ClinicalRadiology (1981)32, 431-439 0009-9260/81/01040431502.00 © 1981 Royal College of Radiologists

Gallium-67 Scanning in the Painful Hip Replacement

Total

FRANK WILLIAMS, IAIN W. McCALL, WILLIAM M. PARK, BRIAN T. O'CONNOR and VALERIE MORRIS

Department of Radiology and Institute of Orthopaedics, Robert Jones and Agnes Hun t Orthopaedic Hospital, Oswestry, Shropshire

Pain following total hip replacement is a significant clinical and diagnostic problem. Technetium scanning has proved a sensitive indicator of infection or loosening but does not differentiate between them. This study assessed the value of gallium-67 to aid this differentiation. Thirty patients underwent revision surgery. Fourteen were proven to be infected and 13 had positive gallium scans as also did two patients without infection. The implications of these false interpretations are discussed. Increased gallium activity was correlated with the patterns of the 99rnTc scans and arthrographic appearances. It is concluded that gallium-67 scanning is a valuable adjunct to the assessment of the painful hip replacement when infection is suspected.

Approximately 40 000 total hip replacements are per- formed per annum in Great Britain. Harris (1977) has indicated that complications in the form of loosening or infection arise in 20% of total hip replacements, and Charnley and Eftekhar (1969) and Benson and Hughes (1975)indicate that infection formedapproxi- mately 5% of this total. Pain is the usual presenting clinical feature and the exclusion or confirmation of infection is important in the continued management of the patient. Plain films and hip arthrography have been shown to have limitations in assessing infection and technetium polyphosphate bone scanning, al- though valuable, represents only increased bone acti- vity and is not specific for loosening or infection. GaUinm-67 citrate has, however, been noted to accu- mulate in areas of infection and this study was there- fore instituted to assess the value of gallium-67 scanning in patients with painful hip prosthesis and to compare and contrast the findings with technetium bone scanning and hip arthrography in the same patient.

METHODS

The study comprised 30 patients with total hip replacement in whom pain was sufficiently disabling to warrant consideration for further surgery for revi- sion of the prosthesis. The ages of the patients ranged from 59 to 78 years (mean 72.5) with 15 males and 15 females. All patients were examined at least six months after surgery. Initially, plain radiographs and full haematological examination, including erythro- cyte sedimentation rate (ESR) estimations were obtained. A bone scan of the hip area was then per- formed using a J & P rectilinear scanner, after an

injection of 10mCi of technetium methylene diphos- phonate.

After completion of this study 2 .3-3mCi of gallium-67 citrate was administered intravenously and images were obtained at 4 8 - 64 h. Following comple- tion of the gallium scan, the hip was examined arthro- graphically.

All patients then underwent exploration of the hip replacement. Macroscopic evidence of infection was noted at surgery and intra-operative cultures were taken; the specimens were immediately trans- ported to the laboratory for bacteriological assess- ment. Infection was confirmed by evidence of a purulent exudate on microscopy in material removed directly from the prosthetic sites. Eight patients out of 30 had an asymptomatic contra4ateral total hip replacement and these patients were used as controls for both gallium and technetium scans.

The patients in whom infection was confirmed were designated Group A. Those in which loosening alone was present at operation were designated Group B and one patient in whom surgery was performed but neither loosening nor infection was found was desig- nated Group C. The controls were designated Group D.

Clinical Findings

Disabling pain was the presenting feature in all patients. Five patients in the series had rheumatoid arthritis and all these were in Group A. The skin overlying the hip was erythematous and inflamed in four patients, all of whom were from the infected group.

Sinuses were present in eight of the patients with infection and one patient who, at operation, showed

432 C L I N I C A L R A D I O L O G Y

only loosening, In this patient, on exploration, the sinus was found to be superficial.

RESULTS

Group A. Infection was confirmed at microscopy following surgery in 14 patients. Only four patients, however, had positive cultures. (three Staphylococcus Albus and one Staph. aureus).

The gallium scan showed increased uptake in 13 (Fig. 1). The distribution o f uptake is shown in Table 1. In all cases the increased uptake occurred either around the hip joint, around the greater troehanter or both. In only three cases was increased activity demonstrated in the femoral shaft and this was never the sole area. One patient with a trochanteric abscess and a sinus had a negative gallium scan despite Staphylococcus albus being cultured at the time of surgery. This patient had received antibiotic treat- ment prior to surgery. The technetium-99m scan showed increased uptake in 13 o f the 14 cases. The

distribution is shown in Table 2 and is similar to that of Group B (Table 3). In one case, the bone phase showed no evidence of increased uptake but a scan performed 15 min after the injection of the techne- tinm-99m MDP showed generalised increase around the hip joint. In this case marked increased gallium uptake occurred around the acetabulum and at sur- gery there was an infected loose acetabular component (Fig. 2).

