Symposium on Common Orthopedic Problems
Radionuclide Bone Imaging in Pediatrics
James J. Conway, M.D.*
Most radioisotopes available for bone imaging prior to 1972 had long half-lives or high energies unsuitable for use with the gamma camera. Radioisotopes such as 85strontium or 18fluorine were used only sporadically in children and often only in those with proven malignancy.19 With the advent of more suitable radiopharmaceuticals, such as the 99mTc phosphorus agents,23 the benefits of bone imaging have become more evident and this technique has assumed a significant role in the diagnosis and management of patients with skeletal disorders. The relative simplicity of current techniques, their noninvasive aspect, and low radiation dose have stimulated utilization in the pediatric patient, adding a significant new dimension to the diagnostic capabilities of the practitioner. This report alerts the referring physician to the current practice of radionuclide bone imaging in children, advocates its use, where appropriate, and encourages evaluation of those conditions for which radionuclide bone imaging might contribute benefit.
RADIO PHARMACEUTICALS 99mTc pertechnetate, the radioisotope which has so favorably influenced the growth and development of nuclear medicine, emits a monoenergetic 140 KeV gamma ray that has a half-life of only six hours. The gamma energy of this radioisotope is efficiently detected by gamma cameras and is sufficiently energetic to penetrate the skeletal and soft tissues of the patient. The short half-life allows administration of multimillicurie doses which result in counting rates that provide sufficient data to produce good resolution images in a time period acceptable to most children. The chemical activity of 99mTc pertechnetate enables labeling of compounds such as the phosphates and, as a consequence, easily preparable kits are available from pharmaceutical manufacturers which readily provide these agents to any clinical labo*Chief, Division of Nuclear Medicine, Children's Memorial Hospital; Associate Professor of Radiology, McGaw-Northwestern University Medical Center, Chicago, Illinois
Pediatric Clinics of North America- Vol. 24, No.4, November 1977
701
702
JAMES J. CONWAY
ratory. The current radiopharmaceuticals of choice for bone imaging are any of the 99mTc compounds such as 99mTc diphosphonate or 99mTc pyrophosphate.
Dosimetry The 99mTc radiopharmaceuticals deliver an acceptable minimal radiation dose to the child. A typical study in a five year old child will deliver approximately 1 to 2 rads to the entire skeleton. 14 The radiation dose to the gonads is considerably less, such that one should not be overly concerned with any risk or hazard. These radiation doses are comparable to those received from roentgenographic skeletal survey examinations and are much less than one would expect from fluoroscopic or angiographic studies. Localization Mechanism Roentgenographic studies are primarily anatomic and are defined with exquisite resolution. Radionuclide localization is primarily dependent on perfusion and function, with the biologic half-life limiting the dose. The number of photons utilized to derive a nuclear image is minute when compared with a roentgenographic image; consequently, resolution is poor. The metabolic and functional aspects of nuclear studies, however, add a fascinating dimension to the derivation and interpretation of the images. Perhaps the most influential factor for skeletal localization is vascular perfusion. Without perfusion, the radionuclide simply would not reach the desired tissues; thus hypovascular or hypervascular lesions are depicted best. A second important factor in localization is bone metabolism. Although the skeleton is often viewed as a static structure, there is a constant active metabolic turnover with osteoblastic and osteoclastic activity throughout. In children, the physes are most active and therefore present a normal variation of increased localization not seen in adults. One should be aware of the normal appearance of pediatric bone images at varying ages. In addition, local as well as generalized alterations in bone metabolism can occur. For example, acute osteoporosis from disuse or the influence of various medications, such as the corticosteroids, may produce unusual bone localization of the radiopharmaceutical. Inflammation or trauma can radically alter the vascular perfusion to skeletal structures (Fig. 1).24 The clinician must be aware of the history and physical findings when attempting to analyze radionuclide bone images and available roentgenographic images should be reviewed.
CLINICAL UTILIZATION Neoplasm The bone scan has been used most often for the diagnosis, staging, and management of patients with neoplastic disease. Neoplasms that
703
RADIONUCLIDE BONE IMAGING
Fig. 1
Fig. 2 Figure 1. A. Intense localization of radionuclide in the mid shaft of the left femur (large arrow) at the site of a bone lesion secondary to histiocytosis X. B. Diffuse localization of radionuclide in the skeletal structures about the left ankle and foot (small arrows) secondary to a reactive hyperemic response produced by the proximal bone lesion. Figure 2. A. The left kidney in a young boy had been removed owing to renal cell carcinoma. B. Intense localization of radionuclide is seen in the proximal portion of the left tibia (arrow). No history of trauma could be elicited. Roentgenograms were compatible with healing fracture. C, Resolution of the fracture localization occurred with healing.
arise primarily within bone, causing bone destruction and repair, profoundly affect the localization of bone seeking agents. Thus osteogenic sarcoma, reticulum cell sarcoma, and Ewing's sarcoma are easily detected and extent of involvement determined. Metastatic bone lesions in children differ considerably from those in adults. The pediatrician is less likely to encounter tumors from the breast, prostate, and lung, but will more likely find central nervous system neoplasms such as neuroblastoma, hematologic lesions such as leukemia, or soft tissue neo-
704
JAMES J. CONWAY
plasms such as rhabdomyosarcoma. These childhood neoplasms commonly involve the bones, and radionuclide imaging efficiently maps out the distribution and extent of the disease. It is well established that the bone scan is a much more sensitive detector for metastatic disease than roentgenographic survey examinations. 17. 20 It is now an accepted oncologic practice to obtain total body bone scans at regular intervals following the establishment of a neoplastic diagnosis. The frequency of these examinations in follow-up management decreases as the patient survives over a number of years. Abnormalities on bone scans may not be the result of metastasis related to the neoplastic disease. In the presence of neoplasia, there is often a hyperemic reactive response to other structures separate from the lesion within the involved extremity.13 This reactive response should not be interpreted as evidence of extension of the known neoplasm. In addition, children receiving chemotherapeutic drugs, have an increased susceptibility to occult skeletal infections which are readily depicted with bone imaging. The bone scan is also sensitive to occult injuries which may not manifest roentgenographic change. The possibility of 'trauma should be considered, particularly when there is a single locus of abnormality, since metastatic lesions more frequently involve multiple sites (F-ig. 2).3 Chemotherapeutic agents have had a marked beneficial effect upon the oncologic disorders of childhood. The practitioner should be aware of the changing disease patterns in these patients. The complications of chemotherapeutic agents such as superimposed infection or osteoporosis with pathologic fracture, and even secondary primary neoplasm will be encountered. Metastatic disease to bone from all types of tumors has and will continue to increase.25 These manifestations of oncologic disease are different from that expected from earlier experience prior to the chemotherapeutic era.
