strengths and limitations of this study
Repeated measurement prospectively during the run was possible only because of the mobile MRI unit used for this research project.
The number of included runners (22) is high compared with other MRI-based studies but may have been too small to detect less frequent lesions.
PMCID: PMC3364457  PMID: 22619270
7.  Automatic detection of the carotid artery boundary on cross-sectional MR image sequences using a circle model guided dynamic programming 
Systematic aerobe training has positive effects on the compliance of dedicated arterial walls. The adaptations of the arterial structure and function are associated with the blood flow-induced changes of the wall shear stress which induced vascular remodelling via nitric oxide delivered from the endothelial cell. In order to assess functional changes of the common carotid artery over time in these processes, a precise measurement technique is necessary. Before this study, a reliable, precise, and quick method to perform this work is not present.
We propose a fully automated algorithm to analyze the cross-sectional area of the carotid artery in MR image sequences. It contains two phases: (1) position detection of the carotid artery, (2) accurate boundary identification of the carotid artery. In the first phase, we use intensity, area size and shape as features to discriminate the carotid artery from other tissues and vessels. In the second phase, the directional gradient, Hough transform, and circle model guided dynamic programming are used to identify the boundary accurately.
We test the system stability using contrast degraded images (contrast resolutions range from 50% to 90%). The unsigned error ranges from 2.86% ± 2.24% to 3.03% ± 2.40%. The test of noise degraded images (SNRs range from 16 to 20 dB) shows the unsigned error ranging from 2.63% ± 2.06% to 3.12% ± 2.11%. The test of raw images has an unsigned error 2.56% ± 2.10% compared to the manual tracings.
We have proposed an automated system which is able to detect carotid artery cross sectional boundary in MRI sequences during heart cycles. The accuracy reaches 2.56% ± 2.10% compared to the manual tracings. The system is stable, reliable and results are reproducible.
PMCID: PMC3083378  PMID: 21477378
8.  Effects of sodium concentration and osmolality on water and electrolyte absorption from the intact human colon 
Journal of Clinical Investigation  1969;48(7):1336-1347.
The influence of sodium concentration and osmolality on net water and monovalent electrolyte absorption from or secretion into the intact human colon was studied in healthy volunteers.
When isotonic solutions containing NaCl and/or mannitol were infused into the colon: (a) a direct linear relationship between luminal sodium concentration (in the range of 23-150 mEq/liter) and rate of net water, sodium, and chloride absorption was found. No water absorption was found when sodium concentration in the luminal fluid was below 20 mEq/liter; (b) water and sodium absorption from the isotonic test solutions was not enhanced by addition of 80-250 mg/100 ml of glucose; and (c) the rate of water and sodium absorption was decreased markedly when chloride was replaced by bicarbonate in the test solution.
When the colon was perfused with hypertonic test solutions containing NaCl and mannitol or urea: (a) water was absorbed from hypertonic NaCl solutions against a lumen-to-blood osmotic gradient of 50 mOsm/kg; (b) when the osmolality of the mannitol solution was increased, water entered the colonic lumen at a more rapid rate. The relationship between the rate of water entering the colon and the osmolality of the test solution was a parabolic one; (c) sodium and chloride entered the colonic lumen at a rate that was lineraly related to that of water entrance when the lumen-to-blood osmotic gradient exceeded 150 mOsm/kg; (d) water flow into the colonic lumen was identical when equimolar urea or mannitol solutions were infused; (e) neither urea nor mannitol was absorbed in significant amounts from the hypertonic solutions; and (f) our results suggest that the equivalent pore radius of the human colon is smaller than the molecular radius of urea (2.3 A).
PMCID: PMC322357  PMID: 5794255

Results 1-8 (8)