Isotope scanning of the musculoskeletal system

Isotope Scanning of the Musculoskeletal System

Iain W a t t

Introduction

500-600 MBq, childhood dose being calculated by the formula: (Age in years + 1) × adult dose (Age in years + 7)

The role of bone scanning in everyday orthopaedic practice is constantly expanding. Rat bone was first labelled some 50 years ago by 32 P-phosphate. Since, for human use, the constituents of bone, calcium and phosphorus, do not provide suitable agents, a number of rare elements including barium and gallium radionuclides were tried. Calcium analogues, such as the alkaline metals, 85 and 87 m strontium were considered but were technically unsatisfactory. In the 1960s 18 fluorine was used as it is incorporated as fluorapatite but the emitted energy is too high, and the half life too short, to be of use in most departments. The introduction of 99 m technetium labelled phosphate complexes marked a revolution in bone and joint imaging. The radionuclide 99 m technetium is ideal for diagnostic purposes since the emitted gamma radiation, at an energy of 140 keV, is efficiently absorbed by thin gamma camera crystals resulting in good counting statistics and spatial resolution. The short physical half life, 6 h, combined with rapid renal clearance results in a low absorbed radiation burden. The radionuclide is eluted from a 99 molybdenum generator. Bone seeking pharmaceuticals are prepared by mixing the eluted sodium pertechnetate with a phosphorus compound and tin as a reducing agent. Whilst, initially, labelled tripolyphosphates were used, now almost all compounds are non-hydrolysable diphosphonates with P-C-P bonds. The agent currently used in this department is hydroxymethylene diphosphonate (TcHDP). T c H D P is readily prepared from a kit, and is relatively low in cost. The adult dose is of the order of

The exact choice of dose is a balance between radiation burden and scanning time, which governs image quality. Gonad dose may be reduced by encouraging fluids and frequent bladder emptying. Other agents are employed to image the skeleton under specific circumstances. 67 laa gallium citrate (hereafter gallium) is a pus/tumour seeking agent which was initially used as a bone scanning agent. Unfortunately it has long physical and biological half lives (72 h and 2 3 weeks respectively). In the first 24 h the radionuclide is excreted in the urine, thereafter by colon. Gallium lacks a single good energy photon peak to image, but retains a specific place in the detection of inflammation/infection and will be mentioned where relevant. III indium chloride labelled white cells have a similar role. Rarely other agents may be employed when relevant, for example 125 iodine scanning for thyroid metastasis. Theoretical Considerations The interpretation of a bone scan is easier if the probable kinetics of the radiopharmaceutical is understood. Perfusion through bone is essential for the uptake of bone seeking agents. However, perfusion is not the sole determinant of skeletal activity. By increasing perfusion four times, a 70% increase in activity is achieved. However a canine tibial osteotomy, whilst causing a flow increase of 100%, results in increased activity of some 800%. 1 Four phases of bone radionuctide extraction are suggested (Figs 1 & 2). 2

Iain Watt MRCP, FRCR, Department of Radiology Bristol Royal

1. Perfusion stage, half life of some 36 s.

Infirmary, Bristol BS2 8HW. Current Orthopaedics (1987)1,324 344 © 1987LongmanGroup UK Ltd

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Fig. 1 - - B o n e extraction of TcHDP from experimental data s h o w s four possible compartments.

2. Diffusion across the perivascular extracellular space. Technetium complexes are ultrafiltrated against a diffusion gradient. Half life of 3.5 min. 3. Diffusion through intraosseous extracellular fluid. Half life 17.5 min. 4. The longest phase, half life of 11.75 h, may represent a true bone crystal absorption. Usually an image is recorded immediately after the injection of radiopharmaceutical, the so-called 'perfusion' or 'blood pool' phase, taking 1-2 min to acquire. The subsequent delayed, or 'bone phase' image is recorded at 2 3 h from injection. From the above it may be seen that the first image almost certainly corresponds to the intravascular and perivascular phases of bone scan evolution and the delayed image to bony extracellular fluid with some crystal effect. Hence any factor which alters bone blood flow (be it greater or lesser) creates bone oedema (for

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Fig. 2 - - T h e s e four compartments are most easily grasped as corresponding to intravascular, perivascular extracellular fluid, bone extracellular fluid and bone itself. This figure is r e p r o d u c e d and redrawn by kind permission of Clinical Orthopaedics

Images are recorded by a gamma camera. This either operates in a whole body mode (the patient lying flat on a couch and the camera tracks over them), or focused on a particular region(s) of interest. The whole body technique requires that both anterior and posterior images are taken to ensure that the whole anatomy is covered. This is appropriate to assess metastasis, but a blood pool image cannot be taken and resolution is tess than for a single area of interest. By using a dedicated computer it is possible to record a radionuclide angiogram immediately after the injection of the radiopharmaceutical. In practice this is seldom necessary except perhaps when an assessment of vessel supply is sought. Computer recording also permits data manipulation, for example creation of regions of interest. The use of pinhole collimators or electronic zooming may give greater detail. Gallium scans are also recorded by gamma camera but the acquisition time is longer and spatial resolution less good. The radionuclide takes longer to reach target organs. Accordingly images are taken at 24 h intervals for up to 96 h.

The Normal Scan Activity is symmetrical on both the blood pool and delayed phases of a bone scan. Asymmetry should be regarded with suspicion. In childhood activity is greatest in the metaphyses (Fig. 3). If the patient is rotated, the side nearest the camera will appear more active. Consequently a wriggling child or scoliosis will create an apparent abnormality. Deficiency of soft tissue thickness, e.g., after mastectomy, will result in apparent enhancement of that part of the image since soft tissue absorption is less. Hence also more activity is recorded on a posterior scan from the thoracic, rather than cervical or lumbar spine, because of the relative kyphosis. Other innocent causes of 'normal' increased activity include-Urinary: As much activity is excreted by the urinary tract, it follows that adequate bladder emptying is necessary to visualise pelvic lesions. Even slight urine staining of underwear, reflux into the vulva and urinary catheters will create problems in interpreta-tion. Summated activity: Where bone crosses bone a 'double count' is recorded, as at the angle of the scapula where it crosses ribs on the posterior scan. Injection artefacts: Foci at sites of injection, due to extravasation should not be mistaken for pathology. Unlabelled radionuclide: If the pertechnetate becomes detached from the diphosphonate it will be excreted by its usual pathway, renal, exocrine glands, thyroid~ stomach and colon.

