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
Schütz et al.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78 (19 July 2012)
TECHNICAL ADVANCE
Open Access
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
Uwe HW Schütz1,2*†, Arno Schmidt-Trucksäss3†, Beat Knechtle4, Jürgen Machann5, Heike Wiedelbach1,
Martin Ehrhardt1, Wolfgang Freund1, Stefan Gröninger6, Horst Brunner1, Ingo Schulze7, Hans-Jürgen Brambs1 and
Christian Billich1
Abstract
Background: 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.
Methods: 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).
Results: 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.
Conclusions: 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
* Correspondence: uwe.schuetz@rocketmail.com
† Contributed equally
1Department of Diagnostic and Interventional Radiology, University Hospital
of Ulm, Germany
Full list of author information is available at the end of the article
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
© 2012 Schütz et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
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: http://www.biomedcentral.com/1741-7015/10/76 and http://www.biomedcentral.com/
1741-7015/10/77
Background
Ultramarathon
Various aspects of the physical characteristics of recrea-
tional and elite level runners up to marathon distance
events have been reported [1-9]. Much less has been
written about the anthropometric characteristics of ultra
endurance runners [10-14]. The case and field studies of
Knechtle et al. developed a growing knowledge about the
physical characteristics of multistage ultra endurance
runners in the past years [15-22]. The German Ultra-
marathon Association (DUV) defines foot-races of 50 km
or longer as ultramarathons (UM). Multistage ultramara-
thons (MSUM) are races in which each stage has a dis-
tance of a UM. Besides a few case reports very little has
been reported about the medical aspects of runners
doing a transcontinental extended MSUM over several
weeks [23]. Until now, there have been no reports pub-
lished regarding UM running over more than 1,500 km.
However, prolonged MSUM races offer the best opportu-
nity to study physical adaptation and the associations of
the physiological parameters of athletes in a longitudinal
setting day by day.
The race
Among some very heroic solo runs, the TransEurope Foo-
tRace 2009 [24] (TEFR09) was the 11th official transconti-
nental competition multistage footrace within living
memory (Table 1) [25-33]. This second European trans-
continental MSUM took place from 19 April to 21 June
2009 from Bari, South Italy (41° 8’ N, 16° 52’ E) to the
North Cape, Norway (71°10’N, 25°47’E) (Figure 1). Sixty-
seven ultra endurance runners (mean age 50.7 years, range
26 to 74 years, male 56 (83.6%)) from 12 nations (Ger-
many, Japan, Netherlands, France, Switzerland, Norway,
Sweden, Finland, Turkey, South Korea, Taiwan, USA) met
the challenge and tried to cross six countries (Italy, Aus-
tria, Germany, Sweden, Finland, Norway). This comprised
running 4,487 km (2,788 miles) in 64 stages without any
day of rest. Thus, they expected to complete an average
stage distance of 70.1 km, representing 1.7 marathon dis-
tances (minimum: 44 km, maximum: 95.1 km) [32].
All participants organized their arrival at Bari on their
own. Following breakfast at 5:00 a.m., the daily stage
started at 6:00 a.m. The race director, together with his
staff, planned the stages with their corresponding distances
and ascent or descent and organized the accommodations
for the runners in halls as well as the food for each stage.
In addition, most of the runners carried individual nutri-
tion on their own. Depending on the stage length, five to
ten stop points for nutrition were placed on the daily
routes. After each stage the runners had time on their
own (nutrition, sleeping, regeneration). Depending on the
stage length and local situation, dinner was served
between 5:00 and 9:00 p.m. The runners slept in camping
grounds (mainly in Italy), local sport halls or local commu-
nity halls at the stage destinations (9:00 p.m. to 4:00 a.m.).
Sometimes the quarters were crowded resulting in difficult
sleeping conditions. In total, the runners had about 7 to
13 hours of rest per day for recuperation. The local sani-
tary conditions also changed daily and from country to
country.
The project
The TEFR09 project is the first observational cohort study
intended to produce unique and comprehensive data from
longitudinal measurements of a large sample of ultra
endurance runners taking part in one of the most extreme
multistage endurance competitions in the world, which
takes the participants to a different level, where the race
becomes a way of life, and where nutrition, sleep, energy
and psychological states have to be carefully managed
[34,35]. It is also the first study using a mobile MRI scan-
ner for continuous examination of the athletes while per-
forming a transcontinental MSUM. The aim was to
explain the wide spectrum of adaptive responses in
humans being exposed to such a chronic physical endur-
ance load with negative energy balancing but without
enough time for regeneration and to identify factors asso-
ciated with inter-individual variation in these responses.
Due to the unique possibility to observe morphological
and physiological changes and the reactions of different
tissues and functional systems on the systemic, organ and
(sub)cellular level with modern MRI techniques, a wide
range of multiple questions, hypotheses and unproven
assumptions regarding injury, adaptation, regeneration,
reparation and overuse processes arose. Therefore, four
different project modules of investigations were created,
focusing on multiple open questions and unproven
hypotheses regarding long distance running:
Project module I: musculoskeletal system
Pre-race injuries and deformation
It is inevitable that pre-race injuries or biomechanical
deviations from the norm (for example, mal-alignment)
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 2 of 33
will lead to progressing focal damage of the lower extre-
mities when performing a transcontinental MSUM. If
any participant who suffers from unhealed pre-race inju-
ries or deformation of the lower extremities reaches the
finish line at North Cape without deterioration, this
hypothesis can be rejected. Furthermore, the TEFR pro-
ject tries to detect reasons for not finishing the race in
detail.
Joints
Recent investigations indicate that running a marathon
does not increase pathologies of structures of the knee
joint [36-39]. Some authors postulate a risk factor of
repeated marathon running for osteoarthritis of the knee
[40]. However, a protective effect of running for knee
joint cartilage is also discussed [41,42]. Nothing is known
about the effect of ultra long distance running over
weeks as in MSUM on knee structures. For the knee car-
tilage, experimental studies on animals using quantitative
microspectrophotometry and polarized light microscopy
showed a decrease of the glycosaminoglycan content of
the superficial femorotibial joint cartilage layer and
degradation and reorganization of the superficial collagen
network [43-45]. With this study, there are two hypoth-
eses to be proven: first, in a MSUM over nine weeks, the
well-trained participants show no increase in pathologies
of the structures of the knee joint; and second, the carti-
lage of the femorotibial joint shows a degradation of the
glycosaminoglycan content with quick regeneration after
the end of the race. The hypothesis that MSUM running
does not indicate a higher risk of osteoarthritis of the
knee in well-trained endurance runners has to be proven
with the TEFR project. Contrary to the femorotibial joint
the following hypothesis for the femoropatellar joint has
to be proven: retropatellar cartilage degeneration is not
caused by MSUM running. The femoropatellar joint is
not a limiting factor for ultra endurance running,
although degeneration arthrosis is already present in
some MSUM participating athletes, respectively. This
hypothesis is based on the fact that retropatellar arthrosis
has a high prevalence in older people [46] and long
Table 1 History of transcontinental footraces
No
race: date
route
total distance
days,
stages
mean stage distance
star -tera
fin-ishera
C.C. Pyle’s International Trans-continental Foot Races (Bunion Derbies 1928, 1929) [25-27]
1.
1928: 4 March - 24 May
Los Angeles -
New York
5,509 km
3,423 miles
84
65.6 km/d 40.8 miles/d
199
55
28%
2.
1929: 21 March - 8 June
New York -
Los Angeles
5,509 km
3,423 miles
84
65.6 km/d
40.8 miles/d
80
31
39%
Trans America Foot Races 1992-95 [28,29]
3.
1992: 20 June - 22 August
Huntington Beach - New York
4,722 km
2,935 miles
64
73.8 km/d
45.9 miles/d
28
13
46%
4.
1993: 19 June - Aug.21
Huntington Beach - New York
4,686 km
2,912 miles
64
73.8 km/d
45.9 miles/d
13
6
46%
5.
1994: June 18 - 20 August
Huntington Beach - New York
4,708 km
2,926 miles
64
73.6 km/d
45.7 miles/d
14
5
36%
6.
1995: 17 June 17 - 19 August
Huntington Beach - New York
4,676 km
2,906 miles
64
73.1 km/d
45.4 miles/d
14
10
71%
Trans Australia Foot Race 2001
7.
2001: 6 January - 11 March
Perth -
Canberra
4,109 km
2,553 miles
63
67.8 km/d
42.1 miles/d
24
14
58%
Run Across America 2002
8.
2002: 15 June - 24 August
New York -
Huntington Beach
4,961 km
3,084 miles
71
68.9 km/d
42.8 miles/d
11
8
73%
10.
2004: 15 June - 24 August
Huntington Beach - New York
4,961 km
3,084 miles
71
68.9 km/d
42.8 miles/d
10
6
60%
Trans Europe Foot Races 2003, 2009 [30-33]
9.
2003: 19 April - 21 June
Lisbon, Portugal - Moscow
5,020 km
3,119 miles
64
79.5 km/d
49.4 miles/d
44
22
50%
11.
2009: 19 April - 21 June
Bari, Italy -
North Cape
4,486 km
2,787 miles
64
70.1 km/d
43.6 miles/d
67
46
69%
Run Across America 2011: LANY (Los Angeles to New York)
12.
2011: 19 June - 27 August
Huntington Beach - New York
5,157 km
3,205 miles
70
73.7 km/d
45.8 miles/d
14
8
57%
atotal: 528 starters, 224 finishers. 42.4% (some of these have made more than one crossing)
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 3 of 33
distance running participation rises with age [47]. This
TEFR project will also prove the same hypothesis for the
joints of the ankle and hindfoot. For the latter no specific
studies have been published until now.
Soft tissues of the leg
The literature on long distance running demonstrates
that injuries mostly occur in the active and passive soft
tissues of the lower extremities [48-54]. Injuries of the
muscles, tendons and fascia of the lower legs are
the most obvious limiting factors for performance and
the most common reasons for not finishing a transconti-
nental footrace. This postulation leads to the following
hypothesis which has to be proven by the TEFR project:
During a MSUM every participant will suffer from differ-
ent injuries and overload of active and passive soft tissues
of the lower musculoskeletal system, resulting in long
lasting damage due to lack of recreation time.
A special problem for endurance runners is a pain syn-
drome of the lower leg, so-called ‘shin splint’. Investiga-
tions over the past years, especially with MRI, showed that
several entities caused by overuse of the lower leg due to
long distance running can be differentiated. Some authors
indicated that bone or periosteal reactions of the ventral
tibia are a typical part of this syndrome [55,56], while
others do not consider this as being mandatory [57].
Depending on the involved tissues and the lack of exact
knowledge of the pathogenesis, the terminology regarding
chronic lower leg pain in runners is broad and has not
been differentiated and defined in detail until now: medial
tibial stress syndrome, shin splint, anterior muscle syn-
drome, (peri-)myositis, periostitis, fasciitis, and so on
[58,59]. With our study design we try to prove the hypoth-
esis that running-associated chronic lower leg pain
includes different entities, such as overuse pathologies of
muscles, fascias, tendons and bone tissues of the lower leg.
The problem begins in the friction areas of the fascia of
the muscles and the tendons (peritendineum) and then
extends to other tissues such as the muscles, periosteum
and bone if the running burden continues and the pain is
ignored by the athlete. As many ultra athletes reported, it
seems to be possible to overrun ‘shin splint’ without
further damage. Whether medial tibial stress syndrome
can end up in a stress fracture or a chronic exertional
compartment syndrome when running is continued with-
out any further rest is not clear [56,60,61]. Perhaps further
understanding and differentiation of soft tissue overuse of
the leg is possible due to this observational cohort study
with a mobile MRI.
Bones
Stress fractures of the lower body often occur in people
doing extensive walking or running without proper train-
ing or adaption to the repeated and persistent mechanical
burden their bones have to deal with. As seen in young
soldiers doing their first long march with full body equip-
ment [62] or amateur runners or beginners in (half-)
marathons [63] our hypothesis is that even well trained
ultra runners, such as the TEFR participants, can suffer
stress fractures, because their skeletal system is not
Figure 1 Route of Trans Europe Foot Race 2009 (4,486 km
from south to north of Europe).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 4 of 33
adapted to this tremendous mechanical burden that
occurs while crossing a continent by foot with a speed of
more than 6 km/hour without any day of rest. The TEFR
project with mobile MRI tries to detect early signs of
bone reaction (for example, subperiosteal new bone for-
mation, adaptive cortical hypertrophy with little true
inflammation, local bone edema or bruising) indicating
overload as precursors of stress fractures [59].
For asymptomatic healthy marathon runners signifi-
cantly higher red bone marrow hyperplasia has been
observed compared to healthy volunteers [64]. This is pos-
tulated to be a response to ‘sports anemia’, which is com-
monly found in highly conditioned trained athletes. The
TEFR project wanted to prove the hypothesis that during
a MSUM lasting more than nine weeks an increase of red
bone marrow occurs in the participants, even though they
are adapted and well trained in ultra running.
Project module II: brain, mind and pain perception
Brain volume
Aerobic exercise protects from insular atrophy in the brain
of healthy volunteers [65,66]. The normal annual volume
loss due to age-related brain atrophy is about 0.11%
[66,67]. Increased atrophy is shown for several diseases,
such as Alzheimers (2% per year) [68,69] anorexia nervosa
[70,71] or malnutrition based on other reasons [72]. Some
hypotheses explain this based on the influence of the stress
hormone cortisol [70] but further pathophysiological prin-
ciples leading to this decrease in brain volume are not
understood [73-76]. Marathon-induced changes in endo-
crine levels [77,78], in fluid balance [79] and amino acid
blood level [80] are known to alter brain metabolism. The
hypothesis that ultra endurance running leads to volume
reduction of the brain cortex could be investigated by the
TEFR project using high resolution cerebral MRI. Com-
bined with specific laboratory analyses of different markers
(for example S100B [81,82]) in blood and urine, reasons
explaining the mechanism may be identified. On the other
hand, when we postulate that an ultra long MSUM, such
as the TEFR09, modifies the plastic brain (state marker)
the hypothesis that the sensomotoric cortex volume -
which is responsible for the lower extremities - will
increase has also to be proven [83].
Brain lesions
Additionally we hypothesize that the well-known exer-
cise-induced hyponatremia due to inappropriate arginine
vasopressin secretion which can lead to encephalopathy
[84-87] is not seen in the highly endurance-trained par-
ticipants of the TEFR09. If an MSUM leads to brain
lesions, water sensitive cerebral MRI sequences of the
TEFR project will show it.
Pain perception, mind and mental stress
All participants in the TEFR09 had previously finished
an ultra marathon. This unique collective of endurance
athletes is eminently suitable for examining the hypoth-
esis that ultra runners have different mental prerequi-
sites (higher auto suggestibility) compared to the normal
population (trait marker). Experienced ultra endurance
runners often mentioned that finishing an ultra race is
more a matter of mind than a matter of the body. The
hypothesis that finishers of MSUM differ from non-
finishers with regard to pain suppression and willpower
can be proven by pain tests combined with functional
MRI of the brain and mental stress markers in serum
samples.
Project module III: cardiovascular system
Heart
The MSUM TEFR09 results in an extreme prolonged
stress for the whole organism. Its effects on the heart can
be discussed controversially. Cardiac dysfunction after
marathon running is verified with biochemical markers
and cardiac ultrasound [88,89]. Investigations with car-
diac MRI are inconsistent; cardiac damage such as myo-
cardial necrosis is seen in middle-aged marathon runners
(57.2 +/- 5.7 years) [90], but not in younger marathon
participants (30 to 50 years) [91,92]. Myocardial function
disorders are reported with cardiac MRI tagging [93].
