Clinical Radiology 66 (2011) 140e152

Contents lists available at ScienceDirect

Clinical Radiology
journal homepage: www.elsevierhealth.com/journals/crad

Review

Guided interventions in musculoskeletal ultrasound: whats the evidence?

J. Davidson*, S. Jayaraman
St Richards Hospital, Spitaleld Lane, Chichester, West Sussex, UK

article in formation Article history: Received 2 March 2010 Received in revised form 13 August 2010 Accepted 21 September 2010

Increasing histological and radiological understanding of the processes involved in soft-tissue injury is leading to novel targeted treatments. A number of reviews have recommended that these treatments should be performed with image guidance. This review describes current ultrasound-guided interventions and injections, together with the level of evidence for these. Discussion of guided interventions will include; percutaneous lavage (barbotage), brisement, dry needling, electrocoagulation, and of guided injections; corticosteroids, autologous substances (blood and platelet rich plasma), sclerosants, and prolotherapy (hyperosmolar dextrose). Representative imaging illustrating some of these techniques is included for correlation with the methods described. As these procedures are often performed in sportspeople, it is essential that the radiologist is aware of prohibited substances and methods outlined in an annual publication from the World Anti-Doping Association (WADA). Finally, future directions, including the use of autologous substances, mesenchymal and stem cells will be discussed. 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction
Ultrasound is essential in soft-tissue injury diagnosis and treatment, including tendon, muscle, and nerve pathologies. Ultrasound-guided interventions straddle conservative and surgical management and improve patients quality of life in those unsuitable for surgery. Ultrasound-guided procedures allow assessment of lesions and evaluation of procedure tolerance. Radiologists must remember that they are clinicians and hone their communication skills to improve the patient experience. Ultrasound allows real-time accurate placement of treatment. Recent government initiatives to increase physical activity will probably increase activity-related injury. There

* Guarantor and correspondent: J. Davidson, 34 The Avenue, Southampton, Hampshire SO17 1XN, UK. Tel.: 44 7894 076 939. E-mail address: jdavidson@doctors.org.uk (J. Davidson).

is an increasing body of evidence from non-radiology specialties performing these techniques, both blind and also under ultrasound-guidance. Radiologists must lead evaluation of these techniques to ensure they are evidence-based and performed safely. Informed consent is essential, assisted by the referring clinician explaining the procedure in clinic. We routinely send an information leaet with the appointment letter. Patients can generally perform activities of daily living but should refrain from strenuous exercise for 72 h. Anaphylaxis is rare but should be considered. A high frequency (7e12 Hz) linear probe should be used. There is surprisingly little evidence in the literature regarding the efcacy of the methods used for infection prophylaxis.1 Our practice is to clean the puncture site with an alcohol solution. The probe is cleaned and sterile saline used as a coupling agent. Our audited injection rates are zero in over 2000 injections with this technique. Readers should be aware that using alcohol directly on the probe

0009-9260/$ e see front matter 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2010.09.006

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may invalidate the warranty. Full draping and probe covers is reserved for deep injections. This is an extensive topic; therefore, biopsy, joint aspiration, and foreign body removal have not been included. The studies cited refer to adult patients only. Almost exclusively published papers have been referenced. We will describe these techniques and the evidence for guided interventions and injections of therapeutic substances. Table 1 lists the included techniques, Table 2 summarizes the current evidence, Table 3 lists the key studies and Table 4 lists information pertaining to regulations of the World Anti-Doping Association (WADA),52 which governs the use of prohibited substances and methods of administration in many sporting bodies.

Guided interventions
Dry needling
This technique involves needle insertion into the lesion site, then repeated puncture aiming to stimulate an inammatory healing response (Fig. 1). Disruption of collagen bres at the lesion causes local haemorrhage. The hypothesis is that inammation leads to granulation tissue formation and tendon strength.2 Indications include: patellar tendinosis,2 lateral epicondylitis,3 medial epicondylitis,4 and plantar fasciitis.5 There is anecdotal evidence in Achilles tendinosis and adductor insertion tendinopathy. To our knowledge, there are no studies in the literature that purely use dry needling, although studies exist that combine dry needling with autologous blood injection.2e4 Further work is needed.

Brisement/percutaneous hydrostatic decompression

This has been described under different terms, including brisement and high-volume image-guided injections. It is suitable for use in Achilles tendinopathy as there is no tendon sheath, surrounded by connective tissue, the paratenon. The development of abnormally oriented vessels and nerves, is felt to contribute to pain.6,7 Therefore, a physical method of disrupting these neurovascular structures is
Table 1 The different ultrasound guided procedures and their mechanisms of action Category Technique Mechanism Calcium fragmentation Tendon repair Neurolysis Neurolysis Neurolysis Diagnostic/analgesic Anti-inammatory Tendon repair Neurolysis Tendon repair Muscle relaxation Tendon repair

