Guided interventions in musculoskeletal ultrasound: what’s the evidence?

Article Outline

• Abstract
• Introduction
• Guided interventions
  • Dry needling
  • Brisement/percutaneous hydrostatic decompression
  • Electrocoagulation
  • Cryotherapy
  • Percutaneous lavage
• Injectable substances
  • Local anaesthetics
  • Corticosteroids
  • Autologous substances (blood and platelet-rich plasma)
  • Sclerosants, phenol/polidocanol
  • Prolotherapy
  • Botulinum toxin type A
• Future directions
• Conclusions
• Acknowledgements
• References
• Copyright

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.

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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 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 leaflet with the appointment letter. Patients can generally perform activities of daily living but should refrain from strenuous exercise for 72h. Anaphylaxis is rare but should be considered. A high frequency (7–12Hz) linear probe should be used.

There is surprisingly little evidence in the literature regarding the efficacy 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 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.

Table 1. The different ultrasound guided procedures and their mechanisms of action

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

Level 1 includes high quality randomized controlled trials and systematic reviews.

Level 2 includes prospective comparative studies.

Level 3 includes case-control studies, retrospective comparative studies.

Level 4 includes case series.

Level 5 includes expert opinion.

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)	Diagnosis	Study details (ultrasound-guided studies only)	Results	Study type (crossover/cohort/controlled/case series, etc)	Limitations
Dry needling		No studies as yet
Brisement	Achilles tendinosis	Chan et al. 200812	Twenty-one patients with chronic Achilles tendinopathy, treated with peritendinous bupivacaine, hydrocortisone and saline. Significant reduction in VISA-A scores for pain and function	Retrospective case series	Small sample size
Electro-coagulation	Achilles tendinosis	Ilum-Boesen et al. 2006 6	Ten patients with painful mid-portion Achilles tendinosis, treated with electrocoagulation. 10 patients satisfied at 6 months with return to normal activity, Likert pain reduced from 7 to 0	Prospective case series	Small sample size, short follow-up period
Cryotherapy	Genitofemoral Nerve	Campos et al. 200920	Single patient treated for chronic inguinal pain by cryoablation of genitofemoral nerve, VAS reduced from 4 to 2 after 3 months	Case report	Short follow-up period
Percutaneous lavage	Rotator cuff calcific tendonitis	Farin et al.23	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 15min	Case series	Small sample size
	Rotator cuff calcific tendonitis	Alna et al. 200124	Fine-needle technique in 30 shoulders, lead to a significant improvement in shoulder pain and disability scores	Prospective case series	Short follow-up time of mean 53 days
	Rotator cuff calcific tendonitis	Serafini et al. 200974	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	Non-randomized, controlled trial
	Rotator cuff calcific tendonitis	Yoo, et al. 200975	Thirty-five 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	Prospective case series	Confounded by subacromial corticosteroid injection
Corticosteroids	Interdigital neuroma	Sofka et al. 200742	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.	Retrospective case series	Addition of local anaesthetic
	Plantar fasciitis	Yucel et al. 200941	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 significant improvement but no difference between the three methods.	Prospective case series, with randomized methods
	De Quervain’s tenosynovitis	Jayapalan et al. 200937	Triamcinolone (20mg) and 0.5% bupivacaine (1ml) for de Quervain’s disease in 17 patients; 15 out of 16 patients had significant symptomatic relief at 7 weeks follow up.	Prospective case series	Short follow-up time, no control group
	Ankle joint	Messiou et al. 200676	Nine athletes with subacute posteromedial ankle impingement underwent steroid injection and dry needling. All patients returned to original level of fitness within 3 weeks, with eight remaining asymptomatic	Prospective case series	Small sample size, no controls
Autologous substances	Patellar tendinosis	James et al. 20072	Dry needling and autologous blood in 47 knees, two sessions 2 weeks apart, pre-procedure VISA-A score 39.8, post-procedure 74.3	Prospective cohort study	Confounding factor of dry needling
	Medial epicondylitis	Suresh et al. 20064	Dry needling and autologous blood in 20 patients, 4 weeks and 10 months follow up, reduction in VAS score and Nirschl scores	Prospective cohort study	Dry needling in addition, small sample size
	Lateral epicondylitis	Edwards et al. 200349	2ml 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	Prospective cohort study	Small sample size
	Lateral epicondylitis	Connell et al. 20063	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	Prospective cohort	Dry needling
Sclerosants	Stump neuromata	Gruber et al. 200857	Up to 0.8ml 80% phenol instillation in 82 patients, with nine pain-free after first treatment and at 6 months 38% experiencing unnoticeable pain	Prospective cohort study	Non-specific scoring method, no control group**
	Achilles tendinosis	Ohberg et al. 200216	Sclerosis of painful neovessels using 2–4ml polidocanol in 10 patients, eight patients reported reduced VAS from 74 to 8 at 6 months	Prospective cohort study	Non-specific scoring method, no control group
	Patellar tendinopathy	Hoksrud et al. 200854	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	Randomised controlled trial, crossover study
	Morton’s Neuroma	Fanucci et al. 200458	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%	Propsective clinical pilot study	Small sample size, no control group
Prolotherapy	Achilles tendonosis	Maxwell et al. 200759	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	Prospective clinical study	Small sample size, non randomized, no control group
	Plantar fasciitis	Ryan et al. 200962	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	Case series	Scoring tool non-specific, no control group
Botulinum Toxin A	Iliopsoas spasticity	Sconfienza et al. 200865	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	Prospective clinical pilot study	Small sample size, non-specific measurement tool
	Lateral epicondylitis	Lin et al. 201067	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	Propsective, randomized, double blind pilot study	Small sample size
Tenocyte-like cells	Lateral epicondylitis	Connell et al. 200972	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	Prospective clinical pilot study	Small sample size, short follow-up time