Until now, diagnostic analyses of long-lasting running
effects on the heart using cardiac biomarkers are difficult
to interpret, for example, the increase in brain natriuretic
peptide (BNP) after 100 km trials [94,95] could show
cytoprotective or growth regulatory effects [89,96] but
also myocardial insufficiency. The TEFR project intends
to prove the following hypotheses: Even in well trained
ultra endurance runners, the running burden of a trans-
continental MSUM of more than nine weeks induces a
progressive cardiac distress and signs of cardiovascular
mal-adaption. Cardiac MRI, stress laboratory tests and
ECG might show signs of cardiac structural and func-
tional restrictions, dysfunctions, damages and insuffi-
ciency. Non-finishers of the TEFR09 will show more
restrictive parameters than finishers. Another hypothesis
contradicting the Morganroth hypothesis [97,98] is pro-
ven: Although an aerobic endurance burden is per-
formed, the TEFR09 finisher will show an increase in
cardiac output and left ventricular mass index and in
ventricular wall thickness, which might be caused by
incomplete or critical left ventricular hypertrophy in
some cases. Using a MR tagging technique, we will try to
prove the hypothesis that the anatomical position of the
heart is going to change (steep position) with a prolonged
aerobic running burden [99].
Arteries
Arteries of the muscular-type, such as the common
femoral artery (CFA) adapt structure and function to
endurance exercise training and elastic-type arteries,
such as the common carotid artery, show functional
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 5 of 33
adaptations to increased endurance exercise training.
Schmid-Trucksäss et al. [100] found an increase of dia-
meter and compliance and a constant shear rate for
CFA using noninvasive vascular ultrasound in highly
endurance-trained athletes compared to sedentary con-
trols. Other authors postulate that endurance exercise
does change arterial wall stiffness and vascular (endothe-
lial) function [101-103]. The TEFR project tries to prove
the hypotheses that the MSUM burden results in cardi-
ovascular adaptations in the form of an increase of
arterial wall compliance in the lower extremities asso-
ciated with an increase in the vessel lumen diameter of
the femoral artery and of the central aortal pulse wave
velocity even in well-trained ultra-endurance runners.
This will result in a decrease of the peripheral arterial
resistance leading to an increase in basic perfusion of
the lower extremities.
Project module IV: body composition
Endurance exercise leads to a reduction of subcutaneous
fatty tissue as demonstrated in several field studies
[104-107]. It is well known that fat is the main energy-rich
substrate for ultra endurance performance [105,107,108].
In contrast, muscle tissue provides lower energy, when
being catabolized. A decrease in skeletal muscle mass due
to ultra endurance performance has only been demon-
strated in case reports [15,23,109] or small series [108].
Different effects for long-lasting or ultra endurance per-
formances on body composition are described in the
literature and seem to depend on the type of endurance
burden. In ultra endurance performance with defined
breaks (for example, during the night), body mass may
remain stable [110-112] or even increase [105] while body
fat is reduced [104,105,113], whereas skeletal muscle mass
seems to be spared [111,113,114] or may even increase
[104]. Ultra endurance performance over hours, days or
weeks without a break, results in a decrease in body mass
[23,107,109,115] in which body fat as well as skeletal mus-
cle seems to decrease as a few case reports indicate
[15,23,109]. With this cohort study we can prove the
hypothesis that due to the immense negative energy bal-
ance during a transcontinental MSUM, not only fat but
also lean tissue is involved in catabolism, even in the leg
muscles. With its mobile whole body MRI protocol, the
TEFR project will be able to measure the different amount
of mass loss in the different functional muscle units of the
leg. We also intend to detect the microstructural and
intracellular adaption processes of leg muscle tissue with
modern MRI methods (MR-spectroscopy, diffusion and
perfusion MR imaging).
Purpose
This report describes the design and conduct of
the TEFR project. We report the pattern of chronic
endurance running exposure, characteristics of the sub-
ject groups and reasons for not finishing. Detailed
descriptions of measuring methods in relation to the
hypotheses and technical challenges encountered in the
realization of the interdisciplinary TEFR project are pre-
sented. We discuss the strengths and limitations of the
study setting.
Methods
After commitment to funding by the German Research
Society (DFG) the 67 TEFR09 participants were asked to
join the TEFR project, which was approved by the local
ethics committee of the University Hospital of Ulm
(UHU, No.: 270/08-UBB/se), Germany (in accordance
with the Declaration of Helsinki) regarding the study
design, risk management plan and individual protocols.
Verbal and written informed consent was obtained from
all concurring subjects.
Mobile MRI
The most important research tool was a 1.5 Tesla whole-
body MR imager (Magnetom Avanto™ mobile MRI 02.05,
software version: Syngo™ MR B15, Siemens Ltd., Erlan-
gen, Germany) mounted on a mobile unit (MRI-Trailer
Model Mob.MRI 02.05, SMIT Mobile Equipment B.V.,
Division AK Specialty Vehicles, Farnham, UK) pulled by a
specially hired truck tractor. The semi-trailer had an inter-
nal diesel generator to power the helium cooling circuit
for the MRI over the ten-week period. However, it did not
generate enough electricity for continuous MRI measure-
ments and was therefore supplemented by a more power-
ful custom made external diesel generator (150 KVA,
Strom Rent™ e.k., Dortmund, Germany) which was pulled
by an additional material van. The mobile hardware had a
total weight of more than 45 tonnes and was nearly 30
meters long. All of the equipment was installed daily at
each stopover and required daily checks and support of all
technical systems (Figure 2).
Study participants
Forty-four (67%) of the race participants (mean age 49.7
years, range 26 to 68 years, male 40 (90.9%), f 4) were
recruited for the TEFR project. The inclusion criterion
obviously was an official acceptance as a participant at
the TEFR09 by the organizers and the race director. The
conditions of participation were: minimum age 18 years,
the presence of a medical certificate not older than
30 days which indicated physical health and clear proof
of appropriate running performance in the field of UM.
The specific running history and performance of the indi-
vidual subjects can be described by different traits, which
were requested before the start of the TEFR09: years of
regular endurance running training, finished (ultra-)
marathons, personal best times in different defined ultra
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 6 of 33
races and extent of training (volume, duration, intensity)
before TEFR09.
The investigators additionally performed a resting car-
diovascular check using a 12-channel PC-ECG system
(Custo cardio 100™, Custo Med Ltd., Ottobrunn, Ger-
many) and blood pressure (RR) measurement using a
manual sphygmomanometer (BOSO Clinicus, Jungin-
genGermany: to the nearest 3 mmHg). Cardiovascular
exclusion criteria were resting blood pressure > 200
mmHg systolic and/or > 110 mmHg diastolic, acute sys-
temic infection, acute chest pain and new arrhythmias
or ECG changes. An orthopedic physical examination
was done focusing on contraindications for endurance
running such as relevant malalignment and painful joint
diseases of the lower extremities. Additional specific
exclusion criteria were contraindications against MRI
scanning (for example, metallic foreign bodies in dan-
gerous locations, specific cochlear or ocular implants,
ferromagnetic vascular clips and relevant claustropho-
bia). None of the volunteers had to be excluded from
study participation due to these criteria.
Investigators
Four members of the TEFR project comprised the inves-
tigator core team that accompanied the TEFR09 for
direct data acquisition before and during the race: two
physicians, one medical student and one radiological
assistant. The latter (HW) was responsible for subject
positioning in the scanner and performance of the MR
examinations. One of the investigators, the initiator and
main organizer of the TEFR project (US), drove the
MR-trailer truck, adapted the daily research program to
the actual circumstances, controlled and checked the
quality of the MR examinations and was responsible for
the technical readiness of the whole mobile MRI and its
functional circuits and equipment with external and
internal diesel generator. Being specialized in radiology
and orthopedic surgery, he also did the initial and fol-
low-up physical musculoskeletal examinations of the
subjects. The second investigator (CB) was responsible
for acquisition of daily anthropometric, laboratory and
ECG data. The medical student (ME) made the daily
anthropological measurements.
The two physicians were solely responsible for the
study and gave neither training advice nor provided
medical help.
Study design
The study design of the TEFR project is shown in
Figure 3.
Pre-race
Baseline studies were performed within the last four
days before the start of the TEFR09 in Bari on every
subject. They included group specific MRI examinations
and anthropometric and cardiovascular physical mea-
surements with urine and venous blood samples.
Additionally, body height measuring using a wall-
mounted stadiometer (to the nearest 5 mm, standing
barefoot) and active range of motion measurement
(AROM) of hip and knee joints using a manual double-
armed universal goniometer (to the nearest 5°) were
done before the start. One experienced orthopedic sur-
geon, trained in a standardized procedure for position-
ing both the subject and the goniometer, collected these
data.
Figure 2 Truck trailer with mobile MRI and external generator in working position.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 7 of 33
Adapted from the methods of Paley et al. [116] and
Weidelich et al. [117], analysis of lower limb alignment
was done on coronal lower body scout views of pre-race
MRI with subjects in the supine position and with
extended legs. Measured parameters were: leg length
(LL), as the straight line from the middle of the femoral
head to the midpoint of the upper talus rim; femoroti-
bial angle (FTA), as the angle between anatomical
femoral and tibial axis; the mechanical axis deviation
(MAD) as the distance from the point of intersection
between the perpendicular and mechanical axis of the
limb (straight line from the middle of the femoral head
to the midpoint of the upper talus rim) to the midpoint
of the knee (medial tibial eminence) and the femoral to
tibial length ratio (F/T) [116-122].
A 240-item, 31-dimensional personality temperament
and character inventory (TCI) [123,124] in addition to a
10-item, 4-scaled questionnaire on self expectancy (Gen-
eral Self-Efficacy Scale, GSE) [125,126] were also inte-
grated into the project before its start.
Additionally, 15 of the 44 subjects had an initial sepa-
rate pre-race test on pain perception (ice-water test)
combined with functional cerebral MRI two weeks
before the start of the TEFR09 at UHU on 1 to 3 April
2009, because these examinations could not be imple-
mented on the mobile MRI due to technical limitations.
Due to the exorbitant physical and mental burden
placed on the subjects, there was no opportunity for
field experiments, invasive tests or application of psy-
chometric instruments during the transcontinental foot-
race.
Field studies
The observant field studies during the TEFR09 were
completed between 15 April and 21 June 2009. Every
morning from 3:45 to 4:30 a.m. urine samples and
anthropometric measurements were taken. The core
team broke down their examination units and drove to
the next stage destination. Before stage length depen-
dent arrival of the first runner they had set their systems
ready and had refuelled the generators and vehicles.
MRI examination time was between 2:30 p.m. +/- 90
minutes and 9:00 p.m.). At the same time anthropo-
metric and cardiovascular physical measurements, blood
and urine samples were collected and ECG was done.
The daily data acquisition also included measurement
Figure 3 Study design of TEFR-project.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 8 of 33
and documentation of daily weather conditions (tem-
perature outside and inside, humidity outside) using a
calibrated electronic thermometer, the stage length and
the individual stage performances of the runners (stage
running time).
MR measurements
For MR measurements two groups (22 subjects each)
were cluster randomized according to the different
research modules. The MR protocols were created in an
interdisciplinary content ensuring multifold specific and
diverse but precise analyses and measurements for
detailed testing of the mentioned hypotheses concerning
long distance running (Table 2).
MRI of feet
For high resolution investigation of the whole foot a
special table fixed boot-like designed 8-channel foot-
ankle coil was chosen and a sagittal orientated water
sensitive T2w MR sequence (TIRM) configured a wide
field of view. If on this sequence any pathology was
detected, a transversal oriented focused water sensitive
sequence with a more structured T2 sequence (fat satu-
rated proton density weighted (PDw)) was added. For
investigation of the joint cartilage a specific T2* map-
ping MR sequence (syngo™ MapIt FLASH T2*w GRE)
in sagittal orientation was used [127-129], allowing
quantitative measurement of hydrophilic changes in the
cartilage layers of tibiotalar, talocalcaneal, calcaneocu-
boid, and calcaneonavicular joints. The specification of
these MR sequences (Table 2) was done for detection of
typical running associated overuse injuries of the feet
[52]: subcutaneous edema, Achilles tendonitis [49,50],
extensor digitorum tendonitis [48,49]), plantar fasciitis
[50], calcaneal apophysitis, arthritis/arthrosis, stress frac-
tures, bone edema, metatarsalgia, Morton’s neuroma,
and ankle inversion injuries (Figure 4).
MRI of knees
With a table-fixed 8-channel knee coil all subjects of
group 1 had both knees examined with a sagittal TIRM
sequence for water detection in knee-related tissues and
evaluation of femorotibial joint. A transversal fat satu-
rated PDw sequence was used to assess the femoropatel-
lar joint. As for the hindfoot joints, specific T2* mapping
MR sequences in sagittal and transversal orientations
were done for quantification of cartilage layers of the
femoropatellar and femorotibial joints regarding intra-
chondral water proportioning [127-129]. The specification
of these MR sequences (Table 2) was done to evaluate
running-associated overuse injuries in the knees [52]:
patella tendonitis (‘runner’s knee’), arthritis/arthrosis
[130], stress fracture, bone edema [64], retropatellar pain
syndrome [48-50], chondromalacia patellae, meniscal
lesions [50] and patellar tendinitis [50] (Figure 5).
MRI of hips/pelvis
One flexible 6-channel body matrix coil was used to
obtain an MR overview of the pelvis with one coronal
water sensitive sequence (TIRM: Table 2) to detect
injuries in this part of the body: hip arthritis/arthrosis
[131], sacroiliac injuries [52], stress fractures of the pel-
vic ring [132-134], muscle overuse injuries and so on.
Additional case specific sequences were added as
necessary (Figure 6).
MRI of upper/lower legs
With three to four flexible 6-channel body matrix coils
total MR examination of upper and lower legs was pos-
sible. To get detailed information about soft tissue
edema, muscle perfusion and injuries of the legs differ-
ent sequences were adapted in transversal orientation
(T1w for adipose tissue separation and acute bleeding
detection, TIRM for high sensitivity in water detection,
fat saturated PDw for structural detailed water sensitive
imaging, DWI for perfusion analysis of muscles and
separation between intra- and extra-cellular water in the
muscles: Table 2). With these sequences all of the typi-
cal running-associated syndromes could be detected and
differential diagnosis done [49,52]: anterior compart-
ment pain/syndrome [48], (medial) tibial stress syn-
drome [50,135,136], gastrocnemius injuries, peroneal
tendonitis, tibialis posterior injury, calcaneal apophysitis,
iliotibial band friction syndrome [50], greater trochan-
teric bursitis, gluteus medius - hamstring - adductor -
abductor - quadriceps injuries, such as tendonitis,
strains or tears. Muscle volumetry of different compart-
ments of the upper and lower leg muscles is possible for
evaluation of changes in muscle volume: Figure 7.
