Charito Love

Nuclear Medicine and the Infected Joint Replacement

Nearly 700,000 hip and knee arthroplasties are performed annually in the United States. Although the results in most cases are excellent, implants do fail. Complications like heterotopic ossification, fracture, and dislocation are now relatively rare and easily diagnosed. Differentiating aseptic loosening, the most common cause of prosthetic joint failure, from infection, is important because their treatments are very different. Unfortunately, differentiating between these 2 entities can be challenging. Clinical signs of infection often are absent. Increased peripheral blood leukocytes, erythrocyte sedimentation rate, and C-reactive protein levels are neither sensitive nor specific for infection. Joint aspiration with Gram stain and culture is the definitive diagnostic test. Its specificity is in excess of 90%; its sensitivity is variable, however, ranging from 28% to 92%. Plain radiographs are neither sensitive nor specific and cross-sectional imaging modalities, such as computed tomography and magnetic resonance imaging, can be limited by hardware-induced artifacts. Radionuclide imaging is not affected by orthopedic hardware and is the current imaging modality of choice for suspected joint replacement infection. Bone scintigraphy is sensitive for identifying the failed joint replacement, but cannot be used to determine the cause of failure. Neither periprosthetic uptake patterns nor performing the test as a 3-phase study significantly improve accuracy, which is only about 50-70%. Thus, bone scintigraphy typically is used as a screening test or in conjunction with other radionuclide studies. Combined bone gallium imaging, with an accuracy of 65-80%, offers only modest improvement over bone scintigraphy alone. Presently, combined leukocyte/marrow imaging, with approximately 90% accuracy, is the radionuclide imaging procedure of choice for diagnosing prosthetic joint infection. In vivo leukocyte labeling techniques have shown promise for diagnosing musculoskeletal infection; their role in prosthetic joint infection has not been established. (111)In-labeled polyclonal immunoglobulin lacks specificity. (99m)Tc-ciprofloaxicin does not consistently differentiate infection from aseptic inflammation. (18)F-fluorodeoxyglucose positron emission tomography has been extensively investigated; its value in the diagnosis of prosthetic joint infection is debatable.

Diagnosing spinal osteomyelitis: a comparison of bone and Ga-67 scintigraphy and magnetic resonance imaging.

Purpose The objective of this investigation was to compare the accuracies of bone and Ga-67 scintigraphy and magnetic resonance imaging (MRI) for diagnosing spinal osteomyelitis and to determine the optimal radionuclide approach to this disorder. Methods Twenty-two patients, with 24 sites of possible spinal osteomyelitis, who underwent three-phase bone scintigraphy with SPECT, Ga-67 scintigraphy with SPECT, and MRI with and without contrast were included in this retrospective review. Bone scans were interpreted as three-phase studies, delayed planar images alone, delayed planar plus SPECT, and SPECT alone (to identify uptake patterns). Sequential bone/ Ga-67 images were interpreted as planar and as SPECT studies. Planar and SPECT Ga-67 images were also interpreted alone. Precontrast MRI studies were used to identify osteomyelitis, whereas postcontrast images were used to identify soft tissue infection. Results Eleven sites of spinal osteomyelitis were identified. Tracer uptake in two contiguous vertebrae, as noted on SPECT, was the most accurate bone scan criterion for detecting spinal osteomyelitis (71%). SPECT bone/Ga-67 was significantly more accurate (92%) than both planar bone/Ga-67 (75%) and bone SPECT (P = 0.15 and P = 0.2, respectively). SPECT Ga-67 was as accurate as SPECT bone/Ga-67 and as sensitive as MRI (91%); the radionuclide study was slightly but not significantly more specific (92% vs. 77%) than MRI. Of 11 sites of extraosseous infection, 10 were identified on MRI, 9 on SPECT Ga-67, 7 on planar Ga-67, and none on bone scintigraphy. Conclusions Spinal osteomyelitis and accompanying soft tissue infection can be diagnosed accurately with a single radionuclide procedure: SPECT Ga-67. This procedure can be used as a reliable alternative when MRI cannot be performed and as an adjunct in patients in whom the diagnosis is uncertain.

Radionuclide imaging of musculoskeletal infection: Conventional agents

The diagnosis of musculoskeletal infection can be clinically challenging, and radionuclide imaging is often performed as part of the diagnostic workup. Conventional studies include bone scan, gallium imaging, and labeled leukocyte imaging. No single test is equally efficacious in all situations, and thus the procedure(s) performed should be optimized for the individual patient. Three-phase bone imaging, readily available and relatively inexpensive, is very accurate in unviolated bone. In the setting of underlying osseous abnormalities, however, the specificity of the test decreases. Four-phase bone, sequential bone/gallium, and labeled leukocyte imaging all have been used in an effort to enhance specificity. Labeled leukocyte imaging is the radionuclide procedure of choice for diagnosing so-called complicating osteomyelitis such as infected joint prostheses, diabetic pedal osteomyelitis, and infection of the neuropathic joint. To maximize the accuracy of the study, complementary bone marrow imaging often must be performed. Labeled leukocyte imaging is of limited value in spinal osteomyelitis, however, because this entity often presents as a nonspecific photopenic defect on white cell studies. The conventional radionuclide study for evaluating spinal osteomyelitis is gallium imaging, which should be performed regardless of the findings on a contemporaneous bone scan. The reasons for this are as follows: Gallium improves the specificity of the bone scan; gallium detects accompanying soft tissue infection, whereas the bone scan does not, and gallium may be more sensitive than the bone scan in elderly patients.