Table 4. This table summarises the WADA regulations, which relate to musculoskeletal radiology procedures. The annual publication divides these into prohibited substances and methods

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Guided interventions 

Dry needling 

This technique involves needle insertion into the lesion site, then repeated puncture aiming to stimulate an inflammatory healing response (Fig. 1). Disruption of collagen fibres at the lesion causes local haemorrhage. The hypothesis is that inflammation 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.

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• 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.

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.², ³, ⁴ 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 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 20ml 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 1ml hydrocortisone and 1ml 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 10ml 0.5% bupivacaine, 25mg hydrocortisone and 4×10ml normal saline, to between the anterior aspect of the Achilles tendon and Kager’s fat pad. Vascularity was assessed with power Doppler and eccentric loading was prescribed. The results from visual analogue scores (VAS), showed a significant improvement in pain in the short term (2 weeks), with a mean change of 50mm, from a mean of 76mm to a mean of 25mm (asymptomatic patients should score a VAS of 0mm). There was also a statistically significant improvement in function with a mean gain of 50mm. The VISA-A (Victorian Institute of Sport Assessment-Achilles tendon)¹³ scores, reflecting symptom extent, showed a significant 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 7.5ml 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.

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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.

Electrocoagulation 

This technique treats painful chronic Achilles tendinopathy. Neovessels and nociceptive fibre formation are hypothesized to cause pain. This was substantiated by 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 16G coagulation needle connected to an ICC 80 electrosurgical Workstation for Minor Procedures (ERBE). This requirement may limit availability. The pilot study by Ilum Boesen’s group⁶ employed 11 patients in a prospective study, all of which had been diagnosed with chronic Achilles tendinopathy. The coagulation wattage was set at 20–25W 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 identified 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 Superficial cryotherapy has been used in physical therapy and anaesthetics.

In a letter to the American Journal of Roentgenology, Neumann and O’Connor,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 five freeze–thaw cycles. There was a good response of 90% 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 benefit 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 3min intervals of treatment were given via the cryoprobe, under direct visualization. The patient remained pain-free at 2 months with no recorded post-procedure complications. These initial publications indicate that ultrasound-guided cryotherapy for painful neuromata may be of benefit 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 calcifications.²¹

Barbotage was first described three decades ago as a fluoroscopic procedure by Comfort and Arafiles (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 18G 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 fine-needle technique (22G) 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. Serafini et al.⁷⁴ have shown improved symptoms at 1 and 3 months and 1 year using this technique.

