AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Background

Osteomyelitis is an infection of bone and bone marrow and can be subdivided into acute, subacute, and chronic stages. Chronic osteomyelitis may appear as such at the initial presentation, as not all patients show progression through the 3 phases. Rarely, a sclerotic nonpurulent form of osteomyelitis occurs; this is termed Garrès sclerosing osteomyelitis. Other related disorders are chronic recurrent multifocal osteomyelitis; tuberculous osteomyelitis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Chronic osteomyelitis is a severe, persistent, and sometimes incapacitating infection of bone and bone marrow. It is often a recurring condition because it is difficult to treat definitively. This disease may result from (1) inadequately treated acute osteomyelitis; (2) a hematogenous type of osteomyelitis; (3) trauma, (4) iatrogenic causes such as joint replacements and the internal fixation of fractures; (5) compound fractures; (6) infection with organisms, such as Mycobacterium tuberculosis and Treponema species (syphilis); and (7) contiguous spread from soft tissues, as in diabetic ulcers or ulcers in peripheral vascular disease.

Pathophysiology

Infective process

Osteomyelitis is an infective process involving all osseous components, including bone marrow. Chronic osteomyelitis results when the inflammatory process continues over time, leading to bone sclerosis and deformity.

The ends of long bones are the most common locus of infection, and Staphylococcus aureus is the most common infective organism involved. Traumatic fractures or previous surgery may be responsible creating the access for infection, which may also originate from sepsis in the hematogenous form.

Infection at the bone locus creates an increase of intramedullary pressure due to inflammatory exudate that strips the periosteum, leading to vascular thrombosis followed by bone necrosis and the formation of sequestra. Usually, necrosis of the large segments of bone leads to sequestrum formation. These sequestra with infected material are surrounded by sclerotic bone that is relatively avascular. The haversian canals are blocked with scar tissue, and the bone is surrounded by thickened periosteum and scarred muscle. Antibiotics cannot penetrate these relatively avascular tissues and are hence ineffective in clearing the infection.

New bone formation occurs at the same time (involucrum). Multiple openings appear in this involucrum, through which exudates and debris from the sequestrum pass via the sinuses. A periosteal reaction acts to circumscribe the sequestrum, producing a thick sheet of new bone or involucrum.

Specific forms of chronic osteomyelitis

Forms of chronic osteomyelitis include a Brodie abscess, tuberculous osteomyelitis, congenital syphilis, and acquired syphilis.

A Brodie abscess is a form of chronic osteomyelitis without a preceding episode of acute osteomyelitis. The lesion causes a localized abscess within the bone, often close to metaphysis.

Tuberculous osteomyelitis of the bone is secondary spread from a primary source in the lung or GI tract. It most commonly occurs in the vertebrae (body) and long bones. Once established, the bacilli provoke a chronic inflammatory reaction. Small patches of caseous necrosis occur, and these coalesce to form larger abscesses. The infection spreads across the epiphysis into the joints. The infection may track along soft tissue to appear as a cold abscess at a distant site (eg, psoas abscess in case of spinal tuberculosis).

The transplacental spread of spirochetes from mother to the fetus results in congenital syphilis. Long bones, such as the tibia, are mainly affected. Congenital syphilis has 2 forms: periosteitis and metaphysitis. In periosteitis, the periosteum is lifted of the diaphysis of long bone with subperiosteal new-bone formation. This process gives the characteristic appearance called sabre tibia. In metaphysitis, the juxtaepiphyseal metaphysis is involved with increased bone resorption. Absent osteoblastic activity results in separation of the epiphyseal from the metaphysis.

Regarding acquired syphilis, bone lesions are manifestations of tertiary syphilis. Gummatous lesions appear as discrete punched-out radiolucent lesions in medulla or destructive lesions within the cortex. The surrounding bone is sclerotic, and no discharge is present.

Frequency

United States

The prevalence of chronic osteomyelitis is 5-25% after an episode of acute osteomyelitis. The prevalence of tuberculous osteomyelitis is 1-5% of the population affected by tuberculosis. The incidence in developed countries is low.

International

The incidence in developing countries is higher than in other countries, although the exact incidence is not known.

Mortality/Morbidity

• Mortality from osteomyelitis was 5-25% in the preantibiotic era. Presently, the mortality rate is approaching 0%.
• Complications of osteomyelitis include (1) septic arthritis, (2) destruction of the adjacent soft tissues, (3) malignant transformation (eg, Marjolin ulcer [squamous cell carcinoma], epidermoid carcinoma of the sinus tract), (4) secondary amyloidoses, and (5) pathologic fractures.

Race

No racial predilection is known.

Sex

No sex predilection is known.

Age

Any age group can be affected.

Anatomy

Sharp loops of nonanastomosing are present at the capillary ends of nutrient artery and enter into large venous sinusoids. This anatomy results in slowing of circulation and reduced oxygen tension. The capillaries do not communicate because columns of calcified cartilage separate them from each other.

Children younger than 2 years of have transphyseal vessels, which cross from metaphysis to epiphysis. This causes the spread of infection into the joint. In children older than 2 years, the transphyseal vessels are absent, and hence the epiphyseal plate acts as a barrier to the spread of infection into the joint.

Cierny and Mader proposed an anatomic classification of chronic osteomyelitis:

1. Type 1 - Endosteal or medullary lesion
2. Type 2 - Superficial osteomyelitis limited to the surface
3. Type 3 - Localized, well-marked legion with sequestration and cavity formation
4. Type 4 - Diffuse osteomyelitis lesions

Clinical Details

Unlike acute osteomyelitis, chronic osteomyelitis causes no acute constitutional symptoms. The presenting features may be those of a long-standing, discharging sinus or chronic bone pain and persist despite treatment. Patients may also present with acute exacerbations and usually have a previous history of acute osteomyelitis, sometimes dating back to childhood. Other symptoms include deep boring pain, especially in cases of a Brodie abscess. In osteomyelitis that occurs after joint replacement, the main symptom is the recurrence of pain.