Cerebral MRI, functional MRI
As for the muscles in the legs, a MRI guided volumetric
analysis of the brain was one focus of the cerebral MRI
measurements. Therefore, a T1 weighted high resolution
(1 mm) turbo FLASH three-dimensional-sequence was
used, making an isovoxel based volumetry (VBM) possi-
ble (Figure 8A). For detection of brain lesions and global
edema a typical T2-sensitive sequence (FLAIR) in coro-
nal orientation was chosen (Figure 8B). With diffusion
weighted imaging (DWI), ischemia detection was possi-
ble. For all these MR sequences (Table 2) a table inte-
grated 12-channel head matrix coil with a head restraint
system was used. The same coil was used on the sta-
tionary scanner for functional MRI (fMRI) using echo-
planar imaging (epi) with blood oxygenation level
dependent (BOLD) contrast to analyze pain perception
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 9 of 33
Table 2 MRI protocols of the TEFR project
MRI in module I: Musculoskeletal System
ankle/foot (PP: FFS, supine):
• TIRM 2D sag; PM: FA 140, TE 60; TR 11320, IR 120, ST 2, SBS 2.4, FOV 900, MS 512*512, PS 0.586 iso, PB 130; IAT: 5:37
• PDw TSE fs 2D tra; PM: FA 150, TE 32, TR 5830, ST 4, SBS 4.4, FOV 256, MS 384*384, PS 0.4167 iso, PB: 150; IAT: 3:46
• syngo™ MapIt FLASH 2D sag: T2*w GRE; PM: FA 60, TE 4.5, TR 1010, ST 2.5, SBS 2.75, FOV 182.25, MS 320*320; PS 0.421875 iso, PB: 250, IN: 12;
IAT: 4:15
knee (PP: FFS, supine):
• TIRM 2D sag; PM: FA 140, TE 50, TR: 4010, TI 150, ST 3, SBS 3.3, FOV 289, MS 256*256, PS 0.664 iso, PB 180; IAT: 3:31
• PDw TSE fs 2D cor; PM: FA 150, TE 31, TR 4400, ST 3, SBS 3.3, FOV 289, MS 512*512, PS 0.332 iso, PB 100; IAT: 4:11
• syngo™ MapIt FLASH 2D tra/sag: T2*w GRE; PM: FA 60, TE 4.18, TR 889/1120, ST 3, SBS 3.3, FOV 289, MS 512*512; PS 0.332 iso, PB: 250, IN: 12;
IAT: 4:21/3:58
Hip (PP: FFS):
• TIRM 2D cor; PM: FA 150, TE 61, TR 6230, TI 145, ST 3.5, SBS 3.85, FOV 1444, MS 384*384, PS 0.9896 iso, PB 130; IAT: 03:38
upper/lower leg (PP: FFS, supine):
• T1w SE 2D tra, PM: FA 90, TE 13, TR 626, ST 5, SBS 5, FOV 1050/722, MS 512*336/256, PS 0.78125/0.7422 iso, PB 115; IAT: 1:54/1:30
• TIRM 2D tra; PM: FA 140, TE 62; TR 12530, TI 130, ST 3, SBS 3.9, FOV 512, MS 384*192, PS 0.833 iso, PB 180; IAT: 2:08
• PDw TSE fs 2D tra; PM: FA 150, TE 39, TR 6730, ST 3, SBS 3.9, FOV 512, MS 320*160, PS 1.0 iso, PB: 150; IAT: 2:14
• DWI (with ADC): SPAIR epi b-value 0-800, 2D tra; PM: FA 90, TE 75, TR 5100, ST 10, SBS 10, FOV 1300/1173.25, MS 128*104, PS 3.125/2.96875 iso,
PB 1030; IAT: 2:32/3:01
MRI in module II: Brain and Pain
Brain (PP: HFS, supine):
• (turbo) FLASH 3D sag: T1 mpr; PM: FA 15, TE 4.75, TR 2100, ST 1, FOV 614.4, MS 240*256, PS 1.0 iso, PB130; IAT: 8:37
• T2w fs FLAIR 2D cor: TIRM; PM: FA 150, TE 120, TR 9000, TI 2500, ST 5, SBS 5.5, FOV, MS 288*384, PS 0.599 iso, PB 150; IAT: 4:43
• DWI (with ADC): SPAIR epi b-value 0-1000, 2D tra; PM: FA 90, TE 98, TR 3700, ST 5, SBS 6, FOV 529, MS 256*256, PS 0, 89844 iso, PB 1000; IAT: 0:49
functional MRI (fMRI) for pain perception: Epi 2d: epi2d_bold; PM: Fa 90, TE 60, TR 2600, ST 5, SBS 6, FOV, MS 384*384 (Start fMRI: 16*16), PS
3.59375, PB 2440; IAT: ~15:20 in total
MRI in module III: Cardiovascular System
Cardiac cine-MRI (PP: HFS, supine), IAT: ~25:00 in total
• Cine SSFP, 2D: GRE cine with retrospective 2d cardiac triggering; PM: FA 80, TE var, TR var, ST 6, SBS 6, FOV 1156/1089, MS 192*192/156, PS 1.771/
1.71875 iso, PB 930, IN: 30
• Phase contrast acquisition 2D; PM: venc 150, FA 30, TE 2.33var, TR 41.1var, ST 6, FOV, MS 180*192, PS 1.875 iso, PB 555, IN:25
• Cine-tagging SSFP, 2D: GRE cine with retrospective 2d cardiac triggering; PM: FA 20, TE var, TR var, ST 6, SBS 18, FOV 1073.25, MS 212*256, PS
1.40625 iso, PB 500, IN: 21
Vascular cine-MRI (PP: HFS, supine), IAT: ~25:00 var in total
• Carotid artery: FLASH 2D tra: T2*w gradient-spoiled GRE cine with prospective 2d cardiac triggering; PM: FA 15, TE ~5.45 var, TR ~34.75 var, ST 6,
FOV 289, MS 320 × 320, PS 0.53125 iso, PB 250, IN: 50/RR-cycle; IAT: ~5:30 var
• Femoral artery: FLASH 2D tra: see carotid artery; PM: FA 15, TE 5.00 var, TR 26.80 var, ST 6, FOV 768, MS 512 × 384, PS 0.625 iso, PB 250, IN: 50/
RR-cycle; IAT: ~4:20 var
• Aortic flow prox./dist.: FLASH 2D tra: PM: FA 20, TE 2.75 var, TR 11.55 var, ST 5, FOV 768, MS 256*192, PS 1.25 iso, PB 590, IN: 100; IAT: ~4:10
MRI in module IV: Morphometry, Body Composition
whole body MRI (PP: HFP/FFP, prone): T1w TSE 2D tra; PM: FA 180, TE 12, TR 490, ST 10, SBS 20, FOV 1991, MS 256*196, PS 1.9922 iso, PB 120, IN:
90-120 var; IAT: appr. 20:00
MR spectroscopy (PP: FFS, supine) for evaluation of intramyocellular lipids (IMCL): Single-voxel STEAM, TE 20, TR 2000, voxel of interest 11 × 11 ×
20 mm3, 40 acq., IAT: appr. 10:00
Tra, transversal (axial); sag, sagittal; cor, coronal; Seq., sequence; ADC, apparent diffusion coefficient; bold, blood oxygenation level dependent contrast; DWI,
diffusion weighted imaging; epi, echo planar imaging; FLAIR, fluid-attenuated inversion recovery; FLASH, fast low angle shot; fs, fat saturated; GRE, gradient echo
seq.; IR, inversion recovery; mpr, MPRAGE (magnetization prepared rapid gradient echo); PDw, proton density weighting; SPAIR, spectral adiabatic inversion
recovery; SSFP, steady state free precision; STEAM, stimulated-echo acquisition mode; T1w, T1 contrast; T2w, T2 contrast; TIRM, turbo inversion recovery
magnitude; (T)SE, (turbo) spin echo; PM, parameters; parameter abbreviations: FA, flip angle (°); TE, time to echo (ms); TR, repetition time (ms); TI, inversion time
(ms); ST, slice thickness (mm), SBS, spacing between slices (mm); FOV, field of view (cm2); MS, matrix size (pixel); PS, pixel size (mm); PB, pixel bandwith; IN, image
number (n); var, variable dependency; venc, velocity encoded gradient echo imaging (cm/second); IAT, image acquisition time (min:second); PP, patient
positioning; HFS, head forward supine; FFS, feet forward supine; HFP, head forward prone; FFP, feet forward prone; cardiac triggering, ECG- gating.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 10 of 33
in 12 participants of the TEFR09 compared to age-
related normal volunteers (Figure 8C).
Cardiac cine MRI
For mobile cardiac cine MRI, a flexible six-channel body
matrix coil was used. Cine SSFP gradient echo sequences
with retrospective cardiac triggering were generated to
obtain plane short axis four-, three- and two-chamber
(Figure 9B) views of the heart. The mitral and aortic flow
(Figure 9D) was measured using phase contrast
sequences with 150 cm/second velocity encoded gradient
echo imaging (venc). This protocol ensured measurement
or secondary evaluation of parameters, such as ejection
fraction (%), end diastolic and systolic volume and, there-
fore, stroke volume (ml), cardiac output (L/minute),
myocardial mass (g) (Figure 9E), muscle volume of ven-
tricles (ml) (Figure 9A), and so on. MR tagging using a
Cine SSFP gradient echo sequence with retrospective
Figure 4 Mobile MRI of the feet. A: male, 39-years-old, stage 53, 3,669 km (fused colored T2* GRE map sagittal: syngo™ MapIt fusion
technique, Siemens Medical solutions, Erlangen, Germany): Colored visualization of focal water concentration in cartilage layers of the ankle joint
(1), subtalar joint (2), talonavicular joint (3) and calcneocuboid joint (4). B: male, 61-years-old, stage 23, 2,176 km (T2 TIRM sagittal): Multiple
running related signs of tissue alteration: Peritendinous fluid accumulation in tendon sheaths (1). Focal bone edema at insertion of plantar fascia
(2) with corresponding subcutaneous edema (3), but without plantar fasciitis. Edema in the Achilles tendon (4). Articular effusion in the ankle
joint (5). C: male, 59-years-old, stage 45, 3,082 km (T2 TIRM sagittal): Peritendinous fluid accumulation in tendon sheaths of foot dorsiflexors (1),
focal arthrosis of the ankle joint with subchondral bone edema (2), plantar subcutaneous edema (3), articular effusion in subtalar and
metatarsophalangeal joint (4). D: male, 54-years-old, stage 32, 2,176 km (T2 TIRM sagittal): Subcutaneous edema (1), arthrosis of midfoot joints (2).
E: male, 30-years-old, stage 12, 789 km (PDw TSE fs transversal): Peritendinous fluid accumulation in Achilles tendon sheath (1) with wide local
subcutaneous edema (2). F: female, 68-years old, stage 15, 1,003 km (PDw TSE fs transversal): Extensive plantar subcutaneous edema (1). G: male,
47-years-old, stage 52, 3,609 km (PDw TSE fs transversal): Severe arthrosis of midfoot joints (1) with perifocal bone edema (2), hallux valgus (3).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 11 of 33
Figure 5 Mobile MRI of the knees. Femoral condyle (1), tibial head (2), patella (3), retropetallar cartilage layer (4), ventral femoral cartilage layer (5),
dorsal femoral cartilage layer (6), tibial cartilage layer (7), medial meniscus (8), lateral meniscus (9), patellar tendon (10). A: female, 45-years-old, stage
44, 3,021 km (fused colored T2* GRE map: syngo™ MapIt fusion technique, A1: medial femorotibial joint sagittal, A2: lateral femorotibila joint sagittal,
A3: femoropatellar joint transversal). B: male, 25-years-old, before start of TEFR09 Cartilage layer segmentation (T2* GRE map: syngo™ MapIt). C: male,
43-years-old, stage 40, 2,738 km (PDw TSE fs, C1: sagittal, C2: coronal, C3: transversal): Severe arthrosis of the patellofemoral joint with retropatellar
cartilage defects (4, 5) and wide subchondral bone edema of the patella (3), intrachondral signal alterations of the femoral (6) and tibial (7) cartilage
layers. D: male, 26-years-old, stage 40, 2,738 km (PDw TSE fs coronal): Nondescript cartilage layers of femorotibial joint.
Figure 6 Mobile MRI of pelvis region and hip joints. A: male, 45-years-old, stage 8, 511 km (PDw TSE fs coronal): Massive edema and (peri-)
myositis of right proximal quadriceps muscle (1). B: female, 46-years-old, stage 48, 3,290 km (PDw TSE fs, B1: coronal, B2,3: transversal): Stress
fracture of left ventral pelvic ring (1: Ramus superior ossis pubis; 2: Ramus inferior ossis pubis) with perifocal soft tissue edema/inflammation (3).
C: male, 41-years old, stage 11, 739 km (T1 TSE coronal): Arthrosis of the left hip (1: acetabular sclerosis, 2: deformation and osteophyte of the
femoral head). D: male, 61-years-old, stage 38, 2601 km (PDw TSE fs transversal): Intraosseus edema in the right Ala ossis ileum (1) with massive
peri-osseal inflammation of the gluteal muscle origin (2).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 12 of 33
cardiac triggering in plane short axis four- and two-
chamber view (Table 2) made quantification of the myo-
cardial motion with its spatial orientation (Figure 9C)
possible.
Vascular cine MRI
For analysis of changes in the arterial aortic stiffness,
measurement of the central pulse wave velocity using
MRI is the gold standard [137]. With detection and
measurement of the proximal and distal aortic flow and
diameter using phase contrast acquisition with venc and
prospective two-dimensional cardiac triggering on mobile
MRI (Figure 10B, C), this and the central hemodynamic
changes (peak and mean shear rate differences) and their
influence on the vascular (aortic) diameter [100] during
the TEFR09 can be calculated. Additionally, T2 weighted
cine FLASH gradient echo sequences with prospective
two-dimensional cardiac triggering were generated
Figure 7 Mobile MRI of upper and lower legs. A: male, 49-years-old (coronal slices): A1: stage 12, 789 km, upper legs (PDw TSE fs): Subfascial
intermuscular fluid, superficial (1), deep peri-neural (2). Partial quadriceps tear (M. vastus intermedius: 3). A2: stage 19, 1,260 km, upper legs (PDw
TSE fs): Subfascial intermuscular fluid, superficial (1), deep peri-neural (2) and peri-vascular (3). Partial muscle edema of M. vastus intermedius (4).
Specific diffusion weight imaging (A3, same slice as A2) is a sensitive method for free water detection. A4: stage 19, 1,260 km, lower legs (T2
TIRM): Subfascial intermuscular (1) and epifascial subcutaneous edema (2) indicating soft tissue inflammation such as perimyositis and panniculitis
(shin splints), respectively. B: male, 31-years-old, B1: start, B2: stage 62, 6,358 km (PDw TSE fs transversal): Segmentation of muscle compartments
of upper leg for functional muscle volumetry. C: male, 53-years-old: C1: start, C2: stage 46, 3,161 km (T2 TIRM transversal): Segmentation of
muscle compartments of lower leg for functional muscle volumetry. Muscle edema in calf muscle (1).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 13 of 33
Figure 8 MRI of the brain. Male, 52-years-old. A1: stage 57, 3,971 km (T1w turbo FLASH 3D sagittal): High resolution isometric three-
dimensional sequence (1 mm) allows isovoxel based volumetry (VBM) of the whole brain. A2: Three-dimensional view shows dominant areas of
volume loss (colored) of grey brain matter occurring during the TEFR09. B: stage 36, 2,448 km (T2w FLAIR): Sensitive sequence for detection of
brain lesions. In this case, no lesions visible. C: 20 days before the start. Functional MRI (fMRI) using blood oxygenation level dependent (BOLD)
contrast for evaluation of pain perception in ultra runners (C1: without pain stimulus, C2: with pain stimulus). C3: Post-processing analysis using
statistical parametric mapping (SPM) shows areas of activation.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 14 of 33
(Table 2) to measure compliance changes of the vessel
wall of the distal common carotid (Figure 10A) and prox-
imal superficial femoral artery (Figure 10D). In total, for
vascular MRI three flexible six-channel body matrix coils
for aortic and femoral artery measurements, one four-
channel phased dual mode neck matrix coil and ECG
triggering makes positioning and preparation of the sub-
jects very time consuming.
