Elena Lazzeri

Added Value of 99mTc-HMPAO–Labeled Leukocyte SPECT/CT in the Characterization and Management of Patients with Infectious Endocarditis

The clinical performance of the Duke Endocarditis Service criteria to establish the diagnosis of infectious endocarditis (IE) can be improved through functional imaging procedures such as radiolabeled leukocytes (99mTc-hexamethylpropyleneamine oxime [HMPAO]–labeled white blood cells [WBC]). Methods: We assessed the value of 99mTc-HMPAO-WBC scintigraphy including SPECT/CT acquisitions in a series of 131 consecutive patients with suspected IE. Patients with permanent cardiac devices were excluded. 99mTc-HMPAO-WBC scintigraphy results were correlated with transthoracic or transesophageal echocardiography, blood cultures, and the Duke criteria. Results: Scintigraphy was true-positive in 46 of 51 and false-negative in 5 of 51 cases (90% sensitivity, 94% negative predictive value, and 100% specificity and positive predictive value). No false-positive results were found, even in patients with early IE evaluated within the first 2 mo from the surgical procedure. In 24 of 51 patients with IE, we also found extracardiac uptake, indicating septic embolism in 21 of 24. Despite the fact that septic embolism was found in 11 of 18 cases of Duke-definite IE, most of the added value from the 99mTc-HMPAO-WBC scan for decision making was seen in patients in whom the Duke criteria yielded possible IE. The scan was particularly valuable in patients with negative or difficult-to-interpret echocardiographic findings because it correctly classified 11 of 88 of these patients as having IE. Furthermore, 3 patients were falsely positive at echocardiography but correctly negative at 99mTc-HMPAO-WBC scintigraphy: these patients had marantic vegetations. Conclusion: Our results demonstrate the ability of 99mTc-HMPAO-WBC scintigraphy to reduce the rate of misdiagnosed cases of IE when combined with standard diagnostic tests in several situations: when clinical suspicion is high but echocardiographic findings are inconclusive; when there is a need for differential diagnosis between septic and sterile vegetations detected at echocardiography; when echocardiographic, laboratory, and clinical data are contradictory; and when valve involvement (especially of a prosthetic valve) needs to be excluded during febrile episodes, sepsis, or postsurgical infections.

Nuclear medicine imaging of bone infections.

The inflammation and infection of bone include a wide range of processes that can result in a reduction of function or in the complete inability of patients. Apart from the inflammation, infection is sustained by pyogenic microorganisms and results mostly in massive destruction of bones and joints. The treatment of osteomyelitis requires long and expensive medical therapies and, sometimes, surgical resection for debridement of necrotic bone or to consolidate or substitute the compromised bones and joints. Radiographs and bone cultures are the mainstays for the diagnosis but often are useless in the diagnosis of activity or relapse of infection in the lengthy management of these patients. Imaging with radiopharmaceuticals, computed tomography and magnetic resonance are also used to study secondary and chronic infections and their diffusion to soft or deep tissues. The diagnosis is quite easy in acute osteomyelitis of long bones when the structure of bone is still intact. But most cases of osteomyelitis are subacute or chronic at the onset or become chronic during their evolution because of the frequent resistance to antibiotics. In chronic osteomyelitis the structure of bones is altered by fractures, surgical interventions and as a result of bone reabsorption produced by the infection. Metallic implants and prostheses produce artefacts both in computed tomography and magnetic resonance images, and radionuclide studies should be essential in these cases. Vertebral osteomyelitis is a specific entity that can be correctly diagnosed by computed tomography or magnetic resonance imaging at the onset of symptoms but only with radionuclide imaging is it possible to assess the activity of the disease after surgical stabilization or medical therapy. The lack of comparative studies showing the accuracy of each radiopharmaceutical for the study of bone infection does not allow the best nuclear medicine techniques to be chosen in an evidence-based manner. To this end we performed a meta-analysis of peer reviewed articles published between 1984 and 2004 describing the use of nuclear medicine imaging for the study of the most frequent causes of bone infections, including prosthetic joint, peripheric post-traumatic bone infections, vertebral and sternal infections. Guidelines for the choice of the optimal radiopharmaceuticals to be used in each clinical condition and for different aims is provided.

Osteomyelitis: clinical update for practical guidelines.