Findings in tuberculosis include the following:

• History of tuberculosis elsewhere
• Attacks of fever and lassitude
• Night cries
• Intense episodes of pain in the affected bones
• Muscle wasting, synovial thickening, and restriction of joint movement in all directions
• Kyphosis, back pain, and symptoms and signs of spinal cord compression in spinal tuberculosis

Findings in syphilis include the following:

• Pain, refusal to move the affected limb
• Restriction of movement in an adjacent joint
• Pain in the bone
• Local swelling, redness, and warmth
• Fever
• Nausea
• General discomfort, uneasiness, or ill feeling (malaise)
• Drainage of pus through the skin (in chronic osteomyelitis)

Additional symptoms that may be associated with this osteomyelitis include the following:

• Excessive sweating
• Chills
• Low back pain
• Swelling of the ankles, feet, and legs

Physical examination shows bone tenderness and, possibly, swelling and redness.

During laboratory testing, a full blood count may show leukocytosis. The erythrocyte sedimentation rate (ESR) is elevated. Blood cultures may help identify the causative organism.

Results of bone lesion biopsy and cultures may be positive for the organism. A skin lesion with a sinus tract (ie, the lesion tunnels under the tissues) may yield pus for culturing.

Preferred Examination

Radiologic assessment of chronic osteomyelitis is performed for the following reasons: (1) to evaluate bone involvement (eg, the extent of active intramedullary infection or abscess superimposed on areas of necrosis, sequestrum and fibrosis) and (2) to identify soft-tissue involvement (areas of cellulitis, abscess, and sinus tracts).

Plain radiographs are usually obtained initially. Ultrasonography can readily depict soft-tissue involvement, but it provides only limited information about bone changes.

Because of its high sensitivity in the detection of bone marrow changes, MRI can provide detailed information regarding the extent and activity of the process by allowing the detection of the intramedullary site of infection and its complications. MRI can also be used to distinguish soft-tissue involvement, allowing differential diagnosis. Other conditions not involving bone marrow, such as cellulitis and myositis, may cause errors with scintigraphy; this study may be indicated for the assessment of local disturbances in vascular perfusion that represent a common condition in chronic osteomyelitis.

Limitations of Techniques

Although plain radiographs may provide important clues for diagnosis (eg, demonstration of bone remodeling, sclerosis, and thickening), the radiographic impression is often equivocal and relies heavily on clinical findings.

CT can depict intramedullary and soft-tissue gas, sequestra, sinus tracts, foreign bodies. However, CT scanning is insufficient for the assessment of the activity of the process.

MRI has limited availability, it is relatively expensive, and it is contraindicated in patients with certain implant devices and metallic clips. In addition, MRI is not tolerated by all patients with claustrophobia or morbid obesity, and young children may require sedation. Good MRIs require patient cooperation because patient motion degrades images.

DIFFERENTIALS

Section 3 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Other Problems to be Considered

Septic arthritis
Other causes of periosteitis
Fungal infections of the bone
Hydatid disease

RADIOGRAPH

Section 4 of 12  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Plain radiographic findings in acute or subacute osteomyelitis are deep soft-tissue swelling, a periosteal reaction, cortical irregularity, and demineralization. The chronic phase of the disease is characterized by thick, irregular, sclerotic bone interspersed with radiolucencies, an elevated periosteum, and chronic draining sinuses.

Sclerosing osteomyelitis of Garré most commonly affects the mandible and appears with a focal sclerosing periosteal reaction on radiologic studies.

Chronic recurrent osteomyelitis is benign self-limiting condition that primarily affects long bones in children and adolescents. The metaphysis of long bones are usually affected, and changes may be symmetrical. The appearances are those of confluent areas of bone lysis.

A Brodie abscess is a subacute osteomyelitis with a predilection for the ends of long bones and the carpus and tarsus. Plain radiographic findings include the following: (1) a central area of radiolucency with a surrounding thick rim of reactive bone sclerosis, which may persist for months; (2) pathognomonic tortuous parallel lucent channels extending toward the growth plate; (3) a variable degree of periosteal new-bone formation; and (4) associated soft-tissue swelling.

Degree of Confidence

Plain radiographs are inexpensive and universally available. For the detection of acute osteomyelitis, the sensitivity is less than 5% at presentation and about 33% at 1 week; however, the sensitivity is 90% 3-4 weeks after presentation. For the detection of chronic osteomyelitis, the sensitivity of plain radiography is high, though the specificity is low.

False Positives/Negatives

Stress fractures, osteoid osteomas, and other causes of periosteitis may mimic acute or chronic osteomyelitis.

CT SCAN

Section 5 of 12  

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• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
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• Multimedia
• References

Findings

CT is of definite value for studying the entire articular surface of bone and periarticular soft tissues; for delineating the extent of medullary and soft-tissue involvement; and for demonstrating cavities, serpiginous tracts, sequestra, or cloacae in osteomyelitis.

CT scans sometimes show soft-tissue edema or bone destruction not seen on plain images, particularly in the setting of acute osteomyelitis. Sclerosis, demineralization, and periosteal reactions are usually well depicted in chronic osteomyelitis.

CT scanning also helps in evaluating the need for surgery, and it provides vital information about the extent of disease. This data helps in planning appropriate surgery. CT is also an important modality in image-guided biopsy.

Degree of Confidence

CT can depict intramedullary and soft-tissue gas, sequestra, sinus tracts, foreign bodies. CT shows more sequestra than does the conventional method. An important advantage of CT is its ability to demonstrate lesions in the medulla and infections in the soft tissues. CT is the standard to look for a sequestrum.