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scepticism. This is particularly so after mastectomy, when many other, benign, factors may operate. Soft tissue lesions: Protein binding (Fig. 4) results in T c H D P localising in leg oedema or pleural effusion. The richer the protein content, the greater the activity. Reduced activity: Absorption by metallic artefacts such as joint replacements, medallions, keys, belt buckles and the like produce areas of reduced activity because the metal has absorbed the emitted photons of energy. Uniformly increased activity--the 'superscan' : The skeleton may be so uniformly avid for radiopharmaceutical that the whole image is enhanced. Often the axial skeleton is predominantly involved, the limbs less so. Enhancement of the sternum may be noted. A helpful clue to this diagnosis is the reduced renal excretion that accompanies it. Common causes include hyperparathyroidism, renal osteodystrophy, diffuse metastasis (particularly from the prostate), Paget's disease and myelofibrosis. Gallium artefacts are greater by virtue of the poorer resolution and less specific tissue localisation. Excretion by the liver and colon produce substantial problems if an abdominal lesion is sought. Comparison of sequential images, during which bowel activity will have moved on, is a practical solution.

Fig. 3 Normal frontal view in a juvenile. Note the metaphyseal distribution, including the costochondral junctions.

Sites oJ degenerative joint disease: Many patients imaged, particularly for possible metastasis, are elderly and have degenerative joints. It is common to see abnormal activity at these sites, including acromioclavicular and sternoclavicular joints: diffusely about the shoulders anteriorly; the patellae: the CMC Joints of the thumbs and the MTP Joints of the great toes: and the spine due to degenerative spondylosis. The last site creates the greatest difficulty in routine practice, since differentiation from metastasis may be virtually impossible. Helpful signs include facet joint osteoarthritis being usually lumbar or cervical, laterally placed on a posterior image. Discal osteophytes mirror the margins of disc spaces, not vertebral bodies or pedicles, and are most marked in predictable sites, that is lumbosacral, thoracolumbar and mid-cervical. No rib or pelvic lesions should accompany them. Patchy activity in ribs is very common and, in the absence of ot.aer pathology, should be treated with

Fig. 4 ~ S o f t tissue artefacts. A skin graft has been taken from the right thigh (arrow) and placed over a skin defect from a mastectomy (arrow). Radiopharmaceutical is shown at these sites as a result of protein leakage.

C U R R E N T ORTHOPAEDICS

Fig. 5--Pulmonary metastases from an osteosarcoma (arrowed). These lesions, whilst obvious in this case, are only detected if relatively superficial, bone forming and viable. (This figure is reproduced by kind permission of The Journal of Bone and Joint Surgery [Britain])

Skeletal Neoplasia (A) Primary Bone Tumours The role of bone scanning in primary tumours has received little attention. Most descriptions of tumours refer to them as being 'hot' or 'cold' but have not addressed the value the scan may have in the management of the primary lesion itself. Of course, a bone scan may demonstrate pulmonary metastasis from a bone forming lesion (Fig. 5), such as an osteosarcoma, or subsequent skeletal deposits elsewhere, in addition to soft tissue recurrence either locally or in regional lymph nodes. However a bone scan has several important roles in the assessment of the primary lesion itself. 3 (1) Tumour detection. Small, occult lesions such as an osteoid osteoma are readily detected (Figs. 6 & 34). Other causes of pain, with apparently normal radiographs, such as stress fractures, can be distinguished (see below). (2) Differential diagnosis. Since the blood pool phase of the scan mirrors vascularity, an avascular lesion (such as a bone island) may be distinguished from a vascular one (osteoid osteoma). Furthermore as bone forming elements result in increased activity, and

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fluid, fat, or histiocytic tissue do not (Figs. 7A & B), it follows that an assessment of the likely tissue may be made, together with an observation about host response. Usually a short differential diagnosis can be made from adequate plain films, the scan refining that list. Fibrous dysplasia may thus be distinguished from a simple bone cyst (Fig. 8A-C). (3) Extent oftumour. To plan a surgical or oncological approach knowledge of exact tumour extent is clearly vital. Certainly in bony and cartilaginous tumours the intraosseous and extraosseous extent of the lesion are well shown. However the size of an osteosarcoma on a scan may exceed that revealed by histology. This socalled 'extended pattern' is due to the reactive zone around the tumour. However this zone is surgically important in prosthetic surgery as it is preferable to excise it with the definitive tumour. If the lesion is essentially photon deficient the scan has little to offer. In this case CT with vessel enhancement, and/or angiography, is the investigation of choice. It is seldom necessary to use other radionuclides in the detection of either primary or secondary tumours. Paget's sarcoma may be shown by a relatively photon deficient zone within otherwise uniformly avid bone, In this case a gallium scan shows increased activity and is diagnostic. Similarly with lymphomas gallium has a major role. On rare occasions other radionuclides may be useful. For example 125 iodine may confirm a bony metastasis from a thyroid primary.

(B) Secondary Bone Tumours It is in the detection of metastases that bone scanning initially became important. A whole body isotope bone scan is often the simplest and most reliable means of detecting many skeletal metastases (Fig. 9). It is cheaper, in terms of money, radiation burden and imaging time than a comparable radiographic skeletal survey. More lesions are detected, at an earlier phase

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Fig. 6--Osteoid osteoma on the thumb (A). Typical appearances are shown with increased activity both on the blood pool (B) and delayed phases (C) of a bone scan.

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Fig, 7 - - A clue to tissue types is shown by the marked avidity of the osteosarcoma (A) compared with the malignant fibrous histiocytoma (B).

of evolution, using a scan. As the majority of bone metastases result in foci of increased activity, interpretation is straightforward. The commonest lesions, those arising from breast and prostatic carcinoma, are predominantly grouped asymmetrically in the axial skeleton. Vertebral lesions may involve all or part of the body and/or posterior elements. Distinction from an osteoporotic fracture can be difficult, but rib and

pelvic lesions should not be present in the latter. If in doubt appropriate radiographs should be taken. Should no obvious benign cause be shown, it must be assumed that the scan lesion is likely to be a metastasis. Particular attention should be paid to lesions shown in major long bones, such as the femur, since prophylactic management may be instituted in order to obviate a pathological fracture.

