The chronic painful Achilles tendon Sonographic findings ...140899/FULLTEXT01.pdf · The chronic...
Transcript of The chronic painful Achilles tendon Sonographic findings ...140899/FULLTEXT01.pdf · The chronic...
1
UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New Series No 860 – ISSN 0346 – 6612 – ISBN 91 – 7305 – 536 - 0
From the Department of Radiation Sciences, Diagnostic Radiology,
and the Department of Surgical and Perioperative Sciences, Sports Medicine,
Umeå University, Sweden
The chronic painful Achilles tendon Sonographic findings and new methods for treatment
by
Lars Öhberg
Umeå 2003
2
Department of Radiation Sciences, Diagnostic Radiology
Umeå University
901 85 Umeå
Sweden
Department of Surgical and Perioperative Science, Sports Medicine,
Umeå University
901 87 Umeå
Sweden
Copyright © 2003 by Lars Öhberg
New Series No 860 – ISSN 0346 – 6612
ISBN 91 – 7305 – 536 – 0
Printed in Sweden by Solfjädern Offset AB, Umeå, 2003
Front cover and illustrations by Claes Öhberg
Back cover photo by Elna Öhberg
Photos by Lars Öhberg
3
CONTENTS
Abstract .....................................................................................................................5
Abbreviations............................................................................................................6
Original papers..........................................................................................................7
Introduction...............................................................................................................8
History ..................................................................................................................8
Anatomy and functions .........................................................................................8
Blood supply .......................................................................................................12
Metabolism .........................................................................................................12
Innervation ..........................................................................................................13
Diagnostics..............................................................................................................14
Clinical examination ...........................................................................................14
Imaging ...............................................................................................................14
Ultrasound...........................................................................................................15
Equipment ...........................................................................................................16
Colour Doppler ...................................................................................................17
Sonographic Anatomy of the normal Achilles tendon........................................18
Ultrasound guided puncture................................................................................19
MRI of the Achilles tendon.................................................................................20
Chronic Achilles tendon pain..................................................................................22
Nomenclature in chronic painful conditions.......................................................22
Proximal pain ..........................................................................................................23
Mid-portion pain (2 – 6 cm from the calcaneal insertion) ......................................23
Histopathology....................................................................................................23
Pain mechanism ..................................................................................................24
Ultrasound...........................................................................................................24
Conservative treatment ......................................................................................25
Surgical Treatment.............................................................................................26
Distal pain (Achilles tendon insertional pain).........................................................27
Histopathology....................................................................................................28
4
Ultrasound...........................................................................................................29
Treatment ............................................................................................................29
Aims........................................................................................................................31
Methods ..................................................................................................................32
Ultrasound scanning technique of the Achilles tendon.......................................32
Ultrasound-guided injection................................................................................34
Statistical methods ..............................................................................................37
Summary of papers .................................................................................................39
Paper I: ................................................................................................................39
Paper II:...............................................................................................................39
Paper III: .............................................................................................................41
Paper IV: .............................................................................................................43
Paper V: ..............................................................................................................44
Paper VI ..............................................................................................................45
Discussion ...............................................................................................................48
Conclusion ..............................................................................................................56
Acknowledgements………………………………………………………………..57
References...............................................................................................................58
5
Abstract
The aim of the present thesis was to evaluate sonographic methods for
investigation of the chronic painful Achilles tendon.
In a prospective study on patients with chronic painful mid-portion Achilles
tendinosis, grey-scale ultrasound (US) showed a decreased tendon thickness and a
“normalized” structure in the majority of patients successfully treated with
eccentric calf-muscle training. By combining US with colour Doppler examination
(CDV), a neovascularisation was shown in the region with structural tendon
changes in all painful tendons, but not in any of the pain-free normal tendons. In a
small pilot study, the sclerosing agent Polidocanol was injected towards the neo-
vessels under US and CDV guidance. The majority of the patients became pain-
free and had no remaining neovessels, while the patients with remaining pain had
remaining neovessels. The combined findings from US, immuno-histochemical
analyses of biopsies, and diagnostic injections, showed that the patients were
temporarily pain-free after US and CDV guided injections of local anaesthesia
towards the region with neovessels, and biopsies from the region with tendon
changes and neovascularisation showed nerve structures in close relation to blood
vessels. The presence of neovessels was shown also in patients with chronic pain
in the Achilles tendon insertion, and it was found that treatment with sclerosing
injections cured the pain in the majority of patients. A good result of treatment
was associated with no remaining neovessels.
In a prospective study on patients with chronic mid-portion Achilles tendinosis
treated with eccentric training, CDV after treatment showed no remaining
neovessels in the majority of the pain-free patients. In the patients with remaining
tendon pain there were remaining neovessels.
In conclusion, the findings in this thesis indicate that neovessels and accompanying
nerves might be the source of chronic Achilles tendon pain. Sclerosing injections
towards the neovessels, and eccentric training, seem to have a potential to cure the
pain.
6
Abbreviations
CDV Colour Doppler Velocity
CDE Colour Doppler Energy or Power Doppler.
GAGs Glucose-amino-glycans
MHz Mega Hertz
MRI Magnetic Resonance Imaging
NSAID Non-Steroidal Anti-Inflammatory Drugs PGE2 Prostaglandin E2
US Ultrasound
VAS Visual Analogue Scale
XR X-ray, plain film radiography
7
Original papers
The thesis is based upon the following papers, which will be referred to by their
Roman numerals:
I. Öhberg L, Lorentzon R, Alfredson H. Eccentric training in patients with
chronic Achilles tendinosis–normalized tendon structure and decreased
thickness at follow-up. Br J Sports Med. Accepted for publication 2003.
II. Öhberg L, Alfredson H. Neovascularisation in Achilles tendons with painful
tendinosis but not in normal tendons: an ultrasonographic investigation.
Knee Surg. Sports Traumatol, Arthrosc (2001) 9 : 233 – 238.
III. Öhberg L, Lorentzon R, Alfredson R. Ultrasound guided sclerosis of
neovessels in painful Achilles tendinosis: pilot study of a new treatment.
Br J Sports Med (2002); 36: 173 – 177.
IV. Öhberg L, Alfredson H. Sclerosing therapy in chronic Achilles tendon
insertional pain – results of a pilot study. Knee Surg Sports Traumatol,
Arthrosc. (2003) 11 ; 339 – 343.
V. Öhberg L, Alfredson H. Effects on neovascularisation behind the good results
with eccentric training in chronic mid-portion Achilles tendinosis?
Submitted.
VI. Alfredson H, Öhberg L, Forsgren S. Is vasculo-neural ingrowth the cause of
pain in chronic Achilles tendinosis? – An investigation using US and colour
Doppler, immunohistochemistry, and diagnostic injections. Knee Surg Sports
Traumatol, Arthrosc. (2003) 11 ; 334 – 338.
8
Introduction
History
The name Achilles tendon originates from the Greek mythology. Achilles was a
son of Peleus and Thesis. His mother, Thesis, who wanted him to be invulnerable,
dipped him into the river Styx, the river of hate, separating the world of the living
from the world of the dead. The purpose was to dip the whole body into the sacred
water of Styx, and become invulnerable. Unfortunately, his heel remained dry, and
therefore his heel was unprotected. In the war against the Trojans, an arrow
wounded Achilles in his unprotected heel. Achilles died from the wound in the
heel.
Anatomy and functions
The Achilles tendon is the strongest tendon in the human body (Józsa and Kannus
1997), and tendon forces equalling 12 times the body weight have been recorded
(Komi et al. 1992).
The Achilles tendon is a part of the gastrocnemius-soleus complex. The
gastrocnemius muscle is divided into a medial and a lateral head, originating at the
posterior, nonarticulated, surfaces of the medial and the lateral femoral condyles.
The soleus muscle is originated from the posterior aspect of the fibular head, upper
1/4 – 1/3 of the posterior surface of the fibula, middle 1/3 of medial border of the
tibial shaft, and from the posterior surface of a tendinous arch spanning over the
two sites of bone origin. The aponeuroses from the three muscle bellies of the
gastrocnemius and soleus muscles join and form the Achilles tendon. The fibres in
the tendon spiral up to 90 degrees from the proximal to the distal end at the
insertion on the calcaneal tuberosity. Consequently, fibres originally positioned
posterior in the proximal part of the tendon become lateral, lateral fibres become
anterior, anterior fibres medial, and medial fibres posterior, at the distal end of the
tendon (Józsa and Kannus 1997). The distal portion of the Achilles tendon attaches
to the mid-posterior calcaneus by a stiff fibrocartilaginous expansion. The osteo -
9
tendinous junction involves a gradual transition from tendon to fibrocartilage and
bone (Józsa and Kannus 1997). Close to the insertion of the tendon are the
subcutanous calcaneal and retrocalcaneal bursaes (Fig 1).
The Achilles tendon is surrounded by a peritendinous sheet (paratenon), with thin
gliding membranes that reduce friction and permits free movement of the tendon
against surrounding tissues (Józsa and Kannus 1997).
The basic elements of tendons are cells, collagen, and ground substance
(extracellular matrix). The natures of the different components are as follows
(Józsa and Kannus 1997):
1. Cells: Tenoblasts and tenocytes comprise 90 – 95 % of the cellular elements in
the tendon. The remaining 5 – 10 % includes chondrocytes at the insertion, and
synovial cells of the tendon surface. The tenoblasts are immature cells with varying
form especially in children. As the children grow older, most of the tenoblasts
transforms to mature tenocytes. These cells are flat, spiderlike, and sparsely
situated between the collagen fibrils. Both the tenoblasts and the tenocytes are
producing procollagen, as well as the ground substance.
2. The collagen, which constitute 65 –75 % of the dry mass in human tendons, is
produced by tenocytes, and arranged in hierarchical levels of complexity. The
smallest elements are tropocollagen, a triple-helix polypeptide chain.
Tropocollagen molecules are stabilised and held together by electrostatic chemical
cross-linking bonds. These chains unite into fibrils, (Fig 2) which are visible in
electron microscope. A bunch of fibrils are united to collagen fibres aligned from
end to end in a tendon. A fine sheath of connective tissue called the endotenon
enfolds each collagen fibre and binds the fibres together. A group of fibres forms a
primary fibre bundle (subfascicle), and a group of primary fibre bundles forms a
secondary fibre bundle (fascicle). Groups of secondary fibre bundles unit to form
tertiary bundles forming the tendon. Each group of bundles is surrounded by the
endotenon. The tendon is covered by the epitenon, a fine, loose connective tissue
sheet that is extending deeper in the tendon forming the endotenon. The vascular,
lymphatic, and nerve supply of the tendon is following the epitenon and the
endotenon into the depths of the tendon. Superficially, the epitenon is surrounded
10
Fig 2: Schematic image of the different structures in a tendon
Fig 1 Schematic image of a foot.
a: Achilles tendon. b: Subcutanous
bursa. c: Retrocalcaneal bursa.
d: Calcaneus
11
by the paratenon, a loose areolar connective tissue composed of collagen fibrils,
some elastic fibrils, and an inner lining of synovial cells.
3. The ground substance consists of proteoglycans and glycoproteins, produced by
the tenocytes. Proteoglycans are composed of a protein core with one or more
glycosaminoglycans (GAGs) covalently attached. They are large, negatively
charged hydrophilic molecules, which can entrain water up to 50 times their
weight, and are mostly entrapped between collagen fibrils and fibres. Human
tendons act as connections between muscles and bone, transmitting the muscular
force to bone, and make movements possible. The maximum force to the tendon
fibres is transmitted parallel to the long axis of the tendon. The collagen fibrils in
the resting, non-strained state are wavy or crimped. The fibres are orientated both
longitudinally, as well as transverse and horizontal, with the longitudinal fibrils
also crossing each other forming spirals and plaits. This complex ultra structure of
the tendon provides a good buffer capacity against longitudinal, transversal,
horizontal, and rotational forces. When the tendon is stretched about 102 % of its
length, the wavy configuration of the tendon fibres disappears. When the tendon is
stretched to approximately 104 %, the tendon is able to return to its original length
when the tensile force is released, and the tendon is also able to resume its normal
wavy appearance. If the strain exceeds approximately 104 %, the tendon fibres are
damaged, and if the strain exceeds a level of 108 % the tendon will rupture (Józsa
and Kannus 1997).
The purpose of the ground substance in the tendon is to provide the collagen fibrils
to resist high compressive and tensile forces with high capacity, and to improve the
elasticity of the tendon. The proteoglycans also enable rapid diffusion of water-
soluble molecules, gases, and migration of cells. There is also some evidence that
the ground substance may be the modulating medium that prompts cells to change
their pattern of protein synthesis in response to load (O´Brien 1997).
12
Blood supply
Tendons receive their blood supply from three sites (O´Brien 1997, Tuite et al.