Figure 9 Mobile cardiac cine-MRI. A: male, 52-years-old, stage 23, 1,569 km (cine SSFP GRE, 2-chamber view): Focus is the left ventricle (1),
myocardium (2). papillary muscles (3), right ventricle (4), lung (5), liver (6), left kidney (7), spleen (8), stomach (9). A2, A3: Specific post-processing
makes functional volumetry of left ventricle and myocardium possible (green line: epicardium, red line: endocardium). B: male, 52-years-old, stage
25, 1,706 km (cine SSFP GRE, 3-chamber view): left ventricle (1), myocardium (2), papillary muscles (3), left atrium (4), lung (5), mitral valve (6), aortic
valve (7), pulmonary vein (8), aorta (9), thoracic spine (10). C: male, 49-years-old, stage 26, 1,770 km (cine tagging SSFP GRE, four-chamber view): MR
tagging of the left ventricle (1) makes quantification of the myocardial (2) motion with its spatial orientation possible. D: female, 45-years-old, stage
38, 2,601 km (phase contrast transversal): Ascending aortic (1) flow is measured by specific velocity-encoded (venc) MR imaging. Descending aorta
(2), pulmonary artery (3), liver (4), lung (5). E: Selection of possible cardiac parameters measurable by cardiac cine-MRI.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 15 of 33
Whole body MRI
For total body MRI, change of subject positioning from
prone head forward to prone feet forward was necessary
during a T1 weighted turbo spin echo sequencing using
an adapted protocol developed on adipose and diabetic
volunteers [138] (Table 2). With topographic tissue seg-
mentation and mapping of the athlete’s body using a
fuzzy c-means algorithm according to Würslin et al.
[139] a simple and time-saving strategy for assessment
and standardization of the tissue distribution in the entire
body was possible. With additional manual adaption due
to the non-fasting condition of the subjects changes in
different lean and adipose body compartments could be
measured during the TEFR09 (Figure 11).
Figure 10 Mobile vascular cine-MRI: male, 52-years-old, stage 27, 1,838 km. A1: MR localizer sagittal, A2,3: FLASH transversal: Automatic
functional measurement of common right carotid artery diameter just below carotid bifurcation (1). Left carotid artery (2), right deep jugular
vein (3). B1: MR localizer, B2: phase contrast transversal: Ascending aortic (1) diameter and flow is measured by specific velocity-encoded (venc)
MR imaging. Descending aorta (2), pulmonary artery (3), lung (4). B3: graphic depiction of aortic pulsatile flow (ml/second). C1: MR localizer
coronal, C2: phase contrast transversal: Distal descending aortic (1) diameter and flow is measured by specific velocity-encoded (venc) MR
imaging just above the aortic bifurcation. Inferior vena cava (2), liver (3), intestines (4). D1: FLASH transversal: Functional measurement of
superficial right femoral artery diameter just below bifurcation (1), left femoral artery (2). D2: Manual diameter measurement (1), D3: Automatic
diameter measurement (1). Femoral veins (2).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 16 of 33
Figure 11 Semiautomatic tissue separation with mobile whole body MRI of a 32-year-old male finisher of the TEFR09. A: Right row
(before start): green: total lean tissue, red: somatic adipose soft tissue, yellow: visceral adipose tissue, blue: adipose bone marrow. Left row (after
4,120 km): green: total lean tissue, red: somatic adipose tissue (= somatic adipose soft tissue + adipose bone marrow), yellow: visceral adipose
tissue. (selected slices: I: ankles, II: middle of lower legs, III: knees, IV: middle of upper legs, V: hip/pelvis, VI: umbilical level, VII: upper abdomen,
VIII: heart/mediastinum, IX: shoulder girth, X: elbows). B: Right row (before start): green: somatic lean tissue, red: somatic adipose tissue, grey:
total visceral volume. Left row (after 4,120 km): green: total lean tissue, red: somatic adipose tissue (= somatic adipose soft tissue + adipose bone
marrow), yellow: visceral adipose tissue, blue: intraluminal nutrition fat in intestinal tract. (selected slices: V: hip/pelvis, VI: umbilical level, VII: upper
abdomen, VIII: heart/mediastinum). C: Loss of total lean and total adipose tissue during the TEFR09.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 17 of 33
MR-spectroscopy
Proton MR-spectroscopy with a flexible six-channel body
matrix coil for measurement of the intramyocellular lipid
(IMCL) content of the tibialis anterior and soleus muscle
required the stimulated-echo acquisition mode (STEAM)
technique (Table 2) and manual shimming of the magnetic
field [140], which makes generation of valuable results on
a mobile MRI difficult and unpredictable (Figure 12).
Focused supplementary sequences
In addition to the mentioned study protocol, additional
MR examinations were done on subjects and TEFR par-
ticipants, if acute injuries (for example, stress fractures
[52]) and pain syndromes (for example, low back pain
[49,52]) occurred and a specific diagnostic finding was
necessary to prevent further injuries or complications
on the endurance runners (Figure 13).
Anthropometric and cardiovascular physical
measurements
Anthropometric and cardiovascular physical measure-
ments were done on all subjects (Figure 3) every fourth
day. Therefore, the 44 subjects were randomly assigned
to one of four groups. Body mass was measured with
BIA using a Tanita BC-545™ BIA scale (Arlington
Heights, IL, USA: to the nearest 0.1 kg). This balance
gave additional results about percentage of body fat and
lean body mass based on MR validated calculation pro-
cedures [141]. The measurements took place in the
morning (between 4 a.m. and 5 a.m.) and after the stage
(between 3 p.m. and 9 p.m.) together with measurement
of blood pressure and body temperature (T) using an
infrared ear thermometer (ThermoScan IRT 4020 ™,
Braun, Germany: to the nearest 0.2°C. After the stage
between 3 p.m. and 9 p.m., the skinfold (SF) thickness
of the same subjects was measured using a skinfold cali-
per (GPM ™, Silber and Hegner, Zurich, Switzerland: to
the nearest 2 mm) and their segmental body circumfer-
ence (CF) was measured using a retractable measuring
tape (to the nearest 1 mm). For SF, the mean value was
calculated from three consecutive intra-individual mea-
surements at eight regions on the right side of the body
according to Ball et al. [142]: chest, midaxillary (verti-
cal), triceps, subscapular, abdominal (vertical), suprailiac
(at anterior axillary), thigh, and calf. For CF, mean value
was calculated from three consecutive intra-individual
measurements at six regions on the right side of the
body according to Lee et al. [143]: upper arm (largest
part of the limb), waist, hip, thigh (10 cm/20 cm above
upper patella pole), and calf (largest part of the limb).
Figure 12 Mobile MRI H1-spectroscopy.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 18 of 33
To avoid inter-observer error all the anthropometric
measurements were done by the same, specifically
trained investigator. Every 800 km a short term ECG
was planned on every subject.
Lab samples
Midstream urine samples were taken from all subjects
twice each day. Before breakfast in the morning between
4:00 a.m. and 5:00 a.m. and after each stage in the eve-
ning after dinner between 7:00 p.m. and 9:00 p.m. Blood
samples were taken every 1,000 km from the cubital
vein after stage. The samples were immediately centri-
fuged and frozen (below -20°C) and put on -80°C after
the race.
Post-race/follow-up
On the day they dropped out, non-finishers (NF) had a
last complete measurement of all specific MRI protocols
and physical examinations (BIA, SF, CF) and provided
blood- and urine-samples. Nearly eight months after the
TEFR09, 15 of the 44 subjects (all of them finishers of
the TEFR09) had a follow up examination at UHU on
the same topics involved during the field studies: speci-
fic MRI examinations, anthropometric measurements,
ECG and blood and urine samples.
Statistical analysis
For statistical analysis the software ‘SPSS 12.OG for
Windows, Version 12.0.1’ was used. Data are presented
as mean (SD, range) and median (IQR) as appropriate.
The coefficient of variation (CV (%) = 100*SD/mean)
was calculated only for measured absolute data on per-
formance. The stage severity index (SSI) is an indirect
parameter calculated from the mean stage velocity of all
runners without a severe handicap v;¯ STAGE* in relation
to the total mean velocity of the whole race v;¯ TEFR*.
Therefore, the SSI represents the relative burden of each
stage, which is dependent on the mentioned multiple
external factors that changed daily. It reflects the sum of
daily weather and route conditions:
SSI = vSTAGE
vSTAGE*
vTEFR*
*: values are only integrated in calculation, if the stage
performance of the specific runner is more than 87% of
his mean race performance
Results
Race conditions
The mean stage length was 70.1 km (SD 11.8 km, range
44 to 95.1 km) and influenced the SSI positively (Figure
14). Temperature and humidity were also factors influ-
encing the SSI and showed a mean (mean of three daily
measures at 6:00 a.m., 10:00 a.m. and 2:00 p.m.) of 15.2°
C (SD 4.7°C, range 3.7 to 25.1°C) and 55.6% (SD 14.3,
range 26.5% to 82.7%), respectively. Altitude differences
were not measured. The longest stages occurred in the
last third of the race and the coldest, wettest and most
humid and, therefore, most severe stages, were at end of
the TEFR09 which pushed the runners to their limits
(Figure 14).
Changes of study plan due to hazards in TEFR
For every research topic, distance intervals of measure-
ment (MI) throughout the TEFR09 were defined. The
discrepancies between these planned and the realized
MI can be shown as mean absolute deviations (Figure
15). For MRI, data showed mean deviations between
100 and 300 km. For MR spectroscopy it raised up to
400 km, because this special MR technique was highly
dependent on the locations with their local magnetic
field disturbances (such as, traffic and so on). However,
reasons for the deviations were multifold.
Study staff had to deal with many influencing factors,
which made daily adaptation of the research plan neces-
sary: acute or chronic illness of study staff, bad weather
conditions (Figure 14) which sometimes influenced
operability of the mobile MRI, accidents and technical
problems (Table 3) and local situations at stage destina-
tion which sometimes made a nearby commissioning of
the mobile MRI difficult. However, the strongest influ-
ence forcing the staff to change and adapt the daily
research work program was the athlete with more or
less daily changes in mental and physical conditions and
necessities: pain, fatigue, fears, doubts, illness, nutrition
time schedules and specific behavior and rituals regard-
ing regeneration from this immense physical and psy-
chological stress. Therefore, it was not always possible
to ensure the exact time of pre- and post-race measure-
ments. Despite these uncertainties, 95% of the measure-
ment protocol could be followed.
Figure 16 shows all performed examinations and mea-
surements done before, during and six months after the
TEFR09. The overall work load includes: 741 MRI proto-
cols with 2,637 MRI sequences (more than 200,000 pic-
ture data), 5,600 urine samples, 1,018 BIA-, 539 SF- and
CF-measurements, 250 blood samples and 205 ECGs.
Baseline characteristics and performances of subjects
The baseline characteristics of the study groups are
summarized in Table 3. Age and gender did not differ
between the two MR groups. None of the 44 subjects
showed different AROM of the hip and knee or any
functional or anatomical mal-alignment of the legs com-
pared to normal values or between the MR groups.
Only active hip extension shows a tendency to be better
in endurance runners (Table 4).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 19 of 33
Regarding the ratio of F and NF there is no relevant
difference between subject group and the whole starter
group (Table 5, Figure 17), but randomly between the
MR groups (Table 4). Reasons for dropping out of the
race were multifold (Table 5, Figure 17). The main rea-
sons for premature exiting the race were overuse syn-
dromes of the soft tissues of the leg, resulting in (peri-)
myotendinous inflammations in the lower and upper
legs (71.4%). Two subjects suffered a stress fracture in
the third part of the race, one high tibia fracture (male,
60 years old) and one ventral pelvic fracture (female, 46
years old). Due to the unspecific pain and the high pain
level, they ran with these fractures for about 200 km to
240 km before they gave up. There was one case of a
rapidly ascending soft tissue abscess of the upper extre-
mity due to an initially minor finger lesion (male, 39
years old) indicating the immense burden of the ultra-
endurance performance to the runners and their immu-
nological system.
Performances
Regarding all participants, the mean speed per stage was
8.35 km/hour (SD = 0.32; CV = 3.8%) and the mean total
race speed of all finishers was 8.25 km/hour (SD = 1.4,
Figure 13 Supplementary mobile MRI examinations during the TEFR09. A: male, 61-years-old, stage 38, 2,601 km (PDw TSE fs, A1: coronal,
A2: sagittal): Stress fracture of the proximal tibia (1) with perifocal bone edema (2) and focal subcutaneous edema (3). B: male, 49-years old,
stage 52, 3,609 km (PDw TSE fs, B1: sagittal, B2: transversal): Retropatellar chondral ulcer (1) leading to bleeding/hematoma of the patellar bone
(2). C: male, 41-years-old, stage 13, 857 km (PDw TSE fs transversal): Massive subcutaneous edema (panniculitis: 1) with focal myositis of deep
flectors (2) and tenosynovitis of Achilles tendon (3).
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 20 of 33
CV = 17.1%). Finishers invested 552 hours (SD = 91, CV =
16.5%) for the 4,486 km in total. There was a wide range
of performance difference between the best and slowest
runner throughout the whole race, independent of the
stage severity (Figure 18). The best runner (male, 28 years
old) performed the race with a mean speed of 11.9 km/
hour (total running time: 378 hours), nearly twice as fast
as the slowest runner (female, 58 years old), with a mean
speed of 6.2 km/hour (total running time: 723 hours. In
the subject group, mean speed per stage was 8.28 km/hour
(SD = 0.33; CV = 3.9%) and the mean total race speed of
the subject finishers was 8.25 km/hour (SD = 1.3, CV =
15.3%), ranging from 11.1 km/hour (male, 26 years old,
total running time: 407 hours, second rank) to 6.5 km/
hour (male, 63 years old, total running time: 696.4 hours,
45th rank). Subjects mean stage speed was on average 8.32
km/hour (SD = 0.33, CV = 3.9%). Figure 18 shows mean
performances in total and per stage.
Figure 14 Daily profile of weather and stage conditions during the entire TEFR09.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 21 of 33
Discussion
History
Looking at transcontinental footrace history, the finisher
rate ranges from 28% to 73% (Table 1). The Bunion
Derbies of the early twentieth century showed the lowest
rate due to lower standards regarding sports equipment,
nutrition features, endurance-associated behavioral
knowledge and the level of organization. These two
Derbies had 150 starters in mean, much more than
nowadays, indicating a high rate of rookies with little or
no experience in ultra running. In the TEFR09, 31% of
the participants (32% of the subjects) did not reach the
finish line (Table 5, Figure 17). This is 18% more fin-
ishers than at the TEFR03. This could be attributed to
the longer distance in 2003 (+540 km) from Lisbon to
Moscow, implying a mean difference of 8.3 km per stage
between the TEFR09 and the TEFR03. Apart from the
TEFR03, running distances of modern transcontinental
footraces (1992 to 2009) were approximately equally long
and the finishing rate of 68% in the TEFR09 lies in the
upper range of the published data (Table 1). Looking at
the rate of participation, being more than 200% higher
Figure 15 Deviation of measurements from projected intervals [km] during TEFR09.
Table 3 Relevant accidents and damage to MRI and vehicles during the TEFR project
No.
stage
location
(Figure 1)
event
(Figure 3)
MR down
time
1
0
Bari, Southern Italy
Defect of MRI table.
24 hours
2
12
Lugo to Alberone, Northern Italy
Truck collision on bridge over the river Po.
-
3
33
Bad Segeberg, Nothern Germany
Roof damage on MRI trailer.