Bone infections represent a diagnostic or therapeutic challenge for the infectivologist, orthopaedic surgeon, radiologist and nuclear medicine physician. Staphylococcus aureus is the major bacterium responsible for bone infections although Mycobacterium tuberculosis is emerging as an infectious agent in Italy because of immigration from Africa and Asia. Osteomyelitis requires long and expensive antibiotic treatment, including rifampicin administered parenterally for several weeks and the use of antimicrobial-impregnated cement in prosthesis substitution. Sometimes it is necessary to carry out surgical debridement of a necrotic bone or the consolidation of compromised bones and joint prosthesis implants. Radiographs and bone cultures are mainstays for the diagnosis of bone infections but are often useless in the lengthy management of these patients. Diagnosis of skeletal infections still includes conventional radiography but magnetic resonance imaging is essential in haematogenous and spinal infections. Bone scans are still useful in acute osteomyelitis whereas scintigraphy using labelled white blood cells is preferred in infections of peripheral bone segments or joint prosthesis. In the axial skeleton a combination of an agent for detecting inflammation (67Ga citrate) and a metabolic agent (99mTc-methylene diphosphonate) enables an infection and an area of increased metabolic activity to be distinguished. [18F]Fluorodeoxyglucose positron emission tomography, where available, has a significant impact in the study of infections using radionuclides: high-resolution tomographic images represent an effective alternative to gallium in the assessment of inflammation of spine lesions but a comparison with morphological examinations (computed tomography or magnetic resonance imaging) is essential.

FDG-PET in Cardiac Infections

Cardiac infections include a group of conditions involving the heart muscle, the pericardium, or the endocardial surface of the heart. Infections can extend to prosthetic material or the leads in case of the implantation of devices. Despite their relative low incidence, these conditions that are associated with high morbidity and mortality involve a relevant burden of diagnostic workup. Early diagnosis is crucial for adequate management of patient, as early treatment improves the prognosis; unfortunately, the clinical manifestations are often nonspecific. Accurate and timely diagnosis typically requires the correlation of imaging findings with laboratory data. (18)F-FDG-PET is a well-established imaging modality for the diagnosis and management of malignancies, and evidence is also increasing regarding its value for assessing infectious and inflammatory diseases. This article summarizes published evidence on the usefulness of (18)F-FDG-PET for the diagnosis of cardiac infections, mainly focused on endocarditis and cardiovascular device infections. Nevertheless, the diagnostic potential of (18)F-FDG-PET in patients with pericarditis and myocarditis is also briefly reviewed, considering the most likely future advances and new perspectives that the use of PET/magnetic resonance would open in the diagnosis of such conditions.

Scintigraphic imaging of vertebral osteomyelitis with 111in-biotin.

Study Design. Early diagnosis of vertebral infection (hematogenous or postsurgical) is necessary to choose a correct therapy and to minimize dramatic complications. All patients suspected to have vertebral infection underwent radiologic imaging and 111In-Biotin scintigraphy. Objective. Biotin is a growth factor used by many bacteria. The aim of our study is to use 111In-Biotin to diagnose vertebral infections. Summary of Background Data. Magnetic resonance imaging, even if endowed with fairly good sensitivity and specificity, shows some limitations in the study of the onset of pathology and in postsurgical conditions. Conventional scintigraphic imaging, like bone scintigraphy with 99mTc-MDP, 67Ga-citrate scintigraphy, or Positron Emission Tomography with [18F]FDG, are limited by relatively low specificity; the use of Streptavidin/111In-Biotin scintigraphy, based on aspecific uptake of tracer in the site of infection, shows good results in term of sensibility and specificity but the use of heterologous protein might engender immunogenic reactions. Methods. All patients (pts) (n = 110) of the study underwent 111In-biotin scintigraphy 2 hours after intravenous injection of the tracer, 71 pts were suspected to have hematogenous vertebral infection (Group I) and 39 pts were suspected to have postsurgical infection (Group II). The reference for final diagnosis was either bacterial cultures, histopathologic analysis, and/or clinical/imaging follow-up for at least 1 year. Results. 111In-biotin scintigraphy showed a sensitivity of 84% and specificity of 98% in Group I and a sensitivity of 100% and specificity of 84% in Group II. Conclusion. Our results showed that 111In-Biotin scintigraphy possess high diagnostic accuracy. This technique is easy to perform and requires short imaging time-point after intravenous tracer injection. Moreover if 111In-Biotin uptake is due only to high proliferation rate of bacteria presents in site of infection, it will be further investigated to discriminate definitely bacterial from sterile inflammation.

Adrenal Masses in Patients With Cancer: PET/CT Characterization With Combined CT Histogram and Standardized Uptake Value PET Analysis