1997): (1) From vessels coming from the muscle, (2) from vessels coming from the
bone and periosteum in the osteotendinous junction, and (3) from vessels in tissue
surrounding the tendon (paratenon, and mesotenon). The blood vessels are carried
deep into the tendons by the endotenon (Hess et al. 1989, Józsa et al. 1991). The
intratendinous network of vessels consists of longitudinally arranged vessels,
where one artery is followed by two veins. The small artrerioles and capillaries that
orginate from the longitudinal arteries form the microvascular units of the tendon
tissue.
Since tendons predominantly are extracellular tissue, with low metabolic
requirements and rates, they have low blood supply compared to many other
tissues, and it has been stated that the middle part of the Achilles tendon has a
relatively poor vascularity (Józsa&Kannus 1997). However, in a recent study of the
blood flow in human Achilles tendons, using Laser Doppler flowmetry (LD), it was
shown that besides a lower perfusion at the calcaneal insertion, there was an even
distribution of blood flow in the tendon (Åström 2000). An increase in peritendon
blood flow during exercise have also been shown using microdialysis technique,
Langberg (1998).
Metabolism
The tendon has three systems of energy metabolism; the aerobic Krebs cycle, the
anaerobic glycolysis and the pentose phosphate shunt (Hess et al. 1989, Józsa &
Kannus & 1997). In young people the metabolism is more aerobic, but with
increasing age it changes to become more anaerobic.
The metabolic rate in a tendon is low, allowing for a long standing increased
tension in the tendon without the risk for ischemia and necrosis. Simultaneously,
because of the low metabolic rate, the tendons have a slow rate of recovery after
activity and healing after injury.
13
Tendons has commonly been considered to be relatively inactive, but recently,
using microdialysis technique Langberg et al. (1999 and 2000) have shown that
peritendinous tissue is more metabolically active in response to activity than
previously thought. Also, Boushel et al. (2000) have demonstrated a marked
increase in metabolism in peritendinous space (Achilles tendon) during plantar
flexion exercise in young individuals.
Innervation
Sensory nerves from the overlying superficial nerves or from nearby deep nerves
supply the tendons. Most of the sensory nerves are located on the surface of the
tendon. There are only few sensory nerve fibres inside the tendons, and they follow
the vascular network in the endotenon. The nerves anastomose with each other via
obliquely and transversely oriented nerve fibres, and finally terminate in the
sensory nerve endings (Józsa&Kannus 1997).
There are four types of receptors inside the tendons: (1) Ruffini corpuscles –
pressure and stretching sensors. (2) Vater-Pacini corpuscles – pressure sensors,
reacting to acceleration and deceleration movements. (3) Golgi tendon organs –
tension receptors. (4) Free nerve endings – pain receptors (Józsa&Kannus 1997,
O´Brien 1997)
Using microdialysis technique, the neurotransmitter glutamate has recently been
identified in human Achilles tendons (Alfredson et al. 1999). Glutamate is a potent
modulator of pain in the human central nervous system, but its function in the
peripheral nervous system is still mainly unknown (Dickenson et al 1997). Also,
glutamate NMDAR1-receptors were found in close relation to nerve structures in
tendinosis and normal tissue from Achilles tendons (Alfredson et al. 2001).
14
Diagnostics
Clinical examination
It is important to carefully collect the patient history, including onset of the
symptoms, level of activities, training pattern, type of footwear, and previous
treatment. It is also important to perform a proper clinical examination. We usually
have the patient standing on his knees on the examination table, with the feet
hanging outside the edge of the table. Thereby, the Achilles tendon is easy to
access, and side-to-side comparisons can be done. Range of motion in the ankle
joint is evaluated, and symptoms from the Achilles tendon are noticed. The
Achilles tendon and the insertion into the calcaneus are inspected and palpated.
Swollen areas, prominences, and tenderness should be recorded. It should be
evaluated whether the superficial calcaneal and deeper retrocalcaneal bursea are
swollen or tender.
The possibility of differential diagnoses such as; tenosynovitis or dislocations of
the peroneal tendons, tenosynovitis of the plantar flexors, assessory soleus muscle,
os trigonum, and radiating pain from lumbar nerve root entrapment, should also be
carefully evaluated.
To classify the tendon pathology more precisely, different imaging techniques can
be used.
Imaging
Three imaging modalities are used in the diagnosis of pathology in the Achilles
tendon, i.e. diagnostic ultrasound US, magnetic resonance imaging (MRI), and
plain film radiography (XR). US is the method of choice used in all studies in this
thesis and will therefore be presented in detail. MRI and XR will only be briefly
presented. The thickness and the structure of the Achilles tendon as well as the
attachment to the muscles and the calcaneal bone can be visualized with both US
and MRI. It is also possible to examine other structures in relation to the Achilles
tendon, to diagnose other conditions responsible for pain in the Achilles tendon
15
region using these methods. Skeletal changes in the calcaneus, calculi or loose
bone fragments in the Achilles tendon insertion to the calcaneus, as well as major
swelling of the tendon can, be visualized by XR, (Kalebo et al. 1990).
Ultrasound
US is a non-invasive and harmless method to examine the human body. The
method was invented at the beginning of the last century. During the Second World
War there was an intense work to develop radar and sonar systems to be used by
the armed forces. Dussik (1942) was one of the first in the world using ultrasound
in diagnostic purpose. Howry recorded the first cross-sectional ultrasonographic
image with a 35-mm camera, and published the first studies of human tissue
visualised by US (Howry 1952). The first systems could only show the anatomy in
black and white, without grey scale, and only major organs and major pathology
could be shown. One of the most important innovations in the development of the
US technique was the scan converter that made it possible to develop the grey-
scale (Kossoff et al. 1974). The first US equipments were static machines, where
the transducer were attached to an arm connected to sensors indicating the position
of the transducer on a screen. Static US images were produced when the examiner
moved the transducer along the human body. Since every single slice had to be
produced manually, it was very time consuming and difficult to learn the US
technique. The static machines were followed by real time machines during the
1980th. These machines were easier to handle and it was easier to learn the method,
since there was a dynamic image visualising the human anatomy. In the first
machines the spatial resolution was not high enough to be used in musculoskeletal
ultrasound, especially not in the diagnosis of structural changes in tendons. During
the digital development in 1980th and 1990th , there was a fast development of US
machines and transducers, with increasing spatial resolution both at the surface as
well as in the deep structures. This development has made the US technique
sensitive and usable for different diagnostic procedures, i.e. it is now possible to
16
examine muscle fibres, tendons, and even ligaments, with good reliability
(vanHolsbeeck & Introcaso 2001).
Equipment
In modern digital US equipments there is a very efficient technology for both
imaging and storage. The critical part in diagnostic US is the US probe (Meire et
al. 1993 vanHolsbeck & Introcaso 2001). The resolution of the US technique has
increased rapidly over the last two decades due to a technical development of both
the piezo electrical crystals as well as computer capacity. Furthermore, the
development has also lead to several dedicated probes, and it is very important to
use the correct probe for a certain investigation. The resolution increases with
higher frequency of the probe, but the penetration decrease. A lower frequency has
consequently a good penetration but a bad resolution. A probe with the frequency 2
– 5 MHz is suitable for abdominal examinations. For musculoskeletal examinations
the optimal frequency is 5 – 15 MHz. Furthermore, the resolution in the image is
not only dependent of the frequency of the probe, but also of the distance from the
probe to the examined structure. In musculoskeletal US, where the most important
tendons to be examined are situated very superficial in the body, linear probes are
preferable due to the high resolution in a short distance from the probe. It is also
possible to hold the linear probe strictly along the tendon fibres, which is not
possible with vector or curved probes that are best suited for abdominal
investigations. Another disadvantage of the sector and vector probes is a narrow
near field of view and near-field blurredness (Meire et al 1993, vanHolsbeeck &
Introcaso 2001). Linear transducer provides optimal images, having their sound
beam perpendicular to the tendon throughout the imaging field (vanHolsbeeck &
Introcaso 2001). In modern scanners, it is, apart from routine adjustments, possible
to select different frequencies, different focusing of the sound beam, and different
field of views.
17
Colour Doppler
An important issue of the US technique is the possibility to study blood flow non-
invasively with the aid of Doppler technique. The first blood flow studies using the
Doppler technique was done in the late 50th in Japan, further developed by Reid et
al (1972). With the first machines, continuous or duplex Doppler machines, the
results were presented graphically. The next step in the development of the
Doppler technique was the colour Doppler technique, which was presented in
Japan by Omoto et al. (1984). Their approach of colour mapping is still in use
today. The colour Doppler technique, or colour Doppler velocity (CDV), visualizes
both the velocity and the direction of the blood flow.
McDicken (1992) presented a new, even more sensitive method to study the
movements of tissues (usually blood). This technique is called Power Doppler, or
Colour Doppler Energy (CDE). Both CDV and CDE are very sensitive to show
blood flow in small vessels. In larger vessels the angle of the probe against the
vessels is more critical with CDV than CDE. With the aid of CDE it is not possible
to show flow velocity or flow direction. Both colour Doppler techniques can be
combined with pulsed Doppler technique, where the flow is presented graphically,
and the flow direction and flow velocity can be estimated. It is also possible to
characterise the flow, i.e.; it is possible to find out if it is arterial or venous flow.
This characterisation can also be presented by sound effects.
In clinical situations, colour Doppler is widely used in different examinations of
blood flow, e.g.; in cardiology, in the diagnosis of venous thrombosis (Theodorou
et al. 2003), and in the diagnosis of atherosclerotic changes in the carotids and
other arteries (Muller et al 2001). During the last years, the development has
proceeded, and it is now possible to examine very small vessels in the near field
with the aid of colour Doppler. It is even possible to visualize vessels with colour
Doppler that are not visible with grey scale US. Also, it is possible to diagnose
regions with decreased perfusion (Dogra et al. 2003). The high sensitivity of the
CDV for low flow, combined with the high spatial resolution in dynamic grey scale
18
US, makes the method suitable for characterisation of structural and vascular
changes in tendons.
During the last years, intravenous contrast material designed for US examinations,
has been developed (Maresca et al. 1998, Correas et al. 2001). These contrast
material consist of micro bubbles with the ability to pass through the capillaries in
the human body. Using this contrast material it is possible to study the blood flow
in tissues. The contrast examination is not combined with Doppler technique.
Instead, it is a dynamic study of the contrast filling the capillaries and the arteries
in human tissues. It is also possible to follow the venous phase, the venous wash
out of micro bubbles. The method has mainly been used to diagnose and to
characterize liver tumours (Albrecht et al. 2003).
Sonographic Anatomy of the normal Achilles tendon
The Achilles tendon is composed of parallel running fibres Fig 3) that are reflective
by US (vanHolsbeeck & Introcaso 2001). The resolution of the fibre pattern is
increased with increased frequency of the US probe (Fessel et al. 1998, Goodwin
2000, Martinoli et al. 1993 & 1999 & 2002).
Fig 3: Us examination of a normal Achilles tendon. Note the echogenic fibril
structure in the tendon.
19
In the longitudinal section, the normal Achilles tendon is equally thick or slightly
thickened distally, with successively diminishing thickness proximally, where the
Achilles tendon becomes a thin aponeurosis between the soleus and the
gastrocnemius muscles (Goodwin 2000). The maximum thickness of the tendon
has been estimated to 6.3 mm ± 0.5 mm in adults 18 – 30 years, and 6.9 ± 1.0 mm
in adults older than 30 years (Koivunen-Niemela et al. 1995, Ying et al. 2003). In
the transversal section the Achilles tendon is ovoid in shape.
The paratenon, surrounding the Achilles tendon, is demonstrated as a reflective line
around the tendon. The normal retrocalcanear bursa can be seen as a thin layer of
fluid. The normal walls of the bursae are too thin to be identified by ultrasound
(vanHolsbeeck et al. 1989). At the dorsal side of the tendon is the highly reflective
skin and subcutaneous fat identified. Ventral to the Achilles tendon is the Kager´s
fat pad, identified as a moderately echogenic, irregular, structure.
In the normal Achilles tendon, colour Doppler shows no vessels. The equipment is
not sensible enough to register the blood flow in the intratendinous vessels.
However, in rare occasions, it is possible to register some minimal vascular flow
entering through the paratenon. Normally, a few small vessels can be seen in the
fatty tissue in Kager´s fat pad.