Arthrography was performed in eight cases. Three failed to show femoral loosening. All eight cases showed extension of contrast medium around the greater trochanter. The ESR in this group ranged f rom 60 to 128 mm h -1 (average 79 mm h-l) .

Group B. Loosening alone occurred in 15 patients. The femoral stem was involved on its own in 13 and both components in two. The gallium scan was nega- tive in 13 patients. Increased gallium uptake occurred in two cases. One showed mild increased activity in the region of the upper femoral stem and at surgery, severe metal reaction involving the femoral compo- nent was found (Fig. 3). The second showed increased

Fig. 1 - Infected femoral prosthesis. (a) Plain film shows non-union of the greater trochanter. There is bone destruction of the femur, both on the inferior margin of the upper shaft and at the lower margin with the trochanter and also on the outer edge of the latter (arrows). (b) The arthrogram shows contrast in cavities around the areas of bone destruction and between the trochanter and femur.

S C A N N I N G T H E P A I N F U L HIP R E P L A C E M E N T 4 3 3

. . . . 99m Mw

: , 6.79 C g , ~

r . . . . ~ f

O

67Ga R MW D 6.79

Fig. 1 - (c) Increased technetium uptake occurs all around the femoral component but is greatest at the greater trochanter and upper femoral shaft. (d) Increased gallium activity is seen in the region of the greater trochanter and upper femoral shaft. A scan eight months earlier was normal_

434 C L I N I C A L R A D I O L O G Y

Table 1 - Distribution o f increased gall ium activity in the infected eases

Table 3 - Distr ibution of increased techne t ium activity in non-infected loose hips

Gal l ium G r o u p A

Hip = acetabular; G.T. = greater t rochanter ; Fern. = femoral s tem. N.B. One negative gallium scan.

Table 2 - Distr ibution o f increased t echne t ium activity in infected cases

99mTc-MDP Group A

Fig. 2 - Infected acetabular componen t . (a) Plain film - osteoporosis is present and the acetabular componen t is deep- seated bu t wi thout specific evidence of loosening or infec- t ion.

99mTc-MDP Group B

S C A N N I N G THE P A I N F U L HIP R E P L A C E M E N T 4 3 5

99m Tc

v

Fig. 2 - (b) The 3-h (bone) phase of the 99mTc MDP scan shows increased activity in the unoperated rheumatoid hip but no activity on the side of the prosthesis. (c) The early 10 min 'perfusion' phase shows increased activity around the right ace- tabular prosthesis as well as the unoperated hip.

436 C L I N I C A L R A D I O L O G Y

67Ga B T

4 7'8

3

® @

ASIS

~ , ~ ~ ~ . . . .

D , f

Fig. 2 - (d) Extensive gallium activity around the acetabular componen t . The unopera ted hip shows no activity. At surgery, the acetabular c o m p o n e n t was ba thed in pus.

activity around the greater trochanter. No explana- tion was found at surgery. Increased technetium-99m MDP activity occurred in all cases and the distribu- tion was demonstrated in Table 3. All cases had increaged uptake around the femoral shaft. Acetabular activity was present in the two cases proven to be loose at surgery and in a further five cases.

Arthrography was performed in 10 cases. The comparison between technetium and arthrography is shown in Table 4. Contrast medium was not demon- strated around the femoral component in three cases and was present around the acetabular component in a further eight cases, five of which were thought to be firm at surgery.

In this group the ESR ranged from 0 to 64, mean 27.8 mm h -1.

Group C. This group contained only one case with an aseptic trochanteric bursitis at surgery. The femoral and acetabular components were not loose. The technetium scan showed activity in the trochani teric region and the upper femur; the gallium scan was normal. No arthrogram was performed.

Group D. Controls. Eight of the 20 patients had asymptomatic total hip replacements of over two years' duration on the contra-lateral side. No evidence

of increased technetium or gallium activity was observed in any of these patients. No arthrograms were performed.

DISCUSSION

The mechanism of gallium accumulation has received considerable attention. Once injectedinto the bloodstream, gallium is bound rapidly to serum pro- teins, principally transferrin and possibly haptoglobin (Hartman and Hayes, 1969). Studies on tumour cells indicate that gallium enters the cells by incorporation of transferrin through specific transferrin binding sites within the cell. In inflammatory lesions the majority of the accumulation occurs through incor- poration in the leucocytes and the latter subsequent migration into the inflammatory area (Gelrud et al., 1974; Handmaker and O'Mara, 1977). Increased vascularity and accumulation of extracellular gallium- 67 bound transferrin are also likely to be factors.