Guided Interventions Percutaneous lavage Dry needling Brisement Electrocoagulation Cryotherapy Injectable substances Local anaesthetics Corticosteroids Autologous substances Sclerosants Prolotherapy Botulinum toxin A Future directions Mesenchymal stem cells

thought to reduce pain. Surgical management of Achilles tendinopathy includes: open or percutaneous tenotomy, peritenon and tendon debridement.7 The review by Cormick8 describes a method using 20 ml of cold 0.9% saline with celestone (betamethasone) and local anaesthetic, which is injected to strip the paratenon off the tendon. No prospective results are available with regard to short- or long-term pain relief. The use of steroids, in the context of abnormal tendon, is not advised because of the potential risk of rupture from inadvertent intratendinous injection.9 However, peritendinous steroid injections have not been shown to be associated with an increased risk of rupture.10 In a retrospective study of 64 patients, one group was given blind peritendinous or intrabursal injections of 1 ml hydrocortisone and 1 ml 1% xylocaine with light training. The second group underwent physical therapies only. Follow-up was performed over 1 year. Two ruptures occurred in each group; however, the image-guided injections gave improved results. A further small study of 28 patients11 divided into two groups, involved the blind peritendinous administration of either bupivacaine and prednisolone or bupivacaine alone. No tendon ruptures occurred. However, there was only a 33% incidence of complete pain relief. A study by Chan et al. (2008),12 a prospective study of 30 patients, with refractory Achilles tendinopathy, underwent an injection of 10 ml 0.5% bupivacaine, 25 mg hydrocortisone and 4 10 ml normal saline, to between the anterior aspect of the Achilles tendon and Kagers fat pad. Vascularity was assessed with power Doppler and eccentric loading was prescribed. The results from visual analogue scores (VAS), showed a signicant improvement in pain in the short term (2 weeks), with a mean change of 50 mm, from a mean of 76 mm to a mean of 25 mm (asymptomatic patients should score a VAS of 0 mm). There was also a statistically signicant improvement in function with a mean gain of 50 mm. The VISA-A (Victorian Institute of Sport Assessment-Achilles tendon)13 scores, reecting symptom extent, showed a signicant reduction after 30 weeks, with a mean VISA-A score pre-procedure of 44.8 points and 76.2 points post-procedure (an asymptomatic patient scores 100 points). In our institution, this technique is used in refractory mid-Achilles tendinosis.14 After clinical and sonographic assessment of the symptomatic Achilles, ultrasound guides the needle between the paratenon and the abnormal tendon. Up to 7.5 ml of 0.5% bupivacaine is then injected into the site over three sessions with the aim of expanding this space (Fig. 2). It is important to combine any interventions with eccentric loading between sessions, as a systematic review of nine studies by Kingma et al.15 demonstrated a 60% mean pain reduction in the eccentric overloading groups compared to 33% reduction in the control groups.

Electrocoagulation
This technique treats painful chronic Achilles tendinopathy. Neovessels and nociceptive bre formation are hypothesized to cause pain. This was substantiated by

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Table 2 This table contains an evidence statement for each procedure based on the available published literature. The evidence levels are taken from the Centre for Evidence Based Medicine77 Evidence Level Guided Interventions Dry Needling There is anecodotal evidence only for its use in tendinosis of the Achilles, patellar, triceps and adductor tendons. No randomised controlled studies have been performed formally as yet. Single prospective, non-randomized study of 30 patients with Achilles tendinosis using local anaesthetic and injectable steroid demonstrated signicant pain and function reduction over 30 weeks. Further work is needed. Single prospective, non-randomized study of 11 patients, which showed symptomatic relief following electrocoagulation of neovessels of the Achilles tendon. Further studies are required at different sites and with control groups. Currently, there are no randomized, controlled studies for cryoablation under ultrasoundguidance. As, there is only one case study for ultrasound-guided cryoablation of the genitofemoral nerve, there is no evidence base as yet. There is strong evidence and understanding of the pathophysiology, in the clinical scenario of calcic tendonitis of the rotator cuff, in particular, the supraspinatus tendon. There are a number of Cochrane systematic reviews assessing the evidence for use in shoulder pain, de Quervains tenosynovitis and trigger nger. Retrospective studies have shown medium-term benet in interdigital neuroma, de Quervains, and subacute posteromedial ankle impingement There are a number of conicting factors in the current studies of autologous blood and platelet-rich plasma (PRP), including combination with dry needling. Follow-up periods have also been relatively short. Further research is needed with comparative therapies and control groups. Studies show that ultrasound guided sclerosant injection produce successful results in stump neuromata, Achilles tendinosis, and patellar tendinopathy. Studies that involve crossover treatments are difcult to evaluate. Small studies performed in Achilles tendinosis and plantar fasciitis have shown reductions in pain. Randomized, controlled studies are required. There are several randomized, controlled studies for use of botulinum toxin type A in iliopsoas spasticity and lateral epicondylitis, which demonstrated medium-term muscle relaxation effects. Further non-ultrasound guided studies on plantar fasciitis have also been published. There is a single study using laboratory prepared cells for treatment of lateral epicondyitis, which demonstrated reduction in pain and functional disability. 5

Brisement

Electrocoagulation

Cryotherapy

Percutaneous lavage Injectable substances Corticosteroids

2 1

Autologous substances

Sclerosants

Prolotherapy Botulinum Toxin A

2 1

Future directions Level Level Level Level Level 1 2 3 4 5 includes includes includes includes includes

Tenocyte-like cells

high quality randomized controlled trials and systematic reviews. prospective comparative studies. case-control studies, retrospective comparative studies. case series. expert opinion.

