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Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

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Int. J. Oral Surg. 1978: 7: 488--493 (.Key words: scanning; Iransplancal;Ofl, bone,' mandible; techlll.'lium) Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury Radionuclide bone imaging STEVEN M. AND ISMAEL MENN":' * Sectioll of Oral Surgery, UCLA Center for Health Sciences, Director of Oral and Nfaxillofacial Surgery, San Bernardino County Medical Center ** Chairman, Division, Nuclear Medicille, Harbor General Hospital, Torrance, California, U. S. A. ABSTRACT - Bone imaging provides two significant advantages over previously available methods for assessing bone processes. First, as scanning is non-invasive, it offers the operator the ability to sequen- tially follow any area of bone without altering it as would a biopsy, The second advantage is the ability of bone imaging to provide current information about the bone being scanned rather than having to deal with the delay that is inherent in conventional radiography. Recent developments in radio pharmaceuticals and instrumentation have made bone imaging a potentially practical clinical tool for the detection and assessment of benign as well as malignant processes affecting bone. This paper presents the results of the use of technetium 99m diphosphonate bone imaging in experimental canine mandibular autografts and surgical soft tissue injury. The implication of these results for the clinical situation will be discussed. (Received for publication 23 May, accepted 23 September 1977) Radionuclide bone imaging, first used clini- cally to detect radiographically occult tu- mor metastasis in the skelton, until recently was limited in its usefulness by difficulties with available radiopharmaceuticals 4 ,7. SUBRAMANIAN 13 labeled a polyphosphate with technetium 99m providing a rela- tively safe and inexpensive agent with opti- mal physical characteristics for bone scan- ning. Subsequently, bone imaging has been investigated to determine its role in the assessment of an increasing number of benign bone processes 2 ,1l,H, The interest in bone scanning is based on the need for more precise and timely information 011 bone processes than is currently available from conventional radiographs. In many instances 50-75 % change in the local cal- ch.lm stores must occur before changes are seen by x-ray examination leading to a vari- able delay between the clinical occurrence and its radiographic manifestation 5 ,6,o,lo. The physiological basis of bone scanning is related to the incorporation of the radio-
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Page 1: Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

Int. J. Oral Surg. 1978: 7: 488--493

(.Key words: scanning; Iransplancal;Ofl, bone,' mandible; techlll.'lium)

Disphosphonate dynamic imaging ofexperimental bone grafts and soft tissue injuryRadionuclide bone imaging

STEVEN M. ROSER~' AND ISMAEL MENN":'

* Sectioll of Oral Surgery, UCLA Center for Health Sciences, Director of Oral andNfaxillofacial Surgery, San Bernardino County Medical Center** Chairman, Division, Nuclear Medicille, Harbor General Hospital, Torrance,California, U. S. A.

ABSTRACT - Bone imaging provides two significant advantages overpreviously available methods for assessing bone processes. First, asscanning is non-invasive, it offers the operator the ability to sequen­tially follow any area of bone without altering it as would a biopsy,The second advantage is the ability of bone imaging to providecurrent information about the bone being scanned rather than havingto deal with the delay that is inherent in conventional radiography.Recent developments in radiopharmaceuticals and instrumentationhave made bone imaging a potentially practical clinical tool for thedetection and assessment of benign as well as malignant processesaffecting bone. This paper presents the results of the use of technetium99m diphosphonate bone imaging in experimental canine mandibularautografts and surgical soft tissue injury. The implication of theseresults for the clinical situation will be discussed.

(Received for publication 23 May, accepted 23 September 1977)

Radionuclide bone imaging, first used clini­cally to detect radiographically occult tu­mor metastasis in the skelton, until recentlywas limited in its usefulness by difficultieswith available radiopharmaceuticals4 ,7.