In the UK, CT is reserved for cases in which fistulae are present and when conventional methods with tomography leave unsolved problems. In the United States, the use of conventional tomography is diminishing and is being replaced by CT. However, CT is insufficient for assessing the activity of the process.

One advantage of CT is that it depicts changes earlier than does plain imaging in patients with acute osteomyelitis. CT is especially good for imaging the spine, pelvis, and sternum.

False Positives/Negatives

Stress fractures, osteoid osteomas, and other causes of periosteitis may mimic acute or chronic osteomyelitis.

MRI

Section 6 of 12  

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• MRI
• Ultrasound
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• Multimedia
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Findings

MRI findings in osteomyelitis are usually secondary to the replacement of marrow fat with water secondary to edema, exudate, hyperemia, and bone ischemia. Findings include the following: decreased signal intensity in the involved bone on T1-weighted images, increased signal intensity in the involved bone on T2-weighted image, and increased signal intensity in the involved bone on short-tau inversion recovery (STIR) images.

Sequestrum of cortical bone appears hypointense on T1-weighted, T2-weighted, and STIR MRIs and shows no gadolinium enhancement. Sequestrum of cancellous bone is hyperintense relative to cortical sequestrum on T1-weighted, T2-weighted, and STIR MRIs and shows no gadolinium enhancement. The involucrum is hypointense on all 3 images and shows gadolinium enhancement.

Granulation tissue is hypointense on T1-weighted images and hyperintense on T2-weighted and STIR images. It shows gadolinium enhancement. Similarly, draining sinuses and soft-tissue inflammation are hypointense on T1-weighted images and hyperintense on T2-weighted and STIR MRIs; however, it does show gadolinium enhancement.

A Brodie abscess is characterized by a double line at the site of the lesion due to the high signal intensity of granulation tissue surrounded by low signal intensity of bone sclerosis on T2-weighted MRIs. The lesion has low-to-intermediate signal intensity that is outlined by a hypointense rim on T1-weighted MRIs.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases ofNSF/NFD. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

MRI has sensitivity and specificity higher than those of plain radiography and CT, and it is particularly good at depicting bone marrow abnormalities. On MRI, marrow signal abnormality is more sensitive than lytic changes on plain images, and findings become positive earlier with MRI than with radiography. Intramedullary bone pathology can be directly visualized with MRI, and in osteomyelitis marrow, these findings may precede bone changes.

The multiplanar capability of MRI is an advantage and provides better anatomic detail and better soft-tissue contrast. MRI is especially good in assessing vertebral osteomyelitis, which has a characteristic pattern of confluent vertebral body and disk involvement. Titanium and other orthopedic devises usually pose no problem apart from artifacts.

However, MRI findings of osteomyelitis are nonspecific, and similar changes can occur as a result of tumors, fractures, and a variety of other intramedullary or juxtamedullary processes that may cause bone marrow edema. The sensitivity and specificity has been reported as 92-100% and 89-100%, respectively. Prior fracture changes due to surgery or the fracture itself are difficult to differentiate from infection.

False Positives/Negatives

Fractures, bone bruises, and benign or malignant bone tumors may all mimic osteomyelitis.

ULTRASOUND

Section 7 of 12  

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• Ultrasound
• Nuclear Medicine
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• Intervention
• Multimedia
• References

Findings

Cleveland and Peck reported a case in which high-resolution ultrasonography was instrumental in establishing a diagnosis of chronic osteomyelitis. Sonograms depicted a periosteal reaction and associated soft-tissue involvement.

Degree of Confidence

The physical properties of bone do not usually lend themselves to ultrasonographic investigation, because of the reflection of sound waves at a soft tissue–bone interface. However, the periosteum, early new-bone formation, and soft-tissue changes alongside dense bone may be imaged. The use of sonography has occasionally been reported in acute osteomyelitis, but its role in evaluating chronic osteomyelitis is probably limited.

False Positives/Negatives

Larcos and associates found that 2 of their 19 patients had a false-positive sonographic diagnosis of acute osteomyelitis. They concluded that ultrasonographic results might be potentially misleading, emphasizing the importance of clinical judgment and results of other tests.

High false-positive and false-negative rates are expected in chronic osteomyelitis.

NUCLEAR MEDICINE

Section 8 of 12  

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• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Technetium-99m diphosphonate bone scanning

A ^99mTc methylene diphosphonate (MDP) bone scans are usually positive 24 hours after an acute infection, and the scans demonstrate a well-defined focus of tracer activity 1-2 hours after the injection. This finding is correlated with radiotracer in same area on dynamic scans.

Bone scintigraphy may show focal uptake at the affected site and is particularly valuable in looking for other sites of infection, as multifocal osteomyelitis may occur.

MDP scans also remain positive in most patients with subacute and chronic osteomyelitis. Increased focal activity may persist in sterile disease for up to 2 years following successful therapy.

The sensitivity of MDP scans can be improved by using a 3-phase bone scan. On such scans, focal activity is usually depicted associated with mild, diffusely increased, regional activity distal to the sight of osteomyelitis. Occasionally, a photon deficient (cold) defects are seen.

Gallium-67 scanning

Mechanisms of ⁶⁷Ga citrate uptake include the following: (1) direct leukocyte and bacterial uptake, (2) lactoferrin and transferring binding, (3) increased vascularity, and (4) increased bone turnover.

Criteria for a positive gallium scan include uptake exceeding that of the bone scan and/or uptake differing in distribution compared with that on bone scans.

Johnson et al evaluated 22 diabetic patients with osteomyelitis by using gallium scans. The results yielded a sensitivity of 100%, a specificity of 40%, and an accuracy of 73%. In Schauwecker's review of the literature, the sensitivity was 81% with a specificity of 69%.