Ultrasound guided puncture
A very important tool in the US technique is the possibility to perform US guided
punctures. One of the pioneers was Holm (1972), who presented a method to use
US as a guide in percutanously puncture procedures. All modern US machines
today are equipped with puncture devices. They consists of software showing
digital lines on the US monitor corresponding to a puncture guide attached to the
transducer, keeping a puncture needle in exact position in the image of the
examined structure, shown on the screen. A sterile rubber coat covers the
transducer, and the puncture device is sterile to minimize the risk of infection. The
puncture device makes it possible to perform US guided punctures in real time. As
an example, the method is used to puncture small tumours in the liver and pancreas
20
percutanously, or small lymph glands in the neck in order to receive tissue for
cytological or histological diagnosis (Solbiati et al. 2001). The use of ultrasound
guided puncture also minimizes the risqué for complications and increases the
possibility to obtain a satisfactory tissue sample, compared to blind puncture
(Nobili et al. 2003). Besides diagnostic punctures there are also therapeutic US
guided interventions, i.e. drainage of fluid or infected collections, or injections of
drugs percutanously into targets not palpable. When a very small structure is
punctured it is important to localize the target exactly, and it is furthermore an
advantage to connect the needle to a syringe with a connecting tube. The US
physician is holding the needle, and an assistant the connected syringe. This
procedure combines the dynamic US guidance with the sensitivity of the finger
tips, and makes it possible to puncture very small structures. To get a good result, it
is very important that there is a good collaboration between the physician and the
assistant.
When very small superficial structure is punctured, it is usually not possible to
connect a puncture device to the transducer, since the needle must be positioned
almost parallel to the skin and very close to the transducer. Instead, the puncture
can be performed either with the needle in the longitudinal plane, or in the
transversal plane of the transducer. It is possible to puncture in real time also with
this method, since the needle is seen in the tissue with US. This technique must be
used, when US is used dynamically to puncture the small vessels anterior to the
Achilles tendon, seen in chronic painful Achilles tendon conditions.
MRI of the Achilles tendon
MRI is a method well suitable to study the Achilles tendon (Soila et al 1999,
Karjalainen et al. 2000, Scweitzer et al. 2000, Tuite et al. 2002). The normal tendon
has low water content, resulting in no signals from the normal tendon.
Consequently, the normal tendon is black in all sequences, and there are no
detectable structures inside the tendon. When there are pathologic changes in the
tendon there is increased water content, and consequently, structural changes
21
within the tendon can be recognised. In recent MRI studies has an enhancement of
gadolinium in the pathological structures been shown (Movin et al. 1998c, Schalabi
et al. 2001&2002). Marshall et al. (2002) also showed, in a patient with chronic
tendinopathy, a small rapidly enhancing focal area of enhancement next to the
insertion of the tendon at the sites of blood supply, and also an early local contrast
enhancement within the tendon.
When comparing MRI and US, MRI is more sensitive to small changes of signals
in the tendon (Soila et al. 1999), but US shows more details in the tendon structure
and has a higher sensitivity to diagnose small intratendionous calculi (Kamel. et al.
2003). On the other hand, MRI can show bone pathology, which is not possible
with US (Karjalainen. et al. 2000). An MRI examination is more time consuming
and more expensive than an US examination. It is furthermore not possible to
perform a dynamic examination with MRI, which is possible with US.
22
Chronic Achilles tendon pain
In this thesis we have focused on the chronic painful condition in the Achilles
tendon, and acute conditions will not be discussed.
Nomenclature in chronic painful conditions
In the literature, the nomenclature for chronic painful conditions in the Achilles
tendon is often confusing, and not reflecting the pathology of the tendon disorders.
The terms “tendinitis” and “tendonitis” are often used even though there is no
inflammatory cell infiltration (Åström 1995, Maffulli et al. 1998, Movin 1998,
Khan et al. 1999, Alfredson&Lorentzon 2000). In recent literature the term
“tendinosis” has become widely accepted, and is being used for patients with a
chronic painful condition in the midportion of the tendon and were imaging (US or
MRI) show tendon abnormality corresponding to the painful area (Alfredson et al.
1998a+b, Khan et al. 1998, Teitz et al. 1997). The term “partial rupture” has also
been used (Ljungqvist 1967, Denstad&Roaas 1979, Åström 1998) for an injury
where a clearly discernible partial discontinuity is demonstrated at surgical
exploration. In patients with a long duration of pain symptoms, where the clinical
findings and imaging often are identical, “tendinosis” and “partial rupture” are
difficult to distinguish from each other. In a study by Åström & Rausing (1995), it
was shown, that when examining the histopathology in patients with chronic
painful Achilles disorders, partial ruptures were always surrounded by non-
inflammatory lesions (tendinosis). It is not known whether the tendon changes
associated with tendinosis precede partial rupture or if the partial rupture initiates
the tendinosis. Altogether, most likely, an acute onset of pain indicates a complete
or partial rupture of the Achilles tendon, while a gradually onset of the pain should
be named tendinosis.
The conditions can also be divided into proximal, mid-portion, and distal injuries.
23
Proximal pain
Chronic pain in the proximal (musculo-tendinous junction) part of the Achilles
tendon is not very common (Williams 1986). It mainly appears as late symptoms
after a total or partial rupture of the medial head of the gastrocnemius muscle.
Chronic pain in the calf can be caused by scar tissue or an organized haematoma
after a traumatic rupture. An important differential diagnosis is deep venous
thrombosis. Other conditions that must be ruled out is ruptured Baker cyst, or
muscle rupture with haematoma in the calf muscle. US combined with colour
Doppler can be used in the diagnosis of muscle ruptures with haematomas (Aspelin
et al.1992, Bianchi et al. 1998), ruptured Baker cysts (Langsfeld 1997) and deep
venous tombosis (vanHolsbeeck & Introcaso 2001, Theodorou 2003). The
diagnostic procedure will not be discussed in details.
Mid-portion pain (2 – 6 cm from the calcaneal insertion)
The midportion of the Achilles tendon is the most common part for the chronic
painful condition. The condition is relatively common among elite and recreational
athletes, especially in the age-group between 30 – 60 years (Kvist 1994). The
aetiology and pathogenesis are unknown, but an association with overuse have
been suggested. However, also non-active individuals have been shown to have
this condition (Fahlström et al. 2003).
The typical patient has a gradual onset of stiffness and pain, and clinical
examination show a tender swelling in the mid-portion of the tendon. Usually there
is no skin reaction (Alfredson&Lorentzon 2000).
Histopathology
Movin et al. (1997) has demonstrated changes in the collagen fibre structure and
arrangement, and an increased amount of interfibrillar glycosaminoglycans
(GAGs) in biopsies from the pathologic tendon (demonstrated with ultrasound).
Furthermore, Åström et al. (1995) showed an irregular, hypervascular pattern, with
24
groups of thick-walled vessels distributed un-evenly in the hyper-cellular tissue in
pathologic tendons. Some vessels had a nodular appearance, and some were
running perpendicular to the collagen fibres.
Pain mechanism
The background to pain in this condition has been largely unknown. The absences
of inflammatory cells in biopsies have indicated that this is a non-inflammatory
condition, but still, in common praxis, it has been treated as inflammation
(Leadbetter 1995, Kvist 1994, Józsa and Kannus 1997). However, recent studies
using intra-tendinous microdialysis, and gene technological investigations of
biopsies, clearly demonstrated that that there is no chemical inflammation involved
in the chronic stage of this condition (Alfredson et al. 1999 and 2003).
Interestingly, in the microdialysis study, a significantly higher concentration of
glutamate was shown in painful tendinosis tendons, in comparison to pain-free
normal tendons. Glutamate is a well-known and potent modulator of pain in the
human central nervous system (Dickenson et al 1997), but besides the finding of
glutamate receptors in bone-tissue (Chenu et al 1998), it had never before been
identified in the peripheral nervous system in humans. The role of glutamate in the
chronic painful Achilles tendon is still not known.
Also, in another study using microdialysis technique significantly higher levels of
lactate was shown in tendinosis tendons compared to normal tendons, and the
lactate concentrations were at about the same level as in working muscle tissue
(Alfredson et al. 2002). This finding indicates ischaemic conditions in tendinosis
tendons, but whether this is associated with ischaemic pain is not known.
Ultrasound
In midportion chronic Achilles tendinosis there is usually a thickening of the
tendon. In the longitudinal view, there is a spool-shaped thickening in the mid-
portion of the tendon, or the tendon is thickened in its whole length (vanHolsbeeck
& Introcaso 2001). In the transversal view, the tendinosis tendon is rounded or
25
oval. There are usually focal hypo-echogenic regions in the affected tendon
(Åström et al.1996, vanHolsbeeck & Introcaso 2001, Kainberger et al. 1990,
Gibbon et al. 2000). Generally it is very difficult to perform an exact measurement
of the size of these hypo-echogenic regions, since they are diffusely demarked.
The hypo-echoic regions inside the pathological tendon are most likely correlating
to the increased amount of GAG´s that have been demonstrated in core biopsies
(Movin et al. 1997).
Conservative treatment
Most of the proposed conservative treatment regimens for chronic painful Achilles
tendinosis are not based on scientific evidence (Almekinders&Temple 1998, Khan
et al. 1999, Alfredson&Lorentzon 2000). Often, biomechanical malalignments are
suggested to be causative factors (Welsh and Clodman 1980, Schepsis and Leach
1987 Hess et al. 1989, Kvist 1991). However, Åström (1998) demonstrated in a
study including 342 consecutive patients with chronic Achilles tendinopathy and
147 controls, that biomechanical “abnormalities” were not important in chronic
Achilles tendinopathy, and questioned the value of orthotics in the treatment of this
condition. Also, Lowdon et al. (1984) demonstrated in a randomized prospective
study including 33 patients with sports induced Achilles tendinitis, that there was
no benefit of treatment with viscoelastic heel pads. Commonly, the initial treatment
is a combination of methods assaulting different presumed etiological factors, such
as; training errors (James et al. 1978, Brody 1987) muscle weakness (Appel 1986),
Renström 1988, Nicol et al. 1991), poor flexibility (Wallin et al. 1985, Kvist 1991),
and poor equipment (Brody 1987, Jörgensen and Ekstrand 1988, Hess et al. 1989).
Different methods of physiotherapy, including stretching and strength training
programs have been utilized (Welch and Clodman 1980, Galloway et al. 1992,
Sandmeier and Renström 1997). Considering strength training, good clinical short-
and mid-term results with painful heavy-load eccentric calf muscle training has
been reported on patients with chronic painful Achilles tendinosis at the 2 – 6 cm
level in the tendon (Alfredson et al. 1998, Fahlström et al. 2003). The results were
26
reproduced in a randomised prospective study, where the results after painful
eccentric calf-muscle training were significantly better than after painful concentric
training (Mafi et al. 2001). The majority (82%) of these patients could return to pre
injury tendon loading activity.
Anti-inflammatory medications, NSAIDs and corticosteroid injections, are very
often used as a complement to other conservative therapies. The effect has been
debated by many authors (Åström &Westlin 1992, Almekinders et al. 1995, Shrier
et al. 1996, Åström 1998), but with the resent research findings in mind (Alfredson
et al. 1999 and 2003), that this is not an inflammatory condition, the use of anti-
inflammatory medication cannot be justified in the chronic phase of this condition.
Surgical Treatment
If it is not possible to cure the patient conservatively, surgical treatment is used. It
is a general opinion that approximately 25% of patients with chronic painful
Achilles tendinosis are treated surgically, and the frequency of surgery increase
with patients’ age, duration of symptoms, and occurrence of pathologic changes in
the tendon (Kvist 1994). Different surgical techniques are used. Usually the
hypertrophic parts of the paratenon and macroscopically abnormal tendon tissue
are excised (Leadbetter et al. 1992, Schepsis et al. 1994, Alfredson et al. 1998a,
Morberg et al., 1997, Movin et al 1997b). Recently Maffuli et al. (1997) have
reported promising results using percutaneous multiple longitudinal incisions in the
region with tendinosis. The short-time results after surgery has been reported to be
good in 80 -100 % of patients. However, there are few prospective studies and few
studies with a long-term follow-up. Leppilahti et al. (1991) reported excellent or
good result in 29/52 patients operated for mid-portion tendinosis and followed
during a 4-year period postoperatively. In a longer follow-up, ranging from 1-13
years, Schepsis et al. (1994) reported a satisfactory result in 67% of the patients.
From that study it was concluded that there were signs of deterioration of the
results of surgery, with time. In a 2-7 years follow-up report by Nelen et al. (1989)
on 50 patients surgically treated for tendinosis, 40 patients (80%) had an excellent
27
or good result. Morberg et al. (1997) reported 80% excellent or good results in 25
patients surgically treated for chronic pain from a partial rupture in the midportion
of the Achilles tendon, and with a follow-up period of 1.5-11 years. In a report by
Movin et al. (1997) including 40 patients surgically treated for intratendinous
pathology, 77% had excellent or good results at follow-up ranging from 1-4.2 years
postoperatively. After percutaneous longitudinal tenotomy (Maffulli et al. 1997) 37
out of 48 patients (77%) had an excellent or good result at follow-up 1.5-5 years
postoperatively.