SUBRAMANIAN13 labeled a polyphosphatewith technetium 99m providing a rela­tively safe and inexpensive agent with opti­mal physical characteristics for bone scan­ning. Subsequently, bone imaging has beeninvestigated to determine its role in theassessment of an increasing number of

benign bone processes2,1l,H, The interest inbone scanning is based on the need formore precise and timely information 011

bone processes than is currently availablefrom conventional radiographs. In manyinstances 50-75 % change in the local cal­ch.lm stores must occur before changes areseen by x-ray examination leading to a vari­able delay between the clinical occurrenceand its radiographic manifestation5,6,o,lo.

The physiological basis of bone scanningis related to the incorporation of the radio-

Page 2: Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

RADIONUCLIDE BONE IMAGING 489

nuclide into the hydroxyapatite crystal asthese are being deposited into immatureosteoid. The scan will become positive inthese areas of bone activity. A change inthe appearance of the same area of boneby conventional radiographs would dependon the maturation of the osteoid which oc­curs later. It is important to remember thatthe bone scan will reflect only reactivechanges in bone, hence tumor cells or ne­crotic bone will not localize activity. It isthe reactive changes in the bone surround­ing these areas which are responsible forthe positive scan.

The use of technetium phosphate com­pounds for assessing experimental bonegrafts in an animal model has recently beendemonstrated3,8,12. ALEXANDER! used scansto evaluate various benign processes affect­ing the facial bones in the clinical setting.There is no doubt that many processes af­fecting bone will appear on the scan priorto detection by conventional radiography.This study was undertaken to provide moreprecise information on the time intervalthat occurs between a positive scan and achange, which reflects the same situation,in the radiograph. In addition, the effectof surgically injured soft tissue on the bonescan was evaluated.

Material and methodsBONE GRAFTSThirteen mongrel dogs weighing between 9and 12 kg were rendered edentulous. Follow­ing a 6-8-week healing period, autogenousgrafts of iliac crest, rib or mandible wereplaced in surgically created unilateral mandi­bular discontinuity defects (Fig. 1). Stabiliza­tion was obtained by either a performedtitanium or dacron mesh tray. Four graftswere made non-viable by either establishing anopening into the oral environment, therebyinfecting the graft, or by coating the graft inSilastic (Dow-Corning) which was heat polymer­ized into a coating on the bone by autoclavingat 220 0 C for 15 min. Six unoperated animals

Fig. 1. Unilateral mandibular body discontinu­ity defect with autogenous iliac crest graft.

served as controls. Scans were performed 2 hfollowing the injection of 10 mCLl of diphons­phonate. Scans were obtained in a submentaland lateral projection at 1, 7, 15, 30, 45, 60,100 days, 6 months and 1 year. The scanswere performed using a stationary solid scintil­lation gamma ray detector. Comparison radio­graphs were obtained at similar intervals.

SOFT TISSUE INJURYSequential submental scans were performed onan additional seven mongrel dogs who receiveda surgical injury to the submandibular softtissues. Identical bilateral 2.5 em soft tissuepockets were created supraperiosteally bothmedially and laterally to the body of themandible avoiding injury to the periosteum(Fig. 2). These were immediately closed and

Fig. 2. Supraperiosteal soft tissue dissectionused to evaluate the effect of soft tissue inj uryon the scan.

Page 3: Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

490 ROSER AND MENA

Fig. 3. Sequential submental scans of a viablebone graft.

scans were performed 3 h post-operatively and1, 3, 7 and 14 days.

ResultsVIABLE GRAFTSConsistently in the scans of the viable graftsactivity appeared in the adjacent host bonewithin 7 days. At 15 days the activity re-

mained in the adjacent host bone and in­tense' activity appeared in the area of thegraft. This intense activity technically pro­hibited visualization of the opposite normalunoperated mandibular body. By 45 days,activity began to diminish in the adjacenthost bone, but persisted in the area of thegraft. At 75 days activity remained in thegraft area and continued to diminish inthe adjacent host bone (Fig. 3). Comparisoninterval radiographs demonstrated essen­tially no changes at 1, 15, and 45 days.Consistently only after 60 days was the as­sessment of the graft status possible (Fig.4).