Gallium scanning has a proven role in the monitoring of treatment.

If patients with suspected acute osteomyelitis are currently untreated and if ^99mTc diphosphonate and gallium scans show concordant pattern, the scans are interpreted as follows: If ^99mTc diphosphonate uptake is less than gallium uptake, infection is suggested. If ^99mTc diphosphonate uptake is greater than gallium uptake, reactive bone is suggested. If ^99mTc diphosphonate and gallium uptake are discordant and if uptake is truly in bone, the likely diagnosis is osteomyelitis.

The sensitivity and specificity are 22-100% and 0-100%, respectively.

Indium-111 WBC and ^99mTc hexamethylenepropyleneamineoxime scanning

¹¹¹In WBC scans may show normal lung uptake up to 7 hours. At 24 hours spleen activity greater than that in the liver and marrow is seen. Uptake is increased in both acute and chronic osteomyelitis. Occasional cold (up to 12%) may occur in areas with significant red marrow, where uptake in the marrow is greater than that in the inflamed site.

^99mTc hexamethylenepropyleneamineoxime (HMPAO) scanning is similar to ¹¹¹In scanning, though more activity may be seen in other organs.

2-[Fluorine 18]-fluoro-2-deoxy-D-glucose positron emission tomography

Meller and associates prospectively compared ¹¹¹In-labeled WBCs and 2-[fluorine 18]-fluoro-2-deoxy-D-glucose (FDG) by using a coincidence dual-head camera. Thirty consecutive nondiabetic patients with possible chronic osteomyelitis were recruited underwent combined skeletal scintigraphy (30 patients), ¹¹¹In WBC imaging (28 patients), and FDG positron emission tomography (PET) (30 patients). During diagnostic work-up, chronic osteomyelitis was proven in 11 or 36 regions of suspected skeletal infection and subsequently excluded in 25. In addition, soft-tissue infection was present in 5 patients, and septic arthritis, in 3. In 28 patients, ¹¹¹In WBC results were true-positive in 2 of 11 regions with proven chronic osteomyelitis; results were true-negative in 21 of 23 regions without further evidence of chronic osteomyelitis.

False-positive results occurred in 2 regions, and false-negative results occurred in 9 regions suspected for chronic osteomyelitis. Most of the false-negative results (7 of 9) occurred in the central skeleton. When the analysis was restricted to the 18 regions with available histology (n = 17) or culture (n = 1) results, ¹¹¹In WBC imaging was true-positive in 2, true-negative in 8, false-negative in 7, and false-positive in 1.

Images obtained with FDG and a dual-headed coincidence camera (DHCC) were true-positive in 11 of 11 regions with proven chronic osteomyelitis and true-negative in 23 of 25 regions without further evidence of chronic osteomyelitis. False-positive results occurred in 2 regions. When the analysis was restricted to 19 regions with available histology (n = 18) or culture (n = 1) results, FDG DHCC images were true-positive in 9 or 9 regions with proven chronic osteomyelitis and true-negative in 10 of 10 regions without further evidence of chronic osteomyelitis.

The authors concluded that FDG DHCC imaging was superior to ¹¹¹In WBC scintigraphy in the diagnosis of chronic osteomyelitis in the central skeleton. Therefore, it should be considered the method of choice for this indication. This seems to hold true for peripheral lesions as well, but in this series, the number of cases with proven infection was too small to permit a final conclusion.

Zhuang and associates examined 22 patients with possible osteomyelitis (5 in the tibia, 5 in the spine, 4 in the proximal femur, 4 in the pelvis, 2 in the maxilla, and 2 in the feet) who underwent FDG PET and in whom operative or clinical follow-up data were available. The final diagnosis was made at surgical exploration or clinical follow-up during a 1-year period. FDG PET correctly depicted the presence or absence of chronic osteomyelitis in 20 of 22 patients. Six had chronic osteomyelitis, and 16 did not have osteomyelitis. FDG PET led to correct identification all 6 patients with chronic osteomyelitis but produced 2 false-positive results.

This study had a sensitivity of 100%, a specificity of 87.5%, and an accuracy of 90.9%. The authors concluded that FDG PET is a highly effective imaging method to exclude osteomyelitis when a negative scan is obtained. However, positive results are caused not only by true osteomyelitis but also by inflammation in the bone or surrounding soft tissues as a result of other causes. Overall, FDG PET may prove to be the preferred study in the care of patients with possible chronic osteomyelitis.

Findings in chronic recurrent osteomyelitis

Bone scans can be positive for up to 2 years after treatment. ¹¹¹In WBC scanning is not ideal because mononuclear cells predominate. Although the sensitivity of ¹¹¹In WBC scanning in an acute infection is in the range of 100%, the sensitivity decreases to 73% in chronic disease. ⁶⁷Ga scanning is probably more sensitive, and with this method, activity returns to normal after effective treatment.

Findings in infected hip and knee prostheses

The clinical presentation of loose and infected prosthesis may be similar, and hence, imaging plays an important role. Characteristically, MDP scans show normal flow and perfusion but increased focal activity at the tip or acetabulum in loosening. With infection, all phases are abnormal, and activity is present along the shaft of the prosthesis. A combined ⁶⁷Ga and MDP scan may increase accuracy when ⁶⁷Ga activity is more intense or incongruent. ¹¹¹In WBC scans are probably better in evaluating infected prosthesis.

Findings in diabetic foot

In the diabetic foot, neuropathic osteoarthropathy and cellulites can be confused with osteomyelitis. MDP scanning is sensitive but not specific. ⁶⁷Ga scans are more specific. In this setting, ¹¹¹In WBCs are superior scanning agents because there is no red marrow in the bones of the feet. Unlike MDP scans, ¹¹¹In WBC scans are not positive in neuropathic bones or joints. The sensitivity and specificity has been reported as 100% and 83-79%, respectively.