sclerosant therapy,16 where reduction in neovascularity, correlated with reduction in pain. Specialized equipment is required. A pilot study by Ilum Boesen et al (2006)6 used a unipolar 16 G coagulation needle connected to an ICC 80 electrosurgical Workstation for Minor Procedures (ERBE). This requirement may limit availability. The pilot study by Ilum Boesens group6 employed 11 patients in a prospective study, all of which had been diagnosed with chronic Achilles tendinopathy. The coagulation wattage was set at 20e25 W and operated via a foot pedal. The procedure was performed under asepsis with local anaesthetic cover. Using ultrasound guidance, the needle was positioned against vessels entering the Achilles, equating to the position used in sclerosant therapy. Doppler identied neovessels initially and also response to treatment. Ice compression was used to reduce reactive hyperaemia. Gentle exercise was permitted. The Likert box scale (0 to 10) pain score was employed. All patients were given at least one treatment, with further treatment offered if symptoms persisted with intratendinous hyperaemia. After 6 months, the mean pain score

reduction was 7 (activity) and 1 (rest). At 6 months, there was no change in vascularity or size of tendon. Postulated complications included infection at the insertion site, nerve damage to the sural nerve, and tendon rupture.6 Electrocoagulation is an emerging technique that may have potential in the treatment of chronic tendinopathy.

Cryotherapy
Data on percutaneous cryotherapy for painful neuromata are beginning to become available.17 This technique has been applied to treat trigeminal neuralgia18 and renal tumours.19 Supercial cryotherapy has been used in physical therapy and anaesthetics. In a letter to the American Journal of Roentgenology, Neumann and OConnor,17 describe a pilot study of 10 patients who presented with refractory stump neuroma pain. The cryoprobe was positioned according to electrophysiological parameters. The endpoint of the treatment was either cessation of local tenderness or completion of ve freezeethaw cycles. There was a good response of 90%

Table 3 This table shows the key papers for each procedure, with the level of evidence and limitations of the different studies Technique (ultrasound-guided only) Dry needling Brisement Diagnosis Study details (ultrasound-guided studies only) No studies as yet Chan et al. 200812 Results Study type (crossover/cohort/ controlled/case series, etc) Retrospective case series Limitations

Achilles tendinosis

Electro-coagulation

Achilles tendinosis

Ilum-Boesen et al. 2006

Cryotherapy Percutaneous lavage

Genitofemoral Nerve Rotator cuff calcic tendonitis Rotator cuff calcic tendonitis Rotator cuff calcic tendonitis

Campos et al. 200920 Farin et al.23

Alna et al. 200124 Serani et al. 200974

Rotator cuff calcic tendonitis

Yoo, et al. 200975

Corticosteroids

Interdigital neuroma

Sofka et al. 200742

Plantar fasciitis

Yucel et al. 200941

De Quervains tenosynovitis Ankle joint

Jayapalan et al. 200937

Messiou et al. 200676

Twenty-one patients with chronic Achilles tendinopathy, treated with peritendinous bupivacaine, hydrocortisone and saline. Signicant reduction in VISA-A scores for pain and function Ten patients with painful mid-portion Achilles tendinosis, treated with electrocoagulation. 10 patients satised at 6 months with return to normal activity, Likert pain reduced from 7 to 0 Single patient treated for chronic inguinal pain by cryoablation of genitofemoral nerve, VAS reduced from 4 to 2 after 3 months Two patients with atraumatic shoulder pain, treated with needle punctures, aspiration and lavage under ultrasound, both pain-free with return to full range of movement, one at day 3, one at 15 min Fine-needle technique in 30 shoulders, lead to a signicant improvement in shoulder pain and disability scores Short-term and 10-year outcomes in 219 patients, with control group. Percutaneous treatment with saline. Decrease in symptoms at 1 month and 1 year. No difference between treated and control at 5 and 10 years Thirty-ve shoulders underwent needle decompression and subacromial corticosteroid injection. Results at 1, 3, and 6 months, showed 71.4% improvement in American Elbow and Shoulder Surgeons and Constant scores. In 10 patients, lack of reduction in size of deposit correlated with minimal change in symptoms Interdigital neuroma injection of lignocaine, bupivacaine and triamcinolone, 44 injections in 24 patients. Pre-procedure pain score 5.2, post-procedure of 2.2 with plateau at 3 days. Steroid injection to plantar fasciitis, guided under three different methods (ultrasound, scintigraphy, palpation), 35 heels randomly assigned to the different groups. Outcomes assessed by VAS, plantar fascia thickness and fat pad thickness all showed signicant improvement but no difference between the three methods. Triamcinolone (20 mg) and 0.5% bupivacaine (1 ml) for de Quervains disease in 17 patients; 15 out of 16 patients had signicant symptomatic relief at 7 weeks follow up. Nine athletes with subacute posteromedial ankle impingement underwent steroid injection and dry needling. All patients returned to original level of tness within 3 weeks, with eight remaining asymptomatic

Small sample size

Prospective case series

Small sample size, short follow-up period Short follow-up period Small sample size J. Davidson, S. Jayaraman / Clinical Radiology 66 (2011) 140e152