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C Fig. 8--Bone scan differential diagnosis. This child has an eccentric, lytic, expansile cortical lesion in the distal femur (A). Included in the differential diagnosis are, fibrous dysplasia and an unusual simple cyst. The blood pool phase (B) of the bone scan shows it to be avascular, and the delayed phase (C) demonstrates that the lesion is not active. These findings make the diagnosis of fibrous dysplasia unlikely. A simple cyst was found at surgery (This figure is reproduced by kind permission of The Journal of Bone and Joint Surgery [Britain]).

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Fig. 9 - - B o n y metastases from breast carcinoma. Typical lesions are shown, predominantly in an axial distribution. Note the asymmetry of the foci together with involvement of both spine and ribs, unlike Looser's zones.

Pitfalls in Interpretation Not all metastases are photon rich; Some metastases are intensely photon rich (prostate and breast), others, particularly from pelvic soft tissue tumours (cervix and body of uterus, rectum) may be photon deficient (Fig. 10). A bone scan defect is much more difficult to observe than a focus of increased activity. Consequently some metastases may be quite large before they are appreciated on a scan. With these primary tumours, radiographs of the appropriate part (lumbar

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spine and pelvis) may be much more reliable in demonstrating metastases. Similarly most cases of myeloma do not produce increased activity, with the exception of rib lesions with fractures. Hence a radiographic survey is superior to a scan. Histiocytosis also is better imaged by radiographs. Metastases may be obscured; this is especially likely to happen in the pelvis when bladder and urinary contamination obscures the field. Minor metaphyseal lesions in childhood also are particularly difficult to detect, granted the already high normal activity at this site. Benign disease may be misinterpreted; as previously emphasised, foci of abnormal activity are common in the elderly due to benign causes. Indeed metastasis, old trauma and benign lesions may be very difficult to differentiate. Consequently, in cases of doubt, radiographs should be obtained. Even then the diagnosis may not be straightforward. Degenerative disease of the spine and patchy rib activity are the commonest areas of difficulty. Multiple rib fractures, without spinal disease, should suggest trauma (Fig. 11), especially if they are in a line, and if the skeleton is also uniformly avid, osteomalacia should be considered (see below) (Fig. 37). Solitary rib foci are statistically unlikely to be a metastasis, and usually represent benign disease. 4 Generalised skeletal avidity may be overlooked; the 'superscan' is easy to miss unless the possibility is constantly considered (Figs 12 & 36). Bone scanning in Patient Management Emerging data suggest that in many instances 'routine' scanning is not justified. For example, the yield in

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Fig. lO--Sacral metastases with reduced activity. The primary was an adenocarcinoma of the rectum. These lesions are difficult to detect unless large and obvious.

Fig. 11--Rib fractures not metastases. Foci of increased activity are shown in the ribs arranged in a row. This patient had sustained a fall several days before the scan.

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Fig. 1 2 - - A 'Super Scan'. In this case the scan abnormality was due to diffuse prostatic metastases. Note the relatively reduced renal excretion and the enhanced quality of the bone image. Note also this is most marked in the axial skeleton. carcinoma of the cervix is very small, and it has been suggested that bone scanning has no value in staging renal-cell, bladder or even perhaps breast carcinoma.5 It has been suggested also that once a metastasis from an adenocarcinoma has presented, prognosis is not influenced by knowing whether it is solitary or not, and that 'chasing the primary' is not justified. 6 Consequently once an apparently solitary bone metastasis has been found, with an occult primary source, it may be reasonably argued that the next investigation of choice is a bone biopsy, not a scan. The role of a bone scan in patient m a n a g e m e n t may be summarised thus a) To detect metastases if, by so doing, treatment regimes are to be modified or changed, or prophylactic surgery performed. b) To confirm that metastases are the cause of local symptomatology, prior to radiotherapy, remembering that the incidence of false positive and negative scans varies appreciably with the primary. c) To assess clinical trials.

Iatrogenic bone scan changes" Radiotherapy may result in reduced activity in normal bone that has been included in a radiation field (Fig. 13). This artefact usually has a straight margin, corresponding to a field edge, and occurs, typically, 46 months after therapy when it has exceeded 2000 R. 7 Defects may persist for m a n y years. Radiation necrosis, with pathological fracture, is typically photon

Fig. 13--The effect of radiotherapy is shown by reduced activity over the upper thoracic spine. deficient. It cannot be easily distinguished from an insufficiency fracture particularly as the latter occur in elderly, osteoporotic ladies who are receiving, or have been receiving, radiotherapy or systemic steroids (Fig. 14). Radiation induced sarcoma presents a variable appearance. I f predominantly an osteosarcoma the scan m a y be quite active; most anaplastic sarcomas are not however. A gallium scan m a y confirm that a destructive bone lesion in a former radiation field is a sarcoma.

Trauma Skeletal scintigraphy has a number of valuable in the assessment of traumatic lesions of both and soft tissue. Because it detects change in perfusion, protein binding in oedema and remodelling it is extremely sensitive.

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Stress Lesions Stress fractures. Bone scans reliably detect stress fractures, before radiographic features have evolved and, in some cases, without X-ray changes ever

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Fig. 14~Trauma, infection or tumour? This elderly lady had been treated locally for carcinoma of the breast. She sustained a minor fall. An X-ray (A) revealed abnormalities of the bodies of the pubis. A bone scan demonstrated only slight changes, related to these lesions (B). Note the urinary artefacts. Bony repair, without treatment, is shown 6 months later (C). These appearances are the typical evolution of insufficiency fractures.

developing. Several studies have been published, in which young military recruits and sportsmen have been examined. In one, with a 2 6 week follow up, only about half the patients eventually demonstrated a radiographic abnormality. 8 The exact distribution of the lesions varies from series to series, and from physical activity to activity. The commonest sites are metatarsals, tibiae, calcanei and femora. At each the scan features are usually typical. For example the classical lesion in the upper tibia mirrors the known plain film changes, being transverse and most marked posteromedially (Fig. 15). The direction of the fracture

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is at right angles to the force vector inducing it. This is important at some sites since specialised views, not only scintigraphic but also radiographic, are required to identify them, for example the tarsal navicular. Scintigraphic detection of stress fractures of the partes interarticulares is less clear cut. An early or evolving stress lesion may be readily detected and, if plain films are normal, confirmation may be sought by CT (Fig. 35). In the follow-up of these lesions the reversion of the scan to normal implies an absence of bone activity or remodelling and occurs either when the fracture has healed or non-union established. Consequently,

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Fig, 15--Upper tibial stress fracture. A radiograph shows an area of sclerosis crossing the upper tibial shaft (A), with some lucency posteromedially. A pinhole view (B) of a bone scan confirms the typical transverse appearances of a stress fracture.