¹¹¹In leukocyte and ^99mTc sulfur-colloid scintigraphy

Palestro and associates evaluated the role of combined leukocyte and marrow scintigraphy in the assessment of radiographically confirmed neuropathic or Charcot joints in 17 patients. Studies demonstrating labeled leukocyte accumulation without corresponding activity on marrow images were classified as positive for osteomyelitis. Six patients also underwent 3-phase bone scintigraphy. Bone scans were interpreted as positive for osteomyelitis when focal hyperperfusion, focal hyperemia and focal bony uptake were present on delayed images.

Bone images were also interpreted with labeled-leukocyte images by using 2 criteria for a positive study. One criterion was labeled-leukocyte activity in a region demonstrating abnormal activity on the bone scan, which was more intense than adjacent marrow activity or marrow activity in the corresponding region of the contralateral foot. The second criterion was either a spatially incongruent distribution of the 2 tracers or hyperintense activity on the leukocyte study, as compared with the bone scan.

The results showed that the leukocyte and marrow studies were positive for osteomyelitis in 4 of 20 neuropathic joints. Osteomyelitis was present in 3 joints, whereas in the fourth, infection was confined to overlying soft tissues. None of the 16 neuropathic joints with negative leukocyte and marrow scans were infected. In 1 patient who underwent below-the-knee amputation, histologic analysis confirmed hematopoietically active marrow, which corresponded to areas of congruent activity on the leukocyte and marrow images.

Three-phase bone scintigraphy was positive in all 6 neuropathic joints studied; osteomyelitis was present in 2. With the first criterion, leukocyte and bone imaging was also positive in all 6. With the second criterion, leukocyte and bone imaging was positive in the 2 infected neuropathic joints, as well as in 3 uninfected ones. Leukocyte and marrow scintigraphy was positive in both infected joints and negative in the 4 without infection.

The authors concluded that labeled-leukocyte accumulation in the uninfected Charcot joint does occur and is related, at least in part, to hematopoietically active marrow. They found that leukocyte and marrow scintigraphy a reliable way to differentiate between marrow and infection as the cause of labeled-leukocyte accumulation in the neuropathic joint. In their series, combined leukocyte and bone scintigraphy was superior to both 3-phase bone scanning and leukocyte scintigraphy.

^99mTc sulfur colloid scanning

Lichenstein and associates examined 32 patients with fractures of the limbs 15-30 minutes following and injection of ^99mTc sulfur colloid. In 17 of 19 patients in whom osteomyelitis was superimposed on various fractures, significant uptake of sulfur colloid was noted at the fracture sites. The sensitivity for the test was 89.5%. In 12 of 13 cases in which osteomyelitis was absent, the sulfur colloid scan was negative, giving a specificity of 92.3%. Hence, ^99mTc sulfur colloid scan may be a successful method for detecting osteomyelitis as a complication of a limb fracture.

Degree of Confidence

MDP scanning

MDP scans are highly sensitive, and the whole body can be imaged with a relatively low whole-body radiation dose. The sensitivity of MDP has variably been reported in the range of 32-100%, but the overall sensitivity is more than 90% in adults without complicating factors. Sensitivity is lower with earlier studies; in neonates; and in elderly persons with osteoporosis, severe peripheral vascular disease, and metabolic bone disease. The specificity is variably reported in the range of 0-100%.

⁶⁷Ga scanning

⁶⁷Ga scanning is more specific than MDP scanning, with relatively good images. ⁶⁷Ga is a better imaging agent for chronic osteomyelitis and particularly good for imaging fungal infections. It also appears a better than WBC for detecting vertebral osteomyelitis. The main disadvantages are its longer imaging time (72 h), higher radiation dose, and unsuitability for use in pediatric patients.

¹¹¹In and ^99mTc HMPAO scanning

¹¹¹In-labeled WBCs are generally more specific than MDP or ⁶⁷Ga and enable faster imaging than ⁶⁷Ga scanning. Previous antibiotic or steroid therapy does not affect the sensitivity. The disadvantages include the need for 50 mL blood for labeling, its complicated formulation, and a higher radiation dose. Hence, ¹¹¹In techniques are not suitable for pediatric patients. The images are also relatively poor and may take up to 24 hours to acquire because of the low dosage. The sensitivity is 83%, and the specificity is 94%.

The main advantages of ^99mTc HMPAO WBC scanning is faster imaging, lower radiation dose, and lower-energy photons for better images. Also, single photon emission CT (SPECT) images can be obtained if required. The disadvantages include the need for phlebotomy, complicated labeling, and a "dirtier" image. The sensitivity and specificity are 95% and 85%, respectively.

However, FDG is a nonspecific tracer that accumulates at sites of infection and inflammation. FDG PET imaging will play a major role in the treatment of patients with suspected infection and inflammation. PET has shown value in the diagnosis of chronic osteomyelitis, infected prostheses, and fever of unknown origin. Because of its ability to quantitate the rate of FDG uptake, PET may prove to be a powerful modality for monitoring disease activity and responses to therapy. Thus, the detection and characterization of infection and inflammation may become a major clinical indication in the day-to-day practice PET imaging.

Zhang and associates have shown a sensitivity of 100%, a specificity of 87.5%, and an accuracy of 90.9% in excluding chronic osteomyelitis with FDG PET.

False Positives/Negatives

MDP scanning

Cold defects are probably related to a combination decreased flow secondary to subperiosteal pus, joint effusion, soft-tissue swelling and vasospasm, lytic lesions with a loss of osseous tissues, bone infarct, and/or extremely rapid and progressive destructive process. Cold defects are particularly prevalent in early infection and pediatric patients. Cold defects can be missed if small or subtle. False-positive scans can occur in diabetic osteoarthropathy.

