bone scintigraphy in the musculo-skeletal system

Bone Scintigraphy in the Musculo-Skeletal System

G. Buirski, C. Styles

Introduction

Bones are capable of growth, remodelling and repair in addition to inflammation and neoplastic responses. The hormonal, chemical, vascular and nutritional environment further modulates these processes. Bone scanning with Technetium-99m methylene disphonate (Tc-99m MDP) relies upon blood flow to and within the bone and then surface apposition of the Tc-99m MDP complexes on to the hydroxyapatite crystal matrix.‘, * Where there is increased blood flow, growth, remodelling, or repair in response to inflammatory, traumatic or neoplastic processes, there is in most cases increased hydroxyapatite crystal turnover and therefore increased bone tracer activity.

It is the dynamic functional repair and turnover concept that sets bone scintigraphy apart from other skeletal imaging techniques and makes it a very sensitive but non-specific marker for bone pathology.

Principles of Bone Scanning

The Tc-99m MDP complex is water soluble (Molecular wt. = 172) and following injection approximately one half the dose is excreted in the urine.3 The remainder is predominantly concentrated in the skeletal system with occasional spurious areas of activity elsewhere (Table 1). An important modifying factor in skeletal distribution is the regional and bone blood flow. The usual dose for a standard bone scan is approximately 10 MBq of Tc-99m MDP/kg. body weight.

Where localised bone pathology is suspected early ‘dynamic imaging’ is performed. This consists of a

Graham Buirski MB, B!3, MRCP(UK), FRCR, FRACR, Consultant Radiologist, Department of Radiology, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia, Colin Styles MB, BS, FRACP, FRACR, Director Department of Nuclear Medicine, St Vincent’s Hospital, Melbourne, Victoria, Australia.

Table 1-Artefacts and Coincidental Findings leading to increased tracer activity in whole body Bone Scintigraphy

1. 2. 3. 4.

5. 6. I. 8. 9.

10. 11. 12.

Free pertechnetate in stomach, bowel and thyroid gland. Injection and catheter sites. Visualisation of urinary tracts. Soft tissue calcification, myonecrosis, muscle haematoma or abscess. Unexpected bone injury (e.g., bone biopsy). Radiotherapy. Recent cerebral infarct. Recent myocardial infarct. Calcified liver metastases. Calcified costal cartilages. Lung activity secondary to hypercalcaemia. Soft tissue inflammation (e.g. thrombophlebitis).

series of regional l-2 s images (first phase) which reflect the initial blood flow (Fig. 1) and an early equilibrium image (second phase) of approximately 5 min reflecting blood and extracellular concentrations (Fig. 2).

Static delayed bone imaging is performed at approximately 2.5-3 h (third phase). Images of the whole body can be obtained as ‘screening test’ (Fig. 3) but where high resolution is required the following should be considered :

1.

2. 3.

4.

5.

Multiple and appropriately chosen projections similar to those obtained in routine radiography. Adequate count density. Choice of collimator to achieve desired resolution (usually a parallel hole collimator). Optimal resolution by placing the affected part as close to the gamma camera as possible. Tomography.

Image quality can be improved with the use of modem high resolution equipment and collimators. SPECT (Single Photon Emmission Computed Tom- ography) provides localisation of abnormalities in the

CurrenrOrfhopoedic~(l991)5, 188-198

0 1991 Longman Group UK Ltd 188

BONE SCINTIGRAPHY IN THE MUSCULO-SKELETAL SYSTEM 189

Fig. l--Initial blood flow image centered on the pelvis and both hips. Note that the isotope can be seen directly within the iliac and femoral vessels (arrows). Increased activity is seen around the right acetabulum (arrow-head) due to infection in an acetabular prosthesis after total hip arthroplasty.

.

Fig. 3-Whole body bone scan in an adult male patient with widespread metastatic disease. Apart from the forearms and feet, the whole skeleton has been demonstrated on one scan, The focal areas of increased tracer activity in the ribs and particularly the spine represent metastases.

Fig. 2-Equilibrium blood pool image of both wrists. There is increased tracer accumulation in the right wrist representing increased vascularity or inflammation.