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PainJul normal variants. Occasionally patients present with pain and tenderness over a so-called normal variant, such as an os naviculare (Fig. 17). Bone scanning in such cases reveals abnormal activity presumably due to recurrent low-grade trauma. The importance of scan detection in these lesions lies in patient management. Since they may be shown easily by a scan before any radiographic lesion, or indeed pathological fracture occurs, appropriate alterations in exercise patterns may be made at an early stage. Furthermore the relatively modest radiation burden of a scan means that a repeat study can be justified in the follow-up of recalcitrant lesions. Occult injury Fig. 16--Shin splints. Frontal (left) and lateral (right) views of the shins reveal ill-defined foci of increased cortical activity, for which no radiographic counterpart was found.

comparison between the scan and plain film findings is of some importance and the former should be reserved for either early diagnosis or prior to surgery. Continued activity may be evidence that a potential for bone healing remains. Shin splints. This lower leg abnormality is clearly demonstrated scintigraphically. Blood pool images are normal but delayed images demonstrate classical focal cortical abnormalities (Fig. 16). It is most unusual for a radiographic lesion to be detected.

Scant attention has been paid to the potential for radionuclide scanning to detect occult fractures and soft tissue injuries. One series has highlighted the role of scintigraphy in detecting carpal injuries. In that study 99 patients who were scanned but had no X-ray abnormalities were reported. 9 Approximately half the images had abnormal foci, about 40% of those subsequently developing a radiographic abnormality. Whilst 52% of all lesions were in the scaphoid, many other sites were shown to be involved, occasionally multiple lesions were present (Fig. 18). The early management of these patients must clearly be valuable. Scintigraphy is a potent means of detecting occult fractures at sensitive sites elsewhere, such as femoral necks in the elderly. Bone scans become abnormal

B Fig. 17--Painful os naviculare. A plain film (A) shows an apparently unremarkable os. The bone scan (B) shows that abnormal activity is present at this site. Local pain and tenderness settled with conservative treatment.

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Post-traumatic indications

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Fig. 18--Bilateral scaphoid fractures. This patient had fallen on his outstretched hands but had normal radiographs at presentation. A scan at 24 h revealed bilateral, occult fractures.

very soon after injury, so that imaging may be performed in the first 48 h. Indeed delay is undesirable since the development of disuse osteoporosis may obscure foci of injury. Soft tissue traumatic lesions are seldom considered an indication for bone scanning. Nonetheless valuable information as to the exact site and extent of a lesion may be obtained in some cases. Recent data suggests that a scan of the foot in patients with persisting pain after injury has successfully expedited treatment (Fig. 19).

Reflex sympathetic dystrophy (RSD). This condition of unknown aetiology is characterised by a diffuse regional increase in both the blood pool and delayed phases of a bone scan, similar to that occurring after sympathectomy (Fig. 20). This can be distinguished from disuse osteoporosis in which the increased activity is local to the site of injury and largely confined to the position of the former metaphyses. RSD is essentially indistinguishable from Regional Migratory Osteoporosis (see below). The clinical relevance of scintigraphy lies in the therapeutic benefits to be obtained by early mobilisation and steroid therapy. Myositis ossificans. Whatever the aetiology, traumatic or post paretic, myositis ossificans may be detected by a bone scan before radiographic features have emerged. It can also assess the biological activity on sequential scans. Bone grafts. Bone scans are being used with increasing frequency to assess the viability of grafts both free vascularised and not. In both, increased activity on a bone scan must indicate that the imaged bone has a blood supply and may be viable. This may have particular value when a less than perfect insertion has been achieved or in the presence of infection (Fig. 21). Also a scan may be used to assess whether or not a graft has fully incorporated into host bone. In one series patients with fusion masses for scoliosis surgery were scanned at 6 months from surgery. The majority of those with pseudarthroses due to non-union were detected by focal bone scan abnormalities. Fracture healing. Considerable benefits might accrue

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Fig. 19--Ligamentous injury. This patient had suffered a forced eversion injury some weeks earlier and complained of persistent, Iocalised pain. A scan (A) demonstrates abnormal activity in the line of the tibialis sheath and deltoid ligament. A subsequent ankle arthrogram (B) confirms joint rupture through the deltoid ligament into the tibialis sheath.

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ISOTOPE SCANNING OF THE MUSCULOSKELETAL SYSTEM

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Fig. 20--Reflex sympathetic dystrophy. A trivial foot injury was accompanied by persistent pain, swelling and disuse osteoporosis on X-ray (A). The scan shows a marked regional increase in activity, both on perfusion (B) and the delayed phase (C). Note the gross asymmetry, the right foot being barely visible !

from knowledge as to whether or not a fracture was healing, or if delay or non-union was likely. Experimental data suggests that this is possible with sequential bone scans. Indeed much of our understanding of the mechanisms of bone radionuclide uptake has come from studying bony injury in the experimental animal. 1° Surprisingly, perhaps, little data is available in human fractures. One group reported an attempt to predict the future bony healing of tibial

fractures scanned at 6 weeks from injury, l 1 A fracture ratio was produced and a good correlation was shown between it and subsequent time to sound bony union clinically. Similarly, visual assessment of the extent and quality of the foci of activity also correlated with outcome in so far as the more intense and diffuse the increase in activity, the more likely was early union. Others have reported similar data. It is obviously unnecessary to scan all fractures routinely but it may be an option at sites of high risk of non-union, such as the tibia, with co-existent infection or extensive soft tissue loss. The correlation between the degree of uptake shown by a scan and the mechanical stiffness or stickiness at a fracture site is not known. The latter may be more relevant to healing time. Avascular necrosis. Some data suggest that both bone and marrow scanning have a role in the early diagnosis of this complication (see below).

Non-accidental injury

Fig. 21--Assessment of a vascularised graft. A live fibula graft had been inserted for a segmental defect of the femur following a compound fracture (A). Sepsis loosened the fixation and the scan was undertaken to assess viability. The images (composite of two) confirm that it is alive. Bony repair is proceeding at its insertions. A fracture of the right femoral shaft is also present. The graft subsequently incorporated and united without difficulty.