Inflammation Another major change in pediatric practice brought about by radionuclide bone imaging has been in the differentiation of septic arthritis, cellulitis, and osteomyelitis. As in the detection of metastatic disease, the bone scan is a much more sensitive indicator of bone injury from inflammatory or infectious disease than is the roentgenogram. 7. 12. 16. 27 The bone scan remains abnormal for weeks to several months depending upon the extent and degree of bone destruction from the infectious process. In the instance of isolated septic arthritis, the bone scan often remains normal since an infection strictly within the jOint space should not localize bone seeking agents because the isotope does not enter the joint to any degree. More commonly, there is moderate localization of radionuclide about the joint since accompanying cellulitis and hyperemic response to the inflammatory process are often associated with the septic joint process. In cellulitis, there is usually a reactive increased perfusion to the involved and adjacent soft tissues (Fig. 3). In chronic cellulitis, diffuse
RADIONUCLIDE BONE IMAGING
705
soft tissue localization of radionuclide may be associated with a mild generalized increased bone localization, particularly at the physes. Other factors such as disuse demineralization and osteoporosis representing a chronic heightened bone metabolism will also increase bone localization of the radionuclide. This is separable from osteomyelitis since bone sites not involved in the inflammatory process of the extremity are often involved. Osteomyelitis rapidly produces intense localization of the radionuclide at the site of the bone involvement. It is now well established that the bone scan becomes abnormal within a matter of hours, whereas it takes days to weeks for x-ray changes to occur. The mechanism for hematogenous spread of osteomyelitis is an initial deposition of the infectious agent into the intramedullary canal via the nutrient arteries. The proliferation of bacteria and the response mechanism of the host initially occlude local blood vessels, resulting in a localized decreased vascular perfusion. Therefore bone scans at the earliest stage of osteomyelitis (within the first few hours) may exhibit normal or decreased localization of radionuclide at the site of infection. Other unusual situations that impair the vascular supply may also create the appearance of a negative bone scan in the presence of osteomyelitis. 22 ,26 Osteomyelitis in the femoral head and neck has been documented to be associated with a septic hip joint. The joint distention and increased intracapsular pressure by pus occlude the retinacular blood supply; consequently the radionuclide does not localize within the bone. These examples of normal or negative bone scans in the presence of proven osteomyelitis are extremely rare, but the practitioner should be aware of the circumstances or conditions with which the phenomenon may occur. Radionuclide imaging has proved of great value in localizing infectious processes at unusual sites such as within the spine or the sacroiliac joints (Fig. 4).1 This is important sinc~ there is a lessened tendency to perform invasive diagnostic techniques such as needle aspiration at these sites. The positive bone scan will serve as impetus to evaluate such lesions at an earlier stage of the infectious process. Bone imaging has been advocated to differentiate osteomyelitis from infarction in patients with sickl~ cell disease. 15 • 16 Early (minutes) and delayed (hours) images are obtained to differentiate the hypovascular process of infarction from the hypervascular process of inflammation and infection. Theoretically, the infarction from sickle cell disease should show decreased localization of radionuclide on early as well as on delayed images (Fig. 5). However, an increased reactive perfusion can occur rather rapidly following an infarction, and images obtained several days after the onset of symptoms often illustrate increased localization suggesting osteomyelitis. If one is not aware of the clinical presentation, duration of symptoms, and physical findings, interpretation of such images may prove difficult. Examples of discitis of the spine in children have been studied (Fig. 6).9 Involvement of vertebral bodies adjacent to the disc site may be apparent before roentgenographic findings are evident. An earlier
706
JAMES J. CONWAY
Figure 3. Localization of radionuclide occurs in the soft tissues at the site of a cellulitis (arrows). There is no significant localization of radionuclide within the bone to suggest associated osteomyelitis.
Figure 4. This young girl presented with fever and back pain. Roentgenograms were normal. Localization of radionuclide is found in the left sacroiliac joint. Needle aspiration cultured Staphylococcus aureus. Roentgenograms remained normal following treatment.
RADIONUCLIDE BONE IMAGING
707
Figure 5. Decreased localization of radionuclide within the medial condyle. of the distal end of the right femur (arrow) is evidence of localized infarction secondary to sickle cell crisis.
diagnosis of discitis in a young child with back pain may assist in management of this condition. Other inflammatory conditions such as the arthritides can be documented by bone imaging. The sensitivity of radionuclide imaging to joint involvement is much greater than roentgenographic or clinical evaluation. 2. 6 The degree and extent of bone involvement can be determined and repeat studies are used to indicate the success or failure of therapy.