The effect of surgery is debated. Many authors state, that surgery promotes a new
repair process, and improves the vascularity in tendon (Leadbetter et al. 1992,
Maffuli et al. 1997). However, the good results of quite different techniques might
also indicate that the effect of surgery is simply caused by extended denervation.
There are also other factors like the postoperative rehabilitation that might be of
significant important for the result (Leadbetter et al. 1992, Sandmeier&Renström
1997). However, it is important to keep in mind that the background to the
sometimes good results with surgical treatment has not been scientifically clarified.
There are few well-designed studies with long-term follow-ups of well defined
patient groups, and there are no randomized studies comparing different surgical
methods.
Distal pain (Achilles tendon insertional pain)
The distal part of the Achilles tendon is also relatively common for the chronic
painful condition, mainly in adult individuals. It can affect elite or recreational
athletes, but also non-active individuals. The aetiology and pathogenesis have not
been scientifically clarified, but there might be shoe-induced problems. The shoes
can be either too tight or too big, or having too high heel-caps (Hoppenfeld 1976).
The result can be mechanically induced injuries, such as friction induced
subcutaneous or retrocalcanear bursitis.
The condition is more complex compared to mid-portion pain, since the tendon,
bursae, and bone (calcaneus), alone or in combination, can be involved (Järvinen et
28
al. 1997). A prominent posterior angle of the calcaneal bone, Haglund´s deformity,
has been suggested to cause a painful “impingement” on the tendon with ankle
dorsiflexion (Vega et al. 1984). Most often the symptoms start gradually, with pain
during tendon loading activities. Clinical examination commonly shows a tender
swelling of the insertion region of the Achilles tendon. The upper lateral or medial
part of the calcaneus is often prominent and tender, and the patients have
difficulties to wear shoes with heel-caps.
Painful conditions in the Achilles tendon insertion, often called insertion
tendinopathy, are well-known to be difficult to treat (Kvist 1991). In the acute
phase conservative treatment is recommended, but with chronic pain, surgery is
often required (Kvist 1991 and 1994, Järvinen et al. 1997). There are several
theories explaining the origin of pain in this condition. It is suggested that the
retrocalcaneal bursae might be focus for a chronically inflammation (Kvist 1991
and 1994, Järvinen et al. 1997), and consequently could be a source for nociceptive
pain. Also, an impingement between a spur or prominence of the upper posterior
calcaneus, and a thickened or normal tendon, might mediate nociceptive pain from
the bone (periosteum) and/or tendon. Furthermore, a partially or totally detached
bone fragment, and maybe also calcifications, may cause pain. These different
tissues alone, or together, might all be responsible for the painful condition.
Therefore, in clinical praxis, it is often difficult to judge were to address the
treatment. Importantly, the scientific evidences for these theories are missing, and
there might be other sources for the pain.
Histopathology
The condition is commonly called insertion tendinitis, despite inflammatory cell
infiltration has not been demonstrated in the tendon (Järvinen et al. 1997). In distal
Achilles tendon pain there is often tendon changes defined as tendinosis. However,
there might well also be a subcutaneous and retrocalcanear bursitis, showing the
classical signs of inflammation. A common finding is also calculi and loose bone
29
fragments in the distal tendon. Frequently, there are bony spurs at the attachment of
the Achilles tendon into the calcaneus.
Ultrasound
In a case with isolated distal Achilles tendinosis, the tendon is thickened, and the
structure is irregular. The tendon fibres are irregularly organised and separated by
hypo-echoic areas (vanHolsbeeck & Introcaso 2001), Gibbon et al. (2000)
Like in mid-portion Achilles tendinosis, it is usually difficult to measure the
structural changes in the tendon. An enlarged subcutaneous or retrocalcanear bursa,
with thickened walls and increased content of fluid, can be found (Kainberger et al.
1990, vanHolsbeeck & Introcaso 2001, Gibbon et al. 2000). It is often more
difficult to penetrate the tissue anterior to the distal tendon following surgery, and
the frequency of the transducer must be reduced to improve penetration. This is
most likely due to absorption of the sound waves in the scare tissue. Furthermore,
there are often echogenic calculi inside the distal Achilles tendon at the insertion
into the calcaneus. There is a characteristic acoustic shadow behind the high-
echogenic calculi. Often there are well-demarked bony spurs adjacent to the
insertion of the Achilles tendon into the calcaneus (Kamel et al. 2003).
Treatment
The chronic painful condition in the Achilles tendon insertion is well known to be
difficult to treat. Because of the relatively poor knowledge about the source of
pain, it is often difficult to judge were to address the treatment in clinical praxis.
An isolated bursitis can sometimes be successfully treated with a local injection of
corticosteroids, but besides bursitis, the general opinion is that there are no
indications for corticosteroids in this condition (Leach et al. 1983, Renström and
Johnson 1985). Painful eccentric training has in a scientific study been shown to
have a poor effect on this condition (Fahlström et al. 2003). Other types of strength
training have, to our knowledge, not been scientifically evaluated.
30
When conservative treatments fail, surgical treatment is instituted. During surgery,
the main question is from what tissue the pain comes? Is it from the tendon, the
bursae, or bone (spurs, fragments, prominent deformity), alone, or in combination?
Consequently, the surgical technique is varying. Some authors address the surgery
towards a presumed impingement between the cranial part of the calcaneus and the
tendon, and state that a resection of the upper cranial calcaneus is necessary. Some
focus on the bursae, others focus the surgery on the distal tendon, while some
address the surgery to the tendon, bursa and bone in combination (Järvinen et al.
1997). Importantly, the scientific evidence for treatment results following different
surgical procedures except for pure bursitis is missing .
31
Aims
The general aim with the present thesis was to evaluate sonographic methods in
the investigation of the chronic painful condition in the mid-portion of the Achilles
tendon.
Specific aims were:
• To use grey-scale US to describe tendon thickness and structure in the
chronic painful condition located in the mid-portion of the Achilles tendon,
before and after treatment with eccentric training (paper I)
• To use grey-scale US combined with colour Doppler (CDV) technique to
describe the chronic painful condition in the mid-portion of the Achilles
tendon (paper II).
• To evaluate the combined findings from grey-scale US and colour Doppler
examinations, immunohistochemical analyses of biopsies, and diagnostic
injections, in the chronic painful condition in the mid-portion of the
Achilles tendon (paper VI).
• To describe the colour Doppler findings in the chronic painful condition of
the mid-portion Achilles tendinosis, before and after treatment with
eccentric training (paper V)
• To evaluate the effects of a new US guided treatment method (papers III,
IV), based on the findings in papers II and VI.
32
Methods
Ultrasound scanning technique of the Achilles tendon
The patient is placed in prone position with the feet hanging free below the foot-
end of the examination table (Fig 4). The posture must be comfortable, avoiding
tensions in the calf muscles.
Fig 4: Patient in position prepared for US
examination of the Achilles tendon.
After a careful palpation of the Achilles tendon, a generous amount of contact gel
is placed on the skin over the tendon, and the US examination is performed. A
stand of pad can be used to position the tendon within the transducers field of view
(Fornage et al. 1984). This stand-off pad can only be used when the thickness of
the tendon is measured, and when the structure is evaluated. When colour Doppler
examination is performed, the stand- off pad must be removed, since the sensibility
of the method will be better without the stand-off pad (the stand-off pad absorbs or
hinder the sound-waves).
A high quality US equipment must be used. (In the present studies an Acuson
Sequoia - Siemens Medical Solution was used). A linear transducer with high
frequency (13 – 15 MHz) is positioned parallel to the longitudinal axis of the
tendon (Martinoli et al. 1999 & 2002, vanHolsbeeck & Introcaso 2001). It is
33
important to place the probe perpendicular to the tendon, parallel with the tendon
fibres, to minimise artefacts. One important artefact in the classification of
structural changes in tendons is anisotropy (Connolly et al. 2001 Martinoli et al.
2002), which arises when the probe is placed in an improper angle to the tendon,
causing a low echogenic image even in a normal, high echogenic Achilles tendon.
The artefact is caused when the reflected sound-beams from the tendons do not hit
the probe, and consequently, the tendon structure will be shown as low echogenic.
Anisotropy is especially a problem where tendons are in a curved position, i.e. the
Achilles tendon insertion in the calcaneus.
The Achilles tendon is examined from the musculotendinous junction to the
attachment into the calcaneal bone. The whole length of the tendon is evaluated in
both longitudinal and transversal view (Fig 5), and the thickness and the structure
of the tendon is visually evaluated. Following questions should be answered: Is the
Achilles tendon thickened? Is it possible to distinguish the fibre structure of the
tendon, or are the fibres disorganized? Are there any hypo- or hyper-echogenic
regions in the tendon? During the examination also the structures adjacent to the
tendon are examined. Are there any hypo- or hyper-echoic regions around the
tendon?
A B
Fig 5: US examination of the Achilles tendon. A: Longitudinal scan.
B: Transversal scan. Note the generous amount of contact gel.
Is the structure of the fatty tissue in Kager´s fat pad normal? Is the retrocalcanear
bursa visible? If there are symptoms from the proximal part of the Achilles tendon,
34
or the calf muscle, the whole length of the calf, including the vessels and the
aponeurosis, must be examined.
When the grey scale examination is completed, the study continues with colour
Doppler examination of the tendon. CDV or CDE can be utilized. It is important to
adjust the system to make it possible to measure very low flows, since the vessels
related to tendons are very small and not even visible with grey scale US. It is also
very important to minimize the movements of the transducer to avoid artefacts. The
CDV examination must include both the Achilles tendon, as well as the
surrounding structures. As an example, it is important to find out if there is
increased vascularity inside or around the subcutaneous and retrocalcaneal bursaes.
To be able to perform a proper examination and to accurately evaluate the results,
the operator must be experienced in how to handle the equipment, and how to
optimise the technical settings of the machine.
Ultrasound-guided injection
The patient is placed in prone position with the feet hanging free below the foot-
end of the examination table. The posture must be comfortable, avoiding tensions
in the calf muscles. A generous amount of contact gel is placed on the skin, and the
Achilles tendon is examined without a standoff pad. A careful US examination as
described above is performed prior to the treatment. The thickness and the structure
of the tendon is evaluated and registered. The Achilles tendon is also carefully
examined with CDV to evaluate the extension of neovessels in the tendon, and the
strategy for injection is determined. The skin is washed carefully with an antiseptic
solution before injection. The leg is dressed with a sterile paper cover only leaving
the Achilles tendon free. The injection is performed either with an injection
35
Fig 6: Dynamic US-guided puncture from the medial side of the Achilles tendon.
Fig 7: Dynamic US-guided injection of Polidocanol against vessel entering
the Achilles tendon anteriorly.
Fig 8: After injection of Polidocanol. No remaining circulation in the
neovessels.
36
needle attached to a syringe or with a thin connecting tube between the needle and
the syringe. The latter procedure is preferred, since the targets to be punctured are
very small, and it is easier to perform a correct puncture when the operator has full
control over the procedure.
The syringe and the needle (including the connection tube) are filled with
Polidocanol 5 mg/ml, (2 – 4 ml). The active substance in Polidocanol
(Aethoxysklerol, Inverdia AB, Stockholm, Sweden) is an aliphatic, non-ionised
nitrogen free substance with a sclerosing and local anaesthetic effects. Polidocanol
has been widely used as sclerosing agent, with good clinical results in the treatment
of varicose veins in the legs and oesophagus, haemorrhoids, telangiectasis, and
gastroduodenal lesions (Guex 1993, Conrad et al. 1995, Winter et al. 2000).The
probe is covered with a sterile coat and a sterile contact gel is located on the skin.
The operator also wears sterile rubber gloves. The operator must be able to handle
the functions of the US machine either with a foot pedal, or there must be an
assistant handling the machine, since it is important to be able to shift momentary
between grey scale and CDV when the puncture is performed. The puncture is
always done from the medial side (Fig 6), to avoid a puncture of the sural nerve.
The needle is positioned just below the Achilles tendon (Fig 6&7), and the
puncture is performed dynamically with the aid of US. The needle tip is placed
against/into the small vessels entering the anterior surface of the Achilles tendon.
Puncturing of the tendon must be avoided, but the needle should be positioned
adjacent to the surface of the tendon. During the whole procedure the positioning
of the needle is continuously controlled with grey scale US and CDV. When the
needle tip is in correct position a small amount (0.1 – 0.2 ml) of Polidocanol is
injected, and the result is immediately visualized on the screen. If the position is
correct, the injected substance is spread along the anterior surface of the Achilles
tendon, and the circulation usually stops instantly in the vessels in the region.
Usually, it is possible to find several vessels entering the Achilles tendon from one
puncture of the skin. It is possible to alter the direction of the needle
subcutaneously and reach several targets. If it is not possible to reach all vessels
from one puncture, another punctures should be performed. It is important to
37
inform the patient that the puncture sometimes can be very painful, but that the
pain usually diminishes because of the local anaesthetic effect of Policocanol.