Fig. 4-Whole body bone scan in a 6-year-old child showing the normal high tracer activity at the sites of growth plates at all major joints (cf. Fig. 3). Assymmetric increased activity is also seen in the right sacro-iliac joint and in the distal femoral metaphysis (arrows) representing multifocal areas of osteomyelitis. Note the significant tracer accumulation in the bladder (arrow-head) due to normal renal excretion.

190 CURRENT ORTHOPAEDICS-IMAGING

axial, coronal or sagittal planes: patient movement must be excluded or images will be degraded.

The radiation exposure following a bone scan (adult dose 740 MBq.) is 6 mSv., Effective Dose Equivalent.4 The kidney and bladder receive a higher dose because of urinary excretion. This dose is comparable (or marginally less) to critical organs such as bone marrow and gonads when compared to either a lumbar spine X-ray series or CT scanning of the lumbar spine or pelvis.

Image Interpretation

Although bone scintigraphy is a sensitive disease marker, it is non-specific and has some limitations (Table 2). Artefacts and coincidental findings on scans

Table 2-Limitations of Bone Scintigraphy

1. Image resolution inferior to Radiography. 2. Diffuse bone processes may be poorly displayed, e.g.,

osteoporosis. 3. The test is non-specific. 4. Bone marrow involvement may not be demonstrated.

are not infrequent and may lead to incorrect interpretation (Table 1). Scans cannot be interpreted in isolation and additional information is usually necessary. The following points need consideration:

1.

2.

3.

4.

5.

Relevant history of trauma, surgery, neoplasm, sepsis, radiotherapy, etc, is often essential. In localised bone abnormalities, it is important to determine whether the activity is related to the joint, bone surface (e.g., periosteal reaction), runs transversely (e.g., fracture), focally within bone (e.g., infection or tumour), or in the adjacent soft tissues (e.g., bursitis). Correlation of an abnormality with recent X-rays is generally necessary and the scan may indicate that further radiographic views are required. Most bone lesions are associated with increased bone tracer activity but there are situations where ‘cold’ or photopenic regions do occur. For example, in early bone infarction, some metastases (renal cell carcinoma) and multiple myeloma. The detection of an abnormality is generally dependent upon alteration in bone activity, i.e., ‘hot’ or ‘cold’, reflecting differences in image contrast. The characterisation of the abnormality, however, depends upon resolution and this on average is 4 mm at the collimator surface, 7 mm at 5 ems and 10 mm at 10 ems distance from the gamma camera.

Specialised Applications

Radiotherapy with isotopes

Radiotherapy with Yttrium 90 colloid injected into the joint space in patients with Rheumatoid arthritis, confined to predominantly a large joint, is useful in

achieving a radiation synovectomy. The injection must be intraarticular, as extravasation may lead to local radiation necrosis. This technique has also been used successfully in patients with haemophilic arthritis.

Other isotopes are under evaluation : a shorter lived isotope, Dysprosium-165 has the advantage of a shorter time of joint immobilisation and greater radiation safety.5 Samarium-153 may be useful in the radiotherapeutic treatment of bone metastases6

Gaffium and white ceil scanning

Gallium-67 Citrate is an isotope that is bound to carriage proteins (e.g., transferrin) and via cellular, bacterial and other non-specific mechanisms leads to increased concentration at sites of infection. Any inflammatory process will concentrate Gallium and there is a normal low level of activity in bone. Therefore, comparison of Gallium scans with a recent Tc-99m MDP scan is essential in the assessment of suspected bone sepsis.

In an effort to achieve a specific diagnosis of infection, particularly in joint prostheses (see below), neutrophil or mixed leukocyte scanning has been performed with various labels: the most common being Indium-1 11 Oxime. Its usefulness is yet to be established in chronic low-grade infection which may not be associated with a marked cellular response.

Clinical Indications

In many symptomatic patients clinical and routine serial radiological examinations will be normal. It is in these patients that isotope imaging may provide the clue that an intrinsic bone or localised inflammatory soft tissue lesion may be responsible for symptoms.

Special consideration must be given to the normal increased osteoblastic activity around the epiphyseal growth plates in children (Fig. 4). Clinically relevant conditions are different in the younger population with a preponderance of soft tissue injury, stress fractures, osteomyelitis, and avascular necroses.