¹¹¹In WBC scanning

False-positive studies may occur with tumors, especially histiocytic lymphomas and bone metastasis, sterile hematomas, GI uptake after enemas, vasculitis, ischemic bowel, swallowed sinusitis/lung infection, cerebral infarction, injection site, endocarditis, cystic fibrosis, and acute respiratory distress syndrome (ARDS).

Questions have been raised about the effect of antibiotic therapy on the sensitivity of leukocyte scanning. However, the general belief is that antibiotics do not appear to have a significant effect on sensitivity. By reducing the number of bacteria at an inflammatory site, antibiotics reduce the amount of chemotactic inhibitors. In addition, some antibiotics directly stimulate leukocyte chemotaxis. Hemodialysis, hyperalimentation, hyperglycemia, and steroid use are other factors that can reduce leukocyte function. These do not appear to reduce the sensitivity of labeled leukocytes for infection (Datz, 1994).

FDG PET imaging

FDG is a nonspecific tracer, and images show uptake in several benign and malignant tumors and in inflammatory and infective disorders.

ANGIOGRAPHY

Section 9 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Angiography has no role in the diagnosis of chronic osteomyelitis.

INTERVENTION

Section 10 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

White and associates examined 25 patients with suspected osteomyelitis to determine the utility of combined histologic and microbiologic evaluation of percutaneous biopsy samples. Biopsy samples were obtained with usual trephine techniques under radiologic guidance. Core and aspiration biopsy samples were obtained for both histologic and microbiologic analyses.

Sixteen biopsy specimens demonstrated histologic evidence of osteomyelitis. Of these, 8 also had positive cultures. Seven of the 8 culture-negative, histologically positive cases were interpreted as chronic osteomyelitis. In no patient were cultures positive and histologic findings negative. Three of 19 patients with proved osteomyelitis had negative histologic and microbiologic findings.

The sensitivity of culture in the diagnosis of osteomyelitis in this study was 42%. The sensitivity of both culture and histologic findings was 84%. The authors concluded that, although the volume of a biopsy specimen was a major determinant of culture yield, a portion of a percutaneous biopsy sample should be histologically evaluated for possible osteomyelitis.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Media file 1:  Osteomyelitis, chronic. Sclerosing osteomyelitis of the lower tibia. Note the bone expansion and marked sclerosis.
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Media file 2:  Osteomyelitis, chronic. Sequestrum of the lower tibia.
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Media file 3:  Osteomyelitis, chronic. Image in a 56-year-old man with diabetes shows chronic osteomyelitis of the calcaneum. Note air in the soft tissues.
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Media file 4:  Osteomyelitis, chronic. Radiograph (left) and isotopic bone scans (right) show sclerosing osteomyelitis of the tibia.
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Media file 5:  Osteomyelitis, chronic. This 24-year-old man with psoriatic arthropathy presented with pain over the first metatarsal bone, hallux, and heel, with increased plasma viscosity. Radiographs of the right foot show a normal first metatarsal bone, but the cortex of the proximal phalanx of the hallux is irregular (see also Images 6-8).
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Media file 6:  Osteomyelitis, chronic. Three-phase technetium-99m diphosphonate bone scans (perfusion component) show increased activity in the whole of the heel, the tarsus, the proximal and distal phalanges of the hallux, and the proximal phalanx of the second toe (see also Images 6-8).
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Media file 7:  Osteomyelitis, chronic. Three-phase technetium-99m diphosphonate bone scans (static component) show increased activity in the heel and in the first and second toes and in the fifth tarsotarsometatarsal joint (see also Images 6 and 8).
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Media file 8:  Osteomyelitis, chronic. Nonenhanced axial CT scans through the first and second toes in the same patient as in Images 5-7 shows cortical irregularity of the distal phalanx of the hallux; this finding is suggestive of chronic osteomyelitis. The final diagnosis was osteomyelitis of the first and second toes, plantar fasciitis, and psoriatic arthritis of the fifth metatarsal-phalangeal joint.
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Media file 9:  Osteomyelitis, chronic. Plain radiographs show Garrès sclerosing osteomyelitis.
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Media file 10:  Osteomyelitis, chronic. Technetium-99m diphosphonate bone scans of the same patient as in Image 9 show increased activity in the region with Garrès sclerosing osteomyelitis.
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Media file 11:  Osteomyelitis, chronic. CT scans show vertebral osteomyelitis associated with a psoas abscess.
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Media file 12:  Osteomyelitis, chronic. Chest radiograph of a 12-year-old patient presenting with pain and swelling of the left clavicle. Note the expansion, sclerosis, and periosteal reaction of the clavicle (see also Images 13-15).
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Media file 13:  Osteomyelitis, chronic. Conventional tomograms of the left clavicle on the same patient as in Image 12 show the inflammatory lesion in the clavicle more clearly.
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Media file 14:  Osteomyelitis, chronic. Short-tau inversion recovery (STIR) MRIs of the same patient as in Images 12-13 show bone marrow edema of the clavicle and periclavicular fluid (pus).
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Media file 15:  Osteomyelitis, chronic. T1-weighted nonenhanced (top) and gadolinium-enhanced (bottom) axial MRIs show the enhancement at the inflammatory site in the clavicle (in the same patient as in Images 12-14).
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Media file 16:  Osteomyelitis, chronic. Radiographs of the foot of a 52-year-old diabetic man with symptoms show no bone abnormality.
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Media file 17:  Osteomyelitis, chronic. Radiographs of the foot of the same patient as in Image 16 obtained 2 weeks later show patchy loss of bone density in the distal fourth metatarsal bone.
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Media file 18:  Osteomyelitis, chronic. Three-phase technetium-99m diphosphonate bone scans in the same patient as in Images 16-17 show increased activity in the third and fourth metatarsal bones and in the third toe.
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Media file 19:  Osteomyelitis, chronic. Indium-111–labeled WBC scans show an infected right-knee prosthesis.
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Media file 20:  Osteomyelitis, chronic. A 20-year-old who underwent intramedullary nail fixation of a tibial fracture 2 years before. The patient presented with a painful leg. Radiographs show no evidence of osteomyelitis.
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Media file 21:  Osteomyelitis, chronic. Three-phase technetium-99m diphosphonate bone scans in the same patient as in Image 20 show changes suggestive of osteomyelitis.
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Media file 22:  Osteomyelitis, chronic. This 69-year-old man presented with epigastric pain. Plain radiograph of the lumbar spine shows changes of osteoarthritis (see Images 23-25).
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Media file 23:  Osteomyelitis, chronic. Axial CT scans show destruction of L1. Note the air in the soft tissues.
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Media file 24:  Osteomyelitis, chronic. Technetium-99m diphosphonate bone scan in the same patient as in Images 22-23 show increased activity in the upper lumbar spine.
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Media file 25:  Osteomyelitis, chronic. T1- and T2-weighted sagittal MRIs in the same patient as in Images 22-24 show bone marrow edema in L1 and obliteration of the disk space between L1 and L2.
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REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