The rapid and reliable assessment of children in whom non-accidental injury is considered is an important and evolving role for skeletal scintigraphy. Since the whole skeleton is imaged following a single injection of radiopharmaceutical it is straightforward to do a skeletal survey without either arousing suspicion or incurring an excessive radiation dose. Spiral or transverse fractures are clearly demonstrated (Fig. 22). Difficulty, however, may be found in the metaphyses since the normal paediatric skeleton is avid for radiopharmaceutical in this site. Detection of asymmetry and a high index of suspicion are useful. The demonstration of multiple lesions may be considered diagnostic, and, granted the medicolegal significance, confirmatory radiographs may then be taken. It must be anticipated however that, akin to stress lesions, more foci of abnormal activity may be shown than are found by subsequent radiography.

CURRENT ORTHOPAEDICS 335 supply is necessary for bone to accumulate radionuclide, the immediate abnormality is a photon deficiency (Fig. 23). This is only appreciated on the delayed scan, since the contribution by normal bone to the perfusion scan is slight. Defects precede the development of radiographic change, and may give an idea of their extent. Lesions may develop on a scan that do not have a radiographic counterpart. Later in disease evolution, at revascularisation, activity is increased, presumably due to a mixture of repair and inflammatory response around the lesion. Few data are available to know whether a scan can 'age' an infarct. For practical purposes it may be assumed that an acute infarct will be shown as a photon deficiency for at least the first 1-2 weeks. In systemic disorders, such as sickle cell disease (Fig. 24) or Gaucher's syndrome (Fig. 23), multiple lesions may be present at various stages of evolution.

Perthes' disease and irritable hips

Fig. 22--Non-accidental injury. Note bilateral forearm fractures, together with multiple rib lesions. (This figure is reproduced by kind permission of Dr Helen Carty, Liverpool)

Avascular Necrosis Scintigraphy, using bone scanning agents, has been widely employed in the detection of idiopathic avascular necrosis. The radionuclide image depends upon the phase of evolution of the lesion. Since a blood

These two disorders may be discriminated reliably by bone scanning. 12 Pin hole collimator pictures give good detail of the femoral capital epiphyses, though take some time to acquire because the count rate is slow. Three patterns are recognised. In the first a photon deficient area is shown (Fig. 25), typically the lateral two thirds of the femoral head, thought to correspond to infarcted bone, and perhaps giving some idea of the extent of head involvement. The second is increased activity in the metaphysis and a flattened epiphysis, thought to be due to the revascularisation phase of the disease. The third, a mixed appearance, may also be seen. Correlation with Catterall grading does not seem clear cut. In irritable hips, due to synovitis, the scan is usually normal. Occasionally increased activity is seen. Only rarely is

Fig. 23--Gaucher's disease, acute bone infarction. A 13-year-old girl complained of sudden left hip pain. A scan (A) shows that the whole of the femoral head is photon deficient. Enhanced activity is present around the acetabulum and upper femoral shaft. Close scrutiny of the radiograph (B) reveals a slightly increased density in the medulla at these sites, presumably due to previous infarction, A subsequent scan showed a return of activity in the femoral head which has not collapsed to date.

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ISOTOPESCANNING OF THE MUSCULOSKELETALSYSTEM 3) Because bone seeking isotopes may be accumulated in tissues which obscure the area of interest, marrow scanning may be helpful. 10-15 mCi of 99 m Tc labelled sulphur colloid are injected intravenously, and imaged 1-2 h later, the agent then being bound in the reticuloendothelial system including red bone marrow.

Infection

Fig. 24~-Sickle-cell crisis. An 11 -year-old Arab boy presented with an 8 h history of severe low back pain. Photon deficiency of a high lumbar and lower thoracic vertebra is seen, consistent with acute avascular necrosis. Patchy increased activity in other vertebrae reflect previous, healing lesions. a photon deficient hip seen, and then confusion with Perthes' disease is possible. Post-traumatic avascular necrosis It would be helpful to predict avascular necrosis soon after injury. For example if the femoral head could be shown to be dead within the first 24 h, an elective decision could be made to proceed to joint replacement. Unfortunately scanning after acute injury is difficult. Increased activity occurs due to the fracture itself, haematoma and general protein leak. This may obscure an area of photon deficiency. Several means of coping with this problem have been tried. l) Computed areas of interest may be created over the femoral heads and ratios derived. 2) Overlying structures may be subtracted if an axial projection is constructed. This may be done either by emission computed tomography (ECAT) with 99 m T c H D P or positron emission tomography (PET) with 18 fluorine. Early results with P E T in Perthes' Disease seem promising.

Scintigraphy cannot detect the presence of infecting organisms. What it may do, however, is to detect significant inflammation by virtue of change in blood flow, capillary leakage or white cell infiltration. In the case of a T c H D P scan the presence of infection may be inferred by an increase in activity during the blood pool phase, usually ill-defined and diffuse. This is akin to the plain film findings and is accompanied by an increase in activity on the delayed phase. Because T c H D P accumulates in oedema fluid, it is important to remember that soft tissue inflammatory lesions, similar to traumatic abnormalities, may themselves be demonstrated on a bone scan. A dynamic acquisition may help to distinguish between soft tissue and bony sepsis. The presence of abnormal numbers of white cells may be gauged either directly by III indium chloride labelling or by identifying macrophage activity by the use of gallium. Acute osteomyelitis The evaluation of the bone scan in experimental osteomyelitis has been documented. It was shown that abnormal perfusion occurred very early after inoculation and could be the only abnormality shown on a bone scan at this stage. This may account for reports of false negative scans in acute osteomyelitis. Increased activity on the delayed phase followed some days later. ~3 Consequently early osteomyelitis may be overlooked if the blood pool phase is not recorded. The presence of oedema fluid, pus or even infarction within the medullary canal may explain why occasionally the delayed phase of the bone scan actually shows an absolute reduction in activity, a true 'cold' bone scan (Fig. 26). Whole body images may detect other occult lesions in a small number of cases.