Case report Case series

Prospective case series Non-randomized, controlled trial

Short follow-up time of mean 53 days

Prospective case series

Confounded by subacromial corticosteroid injection

Retrospective case series

Addition of local anaesthetic

Prospective case series, with randomized methods

Prospective case series

Short follow-up time, no control group Small sample size, no controls

Prospective case series

(continued on next page)

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Table 3 (continued ) Technique (ultrasound-guided only) Autologous substances Diagnosis Study details (ultrasound-guided studies only) James et al. 20072 Results Study type (crossover/cohort/ controlled/case series, etc) Prospective cohort study Limitations

Patellar tendinosis

Medial epicondylitis Lateral epicondylitis

Suresh et al. 20064 Edwards et al. 200349

Lateral epicondylitis

Connell et al. 20063

Sclerosants

Stump neuromata

Gruber et al. 200857

Achilles tendinosis

Ohberg et al. 200216

Patellar tendinopathy

Hoksrud et al. 200854

Mortons Neuroma

Fanucci et al. 200458

Prolotherapy

Achilles tendonosis

Maxwell et al. 200759

Plantar fasciitis

Ryan et al. 200962

Botulinum Toxin A

Iliopsoas spasticity

Sconenza et al. 200865

Lateral epicondylitis

Lin et al. 201067

Tenocyte-like cells

Lateral epicondylitis

Connell et al. 200972

Dry needling and autologous blood in 47 knees, two sessions 2 weeks apart, pre-procedure VISA-A score 39.8, post-procedure 74.3 Dry needling and autologous blood in 20 patients, 4 weeks and 10 months follow up, reduction in VAS score and Nirschl scores 2 ml Autologous blood injections in 28 patients, average follow up 10 months, pain score decreased from 7.8 to 2.3, decreased Nirschl score from 6.5 to 2.0 Dry needling and Autologous blood injection in 35 patients, follow-up at 4 weeks and 6 months, VAS reduced from 9 to 6 to 0 and Nirschl from 6 to 4 to 0 Up to 0.8 ml 80% phenol instillation in 82 patients, with nine painfree after rst treatment and at 6 months 38% experiencing unnoticeable pain Sclerosis of painful neovessels using 2e4 ml polidocanol in 10 patients, eight patients reported reduced VAS from 74 to 8 at 6 months Forty-two tendons in 33 patients, 23 knees randomized to polidocanol, 20 knees in control group (lignocaine/adrenaline injections). Treatment group reported improvement in VISA-A scores from 51 to 62 after 4 months Forty intermetatarsal neuromas injected with solution of 70% adrenaline and 30% ethylic alcohol, procedure repeated every 15 days until resolution of symptoms. Total or partial relief achieved in 90% Intratendinous injection of 25% dextrose for chronic tendinosis of Achilles in 33 tendons, treated over a mean of four sessions. VAS (rest) reduced by 88%, VAS (normal activity) reduced by 84%, VAS (exercise) reduced by 78%. At 12 months, 20 patients were asymptomatic Intratendinous injection of 25% dextrose mixed with lignocaine in 20 patients, demonstrated reduction in VAS (rest) to 36.8 to 10.3, VAS (exercise) from 91.6 to 38.7. Injections given every 6 weeks, average treatment time 22 weeks Ten patients, treatment for iliopsoas spasticity, followed by 4 weeks of physiotherapy, VAS scores reduced from 6.7 before to 2.8 40 days after. The muscle relaxation effect lasted between 3 and 6 months Nineteen affected elbows of 16 patients, randomized to either botulinum toxin or triamcinolone. AT 4 weeks, botulinum group experienced a smaller reduction in pain but increased grip strength over the triamcinolone treated patients Twelve patients, with refractory lateral epicondylitis, underwent injection of laboratory-prepared collage-producing cells at the common extensor origin. Pain and functional disability (Patient rated Tennis Elbow Evaluation) decreased from 78 to 47 at 6 weeks, to 35 at 3 months and 12 at 6 months. Satisfactory outcome in 11 of the 12 patients

Confounding factor of dry needling Dry needling in addition, small sample size Small sample size

Prospective cohort study Prospective cohort study

Prospective cohort

Dry needling

Prospective cohort study

Prospective cohort study

Non-specic scoring method, no control group** Non-specic scoring method, no control group

J. Davidson, S. Jayaraman / Clinical Radiology 66 (2011) 140e152

Randomised controlled trial, crossover study

Propsective clinical pilot study

Small sample size, no control group

Prospective clinical study

Small sample size, non randomized, no control group

Case series

Scoring tool non-specic, no control group

Prospective clinical pilot study

Small sample size, non-specic measurement tool Small sample size

Propsective, randomized, double blind pilot study

Prospective clinical pilot study

Small sample size, short follow-up time

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Table 4 This table summarises the WADA regulations, which relate to musculoskeletal radiology procedures. The annual publication divides these into prohibited substances and methods Regulation Substances S2. Platelet-derived preparations Prohibited if administered intramuscularly. For administration via other routes, a declaration of use is required in accordance with the International Standard for Therapeutic Use Exemptions) S9. Glucocorticosteroids All are prohibited when given by oral, intravenous, intramuscular or rectal routes. Declaration of use must be completed by the Athlete for administration via intra-articular, peri-articular, peritendinous, epidural, intradermal and inhalational routes. Methods M1. Enhancement of oxygen transfer Blood doping, including autologous, homologous, heterologous blood or red blood cell products When prohibited At all times (in and out of competition)

In competition only

At all times

pain relief 3 months after treatment, but at 1 year, only three patients had continued pain relief. The authors suggest that cryotherapy combined with high-resolution sonography may be useful. The benet of cryotherapy over phenol is reduced risk of local tissue necrosis. There is a single case report20 of ultrasound-guided cryoablation of the genitofemoral nerve for inguinal pain. The cryoablation treatment was preceded by a diagnostic injection of local anaesthetic, which provided immediate pain relief. Two 3 min intervals of treatment were given via the cryoprobe, under direct visualization. The patient remained pain-free at 2 months with no recorded postprocedure complications. These initial publications indicate that ultrasound-guided cryotherapy for painful neuromata may be of benet but further trials are needed.