• Adatepe MH, Powell OM, Isaacs GH, et al. Hematogenous pyogenic vertebral osteomyelitis: diagnostic value of radionuclide bone imaging. J Nucl Med. Nov 1986;27(11):1680-5. [Medline].
• Alazraki NP. Radionuclide imaging in the evaluation of infections and inflammatory disease. Radiol Clin North Am. Jul 1993;31(4):783-94. [Medline].
• Azouz EM. Computed tomography in bone and joint infections. J Can Assoc Radiol. Jun 1981;32(2):102-6. [Medline].
• Carek PJ, Dickerson LM, Sack JL. Diagnosis and management of osteomyelitis. Am Fam Physician. Jun 15 2001;63(12):2413-20. [Medline].
• Cleveland TJ, Peck RJ. Case report: chronic osteomyelitis demonstrated by high resolution ultrasonography. Clin Radiol. Jun 1994;49(6):429-31. [Medline].
• Datz FL. Indium-111-labeled leukocytes for the detection of infection: current status. Semin Nucl Med. Apr 1994;24(2):92-109. [Medline].
• De Winter F, Vogelaers D, Gemmel F, Dierckx RA. Promising role of 18-F-fluoro-D-deoxyglucose positron emission tomography in clinical infectious diseases. Eur J Clin Microbiol Infect Dis. Apr 2002;21(4):247-57. [Medline].
• Demharter J, Bohndorf K, Michl W, Vogt H. Chronic recurrent multifocal osteomyelitis: a radiological and clinical investigation of five cases. Skeletal Radiol. Oct 1997;26(10):579-88. [Medline].
• Deysine M, Rafkin H, Teicher I, et al. Diagnosis of chronic and postoperative osteomyelitis with gallium 67 citrate scans. Am J Surg. Jun 1975;129(6):632-5. [Medline].
• Firooznia H, Rafii M, Golimbu C, Sokolow J. Computerized tomography of pelvic osteomyelitis in patients with spinal cord injuries. Clin Orthop. Dec 1983;(181):126-31. [Medline].
• Fletcher BD, Scoles PV, Nelson AD. Osteomyelitis in children: detection by magnetic resonance. Work in progress. Radiology. Jan 1984;150(1):57-60. [Medline].
• Gold R. Radiographic diagnosis of osteomyelitis. Pediatr Infect Dis J. Jun 1995;14(6):555. [Medline].
• Gold RH, Tong DJ, Crim JR, Seeger LL. Imaging the diabetic foot. Skeletal Radiol. Nov 1995;24(8):563-71. [Medline].
• Graham GD, Lundy MM, Moreno AJ, Frederick RJ. The role of Tc-99m MDP and Ga-67 citrate in predicting the cure of osteomyelitis. Clin Nucl Med. Aug 1983;8(8):344-6. [Medline].
• Guhlmann A, Brecht-Krauss D, Suger G, et al. Chronic osteomyelitis: detection with FDG PET and correlation with histopathologic findings. Radiology. Mar 1998;206(3):749-54. [Medline].
• Harvey J, Cohen MM. Technetium-99-labeled leukocytes in diagnosing diabetic osteomyelitis in the foot. J Foot Ankle Surg. May-Jun 1997;36(3):209-14; discussion 256. [Medline].
• Ivancevic V, Dodig D, Livakovic M, et al. Comparison of three-phase bone scan, three-phase 99m-Tc-HM-PAO leukocyte scan and 67-gallium scan in chronic bone infection. Prog Clin Biol Res. 1990;355:189-98. [Medline].
• Jacobson AF, Gilles CP, Cerqueira MD. Photopenic defects in marrow-containing skeleton on indium-111 leucocyte scintigraphy: prevalence at sites suspected of osteomyelitis and as an incidental finding. Eur J Nucl Med. 1992;19(10):858-64. [Medline].
• Jurriaans E, Singh NP, Finlay K, Friedman L. Imaging of chronic recurrent multifocal osteomyelitis. Radiol Clin North Am. Mar 2001;39(2):305-27. [Medline].
• Kaim AH, Gross T, von Schulthess GK. Imaging of chronic posttraumatic osteomyelitis. Eur Radiol. May 2002;12(5):1193-202. [Medline].
• Kak V, Chandrasekar PH. Bone and joint infections in injection drug users. Infect Dis Clin North Am. Sep 2002;16(3):681-95. [Medline].
• Kattapuram TM, Treat ME, Kattapuram SV. Magnetic resonance imaging of bone and soft tissue infections. Curr Clin Top Infect Dis. 2001;21:190-226. [Medline].
• Kern EB. Suppurative (bacterial) sinusitis. Postgrad Med. Mar 1987;81(4):194-8, 203-10. [Medline].
• Ledermann HP, Kaim A, Bongartz G, Steinbrich W. Pitfalls and limitations of magnetic resonance imaging in chronic posttraumatic osteomyelitis. Eur Radiol. 2000;10(11):1815-23. [Medline].
• Lichtenstein M, Andrews J, Scales R. Localization of osteomyelitis with 99mtechnetium sulphur colloid. Aust N Z J Surg. Aug 1983;53(4):339-42. [Medline].