Fig. 25--Perthes' Disease. A patient is shown with a substantial defect of the right femoral head on scan (A), but an initially normal radiograph. The subsequent evolution is shown (B). (This figure is reproduced by kind permission of Dr Helen Carty, Liverpool)

CURRENT ORTHOPAEDICS 337

Chronic osteomyelitis When bony turnover is low only a slight increase in activity is expected on a bone scan. Thus old infection will induce some change for as long as remodelling progresses. Once acute disease has been treated, the blood pool phase of a bone scan should revert to normal. Continued low grade infection is thus mirrored by increased activity on both phases of the scan, the lower the grade of infection, the less the activity. Spinal lesions particularly may be unimpressive. In chronic osteomyelitis particular attention should be paid to any localised focus of activity, which may identify a locus of continued infection, perhaps associated with a sequestrum. This may be confirmed by other techniques, CT being the easiest (Fig. 27).

Septic arthritis Difficulty is seldom encountered clinically in the diagnosis of septic arthritis, with the possible exception of sacroiliac involvement where patients may present with a variety of non-specific clinical features including appendicitis, acute abdomen or severe low back pain.14 A bone scan usually reveals an increase in the perfusion phase early in the disease, but abnormal activity on the delayed phase may not develop until 7-10 days later. Hence the diagnosis may be missed if the blood pool phase has been omitted. The distinction from an inflammatory arthritis may be difficult. For example acute crystal arthritis is clinically very similar, as is the joint aspirate. Any cause of an inflammatory arthritis, including rheumatoid disease, will induce an abnormal bone, and indeed gallium, scan. Hence, distinguishing a septic from an acute non-infective arthritis may not be possible (see below).

Coexistent disease It is not possible to separate absolutely one cause of an abnormal bone scan from another when a combination

of pathologies exists. A scan will not be able to exclude, or confirm, osteomyelitis in a fresh fracture for instance. Again the absolute distinction between loosening and infection of a joint prosthesis may be very difficult (see below), even when employing a gallium or 111 indium chloride scan. Both the latter are influenced by other, inflammatory, non-infective pathologies. In spite of this disadvantage, they may afford very striking results, even in the face of a leukopaenia. 111 Indium labelled white cells may be the most specific technique for infection (Fig. 28). Certainly they are less likely to localise in healing fractures and purely loose prostheses than gallium. They may not penetrate more chronically fibrotic lesions resulting in an apparently false negative scan. Gallium has a much longer biological half life but, on the other hand, requires imaging over 72-96 h to be sure of the result. This delay may be unacceptable clinically. The blood pool phase of a bone scan may afford equivalent data in terms of the presence of an inflammatory focus. 13

Assessment of Joint Replacements With an ageing population, and increasingly sophisticated design technology, joint replacements are becoming more frequent. Apart from immediate perioperative complications, the two most important problems which arise are loosening and infection of these devices. Distinction between these events, which may co-exist, is therapeutically important. Radionuelide scanning has a significant role in their detection and differentiation.IS Close assessment of the plain films will, in most instances, provide good evidence of the presence of loosening either by the detection of migration of either component, or the development of radiolucencies either between device and cement, or cement and underlying bone. Radiolucencies adjacent to acetabular cement, particularly superolaterally, of up to 2 mm in width, are considered normal. Similarly a localised, well-defined lucency superolateral to the

Ant

A Fig. 26--Septic sacroiliitis and iliac osteomyelitis. A true photon-deficient or "cold' scan is shown on the right (A) although the blood pool image (B) is increased. The history was of 6 days severe right lower abdominal pain.

338

ISOTOPE SCANNING OF THE MUSCULOSKELETAL SYSTEM

B

Fig. 27--Chronic osteomyelitis complicated a compound calcaneal fracture (A). Persistent pain was accompanied by continued bone scan activity (B). A CT scan revealed a sequestrum in an old sinus track (arrowed) (C).

femoral neck is also normal. More extensive areas of resorption should be regarded as pathological. Certainly when obvious varus angulation, calcar resorption or cement fractures are present, the need for further radiological investigation is doubtful. Features which suggest the presence of inflammation/infection

are ill-definition of the margins of resorption and periosteal new bone formation. These signs are, however, by no means constant and consequently further investigation is often necessary. Other painful lesions which may develop include stress fractures of bone or implant, ununited trochanteric osteotomies or incidental findings such as Paget's disease or metastasis. These lesions may be demonstrated scintigraphically. The important, and increasingly common, loosening associated with a marked histiocytic response may create difficulty both radiographically and scintigraphically. Here bone erosion with well-defined scalloped defects is the hallmark. 16 The lesions resemble the focal lytic changes seen in myeloma and almost certainly reflect an exaggerated long term response to fragmented polymethylmethacrylate. This is not dissimilar to findings associated with chrome/cobalt sensitivity.

Fig. 28--Osteomyelitis of the femur is shown by 111 indium chloride labelled white cells. The patient was markedly leukopaenic following chemotherapy and donor white cells were used.

The normal, post arthroplasty bone scan Increased activity on the delayed phase is usual declining from an incidence of about 90~ of hips in

CURRENT ORTHOPAEDICS the first 3 months from surgery to about 10~ at 2 years. 17 The increased activity often arises at predictable sites, adjacent to the medial calcar and the tip of the femoral component. These foci presumably represent a degree of varus angutation and subsidence. However, the blood pool phase of the bone scan should revert to normal in the first 3-6 months and continued abnormality on this phase of the scan should be regarded with suspicion.17 Again it should be emphasised that no scintigraphic technique is capable of excluding the presence of infecting organisms, as

339

opposed to inflammation, and abnormalities on the blood pool phase of the bone scan represent the latter.

The painful prosthesis Interpretation of a bone scan in the presence of a painful joint replacement m a y be summarised as follows--

The early and delayed phases of the bone scan are normal. In this case it is most unlikely that the device is significantly loose or infected. A search for an alternative cause of pain should be considered.