Trauma There has been minimal utilization of radionuclides to study trauma. One would expect that the bone scan would be extremely sensitive to alterations in bone metabolism caused by trauma. Indeed, this is indicated by those examples of occult trauma experienced by children which are occasionally discovered in studies obtained for oncologic management. It has been demonstrated experimentally and observed clinically that the bone scan becomes abnormal within a short period of time (hours) following a fracture. 8 • 21 The fracture can be recognized by an ill-defined localization at the site and adjacent areas. This most likely is the result of a reactive perfusion response from the trauma. Within several days there is an intensification of the' localization process at the fracture, and usually by one week the fracture is prominently identified. A moderately intense localization of the radionuclide will remain at the fracture site for extended periods of time, reflecting the healing process. It is assumed that the return to normal is dependent upon the extent of injury to the bone and the host's response to repair the
708
JAMES J. CONWAY
Figure 6. A, This 16 month old boy refused to walk. A normal interspace at L5-S1 was noted. B, Localization of radionuclide in the fifth lumbar and first sacral vertebra depicts the "discitis." The disc space is obscured. C, Serial roentgenograms of the lumbar spine failed to demonstrate abnormality until approximately two months after the onset of symptoms when narrowing of the interspace between L5-S1 (arrow) was visualized.
InJury. An abnormal scan can be found for months following the fracture and may persist for years. In most instances of trauma, bone imaging is of limited value since other modalities are satisfactory for diagnosis and management. It is of great value in those areas difficult to diagnose by ordinary roentgenographic techniques, including the spine and the carpal and the tarsal bones. Carpal navicular fractures are notoriously difficult to diagnose. The bone scan should solve the dilemma of occult fracture versus simple sprain. Another indication is detection of stress fractures. In view of the previous statements regarding the localization of radionuclide in acute fractures, it is logical that there are alterations in the bone at the site of the stress fracture long before symptoms alert the patient to the abnormality. Thus the positive bone image within hours
RADIONUCLIDE BONE IMAGING
709
Figure 7. No history of trauma could be elicited in a child who presented with a limp. Multiple abnormal localizations of mdionuclide are noted: metaphysis of the right radius (A), diaphysis of the left femur (B), middiaphysis of the right tibia and distal diaphysis of the right fibula (C) (arrows). Roentgenograms revealed a healing fracture of the mdius and minimal periosteal new bone formation of the fibula. Discussion with the parent elicited a recognition of child abuse.
of symptoms in a stress fracture reflects more of a chronic than acute process. Bone imaging is of value in instances of child abuse when x-rays are normal yet there is a strong clinical suspicion of abuse. 8 Subclinical trauma to the periosteum is often manifested by significant abnormalities on the bone scan (Fig. 7). Osteoid osteoma, often considered to be a bizarre reparative phenomenon, can present in any skeletal structure. The patient complains of aggravating chronic pain which is most bothersome at night and is often relieved by aspirin. Often the patient will endure pain for years, have multiple roentgenographic examinations, and pass from practitioner to consultant to practitioner seeking relief. Osteoid osteoma may also present with painful scoliosis. Idiopathic scoliosis does not produce significant pain; therefore the bone scan would seem indicated with such a symptom. Indeed, any bone pain of unexplained origin warrants the use of radionuclide bone imaging. Osteoid osteoma intensely localizes the radionuclide. 11, 18. 28 With the clinical history and frequent characteristic roentgenographic appearance of a small lucent nidus surrounded by bone sclerosis, the diagnosis is ensured. The value of the bone scan is in its ability to localize such lesions in areas difficult to examine such as the spine or pelvis (Fig. 8).
Toxic Synovitis Versus Legg-Perthes Disease Because bone imaging is so dependent on vascular perfusion, it is logical that a hypovascular lesion such as avascular necrosis is effectively detected. This is well documented in the instance of LeggPerthes disease. 4 • 5 The bone image, however, is an expensive tool for the diagnosis of such a process when the lesion is evident on roentgenograms. It is more often used in proven Legg-Perthes disease to determine the revascularization status of the involved epiphysis. In the presence of normal or equivocal roentgenographic studies and particu-
710
JAMES J. CONWAY
Figure 8. A, A 12 year old girl complained of a chronic pain in the neck for four years. Multiple roentgenographic examinations and eventual psychiatric consultation failed to determine the etiology for the complaint. B, Intense localization of radionuclide is noted in the right pedicle area of the second cervical vertebra. An osteoid osteoma was removed s urgically.
larly in conditions with an increased predilection for avascular necrosis (steroid therapy), the bone scan can be most informative (Fig. 9). Many children present with symptoms of a painful hip. Commonly, this is "toxic synovitis," which cannot be differentiated clinically or roentgenographically from very early Legg-Perthes disease. Bone scans remain normal in toxic synovitis. Bone imaging enables the practitioner to be more concise in management of the child with acute hip pain. Roentgenograms must still be obtained to exclude displacement of the hip signaling septic arthritis which, if it has not involved the bone, may appear normal on the scan. Detailed studies with magnification are essential in order to obtain adequate images for interpretation. Pinhole magnification views with the gamma camera demonstrate lesions often not discernible on routine bone images.
711
RADIO NUCLIDE BONE IMAGING
Figure 9. Pain in the right hip presented in a boy with a renal transplant on steroid therapy. Roentgenograms of the hips were entirely normaL Pinhole magnification radionuclide images of the hips depict absence of activity in the right proximal femoral epiphysis (left) consistent with avascular necrosis.
Metabolic Bone imaging has been used infrequently for the evaluation of patients with systemic bone disorders. Diffuse systemic bone disorders may produce a scan that appears normal to the unsuspecting eye since th~ lesions may be symmetric in distribution. Perhaps such studies would be of value in the management of patients on medical therapy. Congenital Bone imaging has been used infrequently for analyzing various congenital malformations such as dwarfism, the various dysplasias, or dysostoses. It is certainly warranted to explore the value of this technique in these conditions.