-
4
36
Göteborg to Sjövik, Southern
Sweden
Total system breakdown, damage of one compressor.
16 hours
5
38
Kristinehamn, Central Sweden
Truck sunken in football sand-field.
5 hours
6
45
Hackas, Central Sweden
Severe ankle fracture of MRI assistant.
16 hours
7
56
Svapparaava, Northern Sweden
Total rupture of tractor to trailer cables.
2 hours
8
after
race
nearby Gällivare, Northern Sweden
Reindeer collision on the way back from North Cape: total damage of material
van.
-
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 22 of 33
than the mean starter rate of all modern transcontinental
footraces, the comparably high finishing rate indicates a
professional organization and preparation of both the
runners and organizers of the TEFR09.
Performance
Due to the diverse ways and possibilities to exercise long
distance running (that is, area, length, altitude, distance,
weather, indoor/outdoor, on/off-road, looped course,
combinations with other disciplines and so on), it is
extremely difficult to compare the performances of ultra
athletes in the literature [107,108,145]. Regarding the
present literature, an abundant variety of physiological,
anthropometrical, pre-race and training variables seem to
influence running performance and associated injuries,
depending upon the length and duration of the races
[146-150]. In MSUM, such as the TEFR09, the daily
changing environmental conditions have a direct influ-
ence on stage performances. In the last days of the
TEFR09 weather conditions became more and more diffi-
cult towards the destination, North Cape, leading to a
marked decrease of mean running speed (Figure 18).
Only their indomitable will not to drop out at the end of
race after more than 4,000 km of running, kept many
emaciated participants in the race.
Drop out and injuries
Due to the likely multifactorial nature of running inju-
ries, very few firm conclusions can be made based on
the existing studies. In general, there are intrinsic factors
such as individual biomechanical abnormalities (that is,
mal-alignments, muscle imbalance, stiffness, weakness,
instability) or extrinsic (mostly avoidable) factors such
as poor running technique, improper equipment and
improper changes in training extent and mode or dura-
tion and frequency of the race burden contributing to
overuse injuries [151]. The one year prevalence of run-
ning injuries is 55% in male marathon runners; limb
overuse injuries are the most common [152]. In UM
these entities become much more important. The most
common injuries for runners are multiply cited in the
literature: anterior knee pain (for example, patella-
femoral syndrome), iliotibial band friction syndrome,
tibial stress syndrome (shin splint/injuries), plantar
Figure 16 Realized clinical and MRI-measurements on all subjects during TEFR09.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 23 of 33
fasciitis, Achilles tendonitis and meniscal injuries of the
knee [152-156].
Approximately two thirds of NF dropped out of the race
in the first half of the TEFR09 (Figure 17). As our results
show, the reasons for premature resignation of subjects
were different. Conforming to the literature [20,22], in
more than two thirds of the cases, overuse injuries of the
lower and upper limb were the most common reasons
(Table 5). However, these soft tissue overuse injuries
occurred not only in less experienced ultra runners, but
also in runners who had already successfully finished
transcontinental races such as the TEFR03 or the ‘Run
Across America’. There were only a few subjects and run-
ners without any overuse problems of the limbs in these
64 days. However, not every soft tissue overuse inflamma-
tion leads to the cessation of running. Most runners were
able to ‘overrun’ these specific problems. They reduced
running speed in adaptation to their problems, used topi-
cal application of anti-inflammatory medication and some
of them took non-steroidal anti-inflammatory drugs for a
Table 4 Baseline characteristics of the TEFR study population
all subjects
MR group 1
MR group 2
number (%)
number (%)
number (%)
total
44
22 (50.0)
22 (50)
men
40 (90.9)
20 (90.9)
20 (90.9)
women
4 (9.1)
2 (9.1)
2 (9.1)
Finisher (F)
30 (68.2)
19 (86.4)
11 (50.0)
Non-finisher (NF)
14 (31.8)
3 (13.6)
11 (50.0)
mean/median (SD)
mean/median (SD)
mean/median (SD)
age (years)
49.7 (10.5)
50.3 (9.6)
49.1 (11.5)
prerace history:
years of regular endurance running
17.9 (7.5)
19.1 (7.5)
17.1 (7.4)
finished marathons
91.7 (168.6)
62.0 (93.4)
121.47 (218.8)
finished ultra-marathons
85.4 (63.6)
81.1 (59.0)
89.8 (69.0)
finished multistage ultra-marathons
5.7 (3.6)
5.1 (4.1)
6.3 (2.9)
anthropometry:
height (cm)
175 (8)
175 (6)
174 (9)
BMI (kg/m2)
23.1 (2.2)
22.8 (1.8)
23.4 (2.6)
body fat percentage, BIA (%)
11.2 (4.3)
11.0 (4.1)
11.4 (4.5)
body fat percentage, calculateda (%)
16.6 (4.2)
15.5 (3.2)
16.6 (5.0)
body fat percentage, MRI (%)
-
-
22.7 (6.0)
muscle percentage, calculatedb (%)
49.8 (5.1)
49.7 (4.7)
50.0 (5.7)
somatic lean tissue, MRI (%)
-
-
65.0 (5.3)
active range of hip motion (°)
flexion, 121 (26)c
123 (27)
122 (26)
124 (27)
extension, 19 (16)c
24 (17)
25 (17)
21 (16)
abduction, 42 (22)c
43 (23)
43 (22)
42 (24)
internal rotation, 31 (16)c
31 (16)
30 (16)
32 (16)
external rotation, 32 (18)c
34 (19)
33 (18)
34 (19)
active range of knee motion (°):
flexion, 132 (20)c
134 (19)
135 (20)
133 (19)
lower limb alignment:
-
-
LL difference [mm], 6 (95th: 11)d
2 (3.3), 95th: 9)
FTR, 1.26 (0.05)d
1.17 (0.04)
FTA [°], m: 178 (174-182)e
178 (175-182)
w: 181 (177-185)e
FTA difference
1 (0.8)
MAD (mm), 10 (4-16)e
10 (4-17)
acalculated by the updated DC (DEXA criterion)-equation according to Ball et al. [142], inputs: age, 7SF (chest, midaxillary, triceps, subscapular, abdomen,
suprailiac, thigh); bcalculated estimation of skeletal muscle mass according to Lee et al. [143], inputs: gender, age, race, height, 3 SF and CF (upper arm, thigh,
calf); cnormal AROM-values of hip and knee joints (goniometric data) according to the 1st National Health and Nutrition Examination Survey (NHANES I) [144];
dnormal values of side differences in the lower limb [119], generated with computed tomography gold standard method [117]. FTR: femoro-tibial length-ratio.
Leg length (LL) differences of > 14 mm (3SD) are seen as pathological [122,119,118]; enormal values of femorotibial angle (FTA) and mean axis distance (MAD)
[116,120,121]
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 24 of 33
few days. With adequate behavior many, but not all, ath-
letes recovered and were able to continue the race. Pre-
sumably some athletes could handle more pain than
others [20]. An example is one extreme runner, an experi-
enced 49-year-old male subject, who had multiple severe
overuse-induced soft tissue inflammations with local mus-
cle fiber rupture forcing him to frequently slow down his
speed (Figure 7A). He also showed signs of exertional
compartment syndrome, but did finish the TEFR09. His
ordeal at the TEFR09 is reflected by the red line in Figure
18. Contrary to other reports, Achilles tendonitis or lower
limb joint problems were not a reason for subjects to stop
the TEFR09. Further results of module II research topics
such as specific personality, temperament, character and
pain perception will be presented soon.
Statement of principal findings
The relevance of results in field studies is determined by
the appropriateness of the research questions and hypoth-
eses, by the practicability of methods and measurements
and the consistency of their specific implementation and
by the correct interpretation of results. Due to the mani-
fold open questions and unproven hypotheses in endur-
ance running, the unique opportunity of doing real time
observations of changes in the body of athletes while run-
ning at the upper limit in a MSUM was demanding.
Table 5 Reason for not-finishing the TEFR09
affected region
pathology
subjects
(number = 14,
31.8%)
all
(number = 21, 31.3%)
Soft tissues of legs:
10 (71.4%)
14 (66.7%)
lower legs:
shin splint: myofasciitis, tenditis
5 (35.7%)
7 (33.3%)
Achillodynia
-
1 (4.8%)
upper legs:
myo-tendino-fasciitis, perineuritis
5 (35.7%)
6 (28.6%)
Bone/joint of lower body:
stress fractures: tibia, pelvis
2 (14.3%)
2 (9.5%)
bunion (arthritis)
1 (7.1%)
1 (4.8%)
Upper extremities:
Phlegmon of the hand
1 (7.1%)
1 (4.8%)
Gastrointestinal (GIT):
upper GIT-bleeding (NSAID)
-
1 (4.8%)
GIT infection
-
1 (4.8%)
Mental problems:
Intolerance of crowded small halls at night
-
1 (4.8%)
GIT, gastrointestinal tract; NSAID, non-steroidal anti-inflammatory drug.
Figure 17 Drop-out rate of TEFR09.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 25 of 33
The TEFR project was designed to explore inter-indi-
vidual variability in adaption to the tremendous persist-
ing physical endurance running load on the different
organic and functional systems of the body with regard
to the lack of breaks and time for regeneration.
All technical equipment was tested by the specific man-
ufacturers on reliability and validity under normal clinical
conditions and usage. But daily dismantling, transport
and setting up of the mobile MRI hardware sets extraor-
dinary demands which were initially not totally verifiable
and calculable. Despite some technical problems and
temporal defects (Table 3), our arrival at the North Cape
demonstrated the feasibility of accompanying a large
group of endurance runners (67) with a mobile MRI and
all its necessary equipment ensuring permanent operabil-
ity during the 64 stage ultra marathon.
Throughout the whole TEFR09 our time schedules for
examinations adapted to the daily changing local circum-
stances and the athletes mental state and problems. To
avoid additional stress for the subjects, they could not and
were not forced to follow the study protocol strictly. How-
ever, the efficiency of this strategy was reflected in the
high rate of compliance (98%) until the end of the
TEFR09. Only one subject who finished the race left the
study at stage 36 (km 2,448) due to personal and, expli-
citly, not study related problems. Consequently, the com-
pletion rate of planned examinations over the whole
running distance of 4,486 km was only limited by the
drop-out rate of the subjects from the TEFR09 (Table 4,
Figure 16). In particular, specific implementation of sta-
tionary validated MRI protocols on the mobile MRI on the
truck trailer by a team of MRI experts and training of the
research staff on the mobile MRI before the start ensures
practical experience with the experimental protocols
under field conditions and makes modification of them
possible where necessary.
Strengths of the study
The strengths of the TEFR project are the unique
chance to do a field study with the large number of 44
subjects, the realization of tests and measurements with
the modern technical gold-standard equipment MRI in
a daily changing and increasingly harsh and inhospitable
environment (Figure 14), the complete baseline control
data and the high rate of test completion. Large subject
numbers provide the statistical power to discriminate
between and, identify associations with, different pat-
terns of adaptation as well as to detect differences in
response between subgroups. Matched subject race pro-
files and baseline measurements before the start of the
TEFR09 control for variability of exposure to ascending
running distance and, thereby, permit valid inter-indivi-
dual comparison of responses to this burden (with sub-
jects as their own controls), maximizing the signal (true
physiological differences) to noise (variations in expo-
sure) ratio.
Figure 18 TEFR09 performances.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 26 of 33
The avoidance of invasive or interventional tests on
the subjects’ mechanisms during the TEFR09 and the
descriptive nature of the data may be considered a
weakness of this study. However, the variety of outputs
from different measurement techniques (for example,
functional and cine MRI, physical anthropometrical
measurements and laboratory data including proteomics,
plasma and urine biomarkers) allows observation of con-
sistent patterns of response that may be strongly sugges-
tive of particular mechanisms.
In module I, for example, measured data of T2*-map-
ping of joint cartilage (Figure 4 A and 4.2A/B) will allow
conclusions on the influence of long distance running on
the proteoglycans in the cartilage matrix based on the cur-
rent experimental experiences [43-45,157]. As in most
other mobile MR associated examinations of other mod-
ules, additional laboratory analyses using specific para-
meters on collected blood and urine samples (for example,
cartilage oligomeric matrix protein (COMP) [158-165] for
joint cartilage research) will give further information for
interpretation and verification of image related results.
Another example is the vascular cine MRI studies of
module III. In humans, the relationships of blood flow
changes to structure, function, and shear rate of conduct-
ing arteries have not been thoroughly examined. There-
fore, the purpose of the vascular cine MRI study in
module III (Figure 10) was to investigate these para-
meters of the elastic-type, common carotid artery (CCA)
and the muscular-type, common femoral artery (CFA) in
long-term running, assuming that the impact of activity-
induced blood flow changes on conduit arteries, if any,
should be seen in these highly endurance-trained ath-
letes. These investigations using the gold standard
method, MRI [137], enable further analyses on the cur-
rent status of insights on the question of structural and
functional vascular adaption and associated exercise-
induced blood flow changes on endurance training based
on sonographic B-mode measurements [100].
The manifold investigations of Knechtle et al. on ultra
endurance athletes [15-22,113,145] focused on the ques-
tion which anthropometric parameters of ultra athletes
are predictors of ultra endurance performance. These
authors postulated some direct connections between spe-
cific physical anthropometric markers and ultra endur-
ance performance [16,19,166]. Examinations of module I
and module IV (morphometry, body composition) of the
TEFR project with its possibility of precise and differen-
tiated morphometric analysis (for example, segmental
and functional muscle volumetry) may be able to verify
common experiences and to detect relationships between
anthropometry and morphometry of endurance athletes
and performance in MSUM.
All tissue systems - subcutaneous and visceral adipose
tissues, muscles, ligaments, fascia, tendons, bones and
cartilage - were studied with special quantitative and quali-
tative MR techniques. This should help explain how the
different tissues react to the severe stress that continued
for days and weeks without any pauses for regeneration or
even resting phases as two marathon distances had to be
completed every day.
Individual performance and ability to deal with injuries
and overuse symptoms with regard to decision making
for stopping MSUM is a complex psychosomatic process
and more or less modulated by character traits. Strong
changes of endocrine and metabolic status during mara-
thon runs are described [78,79]. Hormonal changes can
influence pain sensation and show an influence on speci-
fic brain functions [167]. Knowing this, investigations
detecting reasons for dropping out of the race (14 sub-
jects) can focus not only on MR image analysis, but must
also include specific laboratory analysis and psychometric
tests as done or planned in the TEFR project. Serotonin,
tryptophan and endorphin are described for use as stress
markers in UM [3]. The relation of branched-chain to
aromatic amino acids as a model (amino acid dysbalance
hypothesis) to explain running-associated fatigue is
described [80]. The reduction of the pain sensation is
known for cortisol [167]. Considering all these particular
mechanisms influencing performance and decision mak-
ing in ultra athletes, the important dimension of labora-
tory analysis possibilities, in addition to MR data analysis,
becomes obvious for the different parts of the TEFR
project.
Overall, the possibility of cross-validations between phy-
sical, MR-graphic, -functional and laboratory follow-up
data on multiple organic systems during a nearly ten-week
ultra run is a unique strength of this study.
Weakness of the study
The main weakness of this study is the lack of a control
group of non endurance experienced subjects. However,
this is not a feasible option in field studies under race con-
ditions including such an immense amount of physical
and mental load. In order to explore the influence of pre-
race running experience, we will undertake subgroup ana-
lyses investigating the influence of individual pre-race per-
formances on our findings. In the pre-race pain study
(project module II, MR group 2), we recruited a parallel
age-related control group that was tested over the same
pain scale and functional MRI protocol as the MSUM
exposed subjects. This sub-group is, therefore, not con-
founded by self-selection due to prior endurance
tolerance.