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Fig. 29--Infected Charnley hip arthroplasty. Foci of abnormal activity are demonstrated lateral to the femoral vessels on the blood pool image (A) and diffusely around the whole device on the delayed bone scan (B). A subsequent 67 gallium scan (C) reveals similar features to the blood pool image

340

ISOTOPE SCANNING OF THE MUSCULOSKELETAL SYSTEM

The early and delayed phases of the bone scan are diffusely abnormal. This combination strongly suggests the presence of infection (Fig. 29). Soft tissue lesions may also be demonstrated. If no sinus is present to cannulate, the next step is joint aspiration to obtain material for microscopy and culture. Contrast medium should be injected in order to delineate any abnormal joint extension and to show loosening. If a sinus track is present joint aspiration should not be undertaken in the first instance but a sinogram performed to show its extent and whether or not the device is involved. The early phase of the bone scan is normal but the delayed phase is abnormal. This almost certainly represents aseptic loosening, be it simple or histiocytic. The lesions tend to be focal and predictable in site, representing subsidence (Fig. 30) and stress raisers. The logical progression is to proceed to a hip aspiration followed by arthrogram to demonstrate whether or not contrast medium extends around the cement or device. The value of push/pull films and injections under pressure to show these tracks has been emphasised. At the completion of the study, long acting local anaesthetic injected into the joint provides a therapeutic trial, since symptomatic relief suggests that the prosthesis is indeed associated with the cause of pain. Other focal abnormalities. These may point to the diagnosis of a stress fracture, bony or metallic, ununited osteotomy or other incidental finding.

Many accounts have been written describing the use of gallium and III indium chloride labelled white cell in the detection of infection as opposed to loosening. In some hands this has proved extremely reliable. For routine clinical purposes the presence of an abnormality on the blood pool phase of the bone scan is adequate to demonstrate inflammation. The use of further agents is thus seldom required.

Arthritis As has been noted previously, the bone scan demonstration of increased activity in joints of older patients is very common. Typically this is shown at the sternoclavicular, acromioclavicular, patellofemoral, thumb CMC and great toe M T P joints. Indeed a scan is a sensitive indicator of the presence of developing degenerative arthritis. One study has shown a clear relationship between pain, raised intraosseous pressure and scan abnormality in hip osteoarthritis. ~s This diagnostic sensitivity has many potential applications, for example in detecting the presence of an arthritis following previous trauma. The principle roles may be summarised as follows: Is an arthritis present? The scan may distinguish arthralgia from arthritis, on the assumption that the scan is a very sensitive indicator of pathology. The distribution of joint involvement will be shown,

Fig. 30--Varus angulation and subsidence of a Charnley arthroplasty (A) is accompanied by a slight increase in activity adjacent to

its tip and the medial calcar (B).

CURRENT ORTHOPAEDICS

A Fig. 31--Hypertrophic osteoarthritis. The radiograph was normal. The blood pool phase (A) shows increased vascularity related to the fingertips and to periosteum in the forearms. This is confirmed by the delayed scan (B) which also reveal diffuse joint activity involving elbows, wrists and MCPJs.

together with any other abnormality, such as periosteal activity in hypertrophic osteoarthropathy (Fig. 31). Developing degenerative arthritis following injury can be inferred (Fig. 32), leading to early therapeutic intervention. Soft tissue pathology may be shown; for example tenosynovitis is readily demonstrated. A differential diagnosis of the exact arthropathy may be possible.

341

Can the bone scan predict the progression of arthritis ? This possibly provides the most exciting challenge for, and potentially rewarding use of, bone scanning an arthritis. Data suggest that abnormalities are demonstratable on a bone scan in the hands of patients with osteoarthritis before structural joint changes have developed (Fig. 33). 19 This seems likely in other joints. although data is less firm, and raises the possibility of therapeutic interference, either systemically or locally, before joint disruption. Can the bone scan distinguish septic arthritis? As has already been emphasised no radionuclide scan is capable of confirming the presence of infecting orgamsms. The bone scan simply demonstrates joint activity; interpretation will depend upon the clinical story and anticipated prognosis for that joint. Even a gallium scan has this limitation. Disease activity in rheumatoid disease is reflected by the number of white cells present in joint fluid and this number is proportional to the degree of abnormality on a gallium scan. Accordingly, neither a gallium nor a TcHDP bone scan will discriminate between inflammation and infection. Does scintigraphy help in the diagnosis of sacroiliitis ? Considerable controversy has surrounded this question. Several publications have advocated various ratios and regions of interest, relating sacroiliac joint activity to a reference point. Whilst abnormal activity, or increased ratios, may be found in patients with obvious disease, it is common experience that the equivocal case, clinically and radiographically, is often associated with equivocal scans! Thus scans are not often helpful in diagnosing bilateral sacroiliitis. 2° Asymmetrical sacroiliac joint activity should be regarded with suspicion, particularly as it may occur in septic sacroiliitis (Fig. 26).

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Fig. 32--Post-traumatic degenerative arthritis. Following a major proximal row injury a bony fusion of the wrist and intercarpal joints was performed (A). Symptoms recurred some time later and a scan suggests that abnormality is Iocalised around the only remaining, peri-hamate joint. Local injection was therapeutic.

342

ISOTOPE SCANNING OF THE MUSCULOSKELETALSYSTEM

Fig. 33--Progression of joint involvement in hand osteoarthritis. Two views from a series of X-rays (A) and scans (B) in a female patient show the waxing and waning of scan abnormalities which predate radiographic changes. Note particularly the "healing" index finger PIPJ and the disintegrating ring finger PIPJ and thumb CMCJ.

Miscellaneous Uses Regional Migratory Osteoporosis A number of disorders of unknown aetiology are characterised by an exaggerated form of osteoporosis and sympathetic skin changes. Already mentioned is reflex sympathetic dystrophy (see Trauma). Included within this group of so-called algoneural dystrophies are the shoulder-hand syndrome, Sudek's atrophy and regional migratory osteoporosis. All are characterised by excessive or prolonged pain, oedematous skin with increased sweating initially, delayed recovery and trophic changes. Several varieties of Regional Migratory Osteoporosis are recognised. a) Lower limb in the elderly, often following minor trauma. This may not migrate, but may occur on the other side after a similar event. b) Hip, especially in the third trimester of pregnancy. c) Flitting large joint, especially the knees and hips. Radiographically, in all cases, profound demineral-

isation occurs in a regional distribution, as opposed to the subarticular/metaphyseal location of usual disuse osteoporosis. The appearances are reminiscent of a marked synovitis; indeed a septic arthritis may be erroneously considered. Bone scans are markedly abnormal, often prior to the development of the radiographic change, permitting early intervention.