Gallium accumulation in bone infection was first described by Deysine et al. (1975a) who found that the isotope accurately identified the site of infec- tion in 13 patients with chronic osteomyelitis or osteomyelitis secondary to open reduction fractures.

S C A N N I N G THE PAI NFUL HIP REPLACEMENT 4 3 7

B

99r"Tc HA 1.79

Fig. 3 - (a) Arthrogram after subtraction of bone image shows a fractured femoral stem with contrast around both the femora! and acetabular component (arrows). A large false capsule is also present. (b) Increased technetium activity is present around the acetabulum and greater trochanter.

~7

~ ' ~ : 1.79 Fig. 3 - (c) Mild increase in gallium activity is present in the region of the acetabulum.

Their clinical findings were confirmed in animal studies where induced foci of infection rapidly be- came radioactive with intravenously injected gallium-

67 citrate (Deysine e t al., 1975b). The evaluation of septic arthritis with gallium was reported by Lisbona and Rosenthall (1977) who found positive examina- tions in all six patients with septic arthritis. The present series confirms that gallium accumulation occurs in relation to an infected hip replacement. The increased activity we observed is always present in

Table 4 - Comparison of surgical results with technetium- 99m MDP imaging and arthrography in evaluation of the loose non-infected total hip prosthesis (Group B)

99 Tc scan Arthrogram

Loose No t Loose No t loose loose

Acetabulum Loose 2 0 2 0 Not loose 5 8 5 3

Femur Loose 15 0 7 3 Not loose 0 0 0 0

438 C L I N I C A L R A D I O L O G Y

either the region of the false capsule and the top of the femoral shaft or around the greater trochanter. In only three cases was the lower shaft also involved, and never as the sole area of activity. These findings, along with the demonstration on arthrography of large sac-like false capsules often with internal sinuses around the greater trochanter, suggest that the gallium is delineating a septic arthritis, which implies that these are fairly extensive infective lesions.

The inability to differentiate loosening and infec- tion on the technetium-99 MDP scan has been stressed (Mclnerney and Hyde, 1978; Weiss et al., 1979). Williamson e t aI. (1979), however, suggested that a diffuse uptake is more in favour of infection and that localised activity favours loosening. The similarity of technetium uptake patterns in the loosened group compared to the infected group in our series does not support this latter premise. The distribution of activity is of importance in considering particularly the false positive examinations of which there were two in our series. Reing e t al. (1979) scanned 70 patients and had 19 positive gallium scans with no false positive examinations. No consideration of uptake distribution of either gallium or technetium was given in this paper.

Rosenthall e t al. (1979) reported eight of 24 examinations showing increased gallium activity of mild or moderate degree in the absence of proven infection. The concentration of gallium and techne- tium MDP were congruent in these patients. The authors therefore suggest that congruence indicates a false positive increase gallium uptake occurring in non-specific inflammation or increased bone activity. Our findings, however, do not support this as in half of our proven infections the increased gallium and technetium uptake was congruent and in half it was not. In one false positive the increased gallium up- take was probably due to non-specific inflammation secondary to a metal reaction. One false negative occurred in both our series and that of Reing e t al. (1979). In both instances, antibiotics had been pre- scribed prior to surgery. This may have had an effect on the gallium uptake. Rosenthall e t al. (1979) reported no false negatives.

The increased use of the gamma camera, in com- parison with the rectilinear scanner, may increase the dangers of false positive examinations, due to the latter's increased sensitivity (Hoffer e t al., 1977). Conversely, it may also reduce the possibility of low grade osteomyelitis around the lower femoral shaft being a source of false negative examination.

The proportion of bacteriologically positive cul- tures in this series was low, although specialised culture techniques were used. Microscopic examina- tion of operative material indicated bacterial infec-

tion at the bone-metal interface and this points to the difficulty in obtaining accurate bacteriological confirmation in every instance. This has been obser. ved by other investigators, and Charnley and Eftekhar (1969) noted an incidence of one in five negative cultures in their group of infected total hip pros. theses and suggested that this so-called 'sterile' infec. tion was due to an organism of very low pathogen- icity. They also state that the pattern of incidence of the 'sterile' infection does not support a diagnosis of metal sensitivity as the cause of late infections from which no organisms can be cultured.

As a diagnostic method arthrography has been disappointing in the evaluation of the loosened group. Incomplete sealing of the cement around the ace- tabular component allows the passage of contrast without actual loosening being present (Hankey e t aL, 1979). The failure of contrast to track down the femoral shaft may be due to incomplete filling of the false capsule (Hankey e t al., 1979) or fibrosis (Williamson e t aL, 1979) and inflammation around the loose prosthesis. Aspiration of the joint at arthro- graphy with culture of the fluid has been of limited value.