Percutaneous lavage
Percutaneous lavage is synonymous with barbotage or image-guided needle irrigation and aspiration. It is described in a number of review articles21 and can involve either a one or two needle approach to break up intratendinous calcications.21 Barbotage was rst described three decades ago as a uoroscopic procedure by Comfort and Arales (1978).22 The earliest description of an ultrasound-guided technique was by Farin et al.,23 which was a case series of two patients who underwent needle puncture (with an 18 G needle) of their supraspinatus tendons and alternate injection of saline and aspiration of calcium apatite crystals.

A new technique has been described which involves a ne-needle technique (22 G) with lavage of 1% lignocaine, which has led to reduced pain and disability, in a prospective study of 30 patients.24 The measure of pain and function was by the Shoulder Pain and Disability Index (SPADI) questionnaire, using visual analogue scales. Patients attended a follow-up appointment at a mean of 53 days, where the overall SPADI decreased by 27%, with pain reduced by 30.5% and disability by 23.9%. At our hospital, a two-needle technique is performed whereby saline solution is injected through one needle and dissolved calcium extracted through the other. Serani et al.74 have shown improved symptoms at 1 and 3 months and 1 year using this technique. Other therapies used for calcic tendinopathy include (external) ultrasound therapy,25 extracorporeal shock wave therapy,26 active non-operative treatment,27 and open or arthropscopic subacromial decompression.27

Injectable substances
There are a variety of therapeutic agents available. Image guidance is essential and awareness of side effects.

Local anaesthetics
Local anaesthetics provide immediate pain relief and assist in diagnosis. However, signicant adverse effects to the central nervous and cardiovascular systems can occur

Figure 1 Dry needling. (a) Shows a thickened hypoechoic are on the inferior aspect of the patellar tendon (arrowed) with some increased vascularity. (b) Shows the position of the needle within the area of tendinosis during the process of dry needling.

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Figure 2 Brisement: a, b and c demonstrate the process of brisement for treatment of Achilles tendinosis and paratenonitis. (a) Shows a thickened, asymmetric Achilles tendon in transverse section, with hypoechoic areas. (b) Shows the position of the needle (black arrow) between the paratenon and the tendon, with a crescent of hypoechoic saline and local anaesthetic (white arrow). (c) Illustrates the resulting space (black arrows), which correlates with reduction in symptoms at six weeks.

with inadvertent intravascular injection.28 Local adverse effects include chrondrolysis,29 particularly if administered with vasoconstrictors.28 Although not used currently in our hospital, 0.5% ropivacaine (Naropin) has been shown to be less toxic to human articular chondrocytes in vitro compared with 0.5% bupivacaine.30 Indications include joints,31 bursal,31 peritendinous11 lesions, and interdigital neuromata.32 They are often injected simultaneously with corticosteroids to provide pain relief. Local anaesthetics block sodium-specic ion channels on neuronal cell membranes, inhibiting signal conduction, with smaller neurones inhibited rst. There are two main groups: esters (cocaine and procaine) and amides (lignocaine, bupivacaine). Severe allergic reaction is more common with esters. Action is potentiated by the vasoconstrictor action of adrenaline, which decreases vascular absorption. The most commonly used preparations in the UK include: procaine hydrochloride (Novocain); lignocaine hydrochloride (Xylocaine); and bupivacaine hydrochloride (Marcaine). Procaine has the shortest duration (30e60 min), lignocaine moderate (80e120 min) and bupivacaine the longest (180e360 min).28 Bupivacaine is used most frequently for radiological musculoskeletal procedures. A contraindication is previous allergic reaction to amide anaesthetics. Local

sepsis is considered a relative contraindication due to the risk of introducing infection into the joint. The maximum safe dose of bupivacaine is 2 mg/kg. However, there has been recent concern over the toxic effect on chrondrocytes by bupivacaine.29 Injection of corticosteroid concurrently may ameliorate this effect.28

Corticosteroids
Corticosteroid injections are a widely used therapy (blind and ultrasound-guided) for their anti-inammatory properties and to provide medium-term symptomatic relief. Where ultrasound guidance is employed, indications include joints, bursae, tendon sheath, interdigital neuromas, and spinal indications (usually under uoroscopic guidance).28 A reference text, such as McNally Practical Musculoskeletal Ultrasound,33 should be consulted for details of patient positioning. Several studies34,35 have demonstrated that imageguided steroid injections of the shoulder and knee produce improved results over blind injections. Accurate placement is associated with improved clinical response. A prospective study by Eustace et al. (1997)34 with 37 patients in 38 shoulders, and using iohexol as a guide to accuracy of blind steroid placement, demonstrated a 37% success rate in injection placement.