In the forthcoming sections the role of scintigraphy will be stressed in the context of the clinical problem presenting to the rheumatologist.

Unexplained Post-traumatic Pain

Chronic repetitive low-grade trauma may lead to stress fractures, and are an important cause of bone pain in the presence of normal X-rays. Fractures have been reported in many different sites and activities.7 Scans are positive at the onset of symptoms whereas radiographic changes may take several weeks to develop.iO Images usually show extremely localised activity over the area of clinical concern (Figs 5,6) or may be more diffuse. 7 Diffuse activity can also be seen in ‘stress reactions’ (Fig. 7) where there is excessive remodelling and resorption of bone : these patients do


a

Fig. 5-Typical stress fracture of upper tibia (arrow). (A) The importance of direct photographic display is emphasised as the linear nature of the lesion is only shown on the lower contrast setting.

not develop overt fractures and can be treated

conservatively. ‘. 9. lo A normal scan confidently ex- cludes a stress fracture. Osteoporotic bone is generally

more susceptible to minor stress injuries and failure to recognise these fractures can lead to complete separa- tion at the fracture site.

Bone scintigraphy is a sensitive adjunct where an

acute fracture is thought to be clinically present but radiology is equivocal or negative. The most common

sites are those of the scaphoid, neck of femur, and

pelvis. Matin ” found that 957; of fractures were positive 3 days after the initial trauma, whereas only 80% were detected at 24 h. In this latter group of patients, 95”,b under 65 years were positive indicating

A ”

that in the older and osteoporotic population the

osteoblastic response to injury is slower. He similarily observed an evolution in the pattern of the fracture : a

diffuse abnormality is seen immediately becoming

well-defined and linear (8-12 weeks) and thereafter decreasing in activity. The scan may commonly remain

abnormal for up to 2 years and this is prolonged in old age, following surgery, or fracture complication. A

normal pattern of activity is seen in vertebral, long

bone and rib fractures in 60”,/,, 64x, and 79”/, at 1 year

and 90’4, 91% and 93% at two years respectively. A recent prospective study of elderly osteoporotic pa-

tients with acute hip pain and normal X-ray, has

shown that 30% of these patients had abnormal

scintigrams and subsequently proven fractures : the remainder with normal scans were treated conserva-

tively without complication. l4

The assessment of paediatric trauma requires good

nuclear medicine imaging technique with adequate

immobilisation and symmetric views of the limbs so

that subtle metaphyseal abnormalities may be de-

tected. At the Royal Childrens Hospital in Melbourne, the assessment of the potentially ‘battered child’

requires scintigraphy with additional skull X-raysI

The former has been found to be insensitive in detecting skull fractures in contrast to its high

sensitivity at other sites.’ 4

Unexplained Joint Pain

Joint pain may originate from adjacent bone or soft tissues (e.g., bursae, Fig. 8) capsule, synovium (e.g.,

pigmented villonodular synovitis), intracapsular bone,

or the joint cavity itself (e.g., septic arthritis).

Comparison images of the normal contralateral joint

and blood pool images are useful to display inflam-

matory conditions of the synovium or intraarticular sepsis. Delayed scans should be carefully assessed in

order to identify the exact location of activity.

Fig. 6--26~year-old male squash player with chronic right wrist pain. (A) Delayed scans show a localised area of abnormal activity overlying the hamate. (B) CAT scan through the wrist demonstrates a typical stress fracture involving the base of the hook of the hamate (arrow).


Fig. 7-Lateral isotope scan of the tibia in a young patient with stress reaction rather than fracture. Tracer activity is localised and parallel to the cortex and does not traverse the shaft.

-

Scintigraphy has been found useful in complex regions such as the foot to identify the symptomatic joint accurately. l5 Increased activity can be seen in subtalarjoint osteoarthritis, and capsular and ligamentous disorders with the intensity of activity providing some indication as to the degree of ligamentous damage.16 Reflex sympathetic dystrophy can be differentiated from acute disuse osteoporosis on the scan appearances alone. I5 The former increases activity diffusely throughout the foot rather than in a periarticular distribution (Fig. 9).