NONVIABLE GRAFTSScans of nonviable grafts appeared signifi­cantly different from the scans of viablegrafts. Although increased activity in theadjacent bast bone also appeared by 7 days,

Fig. 4. Sequential lateral radiographs of a viable bone graft. Note the similarity in the appear­ance of the radiographs taken at 1, 15 and 45 days.

Page 4: Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

RADIONUCLIDE BONE IMAGING 491

Fig. 5. Sequential submental scans of a non­viable bone graft. The area of activity lateralto the mandible seen at 100 days correlatedwith an abscess formation.

it persisted through 100 days while thegraft itself never localized any significantactivity (Fig. 5). Similar to the comparisoninterval radiographs of viable grafts, signifi­cant changes in the appearance of the graft

Fig. 7. Soft tissue injury at 1 and 7 days. Thearea of activity correlated well with the in­cision. Activity localized only on one side inthis animal.

on the radiographs did not occur until after60 days (Fig. 6).

SOFT TISSUE INJURYIncreased uptake in the surgerized areas

Fig. 6. Sequential lateral radiographs of a nonviable bone graft. Note similarity of the radio­graphs through 75 days. A dacron mesh tray which is radiolucent was used to stabilize thegraft.

Page 5: Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

492 ROSER AND MENA

Fig. 8. Lateral radiographs of a viable andnonviable bone graft at 45 days. Note thesimilarity of their appearance.

was seen by the first day, but was di­minished by 14 days. The area of activitycorrelated well with thc area of dissection(Fig. 7).

DiscussionComparison of the scans and radiographsdemonstrated the value of bone imagingin early assessment of graft outcome. Asearly as 15 days, three of the four scansof viable grafts were true positives, that is,demonstrated the pattern seen in a viablegraft. At the same time, none of the fourgrafts demonstrated any significant radio­graphic signs that could be used to predicttheir outcome. It required between 45-75days for the radiographs to become con­sistently reliable in predicting graft outcome(Table 1). A similar situation existed forthe nonviable grafts (Table 2). An illustra-

Fig. 9. Scans of a viable and nonviable bonegraft at 15 days.

tion of the problem an operator can en­counter when using radiographs to followbone grafts can be seen in the similar ap­pearance of a viable and nonviable graft at45 days (Fig. 8). It is also worth notingthat when a metal appliance is utilized tostabilize the graft, much of the bone graftis often obscured. This is particularly truein the case ofparticulate bone grafting whichoften requires a metallic tray. By compari­son, scans of a viable and nonviable graftof 15 days demonstrate significant differ­ences in their appearances (Fig. 9).

Hence it is apparent from our data thatthe bone scans provide the operator withinformation pertinent to the status of thegraft usually 30 days before similar infor­mation is available from the radiographs.Surgically injured soft tissue adjacent tobone consistently localized activity. Al­though efforts were made not to injure

Table 1. Viable grafts. Table 2. Nonviable grafts.

Scans Radiographs Scans Radiographs

True False Diag- Non- True False Diag- Non-posi- nega- nostic nostic nega- posi- nostic diag-tive tive diag- tive tive nostic

15 days 3/4 1/4 0/4 4/4 15 days 1/2 1/2 0/2 2/230 days 9/9 0/9 1/9 8/9 30 days 4/4 0/4 0/4 4/460 days 919 0/9 919 019 60 days 4/4 0/4 4/4 0/4

Page 6: Disphosphonate dynamic imaging of experimental bone grafts and soft tissue injury

RADlONUCLIDE BONE IMAGING 493

the periosteum, it would be impossible tosay which soft tissue localized activity.However, the increased uptake of activityin the tissue was transient and limited to14 days, therefore, changes in activity seenin the bone scans of the grafts could not beattributed to uptake by so·ft tissue.