Diagnosis of acute cholecystitis: Sensitivity of sonography, cholescintigraphy, and combined sonography-cholescintigraphy

BACKGROUND Radiographic diagnosis of acute cholecystitis can be established using ultrasonography (US), cholecystoscintigraphy (HIDA), or both. Although both modalities have been effective in diagnosing acute cholecystitis (AC), physicians from the emergency department and admitting surgeons continue to request both tests in an attempt to increase the diagnostic accuracy of AC. This article reports the institutional experience of a large tertiary care health care facility, with respect to the sensitivity of US, HIDA, and combined US and HIDA. STUDY DESIGN We conducted a retrospective review of 132 patients diagnosed with AC who underwent laparoscopic cholecystectomy during the same hospitalization. Patients were stratified into three groups: Group 1 (Gp1, n = 50) included patients who underwent US alone, group 2 (Gp2, n = 28) included patients who underwent HIDA scan alone, and group 3 (Gp3, n = 54) included patients who underwent both US and HIDA. RESULTS The three groups did not differ with respect to age, liver chemistry, time to operation, and hospital length of stay. The sensitivity of US, HIDA, and combined US/HIDA as diagnostic modalities for acute cholecystitis was referenced to histopathologic confirmation. Sensitivity was 24 of 50 (48%), 24 of 28 (86%), and 49 of 54 (90%) for US, HIDA, and the combination of US/HIDA, respectively. CONCLUSIONS HIDA scan is a more sensitive test than US in diagnosing patients with AC. Based on the results of this study, we recommend that HIDA scan should be used as the first diagnostic modality in patients with suspected acute cholecystitis; US should be used to confirm the presence of gallbladder stones rather than to diagnose AC.

Infection and Inflammation

Despite dramatic advances in its prevention and treatment, infection remains a major cause of morbidity in children, accounting for approximately 30 % of childhood deaths worldwide (Children’s Infection Defense Center, St. Jude Children’s Research Hospital, 2004). The development of powerful antimicrobial agents has improved patient survival, but timely diagnosis is equally, if not more, important. In adults, most infections can be diagnosed with a thorough history, a complete physical examination, and appropriate laboratory tests. In the pediatric population, unfortunately, this is a difficult task. Children do not, or will not, verbalize their feelings, and often the history is little more than secondhand information obtained from a parent. The physical examination of an ailing child can be difficult, if not impossible. Further complicating matters is the fact that conditions such as vasculitis and other inflammatory diseases can mimic infection. Consequently, empiric treatment with antibiotics, which may be neither appropriate nor effective, often is instituted. Imaging procedures usually are reserved for those patients in whom symptoms or physical findings point to a specific region of the body. Because of concerns about radiation exposure, pediatricians tend to utilize radionuclide imaging only as a last recourse after all other resources have been exhausted. The nuclear physician often is faced with the formidable task of diagnosing and localizing infection and inflammation late in the course of an illness when an expeditious and correct diagnosis is even more critical.

Diagnostic imaging tests and microbial infections

Despite significant advances in the understanding of its pathogenesis, infection remains a major cause of patient morbidity and mortality. While the presence of infection may be suggested by signs and symptoms, imaging tests are often used to localize or confirm its presence. There are two principal imaging test types: morphological and functional. Morphological tests include radiographs, computed tomography (CT), magnetic resonance imaging, and sonongraphy. These procedures detect anatomic, or structural, alterations produced by microbial invasion and host response. Functional imaging tests reflect the physiological changes that are part of this process. Prototypical functional tests are radionuclide procedures such as bone, gallium, labelled leukocyte and fluorodeoxyglucose (FDG)‐positron emission tomography (PET) imaging. In‐line functional/morphological tomographic imaging systems, PET/CT and single photon emission tomography (SPECT)/CT, have revolutionized diagnostic imaging. These devices consist of a functional imaging device (PET or SPECT) joined together with a CT scanner. The patient undergoes both tests sequentially without leaving the examination table. Images from each study can be viewed separately and as fused images, providing precisely localized anatomic and functional information. It must be noted, however, that none of the current morphological or functional tests, either alone or in combination, are specific for infection and the goal of finding such an imaging test remains elusive.