Hip pain in children is a common clinical problem. Scintigraphy may help differentiate infection from Legg-Perthe’s disease (avascular necrosis) : l7 the former has increased activity on three phase scanning whereas the latter will show decreased activity reflecting the reduction in blood supply (Fig. 10). Although a slipped upper femoral epiphysis is a radiographic diagnosis, scintigraphy provides valuable information regarding the vascularity of the femoral head and the activity of the adjacent growth plate.18 Surgical pinning should be recommended if the growth plate remains active.

There are a number of other skeletal sites apart from the hip where bone perfusion and metabolism are at critical levels. Bone death can be caused by vascular or other influences such as steroids, SLE, cytotoxics, trauma, or excessive alcohol.19 Sites include the lower femoral condyles, subarticular tibia1 locations, humeral head, and the heads of the second

Fig. &Pre-patellar Bursitis. (A) Anterior equilibrium blood pool scan of right knee (slight external rotation). Marked tracer accumulation is present around and below the patella. (B) Lateral delayed scan confirms soft tissue swelling and increased activity (arrow) lying below the patella. The knee joint is also active due to mild inflammatory osteoporosis.

BONE SCINTIGRAPHY IN THE MUSCULO-SKELETAL SYSTEM 193 __- _

B

Fig. S-Reflex sympathetic dystrophy of the right foot (A) Blood pool phase is abnormal due to the increased vascularity in the affected region. (B) Bone tracer accumulation in this delayed scan is increased throughout the whole foot rather than in a periarticular distribution

and third metatarsals. Scintigraphy, with a sensitivity of between 77.5’?~-89%,‘“~ z1 demonstrates absence of

tracer activity in non-vascularised bone and later

increased activity as repair takes place. Medullary

bone infarcts, typically in the long bones, usually

produce increased activity which must not be confused

with metastatic disease. Magnetic Resonance Imaging (MRI) can perform to a greater sensitivity and

specificity (88% and 100% respectively),“3 but access

to MRI units is limited and scintigraphy will often be the initial investigation of choice. Osteoid osteomas

near joints can present as monarticular arthritis and

the diagnosis may be occult. Scintigraphy, which is

universally positive with osteoid osteoma, can be the decisive diagnostic test (Fig. 11). Precise localisation

of the lesion may require CT scanning since the bone

reaction may not, necessarily, be maximum at the site

of the tumour.

Fig. lo---Avascular Necrosis. Delayed scan of both hips showing reduced tracer accumulation in the right femoral head (arrow) reflecting the absence of blood supply. Increased activity in the metaphysis is due to attempted revascularisation and repair.

Multiple fractures from osteomalacia may simulate metastases on a bone stint and present with joint or ‘total body’ pain (Fig. 12). Comparison with plain

radiographs is essential.

Arthritis

Although scintigraphy is more sensitive than radiography’? in revealing inflamed joints (Fig. 13), it

is generally non-specific. It may provide information regarding the distribution pattern of the joint disease,

and allow demonstration of inflammation at inacces-

sible joints such as the axial skeletonz3 and at joints which may not be symptomatic at the time of

examination.‘4 Abnormal activity on scans has been

shown to predict those rheumatoid joints that will

develop erosions and that the destruction is greater in

the feet than the hands.2s Similar predictive changes

have been shown in generalised nodal osteoarthritis of the hands by Hatton et al:‘6 based on the scan

appearances they have suggested that osteoarthritis is

a phasic process where some diseased joints may be inert and others extremely active.

Once radiographic joint changes of an inflammatory arthritis have occurred, Tc 99m MDP scanning is of little value being ‘hot’ in both inactive and active

phases of the disease. It is often difficult to distinguish

an acute arthritis from sepsis and joint aspiration may be required. Recent studies would suggest that Tc.

labelled liposome scanning will demonstrate only

actively inflamed joints .27 The method of isotope accumulation is unknown but is thought to be due to incorporation of the liposomes into the phagocytes of the synovium.

Spinal Pain

Spinal or back pain should be distinguished from that associated with nerve root compression. In the latter, isotope scintigraphy has no role to play and imaging

..____


Fia. 1 l-The blood DOOI (A) and delayed (B) scans are typical of osteoid osteoma. Extreme focal activity in both phases (arrows) . reflects the highly vascular nature of the lesion.

techniques more suitable for demonstrating nerve roots (e.g., CT) should be employed.