SUMMARY Radionuclide imaging provides a functional as well as anatomic evaluation of bone and is particularly valuable in diagnosis, staging, and management of oncologic disorders, in differentiation of inflammatory conditions and trauma, and in hypo vascular disorders of bone. The practitioner should be aware of those areas in which bone imaging is clinically effective for patient care. Radionuclide bone imaging is efficacious, noninvasive, delivers minimal radiation, and offers a functional method of evaluation for children with skeletal disorders. ACKNOWLEDGMENTS
The author is grateful to Jim Everette, R.T. and Sue Weiss, B.S., R.T. for their technological expertise, and to Lillette Knowlton for her assistance in the preparation of this manuscript.
712
JAMES J. CONWAY
REFERENCES 1. Ailsby, R L., and Staheli, L. T.: Pyogenic infections of the sacroiliac joint in children: Radioisotope bone scanning as a diagnostic tool. Clin. Orthop., 100:96-100, 1974. 2. Bekerman, C., Genant, H. K, Hoffer, P. B., et al.: Radionuclide imaging of the bones and joints of the hand. Radiology, 118:653-659,1975. 3. Corcoran, R J., Thrall, J. H., Kyle, R W., et al.: Solitary abnormalities in bone scans of patients with extraosseous malignancies. Radiology, 121 :663-667,1976. 4. Danigelis, J. A., Fisher, R L., Ozonoff, M. B., et al.: 99mTc polyphosphate bone imaging in Legg-Perthes disease. Radiology, 115 :407-413, 1975. 5. Danigelis, J. A.: Pinhole imaging in Legg-Perthes disease: Further observations. Semin. Nuc1. Med., 6:69-82, 1976. 6. Desaulniers, M., Fuks, A., Hawkins, D., et al.: Radiotechnetium polyphosphate joint imaging. J. NucI. Med., 15:417-423, 1974. 7. Duszynski, D.O., Kuhn, J. P., Afshani, E., et aI.: Early radionuclide diagnosis of acute osteomyelitis. Radiology, 117:337-340, 1975. 8. Fordham, E. W., and Ramachandran, P. C.: Radionuclide imaging of osseous trauma. Semin. Nuc1. Med., 4:411-429, 1974. 9. Gates, G. F.: Scintigraphy of discitis. Clin. Nuc1. Med., 2:20-25,1977. 10. Geslien, G. E., Thrall, J. H., Espinosa, J. L., et al.: Early detection of stress fractures using 99mTc polyphosphate. Radiology, 121 :683-687, 1976. 11. Gilday, D. L., and Ash, J.: Benign bone tumors. Semin. NucI. Med., 6:33-46, 1976. 12. Gilday, D. L., Paul, D. J., and Paterson, J.: Diagnosis of osteomyelitis in children by combined blood pool and bone imaging. Radiology, 117:331-335, 1975. 13. Goldman, A. B., and Braunstein, P.: Augmented radioactivitiy on bone scans of limbs bearing osteosarcomas. J. Nuc1. Med., 16:423-424,1975. 14. Handmaker, H., and Lowenstein, J. M.: Radiation dose to critical organ and gonad for selected radiopharmaceuticals. In Nuclear Medicine in Clinical Pediatrics. Society of Nuclear Medicine, Inc., New York, 1975, pp. 276-277. 15. Lutzker, L. G., and Alavi, A.: Bone and marrow imaging in sickle cell disease: Diagnosis of infarction. Semin. NucI. Med., 6:83-93, 1976. 16. Majd, M., and Frankel, R S.: Radionuclide imaging in skeletal inflammatory and ischemic disease in children. Am. J. RoentgenoI. Radium Ther. Nuc1. Med., 126:832-841, 1976. 17. Mall, J. C., and Hoffer, P. B.: Use of bone scanning and skeletal radiography in the diagnosis of bone metastasis. Med. ColI. Va. Quart., 3: 108-115, 1975. 18. McCombs, R K, and Olson, W. H.: Positive 18F bone scan in a case of osteoid osteoma; Case report. J. Nucl. Med., 16:465-466, 1975. 19. McNeil, B. J., Cassady, J. R, Geiser, C. F., et al.: Fluorine-18 bone scintigraphy in children with osteosarcoma or Ewing's sarcoma. Radiology, 109:627-631, 1973. 20. Pistenma, D. A., McDougall, I. R, and Kriss, J. P.: Screening for bone metastases. J.A.M.A., 231 :46-50, 1975. 21. Rosenthall, L., Hill, R 0., and Chuang, S.: Observation on the use of 99mTc phosphate imaging in peripheral bone trauma. Radiology, 119:637-641, 1976. 22. Russin, L. D., and Staab, E. V.: Unusual bone scan findings in acute osteomyelitis: Case report. J. Nuc1. Med., 17:617-619, 1976. 23. Subramanian, G., and McAfee, J. G.: A new complex of 99mTc for skeletal imaging. Radiology, 99:192-196,1971. 24. Thrall, J. H., Geslien, G. E., Corcoron, R J., et aI.: Abnormal radionuclide deposition patterns adjacent to focal skeletal lesions. Radiology, 115 :659-663, 1975. 25. Tofe, A. J., Francis, M. D., and Harvey, W. J.: Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans. J. Nuc1. Med., 16:986-989,1975. 26. Trackler, R T., Miller, K E., Sutherland, D. H., et al.: Childhood pelvic osteomyelitis presenting as a "cold" lesion on bone scan: Case report. J. Nucl. Med., 17:620-622, 1976. 27. Treves, S., Khettry, J., Broker, F. H., et al.: Osteomyelitis: Early scintigraphic detection in children. Pediatrics, 57:173-186, 1976. 28. Winter, P. F., Johnson, P. M., Hilal, S. K, et al.: Scintigraphic detection of osteoid osteoma. Radiology, 122:177-178, 1977. Division of Nuclear Medicine Children's Memorial Hospital 2300 Children's Plaza Chicago, Illinois 60614
Radionuclide Bone Imaging in Pediatrics
James J. Conway, M.D.*
Most radioisotopes available for bone imaging prior to 1972 had long half-lives or high energies unsuitable for use with the gamma camera. Radioisotopes such as 85strontium or 18fluorine were used only sporadically in children and often only in those with proven malignancy.19 With the advent of more suitable radiopharmaceuticals, such as the 99mTc phosphorus agents,23 the benefits of bone imaging have become more evident and this technique has assumed a significant role in the diagnosis and management of patients with skeletal disorders. The relative simplicity of current techniques, their noninvasive aspect, and low radiation dose have stimulated utilization in the pediatric patient, adding a significant new dimension to the diagnostic capabilities of the practitioner. This report alerts the referring physician to the current practice of radionuclide bone imaging in children, advocates its use, where appropriate, and encourages evaluation of those conditions for which radionuclide bone imaging might contribute benefit.