The ESR has, however, proved to be of some value. Benson and Hughes (1975) reviewed 320 hip replacements and found the ESR raised from levels of 4 4 - 1 2 0 m m h -1 in all 17 cases of infection. Reing e t al. (1979) found the ESR helpful but cautioned the value of the raised ESR in rheumatoid patients. Our series supports this latter advice as some overlap of the two groups occurred and the rheumatoid patients were responsible for the very high levels in the infected group. The two false positive gallium scans had low ESRs and that of the one false nega- tive was significantly raised. It is therefore wise, in the presence of a low ESR, to question the positive gallium scan before assuming the presence of infection.

In conclusion, gallium scanning has proved valu- able in the recognition of infection complicating total hip replacement. The technetium scan remains the primary screening examination of choice and when the two modalitie are used in conjunction with ESR measurements, useltfl information is obtained in the management of the patients. The technique, however, is not without pitfalls and some of the vagaries of gallium-67 deposition must be borne in mind.

REFERENCES

Benson, M. K. D. & Hughes, S. P. F. (1975). Infection follow- ing total hip replacement in a general hospital without special orthopaedic facilities. Acta Orthopaedica Scandi- navica, 46, 968-978.

SCANNING THE PAINFUL HIP R E P L A C E M E N T 439

Charnley, J- & Eftekhar, N. (1969). Post-operative infection in total prosthetic replacement arthroplasty of the hip joint. British Journal of Surgery, 56, 641.

Deysine, M., Rafkin, H., Teicher, I., Silver, L., Robinson, R., Manly, J. & Aufses, A. H. (1975a). Diagnosis of chronic and postoperative osteomyelltis with gallinm-67 citrate scans. American Journal o f Surgery, 129, 632-635.

Deysine, M., Rafkin, H., Russell, R., Teicher, I. & Aufses, A. H. (1975b). The detection of acute experimental osteomyelitis with 67Ga citrate scannings. Surgery, Gynae- cology and Obstetrics, 141, 40-42 .

Gelrud, L. F., Arsenean, J. C. & Milder, M. S. (1974). The kinetics of gaUium-67 incorporated into inflammatory lesions. Experimental and clinical studies. Journal of Laboratory and Clinical Medicine, 85, 489-495.

Handmaker, H. & O'Mara, R. (1977). Gallium imaging in paediatrics. Journal of Nuclear Medicine, 18, 1057- 1063.

Hankey, S., McCall, I. W., Park, W. M. & O'Connor, B. T. (1979). Technical problems in arthrography of the pain- ful hip arthroplasty. Clinical Radiology, 30, 653- 656.

Harris, W. H. (1977). Total joint replacement. New England ]oumal o f Medicine, 297, 650-651.

Hartman, R. E. & Hayes, R. L. (1969). The binding of gal- lium by blood serum. Journal o f Pharmacology and Experimental Therapeutics, 168, 193-198.

Hoffer, P. B., Schor, R., Ashby, D., Metz, C., Hattner, R.,

Handmaker, H., Price, D. C., Shames, D. M., Lilien, D. & Lim, C. B. (1977). Comparison of 67Ga citrate images obtained with rectilinear scanner and large field angle camera. Journal o f Nuclear Medicine, 18, 538-541.

Lisbona, R. & RosenthaU, L. (1977). Observations on the sequential use of 99mTe-phosphate complex and 67Ga imaging in osteomyelitis, cellulitis and septic arthritis. Radiology, 123, 123-129.

Mclnerney, D. P. & Hyde, I. D. (1978). Technetium 99mTc pyrophosphate scanning in the assessment of the painful hip prosthesis. Clinical Radiology, 29, 513-517.

Reing, C. M., Richin, P. F. & Kenmore, P. I. (1979). Differen- tial bone scanning in the evaluation of a painful total joint replacement. Journal of Bone and Joint Surgery, 61A, 933-936.

Rosenthal, L., Lisbona, R., Hernandez, M. & Hadjipavlou, A. (1979). 99mTc-PP and ~TGa imaging following insertion of orthopaedic devices. Radiology, 133, 717-721.

Weiss, P. E., Mall, J. C., Hoffer, P. B., Murray, W. R., Rodrigo, J. J. & Genant, H. K. (1979). 99mTc-methylene diphos- phonate bone imaging in the evaluation of total hip pros- theses. Radiology, 133, 727-729.

Williamson, B. R. J., McLaughlin, R. E., Wang, G-J., Miller, C. W., Teates, C. D. & Bray, S. T. (1979). Radionuclide bone imaging as a means of differentiating loosening and infection in patients with a painful total hip prosthesis. Radiology, 133, 723-725.