In the elderly patient with spinal pain, scintigraphy may be difficult to interpret due to the presence of degenerative spinal disease. A normal scan is reassur- ing and focal abnormalities can be assessed with more sensitive imaging techniques. An isolated ‘hot’ vertebral body may indicate the presence of an oestoporotic fracture, isolated metastasis, or other pathology (e.g.,

Fig. 12-Osteomalacia. A generalised avidity for tracer uptake throughout the skeleton is demonstrated. Focal increased activity is noted in many ribs and in the right scapula (arrow): these are due to Looser’s zones or stress fractures. The distribution of activity differs from metastatic disease (cf. Fig. 3).

B

Paget’s disease). Fogleman and Carr have suggested that osteoporotic vertebral fractures of less than 1 year’s duration** show increased tracer uptake. This has been disputed29 and in the osteoporotic skeleton there may be little osteoblastic bone response to fracture. Scintigraphy is the most sensitive method to detect osteoporotic stress fractures (insufficiency frac; tures) of the sacrum in patients with low back pain.30

Spinal pain in the younger patient is common particularly in a society where work compensation programs exist as in Australia. Failure of conservative measures together with normal X-rays should be followed by scintigraphy of the symptomatic area. The classical osteoid osteoma produces increased blood flow and static phase activity and scintigraphy may be the only imaging technique to confirm the diagnosis : intra-operative scanning may be required to isolate the lesion prior to removal.31

Lumbar pain in the active individual can be due to stress fractures of the pars interarticularis (spondylolysis). Scintigraphy in these patients not only consists of AP and lateral views but also oblique scans. Increased activity secondary to attempted repair is diagnostic of a stress fracture (Fig. 14) even in the absence of plain radiographic or CT abnormality.32y 33 In established spondylolysis, the lack of scintigraphic activity implies that non-union has occurred. Immo- bilisation may be indicated when activity persists in order to avoid complete fracture and non-union.34

The quantitative assessment of early sacroiliitis prior to radiographic changes has been attempted but there is substantial evidence to show that it cannot differentiate normal active joints from early disease. Anterior as well as posterior scanning may occasionally be helpful in the assessment of unilateral sacroiliitis.35 Unfortunately, increased activity in the sacroiliac


Fig. 13-Acute Gout. This is the delayed scan of the same

patient as in Figure 2 demonstrating marked tracer uptake in the

right wrist. These appearances represent any acute arthritis but joint aspiration was diagnostic.

joints is non-specific and may be seen in metabolic

bone disease, degenerative joint disease, and structural

abnormalities of the lumbar spine as well as in patients

with joint disease.36 Although scintigraphy has a

limited place in the diagnosis of sacroiliitis, it may provide an objective method of assessing response to

therapy.3’

Bone and Joint Sepsis

The recognition of underlying osteomyelitis in the swollen painful limb can be difficult but is important

if subsequent complications are to be avoided. Bone

scanning is sensitive (approximately 90%) in the diagnosis of non-complicated initial presentation,38

(Figs 6,15). False negative scans have occurred when

imaging was performed within 1 day of the onset of

symptoms but follow-up studies at 3 days were

diagnostic.“” Early blood flow images further add to the diagnostic accuracy improving sensitivity and specificity to 84% and 97% respectively.39 Pitfalls in interpretation can occur in fracture, septic arthritis, and prior antibiotic treatment. A ‘cold’ defect may

also be demonstrated : this is due to thrombosis of the associated nutrient vessel with subsequent ischaemia.

Occasionaily acute osteomyelitis in children may produce whole bone rather than localised activity.

Differential diagnoses should then include : subperios- teal abscess, cellulitis, thrombophlebitis, and child

abuse.40 Specificity can be enhanced in these situations with the use of Indium labelled White Blood Cell scanning performed at the same time as the Techne-

tium study.“’ Debate exists as to the sensitivity of scintigraphy in

neonatal osteomyelitis. 42 Even though this may have

been overstated, it is the practice at the Royal Childrens Hospital (Melbourne) to perform Gallium

scans on all children under 18 months old suspected of having osteomyelitis but with a negative bone scan.’ 3

Whole body imaging is mandatory as multifocal osteomyelitis is not uncommon in this age group.