Until recently, scanning of the facialbones has been limited by the inability ofavailable techniques to remove backgroundactivity such as that coming from the baseof the skull or the vertebral column. How­ever, with use of computer processing andthe recent development of a tomographicscanner, this obstacle should be removed.

CONCLUSIONS1. Technetium 99m diphosphonate scans

provide an effective means for evaluatingthe viability of experimental mandibulargrafts.

2. Activity appears in viable grafts as earlyas 15 days and in adjacent host bone,whether the graft is viable or nonviableby 7 days.

3. Changes in the bone scans precededcomparison interval radiographs by 30days.

4. The increased uptake of activity in softtissue injury was limited to 14 days,therefore, changes in activity seen in thebone scans of the grafts cannot be attri­buted to uptake by the soft tissue.

References1. ALEXANDER, 1. M.: Radionuclide bone

scanning in the diagnosis of lesions of themaxillofacial region. I. Oral Surg. 1976:34: 249-256.

2. BARRETI, J. J. & SMITH, P. B.: Boneimaging with 99M TC-polyphosphate: Acomparison with 18F and skeletal radio­graphy. Sr. J. Radiol. 1974: 47: 387-392.

3. BRIGHT, R. W., FRED, R., STEVENSON,J. S. & STRASH, A. M.: Polyphosphate99M Tc scans: a quantitative method for

evaluating clinical bone formation rates.Surg. Forum. 1973: 24: 475-476.

4. DE NARDO, G. L.: The 85 Sr scintiscan inbone disease. Ann. Intern. Med. 1966: 65:44-53.

5. DE NARDO, G. L., JACOBSEN, S. J. & RA­VENTOS, A.: 85 Sr bone scan in neoplasticdisease. Semlll. Nllc/. Med. 1972: 2: 18-30.

6. EDELSTYN, G. A., GILLESPIE, P. J. & GREB­BELL, F. S.: The radiological demonstra­tion of osseous metastasis: experimentalobservations. CUn. Radial. 1967: 18: 158­162.

7. HARMER, C. L., BURNS, J. E., $.AMS, A. &SPITtLE, M.: The value of fluorine -18 forscanning bone tumors. Clin. Radiol. 1969:20: 204-212.

8. KELLEY, J. F., COYLE, J. O. & STEVENSON,J. S.: Technetium 99M radionuc1ide boneimaging for evaluating mandibular osseousallografts. J. Oral SlIrg. 1975: 33: 11-17.

9. MASHBERG, A., STRAUSS, H., SMALL, M. &MIllER, W. N.: Use of scintillation scan­ning for early detection of bone involve­ment by squamous cell carcinoma of theoral mucosa. Preliminary Report, I. Am.Dent. Assoc. 1969: 79: 1151-1159.

10. O'MARA, R. E.: Bone scanning in osseousmetastasis disease. J. Am. Med. Assoc.1974: 229: 1915-1917.

11. SILBERSTEIN, E., SAENGER, E. L., TOTE,A. J., ALEXANDER, G. W. & PARK, H. M.:Imaging of bone metastasis with 99M TC­SN-EHop (diphosphonate), 18F and skeletalradiography. Radiology 1973: 107: 551-555.

12. STEVENSON, J. S., BRIGHT, R. W., DUNSON,G. L. & NELSON, F. R.: Technetium 99Mphosphate bone imaging: a method forassessing bone graft healing, Radiology1974: 110: 391-399.

13. SUBRAMANIAN, G. & McAFEE, J. G.: A newcomplex of 99M TC for skeletal imaging.Radiology 1971: 99: 192-196.

14. YANO, Y., McRAE, G., VAN DYKE, D. C.& ANGER, H. 0.: Technetium 99M-Iabeledstanous ethane-l-hydroxy-l,l-diphospho­nate: a new bone scanning agent. I. Nucl.Med. 1973: 14: 73-78.

Address:

Steven M. Roser780 East Gilbert StreetSail BemardilloCalifornia 92404U.S.A.


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