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SCIENTIFIC EXHIBIT |
Department of Radiology, Long Island Jewish Medical Center, New Hyde Park, New York
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Introduction |
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 Top Introduction Occult (Soft-Tissue) InfectionOsteomyelitisConclusionsReferences |
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Occult (Soft-Tissue) Infection |
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TopIntroductionOccult (Soft-Tissue) InfectionOsteomyelitisConclusionsReferences |
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A frequently cited disadvantage of Ga-67 imaging, the presence of radiotracer in normal bowel, does not pose a significant problem because bowel activity can be readily distinguished from pathologic accumulations at single photon emission CT and, if needed, at imaging performed at later intervals to allow dissipation of bowel activity.
In-111 Oxine–labeled Leukocytes
Labeled leukocytes accumulate in experimental abscesses with higher target-to-background ratios than does Ga-67, and planar whole-body images obtained with In-111–labeled leukocytes are perhaps easier to interpret owing to lower overall background activity. As a result, labeled leukocyte imaging achieved wide acceptance as the initial examination in patients with fever of unknown origin (5–8). However, its popularity has declined in recent years for a number of reasons. First, because the study involves labeling and reinjection of autologous leukocytes, there is potential for misadministration—a serious risk, particularly in the acquired immunodeficiency syndrome era. Second, with increasing emphasis on cost containment, the complexity of the radiolabeling
process and the manpower requirements are beyond the scope of most hospital-based nuclear medicine facilities and clearly impractical in smaller practice settings. Third, the superiority of labeled leukocyte imaging was suggested at a time when only planar Ga-67 imaging was performed with radiotracer amounts that were roughly one-fourth of what they are today.
It has been suggested that the accuracy of In-111–labeled leukocyte imaging may be greater in acute than in subacute or chronic infection, presumably due to a more pronounced leukocyte response in acute infection. However, the reported data on this subject are limited and conflicting (3,6), and in clinical practice it is often difficult to determine the duration of infection. For simplicity and convenience, therefore, most nuclear medicine practitioners have adopted the use of either Ga-67 or In-111–labeled leukocyte imaging, depending on their expertise and familiarity with the procedure and on cost considerations regardless of the (perceived) duration of infection.
A technical limitation of In-111–labeled leukocyte scintigraphy worth noting is that the accuracy of the test depends on the accumulation of a sufficient number of radiolabeled leukocytes at the infection site and, therefore, in part on the number of white blood cells radiolabeled. As this number decreases due to leukopenia or the availability of only a small blood sample (in younger children), the accuracy of the test is also likely to decrease.
Leukocyte labeling with Tc-99m hexamethyl propylenamine oxime was developed to overcome the count rate limitation of In-111. Although this radiopharmaceutical is particularly advantageous for delineating inflammatory bowel disease and may permit earlier diagnosis of acute abscess, it is limited by changing biodistribution in the bowel and liver, which may necessitate sequential imaging, and by uptake in normal kidneys and gallbladder (8). As with In-111, labeling with Tc-99m hexamethyl propylenamine oxime requires withdrawal of autologous blood and in vitro labeling of separated leukocytes.
Fluorine-18-Fluorodeoxyglucose
Fluorine-18-fluorodeoxyglucose, an established tumor imaging agent, is being used increasingly with the introduction of lower-cost coincidence cameras. Recent studies by Sugawara et al (9) and Chang et al (10) have found fluorodeoxyglucose positron emission tomography to be promising in a variety of infections. Although this is encouraging, fluorodeoxyglucose uptake may also occur in noninfectious inflammatory pro
cesses including postoperative changes in soft tissues and bone (11). Additional data will help define the advantages and limitations of this very exciting approach in different types of infection.
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Osteomyelitis |
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TopIntroductionOccult (Soft-Tissue) InfectionOsteomyelitisConclusionsReferences |
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Notwithstanding such limitations, bone scintigraphy continues to be a valuable tool for the diagnosis of osteomyelitis, particularly one that is not superimposed on neuropathic osteoarthropathy, fracture, or postoperative changes. A normal study rules out osteomyelitis. If abnormal uptake is demonstrated, its location, pattern, and intensity considered together may be quite specific in the appropriate clinical setting. Bone scintigraphy is also suitable as a screening test because the technique is simple and the study is completed in 2–3 hours.
In-111–labeled Leukocyte and Ga-67 Scintigraphy
Phosphonate bone imaging may not suffice in certain types of osteomyelitis, requiring the use of radiolabeled leukocytes and Ga-67 (4–8,12). A discussion of the use of these radiotracers in specific clinical situations follows.