RADIO PHARMACEUTICALS 99mTc pertechnetate, the radioisotope which has so favorably influenced the growth and development of nuclear medicine, emits a monoenergetic 140 KeV gamma ray that has a half-life of only six hours. The gamma energy of this radioisotope is efficiently detected by gamma cameras and is sufficiently energetic to penetrate the skeletal and soft tissues of the patient. The short half-life allows administration of multimillicurie doses which result in counting rates that provide sufficient data to produce good resolution images in a time period acceptable to most children. The chemical activity of 99mTc pertechnetate enables labeling of compounds such as the phosphates and, as a consequence, easily preparable kits are available from pharmaceutical manufacturers which readily provide these agents to any clinical labo*Chief, Division of Nuclear Medicine, Children's Memorial Hospital; Associate Professor of Radiology, McGaw-Northwestern University Medical Center, Chicago, Illinois
Pediatric Clinics of North America- Vol. 24, No.4, November 1977
701
702
JAMES J. CONWAY
ratory. The current radiopharmaceuticals of choice for bone imaging are any of the 99mTc compounds such as 99mTc diphosphonate or 99mTc pyrophosphate.
Dosimetry The 99mTc radiopharmaceuticals deliver an acceptable minimal radiation dose to the child. A typical study in a five year old child will deliver approximately 1 to 2 rads to the entire skeleton. 14 The radiation dose to the gonads is considerably less, such that one should not be overly concerned with any risk or hazard. These radiation doses are comparable to those received from roentgenographic skeletal survey examinations and are much less than one would expect from fluoroscopic or angiographic studies. Localization Mechanism Roentgenographic studies are primarily anatomic and are defined with exquisite resolution. Radionuclide localization is primarily dependent on perfusion and function, with the biologic half-life limiting the dose. The number of photons utilized to derive a nuclear image is minute when compared with a roentgenographic image; consequently, resolution is poor. The metabolic and functional aspects of nuclear studies, however, add a fascinating dimension to the derivation and interpretation of the images. Perhaps the most influential factor for skeletal localization is vascular perfusion. Without perfusion, the radionuclide simply would not reach the desired tissues; thus hypovascular or hypervascular lesions are depicted best. A second important factor in localization is bone metabolism. Although the skeleton is often viewed as a static structure, there is a constant active metabolic turnover with osteoblastic and osteoclastic activity throughout. In children, the physes are most active and therefore present a normal variation of increased localization not seen in adults. One should be aware of the normal appearance of pediatric bone images at varying ages. In addition, local as well as generalized alterations in bone metabolism can occur. For example, acute osteoporosis from disuse or the influence of various medications, such as the corticosteroids, may produce unusual bone localization of the radiopharmaceutical. Inflammation or trauma can radically alter the vascular perfusion to skeletal structures (Fig. 1).24 The clinician must be aware of the history and physical findings when attempting to analyze radionuclide bone images and available roentgenographic images should be reviewed.
CLINICAL UTILIZATION Neoplasm The bone scan has been used most often for the diagnosis, staging, and management of patients with neoplastic disease. Neoplasms that
703
RADIONUCLIDE BONE IMAGING
Fig. 1
Fig. 2 Figure 1. A. Intense localization of radionuclide in the mid shaft of the left femur (large arrow) at the site of a bone lesion secondary to histiocytosis X. B. Diffuse localization of radionuclide in the skeletal structures about the left ankle and foot (small arrows) secondary to a reactive hyperemic response produced by the proximal bone lesion. Figure 2. A. The left kidney in a young boy had been removed owing to renal cell carcinoma. B. Intense localization of radionuclide is seen in the proximal portion of the left tibia (arrow). No history of trauma could be elicited. Roentgenograms were compatible with healing fracture. C, Resolution of the fracture localization occurred with healing.
arise primarily within bone, causing bone destruction and repair, profoundly affect the localization of bone seeking agents. Thus osteogenic sarcoma, reticulum cell sarcoma, and Ewing's sarcoma are easily detected and extent of involvement determined. Metastatic bone lesions in children differ considerably from those in adults. The pediatrician is less likely to encounter tumors from the breast, prostate, and lung, but will more likely find central nervous system neoplasms such as neuroblastoma, hematologic lesions such as leukemia, or soft tissue neo-
704
JAMES J. CONWAY
plasms such as rhabdomyosarcoma. These childhood neoplasms commonly involve the bones, and radionuclide imaging efficiently maps out the distribution and extent of the disease. It is well established that the bone scan is a much more sensitive detector for metastatic disease than roentgenographic survey examinations. 17. 20 It is now an accepted oncologic practice to obtain total body bone scans at regular intervals following the establishment of a neoplastic diagnosis. The frequency of these examinations in follow-up management decreases as the patient survives over a number of years. Abnormalities on bone scans may not be the result of metastasis related to the neoplastic disease. In the presence of neoplasia, there is often a hyperemic reactive response to other structures separate from the lesion within the involved extremity.13 This reactive response should not be interpreted as evidence of extension of the known neoplasm. In addition, children receiving chemotherapeutic drugs, have an increased susceptibility to occult skeletal infections which are readily depicted with bone imaging. The bone scan is also sensitive to occult injuries which may not manifest roentgenographic change. The possibility of 'trauma should be considered, particularly when there is a single locus of abnormality, since metastatic lesions more frequently involve multiple sites (F-ig. 2).3 Chemotherapeutic agents have had a marked beneficial effect upon the oncologic disorders of childhood. The practitioner should be aware of the changing disease patterns in these patients. The complications of chemotherapeutic agents such as superimposed infection or osteoporosis with pathologic fracture, and even secondary primary neoplasm will be encountered. Metastatic disease to bone from all types of tumors has and will continue to increase.25 These manifestations of oncologic disease are different from that expected from earlier experience prior to the chemotherapeutic era.