Activity from bone changes in diabetic osteoarthro- pathy may obscure underlying infection: this can be

confidently excluded when the scan is normal.43 Using Indium labelled leukocytes, Maurer et alsd have shown

a further significant improvement in specificity.

Bone scintigraphy is slightly less sensitive in the diagnosis of septic arthritis where in addition to

increased periarticular tracer concentration photopenic defects can occur due to pressure and vascular

effects.45 Blood flow images and correlation with

Gallium scanning adds to the sensitivity: however, irrespective of tracer activity, diagnosis is obtained by

joint aspiration. Joint involvement of the axial

skeleton in systemic low-grade infections may be more

difficult to recognise clinically and is less accessible to

Fig. l&-Acute Spondylolysis (A) AP and (B) Oblique scans of the lower lumbar spine. The increased tracer activity is located accurately in the right pars interarticularis (arrows).


Fig. 15--Septic sacroiliitis. (A) increased tracer activity in the right sacro-iliac joint. This is non-specific and is usually not as obj as in this case. (B) CAT scan through the affected joint sho IWS sclerosis, fragmentation and destruction due to infection (arrow).

diagnostic aspiration : in these cases scintigraphy, with Gallium or Technetium, may be extremely valuable.46

Joint Prostheses

A significant number of patients under the care of rheumatologists will have joint replacement surgery often of hip or knee. The major two late complications of prosthetic surgery are loosening and infection occurrring in l-36% of all prostheses and being responsible for 75% of all revision surgery.47

The normal bone reaction around cemented com- ponents subsides over a 6-12 month period but in 20% of patients this activity may persist for longer than a year. Diagnostic scanning is therefore of little use under 6 months post-surgery.55, 47 In the more recent cementless, ceramic prosthesis, bone reaction may be prolonged4* and may mimic loosening.49

The diagnosis of infection in joint prosthesis is extremely difficult. Radiography is frequently non- specific or insensitive to early loosening and/or infection. In constrast, bone scanning is very sensitive but also non-specific. The degree of hyperaemia and diffuse reactive bone change is greater for infection but not pathognomic (Fig. 16). Gallium50 and Indium- 111 labelled leucocytes 51 have been proposed as a

specific test for infection (Fig. 17). However, in the chronic, low grade infections where cellular reaction is not extreme, great caution needs to be exhibited and the isotope tests interpreted in the context of all clinical and radiological data.

Paget’s Disease

Patients with Paget’s disease can present with limb pain, disease complication (e.g., fracture), or as an incidental finding. Often it is discovered incidentally and usually produces marked areas of increased tracer concentration particularly in the lytic and mixed phases of the disease (Fig. 18A): radiographs of the affected area are usually diagnostic. During the sclerotic phase of Paget’s increased activity may be absenL5* Scintigraphy has little role in the early detection of complications: activity is so great that new focal changes secondary to complications are masked by the overall technetium accumulation. Occasionally pathological fractures can be identified as a focal ‘hot’ area superimposed over the diffuse activity : radiographs are, however, more useful.

In symptomatic patients who require treatment for Paget’s, a reduction in tracer accumulation has been shown to reflect a reduction in metabolic activity following therapy53 (Fig. 18B).

BONE SCINTIGRAPHY IN THE MUSCULO-SKELETAL SYSTEM 197 -

Fig. 16-Static scan of right hip showing increased tracer accumulation around the acetabulum (arrow). This is the same patient as in Figure 1 and the combined activity on static and vascular scar is suggestive but not diagnostic of infection.

A

Fig. 17-Oblique lndium labelled white cell scan of right hip showing abnormal activity in the acetabulum (arrow) diagno5 of infection. (Same patient as in Figure 16).

B

itic

Fig. 18---(A) Increased activity in the left hemipelvis and in two lumbar vertebral bodies is due to Paget’s disease. This was confirmed radiologically. (B) Following Phosphonate therapy (ADP) a marked reduction in activity has occurred in the Pagetoid bone.

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bone scintigraphy in the musculo-skeletal system

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