When there is no remaining circulation in the neovessels in the Achilles tendon the
treatment is finished (Fig 8).
The local anaesthetic effect will last a few hours. For some days after the injection
there is sometimes pain the region for injection, most likely due to a haemorrhage
caused by the puncture. The patient is allowed to walk freely immediately after the
procedure, and after one week more tendon loading activity is allowed.
The effect of the treatment will follow successively, with diminishing pain, but the
treatment must usually be repeated 1 – 5 times (mean 2 times) with 4 – 6 weeks
interval.
Statistical methods
The SPSS packages (SPSS Inc., USA) version 7.5 – 9.0 for personal computer was
used for descriptive statistics and statistical analysis.
Results are presented as means ± SD.
A non-parametric test for paired samples (Wilcoxon signed ranks test) was used to
test differences over time.
A p-value less than 0.05 was considered significant.
38
Summary of papers
Paper I:
Eccentric training in patients with chronic Achilles tendinosis- normalized
tendon structure and decreased thickness at follow-up
Aim
To use grey-scale US to prospectively study tendon thickness and tendon structure
in patients with chronic painful mid-portion Achilles tendinosis treated with
eccentric calf-muscle training.
Material and Methods
In this study 26 Achilles tendons in 25 patients with a long duration of pain-
symptoms from the mid-portion of the Achilles tendon were included in the
investigation. Grey-scale US was performed before and after the eccentric training
regimen, and the thickness and the structure of the tendons were evaluated.
At follow-up, all patients answered a questionnaire assessing their satisfaction with
the result of treatment, the level of present tendon loading activity, and tendon
related symptoms.
Main results
All tendons with tendinosis showed a localised thickening including structural
abnormalities (hypo-echoic areas and irregular structure) before treatment. At the
follow-up, mean 3.8 years after treatment, the US examinations showed a
significantly decreased thickness of the tendinosis tendons as well as a
“normalised” structure in 19 of the 26 tendons. In 6 out of 7 tendons with
remaining structural abnormalities, the patients experienced pain in the tendon
during tendon loading activity. The non-treated, pain-free normal tendons were
unchanged during the study period.
39
Conclusions
• Grey-scale US can be used to prospectively study Achilles tendon thickness
and structure.
• Treatment with eccentric calf muscle training in patients with chronic mid-
portion Achilles tendinosis seems to be associated with a localised (mid-
portion) decrease in tendon thickness, signs of a “normalised” tendon structure,
and pain relieve.
• Remaining structural tendon abnormalities seems to be associated with
remaining pain from the tendon.
Paper II:
Neovascularisation in Achilles tendons with painful tendinosis but not in
normal tendons: an ultrasonographic investigation
Aim
To use grey-scale US combined with colour Doppler examination to study
vascularity in tendons from patients with chronic painful mid-portion Achilles
tendinosis and in pain-free (normal) tendons.
Material and Methods
In this study, 21 patients (28 Achilles tendons) with chronic mid-portion Achilles
tendon pain and 14 controls (20 Achilles tendons) with no history
of Achilles tendon pain were included. The tendons were examined with grey-scale
US, and thickness and structure of the tendons were evaluated. Blood flow was
registered with CDV.
40
Fig 9: Achilles tendinosis. CDV shows neovessels before treatment.
Fig10 Tendinosis. CDV six months after US-guided injection of Polidicanol.
No remaining vessels in the Achilles tendon. No remaining pain.
Fig 11: Tendinosis. CDV two years after US-guides injection of Polidocanol.
No remaining vessels in the Achilles tendon. No remaining pain.
41
Main results
Neovessels were seen inside and on the ventral side of the region with structural
tendon changes in all Achilles tendons with chronic painful mid-portion tendinosis,
but not in the normal pain- free tendons,
Conclusions
• High resolution grey-scale US combined with colour Doppler examination
adds information about occurrence of a neovascularisation.
• There are neovessels in tendons with chronic painful mid-portion Achilles
tendinosis, but not in pain-free, normal, tendons.
• There might be a correlation between the occurrence of neovessels and
pain in patients with chronic painful mid-portion Achilles tendinosis.
Paper III:
Ultrasound guided sclerosis of neovessels in painful chronic Achilles
tendinosis: pilot study of a new treatment
Aim
To evaluate whether a specific treatment, ultrasound and colour Doppler guided
sclerosing therapy, addressed towards neovessels outside the region with structural
tendon changes, would have any effect on the pain in chronic painful mid-portion
Achilles tendinosis.
42
Material and Methods
Ten patients with chronic painful mid-portion Achilles tendinosis were treated by
US and colour Doppler guided injections of Polidocanol against the neovessels
entering the Achilles tendon from the anterior aspect. The effect on pain during
Achilles tendon loading activity was evaluated using a visual analogue scale
(VAS). The effect on the neovessels was registered using colour Doppler.
Main results
Neovascularisation was found inside and outside the ventral side of the region with
structural tendon changes in all tendons with chronic painful mid-portion Achilles
tendinosis. Before treatment, the mean VAS-score, evaluating the amount of pain
during Achilles tendon loading activity, was 73.6 (range 39-89). At the six month
follow up, 8/10 patients were satisfied with the treatment and mean VAS score had
decreased to 8 (range 0-29), and in the majority of the tendons all neovessels had
disappeared. In the 2/10 patients that not were satisfied with the treatment
(remaining tendon pain), multiple neovessels remained.
Conclusion
• US and colour Doppler guided sclerosing therapy of neovessels in chronic
painful mid-portion Achilles tendinosis seems to have a potential to cure the
pain in the short- term perspective.
43
Paper IV:
Sclerosing therapy in chronic Achilles tendon insertional pain-results of a
pilot study
Aim
To use US and colour Doppler guided sclerosing therapy to destroy the neovessels
and most likely also nerves accompanying the vessels, but not addressing any
treatment to the tendon, bursae, or bone, would affect chronic Achilles tendon
insertional pain in order to receive a pain relieve.
Material and Methods
Eleven patients with chronic insertional Achilles tendon pain were treated by US
and colour Doppler guided injections of Polidocanol against the neovessels
entering the Achilles tendon from the anterior aspect. All patients had distal tendon
pathology, 9 patients also had retrocalcaneal bursitis, and 4 patients had tendon
pathology, retrocalcaneal bursitis, and calcaneal bone pathology (spurs, bone
fragments). The effect on pain during Achilles tendon loading activity was
evaluated using VAS.
Main results
Before treatment, all tendons showed thickening, structural abnormalties (hypo-
echoic areas and irregular structure), and neovessels in the distal Achilles tendon.
Nine cases also had neovessels in close relation to the abnormal retrocalcaneal
bursa, and four cases also had bony spurs, calcifications, or loose bone fragments
in the tendon insertion. Before treatment, the mean VAS-score (pain during tendon
loading activity) was 84 (range 64-100). After the treatment the mean VAS-score
of the successfully treated patients (8/11) was decreased to 14 (range 3-40), and in
44
the three poor cases to 58 (range 49-74). Among the 3/11 patients that not were
satisfied with the treatment, two had bone pathology.
Conclusion
• US and colour Doppler guided sclerosing therapy of neovessels in chronic
Achilles tendon insertional pain seems to have a potential to cure the pain.
Paper V:
Effects on neovascularisation behind the good results with eccentric training
in chronic mid-portion Achilles tendinosis?
Aim
To use grey-scale US and colour Doppler technique to prospectively investigate if
eccentric calf-muscle training might have an effect on the neovessels demonstrated
in chronic painful mid-portion Achilles tendinosis.
Material and Methods
In this prospective study 30 patients (45 tendons) with chronic painful mid-portion
Achilles tendinosis, were included. All tendons were examined with high-
resolution grey scale US combined with colour Doppler, before and after a 12
weeks eccentric calf-muscle training regimen (Alfredson et al. 1998).
Main results
Before treatment, there was local neovascularisation in the region with tendon
changes (hypo-echoic areas, irregular fibre structure) in all tendons.
45
At follow up after treatment, there was a good clinical result in 40/45 tendons, and
a poor result in 5/45 tendons. In 39/40 tendons with a good clinical result of
treatment there was a normal tendon structure, and in 36/40 tendons there was no
remaining neovascularisation. In 5/5 tendons with a poor result of treatment a
remaining neovascularisation was seen, and in 2/5 tendons there were remaining
structural abnormalities.
Conclusions
• In patients with chronic painful mid-portion Achilles tendinosis, a good
clinical result after treatment with eccentric training seems to be associated
with a “normalised” tendon structure and no remaining neovascularisation.
• Dynamic US and colour Doppler examination demonstrated direct effects
on the neovessels (the flow stopped) during the eccentric load.
Paper VI
Is vasculo-neural ingrowth the cause of pain in chronic Achilles tendinosis?
- An investigation using US and colour doppler, immuno- histochemistry, and
diagnostic injections
Aim
To study the possible importance of neovascularisation in chronic Achilles tendon
pain, by evaluating the combined findings from grey-scale US and colour Doppler
examinations, immunohistochemical analyses of biopsies, and the results of
diagnostic injections.
46
Material and Methods
In this study, 25 Achilles tendons in 24 patients with chronic mid-portion Achilles
tendinosis, and 20 tendons in 14 healthy controls with no history of Achilles tendon
pain, were included.
All tendons were examined with grey-scale US combined with colour Doppler. In
all patients with painful tendinosis, under US and colour Doppler guidance, a local
anaesthetic was injected in the area with neovascularisation outside the anterior
part of the tendon.
In 6 patients, biopsies was taken from the region with tendon changes and
neovascularisation were processed for PGP 0.5 (a general nerve marker)
immunohistochemistry.
Main results
In all tendons with painful tendinosis, but not in any of the pain-free normal
tendons, there was a neovascularisation inside and outside the anterior part of the
region with structural tendon changes.
The pain during tendon loading activity was temporarily cured in all tendons, and
the mean VAS-score for heel-raises decreased significantly from 75 to 6 mm
following injection of local anaesthetic. The immunohistochemistry of the biopsies
showed nerve structures in the vicinity of blood vessels.
Conclusion
• Colour Doppler examination showed a region with neovascularisation in
close relation to the region with structural tendon changes, and findings
from the injection of local anaesthetic support that the neovessels in the
region might be the source of pain in chronic mid-portion Achilles
tendinosis.
47
Discussion
Chronic Achilles tendinosis is a most often painful condition with un-known
aetiology and pathogenesis, commonly seen among middle aged recreational
athletes (Kvist 1994, Tuite et al. 1997, Åström 1997, Movin 1998, Alfredson and
Lorentzon 2000). Overuse has been suggested to be the primary causative factor,
but the condition is also seen in physically non-active individuals (Åström 1997,
Fahlström et al. 2003). The background to pain in chronic Achilles tendinosis has
not been clarified (Khan et al. 2000b). For many years, despite the absence of
inflammatory cell infiltrates in tendon tissue samples, an inflammatory component
was considered to be involved. However, recent studies using microdialysis
technique and gene technology have clarified that there is no chemical
inflammation involved in the chronic stage of painful mid-portion Achilles
tendinosis (Alfredson et al.1999 and 2003). Instead, microdialysis studies showed
high levels of the neurotransmitter glutamate and lactate in painful tendinosis
tendons compared with pain-free normal Achilles tendons (Alfredson et al. 1999
and 2002). Glutamate is a well-known and potent modulator of pain in the human
central nervous system, but had never before been identified in tendons. The
possible role of glutamate or lactate in the pain mechanisms in painful tendinosis
has not been clarified, but is focused in present research projects at the Sports
Medicine Unit in Umeå, Sweden.
Chronic painful Achilles tendinosis has been known to be difficult to treat, but
recently a specially designed painful eccentric calf-muscle training regimen has
demonstrated to give very good clinical results (Alfredson et al. 1998, Mafi et al.
2001, Fahlström et al. 2003). The mechanisms behind the good results achieved
with this method are not known, and development of methods suitable for
prospectively studies of the tendons subjected to this treatment have been of high
priority. US is well known to be a good tool for investigations of tendons. Grey-
scale US has been shown to be a good and cost-effective method for examination
of the Achilles tendon (Åström et al. 1996), and a high reliability to locate
structural tendon abnormalities, such as tendinosis (Paavola et al. 1998). Grey scale
48
US alone has been used in most scientific studies evaluating Achilles tendon
problems. During the last years, there has been a rapid development of the US
techniques, with successively improved spatial resolution. Furthermore, Colour
Doppler sonography is an established technique to study blood flow in main
arteries and veins, and in tumours, Theodorou et al. (2003), Muller et al. (2001).