Inflammation Another major change in pediatric practice brought about by radionuclide bone imaging has been in the differentiation of septic arthritis, cellulitis, and osteomyelitis. As in the detection of metastatic disease, the bone scan is a much more sensitive indicator of bone injury from inflammatory or infectious disease than is the roentgenogram. 7. 12. 16. 27 The bone scan remains abnormal for weeks to several months depending upon the extent and degree of bone destruction from the infectious process. In the instance of isolated septic arthritis, the bone scan often remains normal since an infection strictly within the jOint space should not localize bone seeking agents because the isotope does not enter the joint to any degree. More commonly, there is moderate localization of radionuclide about the joint since accompanying cellulitis and hyperemic response to the inflammatory process are often associated with the septic joint process. In cellulitis, there is usually a reactive increased perfusion to the involved and adjacent soft tissues (Fig. 3). In chronic cellulitis, diffuse
RADIONUCLIDE BONE IMAGING
705
soft tissue localization of radionuclide may be associated with a mild generalized increased bone localization, particularly at the physes. Other factors such as disuse demineralization and osteoporosis representing a chronic heightened bone metabolism will also increase bone localization of the radionuclide. This is separable from osteomyelitis since bone sites not involved in the inflammatory process of the extremity are often involved. Osteomyelitis rapidly produces intense localization of the radionuclide at the site of the bone involvement. It is now well established that the bone scan becomes abnormal within a matter of hours, whereas it takes days to weeks for x-ray changes to occur. The mechanism for hematogenous spread of osteomyelitis is an initial deposition of the infectious agent into the intramedullary canal via the nutrient arteries. The proliferation of bacteria and the response mechanism of the host initially occlude local blood vessels, resulting in a localized decreased vascular perfusion. Therefore bone scans at the earliest stage of osteomyelitis (within the first few hours) may exhibit normal or decreased localization of radionuclide at the site of infection. Other unusual situations that impair the vascular supply may also create the appearance of a negative bone scan in the presence of osteomyelitis. 22 ,26 Osteomyelitis in the femoral head and neck has been documented to be associated with a septic hip joint. The joint distention and increased intracapsular pressure by pus occlude the retinacular blood supply; consequently the radionuclide does not localize within the bone. These examples of normal or negative bone scans in the presence of proven osteomyelitis are extremely rare, but the practitioner should be aware of the circumstances or conditions with which the phenomenon may occur. Radionuclide imaging has proved of great value in localizing infectious processes at unusual sites such as within the spine or the sacroiliac joints (Fig. 4).1 This is important sinc~ there is a lessened tendency to perform invasive diagnostic techniques such as needle aspiration at these sites. The positive bone scan will serve as impetus to evaluate such lesions at an earlier stage of the infectious process. Bone imaging has been advocated to differentiate osteomyelitis from infarction in patients with sickl~ cell disease. 15 • 16 Early (minutes) and delayed (hours) images are obtained to differentiate the hypovascular process of infarction from the hypervascular process of inflammation and infection. Theoretically, the infarction from sickle cell disease should show decreased localization of radionuclide on early as well as on delayed images (Fig. 5). However, an increased reactive perfusion can occur rather rapidly following an infarction, and images obtained several days after the onset of symptoms often illustrate increased localization suggesting osteomyelitis. If one is not aware of the clinical presentation, duration of symptoms, and physical findings, interpretation of such images may prove difficult. Examples of discitis of the spine in children have been studied (Fig. 6).9 Involvement of vertebral bodies adjacent to the disc site may be apparent before roentgenographic findings are evident. An earlier
706
JAMES J. CONWAY
Figure 3. Localization of radionuclide occurs in the soft tissues at the site of a cellulitis (arrows). There is no significant localization of radionuclide within the bone to suggest associated osteomyelitis.
Figure 4. This young girl presented with fever and back pain. Roentgenograms were normal. Localization of radionuclide is found in the left sacroiliac joint. Needle aspiration cultured Staphylococcus aureus. Roentgenograms remained normal following treatment.
RADIONUCLIDE BONE IMAGING
707
Figure 5. Decreased localization of radionuclide within the medial condyle. of the distal end of the right femur (arrow) is evidence of localized infarction secondary to sickle cell crisis.
diagnosis of discitis in a young child with back pain may assist in management of this condition. Other inflammatory conditions such as the arthritides can be documented by bone imaging. The sensitivity of radionuclide imaging to joint involvement is much greater than roentgenographic or clinical evaluation. 2. 6 The degree and extent of bone involvement can be determined and repeat studies are used to indicate the success or failure of therapy.