5. Utility of F-18 FDG Imaging for Diagnosing the Infected Joint Replacement

Purpose: F-18 FDG (FDG) is reportedly useful for detecting infection. Because the procedure is simple, with results being readily available, this prospective study was undertaken to evaluate the utility of FDG imaging for diagnosing infected joint replacements.Methods: 26 pts, 18 females and 4 males between 37 and 87 years old, with 31 joint replacements were studied. 21 pts had single joint replacement (10 hip, 11 knee); 5 pts had bilateral replacements (1 hip, 4 knee). Imaging was performed on a Hybrid PET system, with measured attenuation correction, one hour after administration of 150 MBq FDG. Increased peri-prosthetic uptake compared to adjacent, presumably normal, activity was interpreted as positive for infection.Results: 11 of 31 prostheses were infected. Sensitivity, specificity, and accuracy of FDG were 100%, 55%, and 71% respectively. The PPV was 55% and the NPV was 100%. Excluding the 5 asymptomatic prostheses in pts with bilateral joint replacements, the sensitivity, specificity, and accuracy were 100%, 47%, and 69% respectively. The PPV was 58% and the NPV was 100%. 4 pts with infected prostheses underwent a total of 6 follow-up studies after treatment. In 1 pt with persistent infection, all 3 follow-up studies were true positive. In the other 3 pts in whom infection had been eradicated, follow-up FDG studies were false positive.Conclusion: FDG imaging is sensitive but not specific; consequently, its role in pts with suspected prosthetic infection is limited to that of a screening test. These data also suggest that this technique is not useful for monitoring response to treatment.

Pinhole Versus Parallel-Hole Collimators for Parathyroid Imaging: An Intraindividual Comparison

This study was undertaken to determine the effects of collimators on the accuracy of preoperative sestamibi parathyroid imaging of the neck. Methods: Forty-nine patients with primary hyperparathyroidism underwent preoperative 99mTc-sestamibi parathyroid imaging. The protocol included early and late pinhole and parallel-hole imaging. One experienced nuclear physician, without knowledge of other test results or final diagnoses, interpreted studies. For both pinhole and parallel-hole images, focally increased sestamibi accumulation outside the normal tracer biodistribution that persisted or increased in intensity from early to late images was interpreted as positive for a parathyroid lesion. Final diagnoses were operatively confirmed in all patients. Results: Fifty-four parathyroid lesions were resected from the 49 patients. Forty-five patients had single-gland disease. Four patients had multigland disease: 3 had 2 lesions and 1 had 3 lesions. Median lesion weight was 840 mg. Pinhole imaging was significantly more sensitive than parallel-hole imaging (89% vs. 56%; P = 0.0003) for all 54 lesions. Specificity did not significantly differ between pinhole and parallel-hole imaging (93% vs. 96%, P = 0.29). Pinhole imaging was significantly more sensitive than parallel-hole imaging for lesions above (100% vs. 68%, P = 0.003) and below (77% vs. 42%, P = 0.03) the median weight and for single-gland disease (96% vs. 67%, P = 0.001). Pinhole imaging also was more sensitive for multigland disease, although the difference was only marginally significant (55% vs. 0%, P = 0.037). Conclusion: Because sensitivity is significantly higher, sestamibi parathyroid imaging of the neck should be performed with a pinhole collimator.

Pulmonary activity on labelled leukocyte images: Patterns of uptake and their significance

The objective of this study was to characterize, and determine the significance of, pulmonary activity on labelled leukocyte images. This retrospective review included 137 immunocompetent patients who had undergone 111In labelled autologous leukocyte chest imaging and chest X-ray within 7 days. Pulmonary activity was classified as normal, focally increased, or diffusely increased. Images were correlated with chest X-rays and final diagnoses. One hundred and twelve patients (82%) had normal pulmonary activity. Seventy-six had normal chest X-rays; none had pulmonary infection. Thirty-six patients had chest X-ray abnormalities; only one had pulmonary infection. Twenty-five patients had abnormal pulmonary activity. In 13 patients it was segmental or lobar in distribution. The chest X-ray was abnormal in 12: pneumonia (11) and cystic fibrosis (one). The chest X-ray was normal in one patient with pneumonia. Two patients with non-segmental pulmonary activity did not have pulmonary infection. The chest X-ray was abnormal in one (pulmonary edema) and normal in one (sepsis). Ten patients had diffuse pulmonary activity. Chest X-ray was abnormal in two patients: adult respiratory distress syndrome (ARDS) (one) and drug toxicity (one). No patient with diffuse pulmonary activity had pulmonary infection. In summary, negative labelled leukocyte imaging excludes pulmonary infection with a high degree of certainty (the negative predictive value was 99% in this series), and can exclude pneumonia as the cause of a chest X-ray abnormality. Focal pulmonary activity strongly suggests pneumonia, while diffuse pulmonary activity is unlikely to indicate infection.

The Evolution of Nuclear Medicine and the Musculoskeletal System

This article reviews the evolution of nuclear medicine in the evaluation of the musculoskeletal system over the past hundred years, from autoradiography and Geiger counters and rectilinear scanners to sophisticated imaging devices that provide both functional and morphological information. Initially synonymous with bone scanning, radionuclide evaluation of musculoskeletal disorders now includes gallium, labeled leukocytes, FDG, and fluourine-18, indications and applications of which are reviewed.