Diabetic Neuropathic Osteoarthropathy.—At bone scintigraphy, diabetic neuropathy may be associated with abnormalities of the feet not unlike those seen in osteomyelitis. Consequently, phosphonate imaging is generally not helpful in assessing for coexisting osteomyelitis. Of the available radiotracers, the use of In-111–labeled leukocytes has been the most successful in imaging this condition. However, given the paucity of counts (only 0.5 mCi [18.5 MBq] is administered), the spatial resolution is limited, and the smaller bone structures of the foot are difficult to distinguish from overlying soft tissue. Therefore, the In-111–labeled leukocyte study should optimally be combined with phosphonate bone imaging (4,6,12). This combination facilitates not only the differentiation of bone from soft-tissue uptake but also allows more precise localization of the skeletal focus. The combined study is best performed by imaging In-111 and Tc-99m activities simultaneously using separate photopeak analyzer windows to provide identical views for comparison. Images acquired in this manner can also be superimposed to separate soft-tissue from bone uptake.
A Charcot joint, typically of the ankle, is a frequent cause of a false-positive In-111–labeled leukocyte study due to radiotracer accumulation in normal bone marrow. Adjunct bone marrow imaging with Tc-99m sulfur colloid is therefore recommended (4,6,12). Increased uptake of labeled leukocytes alone in the absence of a corresponding uptake of radiocolloid is consistent with infection.
There is insufficient experience with leukocyte labeling with Tc-99m hexamethyl propylenamine oxime in patients with neuropathic changes, and it is probably not as suitable as In-111 labeling for these conditions because it does not allow performance of simultaneous dual radiotracer studies with Tc-99m phosphonates or Tc-99m sulfur colloid (8).
Osteomyelitis Associated with Orthopedic Devices.—Orthopedic implants may be associated with postoperative changes or loosening, resulting in nonspecific abnormalities at bone scintigraphy and necessitating the use of a more specific radiotracer such as In-111–labeled leukocytes to rule out infection. However, labeled white blood cells accumulate in normal bone marrow, and additional imaging with Tc-99m sulfur colloid (as described earlier for Charcot joints) may be required (7). Intense uptake of In-111–labeled leukocytes is generally indicative of infection and unlikely to be related to the presence of marrow. Tc-99m hexamethyl propylenamine oxime–labeled leukocyte imaging does not appear to be suitable in these instances because simultaneous Tc-99m sulfur colloid studies are not possible. In addition, these infections are more chronic and the exchange of leukocytes is slow, so that imaging is best performed 24 hours after injection. The In-111–labeled radiotracer, which has greater stability, is therefore the preferred agent (8).
Ga-67 has also been used for imaging of infection associated with orthopedic hardware. As a sole diagnostic agent for this condition, Ga-67 has an inherent limitation in that it accumulates in healing bones, including those with postoperative changes. Therefore, whereas intense uptake in the periprosthetic region is highly suggestive of infection, modest Ga-67 uptake is usually nondiagnostic. The specificity of Ga-67 may be increased by the addition of phosphonate bone scintigraphy and demonstrating incongruent spatial distribution of the two radiotracers or greater intensity of gallium uptake (12).
In short, either In-111–labeled leukocytes or Ga-67 may be used in patients with orthopedic hardware (depending on individual expertise and cost considerations), although on average, labeled leukocytes have been found to be superior. These radiopharmaceuticals may be used in combination with Tc-99m sulfur colloid or Tc-99m phosphonate as needed.
Vertebral Osteomyelitis.—For unexplained reasons, vertebral osteomyelitis exhibits "atypical" imaging characteristics (6,8). It is usually not associated with increased uptake of In-111–labeled leukocytes and occasionally may fail to demonstrate significant Tc-99m phosphonate uptake. However, this condition is well imaged with Ga-67, which may be used as an adjunct to MR imaging.
Osteomyelitis Associated with Decubitus Ulcers.—A frequent indication for scintigraphy is the clinical suspicion for osteomyelitis in a bedridden patient with decubitus ulcers. In-111–labeled leukocyte imaging combined with phosphonate bone imaging is usually ideal in this situation. Bone imaging helps differentiate uptake in soft tissue alone from that associated with skeletal involvement. However, such differentiation occasionally may be impossible despite the absence of osteomyelitis, particularly if there is little soft tissue overlying the bone.
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Conclusions |
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TopIntroductionOccult (Soft-Tissue) InfectionOsteomyelitisConclusionsReferences |
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References |
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TopIntroductionOccult (Soft-Tissue) InfectionOsteomyelitisConclusionsReferences |
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