Trauma There has been minimal utilization of radionuclides to study trauma. One would expect that the bone scan would be extremely sensitive to alterations in bone metabolism caused by trauma. Indeed, this is indicated by those examples of occult trauma experienced by children which are occasionally discovered in studies obtained for oncologic management. It has been demonstrated experimentally and observed clinically that the bone scan becomes abnormal within a short period of time (hours) following a fracture. 8 • 21 The fracture can be recognized by an ill-defined localization at the site and adjacent areas. This most likely is the result of a reactive perfusion response from the trauma. Within several days there is an intensification of the' localization process at the fracture, and usually by one week the fracture is prominently identified. A moderately intense localization of the radionuclide will remain at the fracture site for extended periods of time, reflecting the healing process. It is assumed that the return to normal is dependent upon the extent of injury to the bone and the host's response to repair the
708
JAMES J. CONWAY
Figure 6. A, This 16 month old boy refused to walk. A normal interspace at L5-S1 was noted. B, Localization of radionuclide in the fifth lumbar and first sacral vertebra depicts the "discitis." The disc space is obscured. C, Serial roentgenograms of the lumbar spine failed to demonstrate abnormality until approximately two months after the onset of symptoms when narrowing of the interspace between L5-S1 (arrow) was visualized.
InJury. An abnormal scan can be found for months following the fracture and may persist for years. In most instances of trauma, bone imaging is of limited value since other modalities are satisfactory for diagnosis and management. It is of great value in those areas difficult to diagnose by ordinary roentgenographic techniques, including the spine and the carpal and the tarsal bones. Carpal navicular fractures are notoriously difficult to diagnose. The bone scan should solve the dilemma of occult fracture versus simple sprain. Another indication is detection of stress fractures. In view of the previous statements regarding the localization of radionuclide in acute fractures, it is logical that there are alterations in the bone at the site of the stress fracture long before symptoms alert the patient to the abnormality. Thus the positive bone image within hours
RADIONUCLIDE BONE IMAGING
709
Figure 7. No history of trauma could be elicited in a child who presented with a limp. Multiple abnormal localizations of mdionuclide are noted: metaphysis of the right radius (A), diaphysis of the left femur (B), middiaphysis of the right tibia and distal diaphysis of the right fibula (C) (arrows). Roentgenograms revealed a healing fracture of the mdius and minimal periosteal new bone formation of the fibula. Discussion with the parent elicited a recognition of child abuse.
of symptoms in a stress fracture reflects more of a chronic than acute process. Bone imaging is of value in instances of child abuse when x-rays are normal yet there is a strong clinical suspicion of abuse. 8 Subclinical trauma to the periosteum is often manifested by significant abnormalities on the bone scan (Fig. 7). Osteoid osteoma, often considered to be a bizarre reparative phenomenon, can present in any skeletal structure. The patient complains of aggravating chronic pain which is most bothersome at night and is often relieved by aspirin. Often the patient will endure pain for years, have multiple roentgenographic examinations, and pass from practitioner to consultant to practitioner seeking relief. Osteoid osteoma may also present with painful scoliosis. Idiopathic scoliosis does not produce significant pain; therefore the bone scan would seem indicated with such a symptom. Indeed, any bone pain of unexplained origin warrants the use of radionuclide bone imaging. Osteoid osteoma intensely localizes the radionuclide. 11, 18. 28 With the clinical history and frequent characteristic roentgenographic appearance of a small lucent nidus surrounded by bone sclerosis, the diagnosis is ensured. The value of the bone scan is in its ability to localize such lesions in areas difficult to examine such as the spine or pelvis (Fig. 8).
Toxic Synovitis Versus Legg-Perthes Disease Because bone imaging is so dependent on vascular perfusion, it is logical that a hypovascular lesion such as avascular necrosis is effectively detected. This is well documented in the instance of LeggPerthes disease. 4 • 5 The bone image, however, is an expensive tool for the diagnosis of such a process when the lesion is evident on roentgenograms. It is more often used in proven Legg-Perthes disease to determine the revascularization status of the involved epiphysis. In the presence of normal or equivocal roentgenographic studies and particu-
710
JAMES J. CONWAY
Figure 8. A, A 12 year old girl complained of a chronic pain in the neck for four years. Multiple roentgenographic examinations and eventual psychiatric consultation failed to determine the etiology for the complaint. B, Intense localization of radionuclide is noted in the right pedicle area of the second cervical vertebra. An osteoid osteoma was removed s urgically.
larly in conditions with an increased predilection for avascular necrosis (steroid therapy), the bone scan can be most informative (Fig. 9). Many children present with symptoms of a painful hip. Commonly, this is "toxic synovitis," which cannot be differentiated clinically or roentgenographically from very early Legg-Perthes disease. Bone scans remain normal in toxic synovitis. Bone imaging enables the practitioner to be more concise in management of the child with acute hip pain. Roentgenograms must still be obtained to exclude displacement of the hip signaling septic arthritis which, if it has not involved the bone, may appear normal on the scan. Detailed studies with magnification are essential in order to obtain adequate images for interpretation. Pinhole magnification views with the gamma camera demonstrate lesions often not discernible on routine bone images.
711
RADIO NUCLIDE BONE IMAGING
Figure 9. Pain in the right hip presented in a boy with a renal transplant on steroid therapy. Roentgenograms of the hips were entirely normaL Pinhole magnification radionuclide images of the hips depict absence of activity in the right proximal femoral epiphysis (left) consistent with avascular necrosis.
Metabolic Bone imaging has been used infrequently for the evaluation of patients with systemic bone disorders. Diffuse systemic bone disorders may produce a scan that appears normal to the unsuspecting eye since th~ lesions may be symmetric in distribution. Perhaps such studies would be of value in the management of patients on medical therapy. Congenital Bone imaging has been used infrequently for analyzing various congenital malformations such as dwarfism, the various dysplasias, or dysostoses. It is certainly warranted to explore the value of this technique in these conditions.
