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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

Transcript of The chronic painful Achilles tendon Sonographic findings ...140899/FULLTEXT01.pdf · The chronic...

Page 1: The chronic painful Achilles tendon Sonographic findings ...140899/FULLTEXT01.pdf · The chronic painful Achilles tendon Sonographic findings and new methods for treatment by Lars

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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

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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

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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

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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

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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.

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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

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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.

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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 -

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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

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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

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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).

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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.

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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).

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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

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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

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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.

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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

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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.

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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

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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

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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.

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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.

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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

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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

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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

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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

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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

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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

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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.

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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 .

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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.

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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

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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,

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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

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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.

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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

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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.

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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.

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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.

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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

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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

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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

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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.

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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

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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

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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

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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.

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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.

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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.

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