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These synthetic corticosteroids are prednisolonederived: methyl prednisolone acetate (Depo-Medrol, Medralone); triamcinolone acetonide (Kenalog); betamethasone acetate/sodium phosphate (Celestone soluspan, Betaject); dexamethasone sodium phosphate (Decadron phosphate, Adrenocot, Decaject); and hydrocortisone. There is a low complication rate: joint infection (<0.001%), tendon rupture (<1%), skin atrophy (<1%), and hypersentivity (<1%).31 The risk of skin atrophy increases with multiple injections.28 It should be noted that due to a transient hyperglycaemia following peritendinous (but not intra-articular) steroid injections, diabetic patients should undergo glycemic monitoring for up to 3 weeks post-procedure. There is variability in the solubility of the different preparations, due to relative content of esters. Dexamethasone and betamethasone sodium phosphate are freely water soluble and therefore more rapidly absorbed by cells, having a rapid onset of action but reduced duration.28 Of note, other substances are contained within the corticosteroid preparation, including preservatives (usually benzyl alcohol) and a drug vehicle (polyethylene glycol), which may rarely cause allergic reactions. There is anecdotal evidence that mixing steroid and local anaesthetic can cause aggregation of the corticosteroid crystals. However, a study by Benzon et al. (2007)36 has shown that corticosteroid crystals retain their shape and size when mixed with lignocaine or iodinated contrast agents. In the upper limb there are a number of indications for corticosteroid injection, including; de Quervains tenosynovitis,37 osteoarthritis of the trapeziometacarpal joint,38 shoulder pain,39 and trigger nger.40 In the lower limb, the indications for corticosteroid injection include; ankle arthritides,32 tarsal tunnel syndrome,32 osteoarthritis of the rst metatarsophalangeal joint,32 plantar fasciitis,32,41,43 and interdigital neuroma42

Autologous substances (blood and platelet-rich plasma)

This is a relatively new development and particularly prominent in the sports medicine literature. In the UK, the government are in the process of assessing the evidence in drawing up guidance (National Institute for Health and Clinical Excellence, NICE).44 The substances include platelet-rich plasma (PRP) and gels, autologous blood, and autologous conditioned serum (ACS). Indications for use of autologous blood include medial epicondylitis,45 lateral epicondylitis,3,45 and patellar tendinosis.2 To date, clinical indications for PRP administered under ultrasound guidance include: medial and lateral epicondylitis45 and plantar fasciitis.46 There is also anecdotal evidence for use of PRP in acute medial collateral ligament injuries (MCL) injuries although the effectiveness of this has not been conrmed in any studies as yet, and not under ultrasound guidance. A single study using ACS to treat muscle strains has shown promising results.47 Platelet gels and PRP are also used in the context of total knee replacement (TKR), wound healing, lumbar spinal fusion, and maxillofacial surgical

procedures.48 It has been postulated that the use of platelet gels and PRP, may be termed as the new developing eld of orthobiologicals. For injection of autologous blood, a 2e3 ml sample is withdrawn from the antecubital fossa (contralateral side if applicable) and injected at the site of the lesion2e4 (Fig. 3). The technique for acquiring PRP is as follows. 30e60 ml of blood is withdrawn using a buttery needle, which avoids trauma and activation of the resting platelets.48 The blood sample is then placed in a centrifuge for 15 min at 3200 rev/min (depending on the device used). This separates the blood into platelet poor plasma (PPP), red blood cells, and PRP. The PPP is extracted through a special port and discarded. This leaves the PRP in a vacuumed space, where it is mobilized for 30 s to resuspend the platelets. After this nal stage, 3e6 ml PRP can be withdrawn (depending on the initial volume collected).48 It has been noted that patients may experience mild or moderate discomfort during the injection, which can be relieved with ice or simple analgesics, such as paracetamol.48 Studies that have been performed using autologous substances (blood and PRP) have also involved dry needling of the tendon prior to injection with no control groups used, which are acknowledged limitations of these studies. A prospective cohort study2 of 47 knees in 44 patients studied the effect of dry needling and autologous blood on refractory patellar tendinosis. The VISA-A score13 was used to assess the response to the intervention. There was a significant improvement after the intervention, with a preprocedure score of 39.8 (mean) and post-procedure of 74.3. Structural changes included reduction in overall tendon thickness, size of area of tendinosis, with a reduction in interstitial tears. All patients underwent a standard physiotherapy regime of eccentric loading exercises. However, as dry needling and autologous blood were used simultaneously, it is not clear which treatment exerted the benecial effects. Further work with control groups would be needed to evaluate these treatments further. A study of the use of autologous blood in the treatment of lateral epicondylitis was performed on 35 patients with refractory lateral epicondylitis.3 Nirschl and VAS scores were performed pre and post-procedure and at 4 weeks and 6 months. The procedure involved injection of 2 ml 0.25% bupivacaine along the surface of the tendon initially. After a few minutes, the 23 G needle was used to dry needle the tendon for 1 min, after which the patients blood was injected at the site of tendinosis. This procedure was repeated at 4 weeks. At 12 weeks, the patients were reassessed and offered a third injection, with a nal ultrasound evaluation at 6 months. Thirty-ve patients completed the course in total, with 26 having two injections and nine having three injections. Two patients failed the treatment and underwent surgery. There was a decrease in the VAS score from 9 pre-procedure to 6 at 4 weeks and 0 at 6 months. No major complications occurred. These are promising results but certain questions arise: is the physical act of needling with internal haemorrhage sufcient for tendon healing? What is the optimal post-procedure management?