As the first attempt in MR research, we tried to per-
form H1-MR-spectroscopy for measurement of IMCL
[140,168,169] with a mobile MRI on a truck trailer. MR
spectroscopy needs a stable magnetic field and, there-
fore, a still and static environment around the scanner.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 27 of 33
Due to the daily changing position of the mobile MRI,
the possibility and feasibility of manual shimming was
not predictable. This is the only measurement with
uncertain validity due to changing environmental condi-
tions in the TEFR project.
Environmental factors, such as ambient weather condi-
tions (Figure 14), subject de- or hyperhydration and con-
current illnesses may also have confounded results.
However, indoor temperature (18.7°C, SD 3.0°C, range
11.7 to 28.5°C) and temperature in the MR trailer (20.5°C,
SD 0.8°C, range 18.5 to 21.8°C) was much less variable
than outdoor temperature (15.2°C, SD 4.7°C, range 3.7 to
25.1°C). All subjects were encouraged to maintain
adequate
hydration (guided by the production of good quanti-
ties of pale urine). There was only one Japanese subject
identified with a severe illness during the race, suffering
from a severe cough which persisted from stage 12 till
stage 32 (day of drop out).
Another weakness of the study was that there was only
rough documentation of nutrition. Nutrition depended on
food availability at the TEFR stages and was provided by
the TEFR organization. The use of doping substances was
forbidden by the terms of participation but not controlled.
Runners did not agree to close measurement and docu-
mentation of food and caloric intake, because this would
have meant too much disturbance of their daily running
routine and compromised compliance due to additional
stress conducted by the research work. Despite initial con-
cerns, mobile MRI examinations did not result in addi-
tional stress for the athletes. On the contrary, most of
them enjoyed relaxing in the MR scanner, having no other
noises and people around them while listening to their
favorite music via headphones.
Strengths and weakness in relation to other studies
In comparison to previous field, laboratory and radiologi-
cal, especially stationary MR studies focusing on long dis-
tance running and its effects on the human body, our
study is unique in several aspects: ultra-long distance run-
ning without any day of rest, cohort size of subjects and
use of a mobile MRI throughout the whole race. This is
the first MR-based follow-up ultra marathon field study
that ensures unique data based on repeated measurements
on ascending distance burden.
We explored the possibility of conducting this study with
a stationary MRI in a fixed local setting. However, this is
not realizable with a large cohort size, because not many
ultra endurance athletes took the challenge to run ultra
long distances in circles in local regions or stadiums day by
day. For example, at the Sri Chinmoy Self-Transcendence
3,100 Mile Race over 5,649 laps of one extended city block
in Jamaica, Queens, New York (http://www.3100.srichin-
moyraces.org) only 10 to 14 participants started regularly.
If a study like this is planned, it has to be adapted to the
race circumstances and not the race conditions to the
study. Only exceptional runners would be willing to take
such a burden under laboratory conditions. It is the experi-
ence of the distance and the environment that motivates
these athletes to run thousands of kilometers. In addition,
such an approach might have incurred significant addi-
tional costs; our subjects were entirely self-funded, whereas
volunteers in chamber studies often expect remuneration.
Unanswered questions and future research
Further research arising from this study will follow two
themes. First, studies in patients to explore the validity
of our model by applying the findings of this study to
pathophysiological problems in a clinical setting. Sec-
ond, collecting additional healthy volunteer data from
subjects exposed to an ultra endurance burden (ultra
marathon, ultra triathlon, ultra cycling and) in further
field studies and chamber studies.
Whether it is possible to initiate future projects using
this model of a mobile MRI field study is critical. First,
this was a unique cohort size in transcontinental ultra
running and it would be difficult to find a size like this
again: the latest Run Across America (Table 1) had only
14 participants. Second, in addition to sufficient funding
a bit of luck is necessary to finish a field study success-
fully when using a sensitive and high-maintenance tech-
nical piece of equipment such as a mobile MRI. Future
studies might answer additional questions by using
alternative or additional measurement techniques or
undertaking novel intervention trials.
Conclusions
The TEFR project was both a challenge and risk together.
It demonstrates the feasibility and safety of conducting a
large ultra endurance cohort study with a mobile MRI
under ‘natural’ conditions over 64 stages and daily chan-
ging environment on the way across all of Europe.
Thanks to the possibility offered by a modern mobile
MR-imager diverse research topics from different fields
of medicine could be implemented in the measurement
protocol to study human adaption to an ultra endurance
burden. Systematic measurements of a large set of vari-
ables were achieved with high-fidelity in 44 subjects and
up to 4,500 kilometers distance running. The resulting
dataset is a unique resource for the study of regeneration
and adaption in relation to a high impact ultra endurance
running burden which may improve specific or general
scientific understanding of responses to critical illness at
the limits of stress and strain of the human body.
Acknowledgements
Contributions to the study
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 28 of 33
The TransEurope FootRace 2009 Project is a research project coordinated by
the Department of Diagnostic and Interventional Radiology, University
Hospital of Ulm, Germany. The aim of the project is to conduct research into
ultra endurance running in order to improve understanding of regeneration
and adaption processes in different kind of tissues, organs and functional
body systems. The TEFR project research groups members all contributed to
the collection and analysis of data described in this paper.
Study funding sources
This project was mainly supported in part by the German Research
Association (DFG: ‘Deutsche Forschungsgemeinschaft’), under Grants SCHU
2514/1-1 and SCHU 2514/1-2. Other non-public funds were received from
Siemens Healthcare Ltd. and the Medical Faculty of the University of Ulm. All
funding was unrestricted. None of the funding bodies had any role in the
study design, data collection, data analysis, data interpretation, manuscript
preparation or decision to publish.
We cordially thank all endurance athletes who took part at this project.
Considering their immense physical and mental stress they showed an
extraordinary compliance every day of the TransEurope FootRace 2009.
Author details
1Department of Diagnostic and Interventional Radiology, University Hospital
of Ulm, Germany. 2Outpatient Rehabilitation Centre at University Hospital of
Ulm, Germany. 3Institute of Exercise and Health Sciences, Sports Medicine,
University of Basel, Switzerland. 4Health Center St. Gallen and Department of
General Practice, University Hospital of Zürich, Switzerland. 5Section on
Experimental Radiology, Department of Diagnostic and Interventional
Radiology, University Hospital of Tübingen, Germany. 6Siemens Healthcare,
Magnetic Resonance, Stuttgart, Germany. 7Main organizer and race director
TransEurope FootRace 2009, Horb, Germany.
Authors’ contributions
US contributed to the conception and design of the study, to the funding,
to the acquisition of data, the analysis of data, the interpretation of data and
drafted the manuscript. AST contributed to the conception and design of
the study, to the acquisition of data, and the analysis and interpretation of
data. BK contributed to the design of the study and the interpretation of
data. JM contributed to the design of the study, to specific MR sequence
protocols and to the analysis and interpretation of data. HW contributed to
the acquisition of data. ME contributed to the acquisition and analysis of
data. WF contributed to the conception of the study, to the acquisition of
data, the analysis of data and the interpretation of data. IS contributed to
the conception and to the acquisition of data. SG contributed to the
creation of specific MR sequence protocols. HB contributed to specific MR
sequence protocols. IS contributed to the conception of the study. HJB
contributed to the acquisition of data. CB contributed to the conception
and design of the study, to the acquisition of data and the analysis and
interpretation of data. All authors read and approved the final draft.
Cooperators and coworkers in data post processing and analysis are
permanently rising. At time of manuscript writing they are as follows: F.
Birklein, M. Breimhorst, DC. Cheng, J. Ellermann, S. Faust, S. Göd, L.
Heisterkamp, E. Kitzenmaier, K. König, S. König, TC. Mamisch, A. Reiner, D.
Schoss, C. Tassler, C. Trattnig, F. Weber, S. Wuchenauer, A. Wunderlich and C.
Würslin.
Authors’ information
Dr Uwe Schütz may also be contacted using his alternative email address:
uwe.schuetz@uniklinik-ulm.de
Competing interests
The authors declare that they have no competing interests.
Received: 16 May 2012 Accepted: 19 July 2012 Published: 19 July 2012
References
1.
Costill DL, Bowers R, Kammer WF: Skinfold estimates of body fat among
marathon runners. Med Sci Sports 1970, 2:93-95.
2.
Davies CTM, Thompson MW: Aerobic performance of female marathon
and male ultramarathon athletes. Eur J Appl Physiol 1979, 41:233-245.
3.
Tittel K, Wutscherk H: Anatomical and anthropometric fundamentals of
endurance. In Endurance in Sport. Edited by: Shephard RJ, Ästrand PO.
Oxford: Blackwell Scientific Publications; 1992:35-45.
4.
Svedenhag J, Sjödin B: Body-mass-modified running economy and step
length in elite male middle- and long-distance runners. Int J Sports Med
1994, 15:305-310.
5.
Speechly DP, Taylor SR, Rogers GG: Differences in ultra-endurance
exercise in performance-matched male and female runners. Med Sci
Sports Exerc 1996, 28:59-365.
6.
Hetland ML, Haarbo J, Christiansen C: Regional body composition
determined by dual-energy X-ray absorptiometry. Relation to training,
sex hormones, and serum lipids in male long-distance runners. Scand J
Med Sci Sports 1998, 8:102-108.
7.
Abe T, Kumagai K, Brechue WF: Fascicle length of leg muscles is greater
in sprinters than distance runners. Med Sci Sports Exerc 2000,
32:1125-1129.
8.
Hoffman MD: Anthropometric characteristics of ultramarathoners. Int J
Sports Med 2008, 29(19):808-811.
9.
Freund W, Billich C, Brambs HJ, Weber F, Schütz UHW: MRI changes of
Achilles tendon in experienced runners and beginners during training
and after (half-) marathon competition. Z Orthop Unfall 2011, 149:407-417.
10.
Davies CTM, Thompson MW: Physiological responses to prolonged
exercise in ultramarathon athletes. J Appl Physiol 1986, 61:611-617.
11.
Sharwood K, Collins M, Goedecke J, Wilson G, Noakes T: Weight changes,
sodium levels, and performance in the South African Ironman Triathlon.
Clin J Sport Med 2002, 12:391-399.
12.
Tomaszewski M, Charchar FJ, Przybycin M, Crawford L, Wallace AM, Gosek K,
Lowe GD, Zukowska-Szczechowska E, Grzeszczak W, Sattar N,
Dominiczak AF: Strikingly low circulating CRP concentrations in
ultramarathon runners independent of markers of adiposity: how low
can you go? Arterioscler Thromb Vasc Biol 2003, 23:1640-1644.
13.
Knechtle B, Wirth A, Knechtle P, Zimmermann K, Kohler G: Personal best
marathon performance is associated with performance in a 24-h run
and not anthropometry or training volume. Br J Sports Med 2009,
43(11):836-839.
14.
Knechtle B, Knechtle P, Rosemann T, Senn O: What is associated with race
performance in male 100-km ultra-marathoners - anthropometry,
training or marathon best time? J Sports Sci 2011, 23:1-7.
15.
Knechtle B, Bircher S: Changes in body composition during an extreme
endurance run. Praxis 2005, 94:371-377.
16.
Knechtle B, Knechtle P, Schulze I, Kohler G: Upper arm circumference is
associated with race performance in ultra-endurance runners. Br J Sports
Med 2008, 42:295-299.
17.
Knechtle B, Kohler G: Running 338 km within 5 days has no effect on
body mass and body fat but reduces skeletal muscle mass - the Isarrun
2006. J Sports Sci Med 2007, 6:401-407.
18.
Knechtle B, Duff B, Schulze I, Kohler G: The effects of running 1,200 km
within 17 days on body composition in a female ultrarunner-
Deutschlandlauf 2007. Res Sports Med 2008, 16:167-188.
19.
Knechtle B, Duff B, Welzel U, Kohler G: Body mass and circumference of
upper arm are associated with race performance in ultraendurance
runners in a multistage race–the Isarrun 2006. Res Q Exerc Sport 2009,
80:262-268.
20.
Knechtle B, Duff B, Schulze I, Rosemann T, Senn O: Anthropometry and
pre-race experience of finishers and nonfinishers in a multistage ultra-
endurance run–Deutschlandlauf 2007. Percept Mot Skills 2009,
109:105-118.
21.
Knechtle B, Wirth A, Knechtle P, Rosemann T: Training volume and
personal best time in marathon, not anthropometric parameters, are
associated with performance in male 100-km ultrarunners. J Strength
Cond Res 2010, 24:604-609.
22.
Knechtle B, Knechtle P, Rosemann T: Race performance in male mountain
ultra-marathoners: anthropometry or training? Percept Mot Skills 2010,
110:721-735.
23.
Knechtle B, Enggist A, Jehle T: Energy turnover at the Race across
America (RAAM): a case report. Int J Sports Med 2005, 26:499-503.
24.
Transeurope Footrace. [http://www.transeurope-footrace.org].
25.
Kastner CB: Bunion Derby: The 1928 Footrace Across America. 1 edition.
University of New Mexico Press; 2007.
26.
Williams G: C.C. Pyle’s Amazing Foot Race: The True Story of the 1928 Coast-
to-Coast Run Across America. Illustrated edition. Rodale Books; 2007.
27.
Griffis ML: Great American Bunion Derby. Eakin Press;, 1 2003.
28.
Lewis B: Running the Trans America Footrace: Trials and Triumphs of Life on
the Road. 1 edition. Stackpole Books; 1994.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 29 of 33
29.
Shapiro JE: Meditations from the Breakdown Lane: Running Across America
Houghton Mifflin Press; 1983.
30.
Schulze I: Transeuropalauf 2003. Lissabon - Moskau 5036 km in 64
Tagesetappen. 1 edition. Engelsdorfer Verlagsgesellschaft; 2004.
31.
Biermanski B: Der härteste Lauf der Welt: In 64 Tagen von Lissabon nach
Moskau (Trans Europa Lauf). 1 edition. Books on Demand GmbH; 2005.
32.
Schulze I: TransEurope-FootRace 2009: Bari - Nordkap - 4.487,7 km in 64
Tagesetappen. Engelsdorfer Verlag , 1 2010.
33.
Secker R: Running across countries Create Space; 2009.
34.
Knechtle B, Knechtle P, Schulze I, Kohler G: Vitamins, minerals and race
performance in ultra-endurance runners-Deutschlandlauf 2006. Asia Pac J
Clin Nutr 2008, 17:194-198.
35.
Knechtle B, Schulze I: Nutritional behaviours in ultra-endurance runners-
Deutschlandlauf 2006. Praxis (Bern 1994) 2008, 97:243-251.
36.
Shellock FG, Deutsch AL, Mink JH, Kerr R: Do asymptomatic marathon
runners have an increased prevalence of meniscal abnormalities? An MR
study of the knee in 23 volunteers. AJR Am J Roentgenol 1991,
157:1239-1241.
37.
Shellock FG, Mink JH: Knees of trained long-distance runners: MR
imaging before and after competition. Radiology 1991, 179:63.
38.
Hohmann E, Wörtler K, Imhoff A: MR imaging of the hip and knee before
and after marathon running. Am J Sports Med 2004, 32:55-9.
39.
Schueller-Weidekamm C, Schueller G, Uffmann M, Bader TR: Does
marathon running cause acute lesions of the knee? Evaluation with
magnetic resonance imaging. Eur Radiol 2006, 16:2179-2185.
40.