Today it is possible to study blood flow, in vivo, in very small vessels. Altogether,
these technical developments have increased the information about the pathology
in the chronic painful Achilles tendon. In Paper I, grey-scale US was used to
study tendon thickness and structure before and after treatment with eccentric calf-
muscle training. The results showed that in the majority of the successfully treated
patients the tendon thickness had decreased significantly, and the tendon structure
looked “normalised”. Consequently, it seems that the eccentric training regimen
has a potential to “normalise” the structural changes in the tendon, or at least is a
part of a process leading to an US evaluated normalised tendon. In this study, due
to practical reasons, the follow-up was performed 3-5 years after the 12 weeks
eccentric training regimen. However, after 3 months of training the majority of
patients were pain-free during Achilles tendon loading activity, indicating early
effects on the pain mechanisms. In Paper I, we focused on patients with the
combination chronic pain in the mid-portion of the Achilles tendon and
corresponding structural tendon changes demonstrated with US. However,
structural changes have also been demonstrated in the proximal part of pain-free
patellar tendons (Khan et al. 1997, Cook et al. 2000a+b and 2001, Fredberg and
Bolvig 2002). Furthermore, a spindle-shaped thickening in the mid-portion of the
Achilles tendon has been shown not to correlate with tendon pain during activity
(Fredberg and Bolvig 2002). It should be stressed that only thickness, not structural
changes was, evaluated in that study. Fredberg and Bolvig (2002) followed a small
group soccer players during one Danish soccer season, and found that only 5/11 of
the tendons with a local thickening became symptomatic during the season. Also,
in 4/11 of the asymptomatic tendons, the tendon thickness normalized during the
season. Altogether, it seems that the findings of a spindle shaped thickening or
49
structural changes alone, not combined with pain during tendon loading activity,
should be evaluated with caution and not render any specific treatment.
All our patients with chronic pain in the Achilles tendon are routinely examined
with grey-scale US. Colour Doppler examination (CDV-technique), was in Paper
II added to the grey-scale US. In consecutive patients referred for examination of
chronic mid-portion Achilles tendon pain, we found a local neovascularisation
inside, and outside the ventral part of the region with structural tendon changes in
28/28 tendons. In 20/20 pain-free tendons, there was a normal tendon structure and
no local neovascularisation. There are only a few studies where CDV or CDE has
been used to study tendons (Weinberg et al.1998, Terslev et al. 2000, Richards et
al. 2001, Khan et al. 2003, Peers et al. 2003, Zanetti et al. 2003). In the studies by
Weinberg et al. (1998) and Terslev et al. (2000), US together with CDVor CDE,
was used to study patellar tendinosis. Both studies showed structural tendon
changes and neovessels in patients with jumper’s knee. Terslev (2000) showed that
there was not always a positive correlation between pain symptoms and US
findings. There were 4/14 asymptomatic patients with both structural changes and
neovessels. Recently, CDV or CDE has been used to study chronic painful
conditions in the Achilles tendon, and in a study by Peers et al. (2003), 22/25 of the
chronic painful tendons with structural changes had a neovascularisation. Six
patients with chronic painful Achilles tendons demonstrated a proliferation of
vessels shown by power Doppler, and structural abnormalities demonstrated by
both standard US and MRI (Richards et al. 2001),. The findings in their studies, a
neovascularisation in the tendons with structural changes and pain, are in line with
the findings in our study. However, Khan et al. (2003) and Zanetti et al. (2003) did
not find any correlation between the occurrence of neovascularisation and pain, in
their studies on patients presenting with Achilles tendinopathy and Achillodynia.
An explanation of the different results might be differences between the patient
groups in the two studies. All patients in our study had structural tendon changes
on US corresponding to a painful swelling localised in the mid-portion of the
Achilles tendon, while only 37/57 tendons in the study by Khan et al. (2003), and
35/55 tendons in the study by Zanetti et al. (2003) had structural changes in the
50
tendons. To be included in our studies, it was not enough to have pain in the
Achilles tendon (tendinopathy, Achillodynia), instead, there needed to be structural
tendon changes on US corresponding to the painful region in the mid-portion of the
tendon. It might be that the patients with “tendinopathy” and “Achillodynia” with
normal US structure of the tendon had other diagnoses. Furthermore, in the study
by Khan et al. (2003) MRI showed that in only 19/34 symptomatic tendons were
there structural changes. This, again, raises the question about the diagnosis, since
MRI is a very sensible method to show pathologic changes in tendons. Another
important parameter to have in mind when evaluating studies using US and
CDV/CDE is the influence of imaging technique. As an example, the position of
the probe is very important since a wrong position of the probe might cause
anisotropy, showing low echogenic regions, even when the tendon structure is
normal. Another important factor is the importance of having relaxed calf muscles
when the examination is performed, since a contraction of the muscles will reduce,
or even stop the flow in the neovessels.
The findings in our study raised questions because most commonly
neovascularisation has been considered to be a positive part of the healing response
(Leadbetter et al. 1992, Ferrara 1999). On the other hand, these patients had had a
long duration of pain symptoms, and if this neovascularisation was a part of the
normal healing response it seems that it was not good enough to cure the pain. How
can the neovascularisation be explained? It is likely that something in the region
with structural tendon changes (tendinosis) is triggering vascular ingrowth. In a
recent study by Pufe et al. (2001), hypoxia and growth factors were possible
stimulators of neovascularisation in cultured rat tenocytes. Interestingly, Alfredson
et al. (2002) have recently demonstrated high levels of lactate in Achilles tendons
with chronic painful tendinosis, compared to normal pain-free Achilles tendons.
Therefore, theoretically, hypoxia might potentially stimulate neovascularisation in
chronic Achilles tendinosis. Also, the high concentrations of glutamate
demonstrated in chronic painful Achilles tendinosis tendons (Alfredson et al.
1999), might possibly be a trigger for vascular ingrowth.
51
To evaluate the importance a local neovascularisation had for chronic pain in the
Achilles tendon, in Paper VI, we combined the findings from US and CDV
examinations, immunohistochemical analyses of biopsies, and the results of
injections of a local anaesthetic. We found that if local anaesthetic was injected
locally against the neovessels entering the structurally changed Achilles tendon, the
patients were temporarily pain-free during heel raises. Furthermore, using the pan-
neuronal marker PGP 9.5 immunohistochemistry on biopsies taken from the region
with structural tendon changes, nerve structures were demonstrated in the vicinity
of blood vessels. This was not an unexpected finding, as it is well known that
nerves usually “travels with” blood vessels. From this study it was concluded that
there is a vasculo-neural ingrowths in the structurally changed part of the tendon
that possibly can explain the pain suffered from chronic painful mid-portion
Achilles tendinosis tendons.
In Paper III the hypothesis that the region with neovessels (vessels +
accompanying nerves) is responsible for the pain was evaluated by, US and CDV
guided injection of the sclerosing substance Polidocanol to destroy the neovessels.
The injections were given in very close relation to the neovessels in the region
anterior of the ventral part of the tendon where the vessels entered the region with
structural tendon changes. The immediate effect was a closure of the vessels
entering the tendon. After the injection the patients were temporarily pain-free
because of the anaesthetic effect of Polidocanol. The results at the 6-months
follow-up showed that after a mean of 2 injections (treatments), the majority of the
patients were satisfied and had no Achilles tendon pain during tendon loading
activity. US and CDV examination showed that these patients had no remaining
neovessels inside the region with structural tendon changes. In patients with
remaining tendon pain during activity, remaining neovessels were seen. These
results indicating that the neovessels and accompanying nerves have a crucial role
in the pain mechanism. However, the follow-up was short, the group of patients
was small, and there was no control group. Recently, a 2-year follow-up of these
patients showed that the same 8 patients were still pain-free and satisfied, and had
no neovessels. Furthermore, the tendon structure was normalised (non-published
52
material). We have now treated more than 70 patients (1-5 injections/treatments
with the sclerosing agent Polidocanol) with chronic painful mid-portion tendinosis,
and about 80 % of the patients are satisfied and pain free. Also, we have a present
ongoing randomised blinded study evaluating the results of injections of a
sclerosing or a non-sclerosing substance.
So far only 1/70 patients have suffered from any complication possibly related to
the sclerosing injections. It was a patient who sustained a total Achilles tendon
rupture at the end of an 800 meter race, six weeks after his second injection. The
rupture was localised in the proximal part of the tendon, not in the distal part were
he had received the injections. Theoretically, if the treatment causes an impaired
local vascularity in the tendon there might be an increased risk for tendon injury.
However, the neovessels might not be a part of the normal circulation, but instead
be considered as “pathological”. Furthermore, the injections are given outside the
tendon, under US and CDV, and only a small region is injected. The trauma using
sclerosing injections is minimal compared to surgical treatment, where excision of
tendinosis tissue or multiple longitudinal incisions is performed. Follow ups are
continuously performed on all treated patients. Furthermore, we routinely take
biopsies from the tendinosis tissue and the tissue surrounding the tendon in patients
who have had a poor result of injections and are treated surgically. Preliminary
results of two cases (the only cases that have needed surgical treatment during the
last two years) that each had received 5 injections of Polidocanol, showed minor
atrophy in the fat tissue on the ventral side of the tendon.
By using grey-scale US and CDV, we found neovessels entering the tendon from
the ventral side, also in patients with chronic pain in the Achilles tendon insertion.
In some patients there were also vessels in relation to an enlarged and
pathologically changed retrocalcanel bursa. Treatment of this condition is known to
be difficult, and often there are difficulties to decide if the treatment should be
addressed to the tendon, bursae, bone, or all these tissues in combination. In a
small non-controlled pilot-study (Paper IV), we tested the hypothesis that it was
the region with neovascularisation in the insertional part of the Achilles tendon that
was source of the pain. As described in Paper III, US and CDV guided injections
53
of the sclerosing agent Polidocanol were given towards the region with neovessels
entering the ventral surface of the tendon. The results showed that sclerosing the
region with neovessels outside the pathologically changed Achilles tendons, close
to the bursal walls and bone (spurs, calcifications, fragment), allowed the majority
of these patients to return to pain-free tendon loading activity. Absence of
neovessels after treatment correlated well with reduced pain from the Achilles
tendon insertion. In a few patients with tendon, bone, and bursal pathology in
combination, there was remaining pain in the tendon insertion after treatment.
These patients had remaining neovessels. In one patient with remaining pain after
treatment, there were no remaining neovessels, but a loose bone fragment.
Naturally, it is unlikely that this therapy would help patients with considerable
bone pathology causing mechanical problems, such as large spurs or loose bone
fragments. The results are interesting, but studies on larger groups of patients are
needed to be able to draw any conclusions on what type of distal pathology this
therapy might be best suited. Anyhow, the results again indicate that the region
with neovessels is involved in the pain mechanism, and submits additional
information of importance for decisions about treatment of this chronic condition.
In Paper V, the primary aim was to use grey-scale US and CDV technique to study
the occurrence of a neovascularisation before and after treatment with eccentric
training, and to relate the findings to the clinical results of the treatment, in patients
with chronic painful mid-portion Achilles tendinosis. For that study, observations
in Paper II was of significant importance. During the US and colour Doppler
examination, passive dorsiflexion in the ankle stopped the flow in the neovessels.
This finding raised questions whether the good clinical effects demonstrated with
painful eccentric training might be due to effects on the region with
neovascularisation? In Paper V, the results showed that before treatment there was
a local neovascularisation in the region with tendon changes in all tendons. At
follow-up after treatment, there was a good clinical result (no tendon pain during
activity) in 90 % of the tendons, and a poor result in 10 % of the tendons. In the
majority of the tendons with a good result, there was no remaining
neovascularisation, but in a few tendons a minor neovascularisation remained. In
54
all tendons with a poor result there was a remaining neovascularisation in the
tendon. Altogether, these findings again indicate that the region with
neovascularisation might be the source of pain in this condition. It is difficult to
explain exactly how the eccentric exercises may influence on the region with
neovessels, but a possible explanation might be the repeated occlusion of the
vessels during the heel-drop. The vessels travel from the soft fatty tissue anterior to
the Achilles tendon, into the hard tendinosis tissue, and there might possibly be a
“breaking point” between the soft and hard tissues. Theoretically, during the
“eccentric heel drop”, when the tendon is stretched, there might possibly be a
mechanical trauma to the neovessels and accompanying nerves. It is tempting to
believe that the severe local pain these patients experience in the region with
tendinosis during the period with eccentric training, especially during the first 2
weeks of treatment, might be due to interference with nerves accompanying the
neovessels.
55
Conclusion
Sonographic methods (grey-scale US and CDV) have provided important
information about the chronic painful Achilles tendon, leading to a better
understanding of the pain mechanism, as well as to a new treatment method.