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Figure 3 Autologous blood. These images show injection of an autologous blood patch in the repair of a partial tear of extensor carpi radialis brevis (ECRB). (a) Shows an anechoic area in the ERCB (white arrow) with associated hypervascularity secondary to neovascularity (black arrow). (b) Illustrates the injection of autologous blood (white arrow) to the site of tear (needle arrowed black). (c) Two months later, the neovascularity has decreased (black arrow) and there has been regeneration of tissue at the site of partial tear (white arrow).

Edwards and Calandruccio49 also performed a small study of 28 patients, where 22 responded to autologous blood injections, with a reduction in the Nirschl score. However, these injections were given blind and mixed with local anaesthetic. To optimize the treatment, we feel that image guidance should be used. A further small study of 27 patients treated with autologous blood for medial epicondylitis4 also showed an improvement in the VAS scores pre and post-procedure. However, dry needling was again performed with no control group. Animal studies have been performed using of PRP in rabbit and horse tendon disease. A small number of human studies are available in the general medical literature. The benet of PRP over autologous blood is that the concentration of platelets is four to ve times higher. The growth factors (GF) contained in the a granules of the platelets become activated at the site of injury and continue to act for the next 7 days. It has been suggested that for this reason, a repeat injection should not be required.48

There are few studies in humans with PRP. Sanchez et al.50 reported a case series of 12 athletes, half of whom underwent open suture repair following complete Achilles tendon rupture, and the other half underwent the same operation but with the addition of a PRP injection to the wounded ends. In the second group, there was an earlier return to normal range of motion, with no wound complications. A larger cohort study of 20 patients with mostly refractory lateral epicondylitis was performed, where ve patients were controls and injected with bupivacaine, and the remaining 15 were given a single percutaneous injection of PRP.45 Injections were made at the site of maximal tenderness. Four weeks post-procedure, the PRP treated patients reported a mean 46% improvement with the control group reporting a 20% improvement. The PRP treated patients continued to have pain relief at 8 weeks and 6 months. ACS is derived from incubating the blood with glass beads and spinning the blood down in order to extract the

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serum, which contains the released GF. However, this method is less popular than producing PRP, as it produces a lower yield of GF.51 A number of potential risks have been postulated for autologous substances.51 Potential local complications include the induction of excessive brosis, due to the presence of TGF-b1 or by concomitant use of non-steroidal anti-inammatory drugs (NSAIDs). Potential systemic risks include; infection (although this is unlikely with autologous substances) and effect on the serum GF levels (which have been shown to decrease in some small studies 52). The caveat in treating sports people is in the WADA prohibited list,53 which is published annually and includes both prohibited methods as well as prohibited substances. Section S2 states that it is prohibited to administer growth factors, including platelet-derived preparations, by an intramuscular route. Other routes of administration would require a declaration of use. In the context of enhancement of oxygen transfer (section M1), blood doping, which includes the use of autologous blood products, is prohibited (see Table 4). The scientic and clinical basis for the use of autologous substances continues to develop in the musculoskeletal eld. More research is needed to integrate ultrasoundguided administration of these substances.

Sclerosants, phenol/polidocanol
These are indicated in patellar tendinosis,54 tennis elbow,55 chronic Achilles tendinosis,16 Mortons56 and stump57 neuromata; the outcomes for which have been assessed in small pilot studies. The most common sclerosants used are phenol or polidocanol. Phenol is used for alcoholization of interdigital neuritis via a percutaneous intraneural route and causes a chemical neurolysis (due to its afnity for nerve tissue), causing dehydration and necrosis.58 Polidocanol is a local anaesthetic agent, which is a licensed drug and used for sclerosis of varicose veins and telangiectasia.16 The proposed hypothesis for its benecial effects in chronic Achilles tendinosis is that the developmental of neovascularity around the abnormal tendon is associated with abnormal nerve growth at the same site15 and pain. The theory is that sclerosis of these neovessels reduces pain. However, it is still unproven whether neovascularity is benecial or detrimental. A pilot study comprising 10 patients16 demonstrated 80% satisfaction. During activity, there was reduced pain with no remaining neovascularity after an average of two injections. In the two patients that had ongoing pain, neovascularity remained. The thickness and structure of the Achilles was unchanged and no side effects were identied. Limitations of this study included small sample size, lack of control group and patients not blinded to the treatment. A prospective study by Magnan et al.56 involved 71 patients who were treated via a dorsal approach to the intermetatarsal space. They used a needle electrode connected to an electrostimulator to accurately locate the nerve by reproduction of paraesthesia to the digits. At this point,