Other therapies used for calcific tendinopathy include (external) ultrasound therapy,²⁵ extracorporeal shock wave therapy,²⁶ active non-operative treatment,²⁷ and open or arthropscopic subacromial decompression.²⁷

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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, significant adverse effects to the central nervous and cardiovascular systems can occur 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-specific ion channels on neuronal cell membranes, inhibiting signal conduction, with smaller neurones inhibited first.

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 (30–60min), lignocaine moderate (80–120min) and bupivacaine the longest (180–360min).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 2mg/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-inflammatory 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 fluoroscopic 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 image-guided 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.

These synthetic corticosteroids are prednisolone-derived: 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 Quervain’s tenosynovitis,³⁷ osteoarthritis of the trapeziometacarpal joint,³⁸ shoulder pain,³⁹ and trigger finger.⁴⁰

In the lower limb, the indications for corticosteroid injection include; ankle arthritides,³² tarsal tunnel syndrome,³² osteoarthritis of the first 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 confirmed 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 field of ‘orthobiologicals’.

For injection of autologous blood, a 2–3ml sample is withdrawn from the antecubital fossa (contralateral side if applicable) and injected at the site of the lesion², ³, ⁴ (Fig. 3).

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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).

The technique for acquiring PRP is as follows. 30–60ml of blood is withdrawn using a butterfly needle, which avoids trauma and activation of the resting platelets.⁴⁸ The blood sample is then placed in a centrifuge for 15min at 3200rev/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 30s to resuspend the platelets. After this final stage, 3–6ml 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 pre-procedure 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 beneficial 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 2ml 0.25% bupivacaine along the surface of the tendon initially. After a few minutes, the 23G needle was used to “dry needle” the tendon for 1min, after which the patient’s 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 final ultrasound evaluation at 6 months. Thirty-five 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 sufficient for tendon healing? What is the optimal post-procedure management?

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 benefit of PRP over autologous blood is that the concentration of platelets is four to five times higher. The growth factors (GF) contained in the α 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 five 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 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 fibrosis, due to the presence of TGF-β1 or by concomitant use of non-steroidal anti-inflammatory 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 scientific and clinical basis for the use of autologous substances continues to develop in the musculoskeletal field. More research is needed to integrate ultrasound-guided administration of these substances.

Sclerosants, phenol/polidocanol 

These are indicated in patellar tendinosis,⁵⁴ tennis elbow,⁵⁵ chronic Achilles tendinosis,¹⁶ Morton’s⁵⁶ 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 affinity 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 beneficial 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 beneficial 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 identified. 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, 2.5ml 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 0.8ml 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 first treatment. At 6 months, 52 patients had reduced pain of varying degrees. Minor complications were identified in 5% of the total treatments given: non-specific painful soft-tissue oedema, painful local myopathy, confined infection, and local soft-tissue necrosis.

Two treatments for lateral elbow tendinosis were compared in a prospective, randomised, controlled, double-blind 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 significantly reduced VAS at 3 and 12 months, with a significantly higher grip strength at 12 months. The overall success rate was 50–62%.

These studies show promising results for the use of sclerosants in Morton’s 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 inflammatory 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 inflammatory 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 significant reductions in pain (from 38 pre-treatment to 4.5 after, 88.2% difference), with minimal change in tendon size (11.7 to 11.1mm thickness). No complications were identified 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 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 beneficial, 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.

Botulinum toxin type A 

This substance is relatively new in the musculoskeletal field, 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 significant improvement in the foot injected with 50 units of botulinum toxin type A in 1ml 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.

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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 tenocyte-like 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 field 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 efficacy have been published.

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Conclusions 

This paper outlines the numerous options for ultrasound-guided therapies currently being explored in the field of musculoskeletal radiology. We have tried to assess the available literature and identify the current evidence-base 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 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.

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Acknowledgements 

The authors thank Dr N. Kendall for her contribution.

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