Low Back Pain Routine bone scanning has no special role in the overall diagnosis or management of low back pain. It is common to find abnormal activity related to facet joint osteoarthritis (when it is laterally placed on the posterior view) or related to degenerative disc spaces. In some circumstances however, a bone scan may be valuable: 1. To detect an occult primary neoplasm, not readily visible on plain films. An obvious example is an osteoid osteoma (Fig. 34A & B) or osteoblastoma. The

A Fig. 34~Osteoid osteoma as a cause of painful juvenile idiopathic scoliosis; bone scan(A), tomogram (B).

CURRENT ORTHOPAEDICS

343

.... @

Fig. 35--Spondylolytic defect. A radiograph was considered normal but a subsequent bone scan (A) d~monstrated abnormal activity in the right pars of L5. An unequivocal spondylolytic defect is shown by CT (B).

detection rate of occult metastasis or infection, in the absence of any other clinical indication, is low indeed 2. In the diagnosis of stress fractures and evolving spondylolysis, and thus possibly useful in low back pain presenting in young athletes (Fig. 35), or m painful adolescent scoliosis when a scan may exclude focal pathology. Metabolic Bone Disease

Abnormal skeletal avidity and reduced renal excretion ('superscan'), should alert one to the possibility of hyperparathyroidism (Fig. 36) or osteomalacia (Fig. 37). Multiple Looser's zones cause abnormal foci of activity that should not be mistaken for metastasis, the clue being the absence of lesions in vertebrae, skull or sacrum. Other metabolic disorders may also be assessed scintigraphically.

Fig. 36--Hyperparathyroidism. A frontal view of a whole Dudy bone scan emphasises the overall marked increase in activity. Note particularly the facial bones, where the orbital margins especially are enhanced.

Fig. 37--Osteomalacia. This patient was cons;dered initially to have metastases because multiple foci of ab~,ormal activity were shnwn in the ribs and femoral shafts. Note, h.uw~ver, the grouping of the rib lesions and the absence of £omal involvement.

344

ISOTOPE S C A N N I N G OF THE M U S C U L O S K E L E T A L SYSTEM

ever expanding. Wherever increased bone activity is present, a scan will be positive.

References

Fig. 38--Paget's Disease. Typical involvement of the skull and pelvis. Note the deformity of both the vault and the pelvis, and the uniform geographical extent.

Paget's Disease Paget's Disease is often an incidental finding during excretion urography or scanning for other purposes, at least in the West of England. Some attention has been paid to the role of scanning in its management. Lesions are more easily and sensitively detected on a scan (Fig. 38). Computer profiles may be used to follow treatment, though these are subject to controversy granted the natural history of disease evolution and resolution. Photon defects in Paget's Disease should be regarded with suspicion and a gallium scan be requested. Increased activity on this indicates malignancy (see above).

Other A scan may be employed in many other miscellaneous situations including possible subtalar bars. The list is

1. Lavender J P, Khan R A, Hughes S P F 1979 Bone blood flow and tracer uptake in normal and abnormal canine bone : comparison with Sr-85 microspheres, Kr-81 m and Tc-99m MDP. Journal of Nuclear Medicine 20: 413 418 2. Hughes S P F, Davies R, Khan R A, Kelly P 1978 Fluid space in bone. Clinical Orthopaedics 134:332 341 3. Watt I 1985 Radiology in the diagnosis and management of bone tumours. Journal of Bone and Joint Surgery 67-B : 520 529 4. Tumeh S S, Beadle G, Kaplan W D 1985 Clinical significance of solitary rib lesions in patients with extraskeletal malignancy. Journal of Nuclear Medicine 26:1140 1143 5. Kunkler I H, Merrick M V, Rodger A 1985 Bone scintigraphy in breast carcinoma: a nine year follow-up. Clinical Radiology 36:279 282 6. Snee M P, Vyramuthu N 1985 Metastatic carcinoma from unknown primary site: the experience of a large oncology centre. British Journal of Radiology 58 : 1091 1095 7. Hattner R S, Hartmayer J, Ware W M 1982 Characterisation of radiation induced photopenic abnormalities on bone scans. Radiology 145:161 163 8. Greaney R B, Greber F H, Laughlin R L et al 1983 Distribution and natural history of stress fractures in US marine recruits. Radiology 146:339 346 9. Rolfe E B, Garvie N W, Khan M A, Ackery D M 1981 Isotope bone imaging in suspected scaphoid trauma. British Journal of Radiology 54 : 762 767 10. Hughes S, Khan R, Davies R, Lavender P 1978 The uptake by the canine tibia of the bone-scanning agent 99mTc-MDP before and after an osteotomy. Journal of Bone and Joint Surgery 60B : 579 582 11. Auchincloss J M, Watt I 1982 Scintigraphy in the evaluation of potential fracture healing : a clinical study of tibial fractures. British Journal of Radiology 55 : 707 713 12. Catty H, Maxted M, Fielding J A, Gulliford P, Owen R 1984 Isotope scanning in the 'Irritable hip syndrome'. Skeletal Radiology 11 : 32-37 13. Norris S H, Watt I 1981 Radionuclide uptake during the evolution of experimental acute osteomyelitis. British Journal of Radiology 54:207 211 14. Horgan J G, Walker M, Newman J H, Watt I 1983 Scintigraphy in the diagnosis and management of septic sacroiliitis. Clinical Radiology 34:337-346 15. Watt I 1986 Failed Joint Replacement. Diagnosis--(ii) Radiological. Current Orthopaedics 1:15 25 16. Scott W W, Riley L H, Dorfman H 1985 Focal lytic lesions associated with femoral stem loosening in total hip prosthesis. American Journalof Roentgenology 144:977 982 17. Norris S H, Watt I 1983 Radioactive isotope scanning; Revision Arthroplasty 2. Franklin Scientific Publications, London, pp 28 32 18. Arnoldi C C, Djurhuus J C, Heerfordt J, Karle A 1980 Intraosseous phlebography, intraosseous pressure measurement and 99m Technetium polyphosphate scintigraphy in patients with various painful conditions in the hip and knee. Acta Orthopaedica Scandinavica 51 : 19 28 19. Hutton C W, Higgs E R, Jackson P C, Watt I, Dieppe P A 1986 99mTcHMDP bone scanning in generalised nodal osteoarthritis. II. The 4 h bone scan image predicts subsequent radiographic change. Annals of Rheumatic Diseases (in press) 20. Dequeker J, Goddeeris T, Walravens M, De Roo M 1978 Evaluation of sacroiliitis : comparison of Radiological and Radionuclide techniques. Radiology 128:687-689