2.5 ml phenol in 5% solution with water was injected followed by local anaesthetic for analgesia. Pain relief was assessed by VAS with treatment proving effective in 80%. No complications occurred over a mean of 36 months. Gruber et al.57 described a prospective study of 82 patients who they treated with sonographically-guided injection of up to 0.8 ml of 80% phenol for stump neuromata. Pain was assessed by VAS. Twelve patients were pain-free after one to three treatments. Nine of these were pain-free after the rst treatment. At 6 months, 52 patients had reduced pain of varying degrees. Minor complications were identied in 5% of the total treatments given: nonspecic painful soft-tissue oedema, painful local myopathy, conned infection, and local soft-tissue necrosis. Two treatments for lateral elbow tendinosis were compared in a prospective, randomised, controlled, doubleblind study of 32 patients.55 In this study, the patients were divided in two groups, one treated with polidocanol, the other with lignocaine and adrenaline. At 3 months, the lignocaine group were offered crossover treatment of polidocanol. Outcomes were assessed by patient satisfaction with treatment, VAS during activity, and maximal voluntary grip strength. No difference between the two groups was seen, both had signicantly reduced VAS at 3 and 12 months, with a signicantly higher grip strength at 12 months. The overall success rate was 50e62%. These studies show promising results for the use of sclerosants in Mortons neuroma and painful tendinopathy.

Prolotherapy
Prolotherapy (also known as regenerative injection therapy) is a technique where a small volume of an irritant substance is injected around a ligament or tendon insertion59 to initiate a local inammatory response. The most commonly used irritant is hyperosmolar dextrose, which has been trialled for the treatment of osteoarthritis of the knee, lower back pain, sacroiliac dysfunction,60,61 and lateral epicondylitis.60 More recently, prolotherapy has been combined with ultrasound guidance in Achilles tendinosis59 and plantar fasciitis.62 Hyperosmolar dextrose is thought to work by osmotic rupture of cells. Other irritants include phenol glycerine glucose (P2 G), which causes local cellular irritation and sodium morrhuate by chemo-attraction of inammatory mediators.21 In a prospective study59 of 33 tendons, 32 patients underwent a mean number of four sessions of 25% dextrose injection at 6 weekly intervals. VAS assessments and tendon size were measured before and during the treatment. There were signicant reductions in pain (from 38 pre-treatment to 4.5 after, 88.2% difference), with minimal change in tendon size (11.7 to 11.1 mm thickness). No complications were identied in this group. However, limitations include lack of control group and absence of blinding. A further study21 examined the use of hyperosmolar dextrose for treatment of refractory plantar fasciitis in 20 patients. Ultrasound-guided intraligamentous 25% dextrose/lignocaine solution was administered at 6 week intervals for a median of three treatments. Overall, 80% had

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a good to excellent outcome. Again, no control group was used and the patients were not blinded to the treatment. However, if further studies show that this technique is benecial, then there is a clear advantage over steroids, which have a risk of rupture of fascial bands. Further small studies have been published using blind injections of dextrose and lignocaine for chronic groin pain63 and coccydynia64 showing promising results, but further studies with ultrasound guidance are awaited.

colleagues about these minimally invasive, percutaneous options, especially, in the context of patients who are not surgical candidates and those patients with refractory symptoms after standard conservative management. All of these treatments, however, should be taken in the context of other non-radiological treatment options such as physiotherapy, podiatry, and orthotics, and it should be borne in mind that if the radiological treatment fails, surgical management might be required.

Botulinum toxin type A

This substance is relatively new in the musculoskeletal eld, with key indications being for muscle spasticity (iliopsoas, gastrocnemius),65 lateral epicondylitis,66,67 plantar fasciitis,68 and in the chronic pain setting. However, in rehabilitation units botulinum toxin is often injected blind. Several studies have emerged demonstrating increased accuracy of placement with sonographic guidance.69,65 In addition, a randomized study68 of 43 feet with refractory plantar fasciitis, using patients with bilateral symptoms, demonstrated signicant improvement in the foot injected with 50 units of botulinum toxin type A in 1 ml of normal saline. The amount of toxin varies, with some studies using up to 120 units.65 For treatment of the plantar fascia,68 a needle is inserted into the fascia via a posterior approach below the calcaneus. For treatment of iliopsoas spasticity,65 the injection is made via an anterior approach, into the pre-insertional segment of the distal iliopsoas, proximal to the myotendinous junction and beneath the inguinal ligament. In our institution ultrasound-guided botulinum toxin injections are used with good effect in stroke patients with muscle contractures.

Acknowledgements
The authors thank Dr N. Kendall for her contribution.

References
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Future directions
Key areas that are anticipated to receive more attention over the next few years include the use of growth factors,51 mesenchymal stem cells,68,70,71 and skin-derived tenocytelike cells72 for the treatment of tendinopathy and muscle injury. Aprotinin (serine protease inhibitor) peritendinous injections may reduce collagen degradation in tendinopathy, as shown in studies on patellar and Achilles tendinopathy without positive results.73 In the eld of sports medicine, Traumeel (a homeopathic medicine) is widely used as an ointment, gel, droplets, tablets, and injectable solution. No randomized controlled trials regarding its efcacy have been published.

Conclusions
This paper outlines the numerous options for ultrasound-guided therapies currently being explored in the eld of musculoskeletal radiology. We have tried to assess the available literature and identify the current evidencebase for the different treatments. However, it is important to recognize that there is a bias towards publishing positive results. It is important to raise awareness in clinical

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