However, since the methods are sensible to investigator technique, it is
fundamental to stress the importance of an experienced radiologist. The
neovascularisation demonstrated by colour Doppler, found in close relation to the
region with structural tendon changes that was demonstrated by grey-scale US, has
been demonstrated to be a very likely source of pain in the chronic painful Achilles
tendon. Treatment with US and CDV guided sclerosing injections of the region
with neovascularisation has shown promising short-term clinical results.
56
Acknowledgements
I would like to thank all who have contributed to this thesis and specially:
Håkan Alfredson, my friend and my tutor who really have encouraged me in my
work with my thesis. He also stimulates me to look forwards towards new exciting
research projects. We also have had much laughter together when we have worked
together with the project.
Katrine Riklund-Åhlström, my friend and colleague, who has supported me in my
writing, and encouraged me to work more with research.
Ronny Lorentzon, my friend, for his help and advices.
Christer Holmgren and Esa Åkerman, my friends and colleagues at the ultrasound
section, who have had a heavy burden in their work with the never ending
ultrasound queue, and therefore have made it possible for me to work with my
thesis.
Birgitta Lundström, who has given me technical support when we have performed
our examinations. Doris Fagerlund och Zara Nilsson-Nordensvärd, who have made
the work possible at the ultrasound section. There is no day without a laugh!
Everyone at the department of diagnostic radiology for help and support.
Finally I thank my wife Elna and my sons, Fredrik, Claes, Henrik and Anders, and
also, of course, my grandchild Oscar and his mother Helena, for all support during
all the years.
57
References
Albrecht, T., et al., Improved detection of hepatic metastases with pulse-inversion US during the liver-specific phase of SHU 508A: multicenter study. Radiology, 2003. 227(2): p. 361-70. Alfredson, H., et al., Achilles tendinosis and calf muscle strength. The effect of short-term immobilization after surgical treatment. Am J Sports Med, 1998a. 26(2): p. 166-71. Alfredson, H., et al., Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis.Am J Sports Med, 1998b. 26(3): p. 360-6. Alfredson, H., K. Thorsen, and R. Lorentzon, In situ microdialysis in tendon tissue: high levels of glutamate, but not prostaglandin E2 in chronic Achilles tendon pain. Knee Surg Sports Traumatol Arthrosc, 1999. 7(6): p. 378-81. Alfredson, H. and R. Lorentzon, Chronic Achilles tendinosis: recommendations for treatment and prevention. Sports Med, 2000. 29(2): p. 135-46. Alfredson, H., et al., Glutamate NMDAR1 receptors localised to nerves in human Achilles tendons. Implications for treatment? Knee Surg Sports Traumatol Arthrosc, 2001. 9(2): p. 123-6. Alfredson, H., et al., High intratendinous lactate levels in painful chronic Achilles tendinosis. An investigation using microdialysis technique. J Orthop Res, 2002. 20(5): p. 934-8. Alfredson, H. and R. Lorentzon, Intratendinous glutamate levels and eccentric training in chronic Achilles tendinosis: a prospective study using microdialysis technique. Knee Surg Sports Traumatol Arthrosc, 2003. 11(3): p. 196-9. Almekinders, L.C., A.J. Baynes, and L.W. Bracey, An in vitro investigation into the effects of repetitive motion and nonsteroidal antiinflammatory medication on human tendon fibroblasts. Am J Sports Med, 1995. 23(1): p. 119-23. Almekinders, L.C. and J.D. Temple, Etiology, diagnosis, and treatment of tendonitis: an analysis of the literature. Med Sci Sports Exerc, 1998. 30(8): p. 1183-90. Appel, H., Skeletal muscle atrophy during immobilization. Int J Sports Med, 1986. 7: p. 1-5.
58
Aspelin, P., et al., Ultrasound examination of soft tissue injury of the lower limb in athletes. Am J Sports Med, 1992. 20(5): p. 601-3. Backman, C., J. Friden, and A. Widmark, Blood flow in chronic Achilles tendinosis. Radioactive microsphere study in rabbits. Acta Orthop Scand, 1991. 62(4): p. 386-7. Bianchi, S., et al., Sonographic evaluation of tears of the gastrocnemius medial head ("tennis leg"). J Ultrasound Med, 1998. 17(3): p. 157-62. Boushel, R., et al., Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans. J Physiol.,2000.Apr 1;524: p.1:305-13. Brody, D.M., Running injuries. Prevention and management. Clin Symp, 1987. 39(3): p. 1-36. Chenu, C., Serre, CM., Raynal, C Burt-Pichat, B., Delmas, PD. (1998). Glutamate receptors are expressed by bone cells and are involved in bone resorption. Bone 22:(4) 295-9 Clancy, W.G., Jr., D. Neidhart, and R.L. Brand, Achilles tendonitis in runners: a report of five cases. Am J Sports Med, 1976. 4(2): p. 46-57. Coggeshall, R.E. and S.M. Carlton, Ultrastructural analysis of NMDA, AMPA, and kainate receptors on unmyelinated and myelinated axons in the periphery. J Comp Neurol, 1998. 391(1): p. 78-86. Connolly, D.J., L. Berman, and E.G. McNally, The use of beam angulation to overcome anisotropy when viewing human tendon with high frequency linear array ultrasound. Br J Radiol, 2001. 74(878): p. 183-5. Conrad, P., G.M. Malouf, and M.C. Stacey, The Australian polidocanol (aethoxysklerol) study. Results at 2 years. Dermatol Surg, 1995. 21(4): p. 334-6; discussion 337-8. Cook, J.L., et al., Patellar tendinopathy in junior basketball players: a controlled clinical and ultrasonographic study of 268 patellar tendons in players aged 14-18 years. Scand J Med Sci Sports, 2000a. 10(4): p. 216-20. Cook, J.L., et al., Prospective imaging study of asymptomatic patellar tendinopathy in elite junior basketball players. J Ultrasound Med, 2000b. 19(7): p. 473-9. Cook, J.L.; Asyptomatic hypoechoic regions on patellar tendon ultrasound: A 4-year clinical and ultrasound followup of 46 tendons. Scand J Med Sci Sports, 2001. Dec;11(6):321-7.
59
Correas, J.M., et al., Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts. Eur Radiol, 2001. 11(8): p. 1316-28. Davidson, E.M., R.E. Coggeshall, and S.M. Carlton, Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport, 1997. 8(4): p. 941-6. Denstad, T.F. and A. Roaas, Surgical treatment of partial Achilles tendon rupture. Am J Sports Med, 1979. 7(1): p.15-7. Dickenson, A.H., V. Chapman, and G.M. Green, The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. Gen Pharmacol, 1997. 28(5): p. 633-8. Dubowitz, V., Muscle biopsy. A practical approach. Baillière Tindall, London, 1985, p. 29 – 34. Dogra, V.S., et al., Sonography of the scrotum. Radiology, 2003. 227(1): p. 18-36. Dussik, K.T. On the possibility of using ultrasound waves as a diagnostic aid. Neurol. Psychiat. 1942, 174:153-168. Fahlstrom, M., et al., Chronic Achilles tendon pain treated with eccentric calf-muscle training. Knee Surg Sports Traumatol Arthrosc, 2003. 11(5): p. 327-33. Fahlström, M., Badminton and the Achilles tendon (dissertion), University of Umeå, Umeå, 2001. Fava, RA., Olsen, NJ., Spencer-Green, G., Yeo, K-T., Yeo, T-K., Berse, B., Jackman, RW., Senger, DR., Dvorak, HF., Brown LF., Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids andrheumatoid synovial tissue. J Exp Med 1994. p.341-6. Fessell, D.P., et al., US of the ankle: technique, anatomy, and diagnosis of pathologic conditions. Radiographics, 1998. 18(2): p. 325-40. Ferrara, N., 1999. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 77:527 – 543. Fornage, B.D., D.H. Touche, and M.D. Rifkin, Small-parts real-time sonography: a new "water path". J Ultrasound Med, 1984. 3(8): p. 355-7. Fredberg, U. and L. Bolvig, Significance of ultrasonographically detected asymptomatic tendinosis in the patellar and achilles tendons of elite soccer players: a longitudinal study. Am J Sports Med, 2002. 30(4): p. 488-91.
60
Galloway, M.T., P. Jokl, and O.W. Dayton, Achilles tendon overuse injuries. Clin Sports Med, 1992. 11(4): p. 771-82. Gibbon, W.W., J.R. Cooper, and G.S. Radcliffe, Distribution of sonographically detected tendon abnormalities in patients with a clinical diagnosis of chronic achilles tendinosis. J Clin Ultrasound, 2000. 28(2): p. 61-6. Goodwin, D.W., Imaging of the Achilles' tendon. Foot Ankle Clin, 2000. 5(1): p. 135-48, vii. Guex, J.J., Indications for the sclerosing agent polidocanol (aetoxisclerol dexo, aethoxisklerol kreussler). J Dermatol Surg Oncol, 1993. 19(10): p. 959-61. Hansson, M., Forsgren, .,. Immunoreactive atrial and brain natriuretic peptides are co-localized in Purkinje fibres but not in the innervation of the bovine heart conduction system. Histochem J 1995. 27: p.222-230. Hess, G.P., et al., Prevention and treatment of overuse tendon injuries. Sports Med, 1989. 8(6): p. 371-84. Hobson, MI., Brown, R., Green, CJ., Terengi, G., Inter-relationships between angiogenesis and nereve regeneration: histochemical study 1997. Br J Plast Surg 50: p. 121-131. Holm, H.H., et al., Ultrasound as a guide in percutaneous puncture technique. Ultrasonics, 1972. 10(2): p. 83-6. Hoppenfeld, S., Physical examination of the spine and extremities. Appelton-Century-Crofts Norwalk, Conneticut, 1976. Howry, D.H. and W.R. Bliss, Ultrasonic visualization of soft tissue structures of the body. J Lab Clin Med, 1952. 40(4): p. 579-92. James, S., B. Bates, and L. Osternig, Injuries to runners. Am J Sports Med, 1978. Mar-Apr;6(2): p. 40-50. Jarvinen, M., et al., Histopathological findings in chronic tendon disorders. Scand J Med Sci Sports, 1997. 7(2): p. 86-95. Jorgensen, U. and J. Ekstrand, Significance of heel pad confinement for the shock absorption at heel strike. Int J Sports Med, 1988. 9(6): p. 468-73. Józsa, L., et al., Three-dimensional ultrastructure of human tendons. Acta Anat (Basel), 1991. 142(4): p. 306-12.
61
Józsa, L. and Kannus, P., Human Tendons: Anatomy, Physiology, and Pathology (ISBN 0-87322-484-1), Human Kinetics, 1997. Kainberger, F.M., et al., Injury of the Achilles tendon: diagnosis with sonography. AJR Am J Roentgenol, 1990. 155(5): p. 1031-6. Kalebo, P., et al., Soft-tissue radiography, computed tomography, and US of partial Achilles tendon ruptures. Acta Radiol, 1990. 31(6): p. 565-70. Kamel, M., H. Eid, and R. Mansour, Ultrasound detection of heel enthesitis: a comparison with magnetic resonance imaging. J Rheumatol, 2003. 30(4): p. 774-8. Karjalainen, P.T., et al., MR imaging of overuse injuries of the Achilles tendon. AJR Am J Roentgenol, 2000. 175(1): p. 251-60. Khan, K.M., et al., Patellar tendinosis (jumper's knee): findings at histopathologic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group. Radiology, 1996. 200(3): p. 821-7. Khan, K., et al., Patellar tendon US and jumper´s knee in female basketball players. Clin J Sport Med, 1997. Jul;7(3): p. 199-206. Khan, K.M., et al., Patellar tendinopathy: some aspect of basic science and clinical management, 1998, Br J Sports Med 32(4): 346-55. Khan, K.M., et al., Histopathology of common tendinopathies. Update and implications for clinical management. Sports Med, 1999. 27(6): p. 393-408. Khan, K. and P. Kannus, Use of imaging data for predicting clinical outcome. Br J Sports Med, 2000a. 34(1): p. 73. Khan, K.M., et al., Where is the pain coming from in tendinopathy? It may be biochemical, not only structural, in origin. Br J Sports Med, 2000b. 34(2): p. 81-3. Khan, K.M., et al., Are ultrasound and magnetic resonance imaging of value in assessment of Achilles tendon disorders? A two year prospective study. Br J Sports Med, 2003. 37(2): p. 149-53. Kirkendall DT., Garrett WE., Functions and biomechanics of tendons. Scand J Med Sci Sports 7(2):62-66, 1997. Koivunen-Niemela, T. and K. Parkkola, Anatomy of the Achilles tendon (tendo calcaneus) with respect to tendon thickness measurements. Surg Radiol Anat, 1995. 17(3): p. 263-8.