Krampla W, Mayrhofer R, Malcher J, Kristen KH, Urban M, Hruby W: MR
imaging of the knee in marathon runners before and after competition.
Skeletal Radiol 2001, 30:72-76.
41.
Cymet TC, Sinkov V: Does long-distance running cause osteoarthritis? J
Am Osteopath Assoc 2006, 106:342-345.
42.
Krampla WW, Newrkla SP, Kroener AH, Hruby WF: Changes on magnetic
resonance tomography in the knee joints of marathon runners: a 10-
year longitudinal study. Skeletal Radiol 2008, 37:619-626.
43.
Arokoski J, Kiviranta I, Jurvelin J, Tammi M, Helminen HJ: Long-distance
running causes site-dependent decrease of cartilage glycosaminoglycan
content in the knee joints of beagle dogs. Arthritis Rheum 1993,
36:1451-1459.
44.
Arokoski J, Jurvelin J, Kiviranta I, Tammi M, Helminen HJ: Softening of the
lateral condyle articular cartilage in the canine knee joint after long
distance (up to 40 km/day) running training lasting one year. Int J Sports
Med 1994, 15:254-260.
45.
Arokoski JP, Hyttinen MM, Lapveteläinen T, Takács P, Kosztáczky B, Módis L,
Kovanen V, Helminen H: Decreased birefringence of the superficial zone
collagen network in the canine knee (stifle) articular cartilage after long
distance running training, detected by quantitative polarised light
microscopy. Ann Rheum Dis 1996, 55:253-264.
46.
Lacey RJ, Thomas E, Duncan RC, Peat G: Gender difference in
symptomatic radiographic knee osteoarthritis in the Knee Clinical
Assessment–CAS(K): a prospective study in the general population. BMC
Musculoskelet Disord 2008, 9:82.
47.
Leyk D, Erley O, Gorges W, Ridder D, Rüther T, Wunderlich M, Sievert A,
Essfeld D, Piekarski C, Erren T: Performance, training and lifestyle
parameters of marathon runners aged 20-80 years: results of the PACE-
study. Int J Sports Med 2009, 30:360-365.
48.
Bishop GW, Fallon KE: Musculoskeletal injuries in a six-day track race:
ultramarathoner’s ankle. Clin J Sport Med 1999, 9:216-220.
49.
Fallon KE: Musculoskeletal injuries in the ultramarathon: the 1990
Westfield Sydney to Melbourne run. Br J Sports Med 1996, 30:319-323.
50.
Fredericson M, Misra AK: Epidemiology and aetiology of marathon
running injuries. Sports Med 2007, 37:437-439.
51.
Schueller-Weidekamm C: Long-term success and risk for marathon
runners. Radiologe 2010, 50:444-452.
52.
Taunton JE, Ryan MB, Clement DB, McKenzie DC, Lloyd-Smith DR,
Zumbo BD: A retrospective case-control analysis of 2002 running
injuries. Br J Sports Med 2002, 36:95-101.
53.
Taunton JE, Ryan MB, Clement DB, McKenzie DC, Lloyd-Smith DR,
Zumbo BD: A prospective study of running injuries: the Vancouver Sun
Run “In Training” clinics. Br J Sports Med 2003, 37:239-244.
54.
Van Middelkoop M, Kolkman J, van Ochten J, Bierma-Zeinstra SM, Koes BW:
Course and predicting factors of lower-extremity injuries after running a
marathon. Clin J Sport Med 2007, 17:25-30.
55.
Johnell O, Rausing A, Wendeberg B, Westlin N: Morphological bone
changes in shin splints. Clin Orthop Relat Res 1982, 167:180-184.
56.
Aoki Y, Yasuda K, Tohyama H, Ito H, Minami A: Magnetic resonance
imaging in stress fractures and shin splints. Clin Orthop Relat Res 2004,
421:260-267.
57.
Wilder RP, Sethi S: Overuse injuries: tendinopathies, stress fractures,
compartment syndrome, and shin splints. Clin Sports Med 2004, 23:55-81.
58.
Detmer DE: Chronic shin splints: classification and management of
medial tibial stress syndrome. Sports Med 1986, 3:436-446.
59.
Batt ME: Shin splints–a review of terminology. Clin J Sport Med 1995,
5:53-57.
60.
Verleisdonk EJ, van Gils A, van der Werken C: The diagnostic value of MRI
scans for the diagnosis of chronic exertional compartment syndrome of
the lower leg. Skeletal Radiol 2001, 30:321-325.
61.
Bong MR, Polatsch DB, Jazrawi LM, Rokito AS: Chronic exertional
compartment syndrome: diagnosis and management. Bull Hosp Jt Dis
2005, 62:77-84.
62.
Lee D, Armed Forces Health Surveillance Center (AFHSC): Stress fractures,
active component, U.S. Armed Forces, 2004-2010. MSMR 2011, 18:8-11.
63.
Harrast MA, Colonno D: Stress fractures in runners. Clin Sports Med 2010,
29:399-416.
64.
Shellock FG, Morris E, Deutsch AL, Mink JH, Kerr R, Boden SD:
Hematopoietic bone marrow hyperplasia: high prevalence on MR
images of the knee in asymptomatic marathon runners. AJR Am J
Roentgenol 1992, 158:335-338.
65.
Gondoh Y, Sensui H, Kinomura S, Fukuda H, Fujimoto T, Masud M,
Nagamatsu T, Tamaki H, Takekura H: Effects of aerobic exercise training
on brain structure and psychological well-being in young adults. J Sports
Med Phys Fitness 2009, 49:129-135.
66.
Peters J, Dauvermann M, Mette C, Platen P, Franke J, Hinrichs T, Daum I:
Voxel-based morphometry reveals an association between aerobic
capacity and grey matter density in the right anterior insula.
Neuroscience 2009, 163:1102-1108.
67.
Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS:
A voxel-based morphometric study of ageing in 465 normal adult
human brains. Neuroimage 2001, 14:21-36.
68.
O’Brien JT, Paling S, Barber R, Williams ED, Ballard C, McKeith IG, Gholkar A,
Crum WR, Rossor MN, Fox NC: Progressive brain atrophy on serial MRI in
dementia with Lewy bodies, AD, and vascular dementia. Neurology 2001,
56:1386-1388.
69.
Fox NC, Crum WR, Scahill RI, Stevens JM, Janssen JC, Rossor MN: Imaging
of onset and progression of Alzheimer’s disease with voxel-compression
mapping of serial magnetic resonance images. Lancet 2001, 358:201-205.
70.
Katzman DK, Lambe EK, Mikulis DJ, Ridgley JN, Goldbloom DS, Zipursky RB:
Cerebral gray matter and white matter volume deficits in adolescent
girls with anorexia nervosa. J Pediatr 1996, 129:794-803.
71.
Castro-Fornieles J, Bargalló N, Lázaro L, Andrés S, Falcon C, Plana MT,
Junqué C: A cross-sectional and follow-up voxel-based morphometric
MRI study in adolescent anorexia nervosa. J Psychiatr Res 2009,
43:331-340.
72.
Geibprasert S, Gallucci M, Krings T: Alcohol-induced changes in the brain
as assessed by MRI and CT. Eur Radiol 2010, 20:1492-1501.
73.
Gunston GD, Burkimsher D, Malan H, Sive AA: Reversible cerebral
shrinkage in kwashiorkor: an MRI study. Arch Dis Child 1992, 67:1030-1032.
74.
Golden NH, Ashtari M, Kohn MR, Patel M, Jacobson MS, Fletcher A,
Shenker IR: Reversibility of cerebral ventricular enlargement in anorexia
nervosa, demonstrated by quantitative magnetic resonance imaging. J
Pediatr 1996, 128:296-301.
75.
Knudsen L, Drummond PD: Cold-induced limb pain decreases sensitivity
to pressure-pain sensations in the ipsilateral forehead. Eur J Pain 2009,
13:1023-1029.
76.
Van den Eynde F, Treasure J: Neuroimaging in eating disorders and
obesity: implications for research. Child Adolesc Psychiatr Clin N Am 2009,
18:95-115.
77.
Kraemer WJ, Fragala MS, Watson G, Volek JS, Rubin MR, French DN,
Maresh CM, Vingren JL, Hatfield DL, Spiering BA, Yu-Ho J, Hughes SL,
Case HS, Stuempfle KJ, Lehmann DR, Bailey S, Evans DS: Hormonal
responses to a 160-km race across frozen Alaska. Br J Sports Med 2008,
42:116-120.
78.
Agawa H, Yamada N, Enomoto Y, Suzuki H, Hosono A, Arakawa K,
Ghadimi R, Miyata M, Maeda K, Shibata K, Tokudome M, Goto C,
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 30 of 33
Tokudome Y, Hoshino H, Imaeda N, Marumoto M, Suzuki S, Kobayashi M,
Tokudome S: Changes of mental stress biomarkers in ultramarathon. Int J
Sports Med 2008, 29:867-871.
79.
Hew-Butler T, Noakes TD, Soldin SJ, Verbalis JG: Acute changes in
endocrine and fluid balance markers during high-intensity, steady-state,
and prolonged endurance running: unexpected increases in oxytocin
and brain natriuretic peptide during exercise. Eur J Endocrinol 2008,
159:729-737.
80.
Lehmann M, Huonker M, Dimeo F, Heinz N, Gastmann U, Treis N,
Steinacker JM, Keul J, Kajewski R, Häussinger D: Serum amino acid
concentrations in nine athletes before and after the 1993 Colmar ultra
triathlon. Int J Sports Med 1995, 16:155-159.
81.
Pickering A, Carter J, Hanning I, Townend W: Emergency department
measurement of urinary S100B in children following head injury: can
extracranial injury confound findings? Emerg Med J 2008, 25:88-89.
82.
Gazzolo D, Frigiola A, Bashir M, Iskander I, Mufeed H, Aboulgar H,
Venturini P, Marras M, Serra G, Frulio R, Michetti F, Petraglia F, Abella R,
Florio P: Diagnostic accuracy of S100B urinary testing at birth in full-term
asphyxiated newborns to predict neonatal death. PLoS One 2009, 4:
e4298.
83.
Jäncke L, Koeneke S, Hoppe A, Rominger C, Hänggi J: The architecture of
the golfer’s brain. PLoS One 2009, 4:e4785.
84.
Stuempfle KJ, Lehmann DR, Case HS, Bailey S, Hughes SL, McKenzie J,
Evans D: Hyponatremia in a cold weather ultraendurance race. Alaska
Med 2002, 44:51-55.
85.
Hew TD, Chorley JN, Cianca JC, Divine JG: The incidence, risk factors, and
clinical manifestations of hyponatremia in marathon runners. Clin J Sport
Med 2003, 13:41-47.
86.
Almond CS, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA,
Duncan CN, Olson DP, Salerno AE, Newburger JW, Greenes DS:
Hyponatremia among runners in the Boston Marathon. N Engl J Med
2005, 352:1550-1556.
87.
Noakes TD, Sharwood K, Speedy D, Hew T, Reid S, Dugas J, Almond C,
Wharam P, Weschler L: Three independent biological mechanisms cause
exercise-associated hyponatremia: evidence from 2,135 weighed
competitive athletic performances. Proc Natl Acad Sci USA 2005,
102:18550-18555.
88.
Urhausen A, Scharhag J, Herrmann M, Kindermann W: Clinical significance
of increased cardiac troponins T and I in participants of ultra-endurance
events. Am J Cardiol 2004, 94:696-698.
89.
Neilan TG, Januzzi JL, Lee-Lewandrowski E, Ton-Nu TT, Yoerger DM,
Jassal DS, Lewandrowski KB, Siegel AJ, Marshall JE, Douglas PS, Lawlor D,
Picard MH, Wood MJ: Myocardial injury and ventricular dysfunction
related to training levels among nonelite participants in the Boston
marathon. Circulation 2006, 114:2325-2333.
90.
O’Connor DT, Frigon RP: Chromogranin A, the major catecholamine
storage vesicle soluble protein. Multiple size forms, subcellular storage,
and regional distribution in chromaffin and nervous tissue elucidated by
radioimmunoassay. J Biol Chem 1984, 259:3237-3247.
91.
Mousavi N, Czarnecki A, Kumar K, Fallah-Rad N, Lytwyn M, Han SY,
Francis A, Walker JR, Kirkpatrick ID, Neilan TG, Sharma S, Jassal DS: Relation
of biomarkers and cardiac magnetic resonance imaging after marathon
running. Am J Cardiol 2009, 103:1467-1472.
92.
Trivax JE, Franklin BA, Goldstein JA, Chinnaiyan KM, Gallagher MJ,
deJong AT, Colar JM, Haines DE, McCullough PA: Acute cardiac effects of
marathon running. J Appl Physiol 2010, 108:1148-1153.
93.
Hanssen H, Keithahn A, Hertel G, Drexel V, Stern H, Schuster T, Lorang D,
Beer AJ, Schmidt-Trucksäss A, Nickel T, Weis M, Botnar R, Schwaiger M,
Halle M: Magnetic resonance imaging of myocardial injury and
ventricular torsion after marathon running. Clin Sci (Lond) 2011,
120:143-152.
94.
Scharhag J, Herrmann M, Urhausen A, Haschke M, Herrmann W,
Kindermann W: Independent elevations of N-terminal pro-brain
natriuretic peptide and cardiac troponins in endurance athletes after
prolonged strenuous exercise. Am Heart J 2005, 150:1128-1134.
95.
Scharhag J, George K, Shave R, Urhausen A, Kindermann W: Exercise-
associated increases in cardiac biomarkers. Med Sci Sports Exerc 2008,
40:1408-1415.
96.
Montgomery HE, Clarkson P, Dollery CM, Prasad K, Losi MA, Hemingway H,
Statters D, Jubb M, Girvain M, Varnava A, World M, Deanfield J, Talmud P,
McEwan JR, McKenna WJ, Humphries S: Association of angiotensin-
converting enzyme gene I/D polymorphism with change in left
ventricular mass in response to physical training. Circulation 1997,
96:741-747.
97.
Morganroth J, Henry WL, Maron RJ, Clark CE, Epstein SE: Idiopathic left
ventricular hypertrophy. N Engl J Med 1974, 290:1047-1050.
98.
Morganroth J, Maron BJ, Henry WL, Epstein SE: Comparative left ventricular
dimensions in trained athletes. Ann Intern Med 1975, 82:521-524.
99.
Naylor LH, George K, O’Driscoll G, Green DJ: The athlete’s heart: a
contemporary appraisal of the ‘Morganroth hypothesis’. Sports Med 2008,
38:69-90.
100. Schmidt-Trucksäss A, Schmid A, Brunner C, Scherer N, Zäch G, Keul J,
Huonker M: Arterial properties of the carotid and femoral artery in
endurance-trained and paraplegic subjects. J Appl Physiol 2000,
89:1956-1963.
101. Kasikcioglu E, Oflaz H, Kasikcioglu HA, Kayserilioglu A, Umman S, Meric M:
Endothelial flow-mediated dilatation and exercise capacity in highly
trained endurance athletes. Tohoku J Exp Med 2005, 205:45-51.
102. Petersen SE, Wiesmann F, Hudsmith LE, Robson MD, Francis JM,
Selvanayagam JB, Neubauer S, Channon KM: Functional and structural
vascular remodeling in elite rowers assessed by cardiovascular magnetic
resonance. J Am Coll Cardiol 2006, 48:790-797.
103. Naylor LH, O’Driscoll G, Fitzsimons M, Arnolda LF, Green DJ: Effects of
training resumption on conduit arterial diameter in elite rowers. Med Sci
Sports Exerc 2006, 38:86-92.