SUMMARY Radionuclide imaging provides a functional as well as anatomic evaluation of bone and is particularly valuable in diagnosis, staging, and management of oncologic disorders, in differentiation of inflammatory conditions and trauma, and in hypo vascular disorders of bone. The practitioner should be aware of those areas in which bone imaging is clinically effective for patient care. Radionuclide bone imaging is efficacious, noninvasive, delivers minimal radiation, and offers a functional method of evaluation for children with skeletal disorders. ACKNOWLEDGMENTS
The author is grateful to Jim Everette, R.T. and Sue Weiss, B.S., R.T. for their technological expertise, and to Lillette Knowlton for her assistance in the preparation of this manuscript.
712
JAMES J. CONWAY
REFERENCES 1. Ailsby, R L., and Staheli, L. T.: Pyogenic infections of the sacroiliac joint in children: Radioisotope bone scanning as a diagnostic tool. Clin. Orthop., 100:96-100, 1974. 2. Bekerman, C., Genant, H. K, Hoffer, P. B., et al.: Radionuclide imaging of the bones and joints of the hand. Radiology, 118:653-659,1975. 3. Corcoran, R J., Thrall, J. H., Kyle, R W., et al.: Solitary abnormalities in bone scans of patients with extraosseous malignancies. Radiology, 121 :663-667,1976. 4. Danigelis, J. A., Fisher, R L., Ozonoff, M. B., et al.: 99mTc polyphosphate bone imaging in Legg-Perthes disease. Radiology, 115 :407-413, 1975. 5. Danigelis, J. A.: Pinhole imaging in Legg-Perthes disease: Further observations. Semin. Nuc1. Med., 6:69-82, 1976. 6. Desaulniers, M., Fuks, A., Hawkins, D., et al.: Radiotechnetium polyphosphate joint imaging. J. NucI. Med., 15:417-423, 1974. 7. Duszynski, D.O., Kuhn, J. P., Afshani, E., et aI.: Early radionuclide diagnosis of acute osteomyelitis. Radiology, 117:337-340, 1975. 8. Fordham, E. W., and Ramachandran, P. C.: Radionuclide imaging of osseous trauma. Semin. Nuc1. Med., 4:411-429, 1974. 9. Gates, G. F.: Scintigraphy of discitis. Clin. Nuc1. Med., 2:20-25,1977. 10. Geslien, G. E., Thrall, J. H., Espinosa, J. L., et al.: Early detection of stress fractures using 99mTc polyphosphate. Radiology, 121 :683-687, 1976. 11. Gilday, D. L., and Ash, J.: Benign bone tumors. Semin. NucI. Med., 6:33-46, 1976. 12. Gilday, D. L., Paul, D. J., and Paterson, J.: Diagnosis of osteomyelitis in children by combined blood pool and bone imaging. Radiology, 117:331-335, 1975. 13. Goldman, A. B., and Braunstein, P.: Augmented radioactivitiy on bone scans of limbs bearing osteosarcomas. J. Nuc1. Med., 16:423-424,1975. 14. Handmaker, H., and Lowenstein, J. M.: Radiation dose to critical organ and gonad for selected radiopharmaceuticals. In Nuclear Medicine in Clinical Pediatrics. Society of Nuclear Medicine, Inc., New York, 1975, pp. 276-277. 15. Lutzker, L. G., and Alavi, A.: Bone and marrow imaging in sickle cell disease: Diagnosis of infarction. Semin. NucI. Med., 6:83-93, 1976. 16. Majd, M., and Frankel, R S.: Radionuclide imaging in skeletal inflammatory and ischemic disease in children. Am. J. RoentgenoI. Radium Ther. Nuc1. Med., 126:832-841, 1976. 17. Mall, J. C., and Hoffer, P. B.: Use of bone scanning and skeletal radiography in the diagnosis of bone metastasis. Med. ColI. Va. Quart., 3: 108-115, 1975. 18. McCombs, R K, and Olson, W. H.: Positive 18F bone scan in a case of osteoid osteoma; Case report. J. Nucl. Med., 16:465-466, 1975. 19. McNeil, B. J., Cassady, J. R, Geiser, C. F., et al.: Fluorine-18 bone scintigraphy in children with osteosarcoma or Ewing's sarcoma. Radiology, 109:627-631, 1973. 20. Pistenma, D. A., McDougall, I. R, and Kriss, J. P.: Screening for bone metastases. J.A.M.A., 231 :46-50, 1975. 21. Rosenthall, L., Hill, R 0., and Chuang, S.: Observation on the use of 99mTc phosphate imaging in peripheral bone trauma. Radiology, 119:637-641, 1976. 22. Russin, L. D., and Staab, E. V.: Unusual bone scan findings in acute osteomyelitis: Case report. J. Nuc1. Med., 17:617-619, 1976. 23. Subramanian, G., and McAfee, J. G.: A new complex of 99mTc for skeletal imaging. Radiology, 99:192-196,1971. 24. Thrall, J. H., Geslien, G. E., Corcoron, R J., et aI.: Abnormal radionuclide deposition patterns adjacent to focal skeletal lesions. Radiology, 115 :659-663, 1975. 25. Tofe, A. J., Francis, M. D., and Harvey, W. J.: Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans. J. Nuc1. Med., 16:986-989,1975. 26. Trackler, R T., Miller, K E., Sutherland, D. H., et al.: Childhood pelvic osteomyelitis presenting as a "cold" lesion on bone scan: Case report. J. Nucl. Med., 17:620-622, 1976. 27. Treves, S., Khettry, J., Broker, F. H., et al.: Osteomyelitis: Early scintigraphic detection in children. Pediatrics, 57:173-186, 1976. 28. Winter, P. F., Johnson, P. M., Hilal, S. K, et al.: Scintigraphic detection of osteoid osteoma. Radiology, 122:177-178, 1977. Division of Nuclear Medicine Children's Memorial Hospital 2300 Children's Plaza Chicago, Illinois 60614