62
Komi, P.V., S. Fukashiro, and M. Jarvinen, Biomechanical loading of Achilles tendon during normal locomotion. Clin Sports Med, 1992. 11(3): p. 521-31. Kossoff, G., Display techniques in ultrasound pulse echo investigations: a review. J Clin Ultrasound, 1974. 2(1): p. 61-72. Kvist, M., Achilles tendon injuries in athletes. Ann Chir Gynaecol, 1991. 80(2): p. 188-201. Kvist, M., Achilles tendon injuries in athletes. Sports Med, 1994. 18(3): p. 173-201. Langberg, H., B. J, and Kjaer, Blood flow in the peritendinous space of the human Achilles tendon during exercise. Acta Physiol Scand., 1998. Jun;163(2): p. 149-53. Langberg, H., et al., Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans. J Physiol., 1999. Nov 15;521: p. 299-306. Langberg, H., et al., Time patern of excercise-induced changes in human type I collagen turnover after prolonged endurande exercise in humans. Calcfif Tissue Int., 2000. Jul;67(1): p. 41-4. Langsfeld, M., et al., Baker's cysts mimicking the symptoms of deep vein thrombosis: diagnosis with venous duplex scanning. J Vasc Surg, 1997. 25(4): p. 658-62. Leach, R.E., E. DiIorio, and R.A. Harney, Pathologic hindfoot conditions in the athlete. Clin Orthop, 1983(177): p. 116-21. Leadbetter, W.B., et al., The surgical treatment of tendinitis. Clinical rationale and biologic basis. Clin Sports Med, 1992. 11(4): p. 679-712. Leppilahti, J., et al., Overuse injuries of the Achilles tendon. Ann Chir Gynaecol, 1991. 80(2): p. 202-7. Ljung, B.O., S. Forsgren, and J. Friden, Substance P and calcitonin gene-related peptide expression at the extensor carpi radialis brevis muscle origin: implications for the etiology of tennis elbow. J Orthop Res, 1999. 17(4): p. 554-9. Ljungqvist, R., Subcutaneous partial rupture of the Achilles tendon. Acta Orthop Scand, 1967: p. Suppl 113:1+. Lowdon, A., D.L. Bader, and A.G. Mowat, The effect of heel pads on the treatment of Achilles tendinitis: a double blind trial. Am J Sports Med, 1984. 12(6): p. 431-5.
63
Maffulli, N., et al., Ultrasound diagnosis of Achilles tendon pathology in runners. Br J Sports Med, 1987. 21(4): p. 158-62. Maffulli, N., et al., Results of percutaneous longitudinal tenotomy for Achilles tendinopathy in middle- and long-distance runners. Am J Sports Med, 1997. 25(6): p. 835-40. Maffulli, N., K.M. Khan, and G. Puddu, Overuse tendon conditions: time to change a confusing terminology. Arthroscopy, 1998. 14(8): p. 840-3. Mafi, N., R. Lorentzon, and H. Alfredson, Superior short-term results with eccentric calf muscle training compared to concentric training in a randomized prospective multicenter study on patients with chronic Achilles tendinosis. Knee Surg Sports Traumatol Arthrosc, 2001. 9(1): p. 42-7. Maity, P., Chakraborty, S., Bhattacharya, P., Angiogenesis-a putative new approach in glutamine related therapy. Pathol Oncol Res 1999:5: p. 309-314. Maresca, G., et al., New prospects for ultrasound contrast agents. Eur J Radiol, 1998. 27 Suppl 2: p. S171-8. Marshall, H., et al., Contrast-enhanced magic-angle MR imaging of the Achilles tendon. AJR Am J Roentgenol, 2002. 179(1): p. 187-92. Martinoli, C., et al., Analysis of echotexture of tendons with US. Radiology, 1993. 186(3): p. 839-43. Martinoli, C., S. Bianchi, and L.E. Derchi, Tendon and nerve sonography. Radiol Clin North Am, 1999. 37(4): p. 691-711, viii. Martinoli, C., et al., Ultrasound of tendons and nerves. Eur Radiol, 2002. 12(1): p. 44-55. McDicken, W.N., et al., Colour Doppler velocity imaging of the myocardium. Ultrasound Med Biol, 1992. 18(6-7): p. 651-4. Meire; H., Cosgrove, D., Dewbury K., Abdominal and General Ultrasound, Churrchill Livingstone, ISBN-0443-04277-2, 1993 Morberg, P., et al., Long-term results after surgical management of partial Achilles tendon ruptures. Scand J Med Sci Sports, 1997. 7(5): p. 299-303. Movin, T., et al., Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients. Acta Orthop Scand, 1997. 68(2): p. 170-5.
64
Movin, T., Aspects of ethiology, pathoanatomy, and diagnostic methods in chronic mid-portion Achillodynia (dissertion), Karolinska Institute Stockholm, Storckholm, 1998a. Movin, T., et al., MR imaging in chronic Achilles tendon disorder. Acta Radiol, 1998b. 39(2): p. 126-32. Movin, T., et al., Intratendinous alterations as imaged by ultrasound and contrast medium-enhanced magnetic resonance in chronic achillodynia. Foot Ankle Int, 1998c. 19(5): p. 311-7. Muller, M., et al., Comparison of color-flow Doppler scanning, power Doppler scanning, and frequency shift for assessment of carotid artery stenosis. J Vasc Surg, 2001. 34(6): p. 1090-5. Nelen, G., M. Martens, and A. Burssens, Surgical treatment of chronic Achilles tendinitis. Am J Sports Med, 1989. 17(6): p. 754-9. Neuhold, A., et al., Degenerative Achilles tendon disease: assessment by magnetic resonance and US. Eur J Radiol, 1992. 14(3): p. 213-20. Nicol, C., P.V. Komi, and M. F, Fatique effects of marathon running on neuromuscular performance. II. Changes in force, integrated electromyographic activity, and endurance capacity. Scand J Med Sci Sports, 1991. 1: p. 10-17. Nobili, V., et al., Blind and ultrasound-guided percutaneous liver biopsy in children. Pediatr Radiol, 2003. O'Brien, M., Structure and metabolism of tendons. Scand J Med Sci Sports, 1997. 7(2): p. 55-61. Omoto, R., et al., The development of real-time two-dimensional Doppler echocardiography and its clinical significance in acquired valvular diseases. With special reference to the evaluation of valvular regurgitation. Jpn Heart J, 1984. 25(3): p. 325-40. O'Reilly, M.A. and H. Massouh, Pictorial review: the sonographic diagnosis of pathology in the Achilles tendon. Clin Radiol, 1993. 48(3): p. 202-6. Paavola, M., et al., US in the differential diagnosis of Achilles tendon injuries and related disorders. A comparison between pre-operative US and surgical findings. Acta Radiol, 1998. 39(6): p. 612-9. Peers, K.H., P.P. Brys, and R.J. Lysens, Correlation between power Doppler US and clinical severity in Achilles tendinopathy. Int Orthop, 2003. 27(3): p. 180-3.
65
Pufe, T., et al., The angiogenic peptide vascular endothelial growth factor is expressed in foetal and ruptured tendons. Virchows Arch, 2001. 439(4): p. 579-85. Reid, J.M. and M.P. Spencer, Ultrasonic Doppler technique for imaging blood vessels. Science, 1972. 176(40): p. 1235-6. Renström, P. and R.J. Johnson, Overuse injuries in sports. A review. Sports Med, 1985. 2(5): p. 316-33. Renström, P., Diagnosis and management of overuse injuries. The Olympic Book of Sports Medicine (ISBN 0-632-01963-8, vol 1, Dirix A, Knuttgen HG and Tiitel K EDS Blackwell Scientific Publications, Oxford, 1988: p. 446-468. Richards, P.J., A.K. Dheer, and I.M. McCall, Achilles tendon (TA) size and power Doppler ultrasound (PD) changes compared to MRI: a preliminary observational study. Clin Radiol, 2001. 56(10): p. 843-50. Sandmeier, R. and P.A. Renstrom, Diagnosis and treatment of chronic tendon disorders in sports. Scand J Med Sci Sports, 1997. 7(2): p. 96-106. Schepsis, A.A. and R.E. Leach, Surgical management of Achilles tendinitis. Am J Sports Med, 1987. 15(4): p. 308-15. Schepsis, A.A., C. Wagner, and R.E. Leach, Surgical management of Achilles tendon overuse injuries. A long-term follow-up study. Am J Sports Med, 1994. 22(5): p. 611-9. Schweitzer, M.E. and D. Karasick, MR imaging of disorders of the Achilles tendon. AJR Am J Roentgenol, 2000. 175(3): p. 613-25. Shalabi, A., et al., MR evaluation of chronic Achilles tendinosis. A longitudinal study of 15 patients preoperatively and two years postoperatively. Acta Radiol, 2001. 42(3): p. 269-76. Shalabi, A., et al., Dynamic contrast-enhanced mr imaging and histopathology in chronic achilles tendinosis. A longitudinal MR study of 15 patients. Acta Radiol, 2002. 43(2): p. 198-206. Shrier, I., G.O. Matheson, and H.W. Kohl, 3rd, Achilles tendonitis: are corticosteroid injections useful or harmful? Clin J Sport Med, 1996. 6(4): p. 245-50. Soila, K., et al., High-resolution MR imaging of the asymptomatic Achilles tendon: new observations. AJR Am J Roentgenol, 1999. 173(2): p. 323-8.
66
Solbiati, L., et al., Ultrasound of thyroid, parathyroid glands and neck lymph nodes. Eur Radiol, 2001. 11(12): p. 2411-24. Teitz, C.C., et al., Tendon problems in athletic individuals. Instr Course Lect, 1997. 46: p. 569-82. Terslev, L., et al., Ultrasound and Power Doppler findings in jumper's knee - preliminary observations. Eur J Ultrasound, 2001. 13(3): p. 183-9. Theodorou, S.J., D.J. Theodorou, and Y. Kakitsubata, Sonography and venography of the lower extremities for diagnosing deep vein thrombosis in symptomatic patients. Clin Imaging, 2003. 27(3): p. 180-3. Tuite, D.J., P.A. Renstrom, and M. O'Brien, The aging tendon. Scand J Med Sci Sports, 1997. 7(2): p. 72-7. Tuite, M.J., MR imaging of the tendons of the foot and ankle. Semin Musculoskelet Radiol, 2002. 6(2): p. 119-31. Wallin, D., et al., Improvement of muscle flexibility. A comparison between two techniques. Am J Sports Med, 1985. 13(4): p. 263-8. vanHolsbeeck, M and Introcaso J , Musculoskeletal Ultrasound, sek ed. , (ISBN 0-323-00018-5), Mosby, 2001. vanHolsbeeck, M. and P.J. Strouse, Sonography of the shoulder: evaluation of the subacromial-subdeltoid bursa. AJR Am J Roentgenol, 1993. 160(3): p. 561-4. Vega, M.R., et al., Haglund's deformity. J Am Podiatry Assoc, 1984. 74(3): p. 129-35. Weinberg, E.P., M.J. Adams, and G.M. Hollenberg, Color Doppler sonography of patellar tendinosis. AJR Am J Roentgenol, 1998. 171(3): p. 743-4. Welsh, R.P. and J. Clodman, Clinical survey of Achilles tendinitis in athletes. Can Med Assoc J, 1980. 122(2): p. 193-5. Williams, J.G., Achilles tendon lesions in sport. Sports Med, 1986. 3(2): p. 114-35. Winter, H., E. Drager, and W. Sterry, Sclerotherapy for treatment of hemangiomas. Dermatol Surg, 2000.26(2): p.105-8. Ying, M., et al., Sonographic evaluation of the size of Achilles tendon: the effect of exercise and dominance of the ankle. Ultrasound Med Biol, 2003. 29(5): p. 637-42.
67
Zanetti, M., et al., Achilles tendons: clinical relevance of neovascularization diagnosed with power Doppler US. Radiology, 2003. 227(2): p. 556-60.
Åström, M. and N. Westlin, No effect of piroxicam on achilles tendinopathy. A randomized study of 70 patients. Acta Orthop Scand, 1992. 63(6): p. 631-4. Åström, M., Westlin, N Blood flow in human Achilles tendon assessed by laser Doppler flowmetry. J Orthop Res, 1994. 12(2): p. 246-52.
Åström, M. and A. Rausing, Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clin Orthop, 1995(316): p. 151-64. Åström, M., et al., Imaging in chronic achilles tendinopathy: a comparison of US, magnetic resonance imaging and surgical findings in 27 histologically verified cases. Skeletal Radiol, 1996. 25(7): p. 615-20.
Åström, M., On the nature and etiology of chronic Achilles tendinopathy
(dissertion). University of Lund, Lund, 1997.
Åström, M., Partial rupture in chronic achilles tendinopathy. A retrospective analysis of 342 cases. Acta Orthop Scand, 1998. 69(4): p. 404-7. Åström, M., Laser Doppler flowmetry in the assessment of tendon blood flow. Scand J Med Sci Sports, 2000. 10(6): p. 365-7.
68