104. Raschka C, Plath M, Cerull R, Bernhard W, Jung K, Leitzmann C: The body
muscle compartment and its relationship to food absorption and blood
chemistry during an extreme endurance performance. Z Ernährungswiss
1991, 30:276-288.
105. Raschka C, Plath M: Body fat compartment and its relationship to food
intake and clinical chemical parameters during extreme endurance
performance. Schweiz Z Sportmed 1992, 40:13-25.
106. Höchli D, Schneiter T, Ferretti G, Howald H, Claassen H, Moia C, Atchou G,
Belleri M, Veicsteinas A, Hoppeler H: Loss of muscle oxidative capacity
after an extreme endurance run: the Paris-Dakar Foot-Race. Int J Sports
Med 1995, 16:343-346.
107. Helge JW, Lundby C, Christensen DL, Langfort J, Messonnier L, Zacho M,
Andersen JL, Saltin B: Skiing across the Greenland icecap: divergent
effects on limb muscle adaptations and substrate oxidation. J Exp Biol
2003, 206:1075-1083.
108. Frykman PN, Harman EA, Opstad PK, Hoyt RW, DeLany JP, Friedl KE: Effects
of a 3-month endurance event on physical performance and body
composition: the G2 trans-Greenland expedition. Wilderness Environ Med
2003, 14:240-248.
109. Bircher S, Enggist A, Jehle T: Effects of an extreme endurance race on
energy balance and body composition: a case study. J Sports Sci Med
2006, 5:154-162.
110. Nagel D, Seiler D, Franz H, Leitzmann C, Jung K: Effects of an ultra-long-
distance (1000 km) race on lipid metabolism. Eur J Appl Physiol 1989,
59:16-20.
111. Dressendorfer RH, Wade CE: Effects of a 15-d race on plasma steroid
levels and leg muscle fitness in runners. Med Sci Sports Exerc 1991,
23:954-958.
112. Väänänen II, Vihko V: Physiological and psychological responses to 100
km crosscountry skiing during 2 days. J Sports Med Phys Fitness 2005,
45:301-305.
113. Knechtle B, Salas OF, Andonie JL, Kohler G: Effect of a multistage ultra-
endurance triathlon on body composition: World Challenge Deca Iron
Triathlon 2006. Br J Sports Med 2008, 42:121-125.
114. Reynolds RD, Lickteig JA, Deuster PA, Howard MP, Conway JM, Pietersma A,
deStoppelaar J, Deurenberg P: Energy metabolism increases and regional
body fat decreases while regional muscle mass is spared in humans
climbing Mt. Everest. J Nutr 1999, 129:1307-1314.
115. Lehmann M, Huonker M, Dimeo F: Serum amino acid concentrations in
nine athletes before and after the 1993 Colmar Ultra Triathlon. Int J
Sports Med 1995, 16:155-159.
116. Paley D, Herzenberg JE, Tetsworth K, McKie J, Bhave A: Deformity planning
for frontal and sagittal plane corrective osteotomies. Orthop Clin North
Am 1994, 25:425-465.
117. Waidelich HA, Strecker W, Schneider E: Computed tomographic torsion-
angle and length measurement of the lower extremity. The methods,
normal values and radiation load. Rofo 1992, 157:245-251.
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 31 of 33
118. Blustein SM, D’Amico JC: Limb length discrepancy. Identification, clinical
significance, and management. J Am Podiatr Med Assoc 1985, 75:200-206.
119. Strecker W, Keppler P, Gebhard F, Kinzl L: Length and torsion of the lower
limb. J Bone Joint Surg Br 1997, 79:1019-1023.
120. Keppler P, Strecker W, Kinzl L: Analysis of leg geometry–standard
techniques and normal values. Chirurg 1998, 69:1141-1152.
121. Keppler P: Normwerte des Beines. 8. Kurs zur Analyse und Korrektur von
Beindeformitäten. Schloss Reisensburg, Günzburg, Germany 2005, 03:16-19.
122. Keppler P, Kinzl L: Diagnostik der posttraumatischen Beindeformitäten.
Trauma Berufskrankh 2006, 8(Suppl 3):303-316.
123. Nagoshi CT, Waler D, Muntaner C, Haertzen CA: Validation of the
Tridimensional Personality Questionnaire in a sample of male drug
users. Personality and Individual Differences 1992, 13:401-409.
124. Hansenne M, Delhez M, Cloninger CR: Psychometric properties of the
temperament and character inventory-revised (TCI-R) in a Belgian
sample. J Pers Assess 2005, 85:40-49.
125. Schwarzer R, Jerusalem M: Generalized Self-Efficacy scale. In Measures in
Health Psychology: A User’s Portfolio. Causal and Control Beliefs. Edited by:
Weinman J, Wright S, Johnston M. Windsor; 1995:35-37.
126. Luszczynska A, Scholz U, Schwarzer R: The general self-efficacy scale:
multicultural validation studies. J Psychol 2005, 139:439-457.
127. Mamisch TC, Trattnig S, Quirbach S, Marlovits S, White LM, Welsch GH:
Quantitative T2 mapping of knee cartilage: differentiation of healthy
control cartilage and cartilage repair tissue in the knee with unloading–
initial results. Radiology 2010, 254:818-826.
128. Welsch GH, Trattnig S, Hughes T, Quirbach S, Olk A, Blanke M, Marlovits S,
Mamisch TC: T2 and T2* mapping in patients after matrix-associated
autologous chondrocyte transplantation: initial results on clinical use
with 3.0-Tesla MRI. Eur Radiol 2010, 20:1515-1523.
129. Apprich S, Welsch GH, Mamisch TC, Szomolanyi P, Mayerhoefer M, Pinker K,
Trattnig S: Detection of degenerative cartilage disease: comparison of
high-resolution morphological MR and quantitative T2 mapping at 3.0
Tesla. Osteoarthritis Cartilage 2010, 18:1211-1217.
130. Schueller-Weidekamm C, Schueller G, Uffmann M, Bader T: Incidence of
chronic knee lesions in long-distance runners based on training level:
findings at MRI. Eur J Radiol 2006, 58:286-293.
131. Schmitt H, Rohs C, Schneider S, Clarius M: Is competitive running
associated with osteoarthritis of the hip or the knee? Orthopade 2006,
35:1087-1092.
132. Major NM, Helms CA: Sacral stress fractures in long-distance runners. AJR
Am J Roentgenol 2000, 174:727-729.
133. Shah MK, Stewart GW: Sacral stress fractures: an unusual cause of low
back pain in an athlete. Spine 2002, 27:E104-108.
134. Alsobrook J, Simons SM: Sacral stress fracture in a marathon runner. Curr
Sports Med Rep 2007, 6:39-42.
135. Fredenicson M, Bergman AG, Hoffman KL, Dillingham MS: Tibial stress
reaction in runners: correlation of clinical symptoms and scintigraphy
with a new magnetic resonance imaging grading system. Am Sports Med
1995, 23:472-481.
136. Bergman AG, Fredericson M: MR imaging of stress reactions, muscle
injuries, and other overuse injuries in runners. Magn Reson Imaging Clin N
Am 1999, 7:151-174, ix.
137. Bolster BD Jr, Atalar E, Hardy CJ, McVeigh ER: Accuracy of arterial pulse-
wave velocity measurement using MR. J Magn Reson Imaging 1998,
8:878-888.
138. Machann J, Thamer C, Schnoedt B, Haap M, Haring HU, Claussen CD,
Stumvoll M, Fritsche A, Schick F: Standardized assessment of whole body
adipose tissue topography by MRI. J Magn Reson Imaging 2005,
21:455-462.
139. Würslin C, Machann J, Rempp H, Claussen C, Yang B, Schick F: Topography
mapping of whole body adipose tissue using a fully automated and
standardized procedure. J Magn Reson Imaging 2010, 31:430-439.
140. Brechtel K, Niess AM, Machann J, Rett K, Schick F, Claussen CD,
Dickhuth HH, Haering HU, Jacob S: Utilisation of intramyocellular lipids
(IMCLs) during exercise as assessed by proton magnetic resonance
spectroscopy (1H-MRS). Horm Metab Res 2001, 33:63-66.
141. Jebb SA, Cole TJ, Doman D, Murgatroyd PR, Prentice AM: Evaluation of the
novel Tanita body-fat analyser to measure body composition by
comparison with a four-compartment model. Br J Nutr 2000, 83:115-122.
142. Ball SD, Altena TS, Swan PD: Comparison of anthropometry to DXA: a
new prediction equation for men. Eur J Clin Nutr 2004, 58:1525-1531.
143. Lee RC, Wang Z, Heo M, Ross R, Janssen I, Heymsfield SB: Total-body
skeletal muscle mass: development and cross-validation of
anthropometric prediction models. Am J Clin Nutr 2000, 72:796-803.
144. Roach KE, Miles TP: Normal hip and knee active range of motion: the
relationship to age. Phys Ther 1991, 71:656-665.
145. Knechtle B, Knechtle P, Andonie JL, Kohler G: Influence of anthropometry
on race performance in extreme endurance triathletes: World Challenge
Deca Iron Triathlon 2006. Br J Sports Med 2007, 41:644-648.
146. Marti B, Abelin T, Minder CE: Relationship of training and life-style to 16-
km running time of 4000 joggers. The ‘84 Berne “Grand-Prix” Study. Int J
Sports Med 1988, 9:85-91.
147. Marti B, Vader JP, Minder CE, Abelin T: On the epidemiology of running
injuries. The 1984 Bern Grand-Prix study. Am J Sports Med 1988,
16:285-294.
148. Macera CA, Pate RR, Woods J, Davis DR, Jackson KL: Postrace morbidity
among runners. Am J Prev Med 1991, 7:194-198.
149. Pate RR, Macera CA, Bailey SP, Bartoli WP, Powell KE: Physiological,
anthropometric, and training correlates of running economy. Med Sci
Sports Exerc 1992, 24:1128-1133.
150. Saunders PU, Pyne DB, Telford RD, Hawley JA: Factors affecting running
economy in trained distance runners. Sports Med 2004, 34:465-485.
151. Wilder RP, Sethi S: Overuse injuries: tendinopathies, stress fractures,
compartment syndrome, and shin splints. Clin Sports Med 2004, 23:55-81.
152. Van Middelkoop M, Kolkman J, Van Ochten J, Bierma-Zeinstra SM, Koes BW:
Risk factors for lower extremity injuries among male marathon runners.
Scand J Med Sci Sports 2008, 18:691-697.
153. Wen DY, Puffer JC, Schmalzried TP: Injuries in runners: a prospective study
of alignment. Clin J Sport Med 1998, 8:187-194.
154. Satterthwaite P, Norton R, Larmer P, Robinson E: Risk factors for injuries
and other health problems sustained in a marathon. Br J Sports Med
1999, 33:22-26.
155. Taunton JE, Ryan MB, Clement DB, McKenzie DC, Lloyd-Smith DR,
Zumbo BD: A retrospective case-control analysis of 2002 running
injuries. Br J Sports Med 2002, 36:95-101.
156. Fredericson M, Misra AK: Epidemiology and aetiology of marathon
running injuries. Sports Med 2007, 37:437-439.
157. Mosher TJ, Liu Y, Torok CM: Functional cartilage MRI T2 mapping:
evaluating the effect of age and training on knee cartilage response to
running. Osteoarthritis Cartilage 2010, 18:358-364.
158. Neidhart M, Müller-Ladner U, Frey W, Bosserhoff AK, Colombani PC, Frey-
Rindova P, Hummel KM, Gay RE, Häuselmann H, Gay S: Increased serum
levels of non-collagenous matrix proteins (cartilage oligomeric matrix
protein and melanoma inhibitory activity) in marathon runners.
Osteoarthritis Cartilage 2000, 8:222-229.
159. Kim HJ, Lee YH, Kim CK: Biomarkers of muscle and cartilage damage and
inflammation during a 200 km run. Eur J Appl Physiol 2007, 99:443-447.
160. Kim HJ, Lee YH, Kim CK: Changes in serum cartilage oligomeric matrix
protein (COMP), plasma CPK and plasma hs-CRP in relation to running
distance in a marathon (42.195 km) and an ultra-marathon (200 km)
race. Eur J Appl Physiol 2009, 105:765-770.
161. Addison S, Coleman RE, Feng S, McDaniel G, Kraus VB: Whole-body bone
scintigraphy provides a measure of the total-body burden of
osteoarthritis for the purpose of systemic biomarker validation. Arthritis
Rheum 2009, 60:3366-3373.
162. Liphardt AM, Mündermann A, Koo S, Bäcker N, Andriacchi TP, Zange J,
Mester J, Heer M: Vibration training intervention to maintain cartilage
thickness and serum concentrations of cartilage oligometric matrix
protein (COMP) during immobilization. Osteoarthritis Cartilage 2009,
17:1598-1603.
163. Berry PA, Maciewicz RA, Wluka AE, Downey-Jones MD, Forbes A,
Hellawell CJ, Cicuttini FM: Relationship of serum markers of cartilage
metabolism to imaging and clinical outcome measures of knee joint
structure. Ann Rheum Dis 2010, 69:1816-1822.
164. Niehoff A, Kersting UG, Helling S, Dargel J, Maurer J, Thevis M,
Brüggemann GP: Different mechanical loading protocols influence serum
cartilage oligomeric matrix protein levels in young healthy humans. Eur
J Appl Physiol 2010, 110:651-657.
165. Pelletier JP, Raynauld JP, Caron J, Mineau F, Abram F, Dorais M, Haraoui B,
Choquette D, Martel-Pelletier J: Decrease in serum level of matrix
metalloproteinases is predictive of the disease-modifying effect of
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 32 of 33
osteoarthritis drugs assessed by quantitative MRI in patients with knee
osteoarthritis. Ann Rheum Dis 2010, 69:2118-2124.
166. Knechtle B, Knechtle P, Rosemann T: Upper body skinfold thickness is
related to race performance in male Ironman triathletes. Int J Sports Med
201, 32:20-27.
167. al’Absi M, Petersen KL, Wittmers LE: Adrenocortical and hemodynamic
predictors of pain perception in men and women. Pain 2002, 96:197-204.
168. Thamer C, Machann J, Bachmann O, Haap M, Dahl D, Wietek B, Tschritter O,
Niess A, Brechtel K, Fritsche A, Claussen C, Jacob S, Schick F, Häring HU,
Stumvoll M: Intramyocellular lipids: anthropometric determinants and
relationships with maximal aerobic capacity and insulin sensitivity. J Clin
Endocrinol Metab 2003, 88:1785-1791.
169. Machann J, Etzel M, Thamer C, Haring HU, Claussen CD, Fritsche A, Schick F:
Morning to evening changes of intramyocellular lipid content in
dependence on nutrition and physical activity during one single day: a
volume selective 1H-MRS study. MAGMA 2011, 24:29-33.
Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1741-7015/10/78/prepub
doi:10.1186/1741-7015-10-78
Cite this article as: Schütz et al.: 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.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color ﬁgure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Schütz et al. BMC Medicine 2012, 10:78
http://www.biomedcentral.com/1741-7015/10/78
Page 33 of 33

The TransEurope FootRace Project: longitudinal data acquisition in a cluster randomized mobile MRI observational cohort study on 44 endurance runners at a 64-stage 4,486 km transcontinental ultramarathon.
Schütz, Uwe H W,Schmidt-Trucksäss, Arno,Knechtle, Beat,Machann, Jürgen,Wiedelbach, Heike,Ehrhardt, Martin,Freund, Wolfgang,Gröninger, Stefan,Brunner, Horst,Schulze, Ingo,Brambs, Hans-Jürgen,Billich, Christian