• Lobo J, McKee M. Musculoskeletal images. Chronic osteomyelitis. Can J Surg. Feb 2003;46(1):47-9. [Medline].
• Lopes TD, Reinus WR, Wilson AJ. Quantitative analysis of the plain radiographic appearance of Brodie''s abscess. Invest Radiol. Jan 1997;32(1):51-8. [Medline].
• Lupi L, Bighi S, Limone GL, et al. The role of computed tomography in chronic osteomyelitis. Rays. Sep-Dec 1987;12(3):27-9. [Medline].
• McAfee JG, Samin A. In-111 labeled leukocytes: a review of problems in image interpretation. Radiology. Apr 1985;155(1):221-9. [Medline].
• Meller J, Koster G, Liersch T, et al. Chronic bacterial osteomyelitis: prospective comparison of (18)F-FDG imaging with a dual-head coincidence camera and (111)In-labelled autologous leucocyte scintigraphy. Eur J Nucl Med Mol Imaging. Jan 2002;29(1):53-60. [Medline].
• Oyen WJ, van Horn JR, Claessens RA, et al. Diagnosis of bone, joint, and joint prosthesis infections with In-111- labeled nonspecific human immunoglobulin G scintigraphy. Radiology. Jan 1992;182(1):195-9. [Medline].
• Palestro CJ. The current role of gallium imaging in infection. Semin Nucl Med. Apr 1994;24(2):128-41. [Medline].
• Palestro CJ, Mehta HH, Patel M, et al. Marrow versus infection in the Charcot joint: indium-111 leukocyte and technetium-99m sulfur colloid scintigraphy. J Nucl Med. Feb 1998;39(2):346-50. [Medline].
• Propst-Proctor SL, Dillingham MF, McDougall IR, Goodwin D. The white blood cell scan in orthopedics. Clin Orthop. Aug 1982;(168):157-65. [Medline].
• Quinn SF, Murray W, Clark RA, Cochran C. MR imaging of chronic osteomyelitis. J Comput Assist Tomogr. Jan-Feb 1988;12(1):113-7. [Medline].
• Rachinsky I, Agranovich S, Lantsberg S. Imaging of bone to skin sinus tract from osteomyelitis of the femur by Tc-99m HMPAO leukocyte scintigraphy. Clin Nucl Med. Dec 2002;27(12):891-2. [Medline].
• Robinson CB, Higginbotham-Ford EA. Determination of sequestrum activity by SPECT with CT correlation in chronic osteomyelitis of the head and neck. J Otolaryngol. Oct 1986;15(5):279-81. [Medline].
• Sartoris DJ. The role of radiology in orthopaedic sepsis. Orthop Rev. Apr 1987;16(4):271-86. [Medline].
• Sato T, Indo H, Kawabata Y, et al. Scintigraphic evaluation of chronic osteomyelitis of the mandible in SAPHO syndrome. Dentomaxillofac Radiol. Sep 2001;30(5):293-5. [Medline].
• Sayle BA, Fawcett HD, Wilkey DJ, et al. Indium-111 chloride imaging in chronic osteomyelitis. J Nucl Med. Mar 1985;26(3):225-9. [Medline].
• Schauwecker DS. Osteomyelitis: diagnosis with In-111-labeled leukocytes. Radiology. Apr 1989;171(1):141-6. [Medline].
• Schauwecker DS, Park HM, Mock BH, et al. Evaluation of complicating osteomyelitis with Tc-99m MDP, In-111 granulocytes, and Ga-67 citrate. J Nucl Med. Aug 1984;25(8):849-53. [Medline].
• Seltzer SE. Value of computed tomography in planning medical and surgical treatment of chronic osteomyelitis. J Comput Assist Tomogr. Jun 1984;8(3):482-7. [Medline].
• Stokkel MP, Takes RP, van Eck-Smit BL, et al. The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis. Eur J Nucl Med. Nov 1997;24(11):1429-32. [Medline].
• Tehranzadeh J, Wong E, Wang F, Sadighpour M. Imaging of osteomyelitis in the mature skeleton. Radiol Clin North Am. Mar 2001;39(2):223-50. [Medline].
• Tehranzadeh J, Wang F, Mesgarzadeh M. Magnetic resonance imaging of osteomyelitis. Crit Rev Diagn Imaging. 1992;33(6):495-534. [Medline].
• Tehranzadeh J, Wong E, Wang F, Sadighpour M. Imaging of osteomyelitis in the mature skeleton. Radiol Clin North Am. Mar 2001;39(2):223-50. [Medline].
• Tumeh SS, Aliabadi P, Seltzer SE, et al. Chronic osteomyelitis: the relative roles of scintigrams, plain radiographs, and transmission computed tomography. Clin Nucl Med. Oct 1988;13(10):710-5. [Medline].
• Tumeh SS, Aliabadi P, Weissman BN, McNeil BJ. Chronic osteomyelitis: bone and gallium scan patterns associated with active disease. Radiology. Mar 1986;158(3):685-8. [Medline].
• White LM, Sch