OBJECTIVE Our purpose was to determine the diagnostic performance of 18F-FDG PET/CT for characterizing adrenal masses in patients with cancer, combining standardized uptake value (SUV) and CT histogram analysis. MATERIALS AND METHODS A total of 117 adrenal masses in 93 patients with cancer (61 men and 32 women; mean [± SD] age, 67.2 ± 10.3 years; range, 38-84 years) were evaluated with FDG PET/CT. Of the 117 lesions, 42 were malignant according to histopathologic analysis or size change, whereas 75 were benign on the basis of stability for 6 months. Size, mean attenuation value, percentage of negative pixels at CT histogram analysis, maximum SUV (SUV(max)), and average SUV were calculated for each adrenal lesion. Moreover, FDG adrenal uptake was compared with radioactivity of the aorta, liver, and spleen by calculating the SUV ratios of adrenal lesion to aorta, adrenal lesion to liver, and adrenal lesion to spleen. PET/CT value was assessed by using independent t tests and receiving operating characteristic (ROC) analysis. RESULTS There was a statistically significant difference in size, attenuation value, percentage of negative pixels, and SUV between benign and malignant masses. All malignant lesions showed FDG activity higher than that in liver, spleen, and aorta, with SUV(max) greater than 2.8 in all cases, whereas with the CT histogram analysis, all lesions with a percentage of negative pixels higher than 10% were benign. Combined SUV and CT histogram analysis yielded 100% sensitivity, 97.3% specificity, 95.7% positive predictive value, and 100% negative predictive value. At ROC analysis, combined SUV and CT histogram analysis (area under the ROC curve [AUC], 0.996) was more accurate than simple SUV(max) analysis (AUC, 0.961) and the combination of SUV(max) and attenuation value (AUC, 0.987). CONCLUSION The combination of SUV and CT histogram analysis allowed us to significantly improve the PET/CT diagnostic accuracy for characterizing adrenal lesions, leading to a significant reduction in the number of false-positive cases.

Trocar site tumor recurrences. May pneumoperitoneum be responsible

AbstractBackground: Port site metastasis following laparoscopy for cancer is reported with increasing frequency and represents one of the most important limitations of the technique. Methods: A scintigraphic model was utilized to evaluate a possible role of pneumoperitoneum in tumor cell dissemination. Labeled red blood cells (RBC) were injected at the level of the gallbladder bed during laparoscopic cholecystectomy (LC) performed for symptomatic cholecystolithiasis. LC was performed in two groups with standard CO2 pneumoperitoneum: in one group an endobag for retrieval of the specimen was utilized. In one group a gasless LC with endobag was performed. Results: Radioactivity in the area of the trocar introduction was observed in almost all the patients who underwent standard (CO2) LC but represented a rare event in patients treated with the gasless method. The utilization of a protective bag for the extraction of the surgical specimen did not modify significantly the results. Moreover all patients treated with pneumoperitoneum demonstrated a wide intraperitoneal diffusion of the tracer not observed in gasless patients. Conclusions: The results of this study confirm that pneumoperitoneum may play an important role in the evolution of port site metastasis after laparoscopy for gastrointestinal cancer.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease

BackgroundThe incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves.Methods and ResultsForty-five consecutive patients (33 men and 12 women; 53±6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis >50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamonds algorithm) was low (45.6%±12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3%±10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4%±4.3% (p<0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3%±5.5% (p<0.003), a level that appeared significantly higher than that of model 2 (p<0.016).ConclusionBoth noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

Can we produce an image of bacteria with radiopharmaceuticals

Bacterial infection is nowadays one of the major causes of morbidity and mortality not only in developing countries but globally. Tuberculosis and multi-drug resistant bacteria are increasing and challenge the diagnostic approaches, the therapeutic schemes and the control of infection. Early diagnosis of infection and capacity to distinguish between bacterial and sterile inflammation is very important to efficiently treat patients and prevent the complications of pathology. Most infections are diagnosed by clinical history, physical examination, laboratory tests, identification of pathogens in body fluids and biopsies and by imaging techniques. There is a substantial difference in the use of non-nuclear medicine imaging techniques and the use of radionuclide techniques. The anatomical imaging techniques such as plain radiography, ultrasonography and computed tomography are sensitive mainly in chronic stages of infection when there are significant anatomical changes. The detection of infection by nuclear medicine techniques relies on the physiological and biochemical changes at the site of lesions, which manifest much prior to the appearance of the anatomical changes. Nuclear medicine has therefore contributed in the last years in the development of several radiopharmaceuticals, used like non-invasive tools, to discriminate between infection and sterile inflammation. However, none of these are “infection specific” because sensitivity and specificity can differ according to the type of infection, to the type of micro-organism, to the infection site and to the host clinical conditions/response. The number of micro-organisms available for targeting seems to be a major discriminating factor for nuclear medicine techniques. The paper by Akhtar and colleagues [1], published in this issue of the journal, describes the relation between bacterial number and 99mTc-UBI 29–41 uptake in mice. This provides important information about the specificity of this radiopharmaceutical but disappointingly evidences that it is difficult to discriminate between 2 × 104 and 2 × 106 bacteria, in this model, and it is probably difficult to image less than 2 × 104 bacteria, at least in a mouse. The question, therefore, arises about the minimum number of bacteria that can be detected in vivo, this being a relevant question to answer before routine clinical application of bacterial imaging in man.

Clinical impact of SPECT/CT with In-111 biotin on the management of patients with suspected spine infection.

Purpose: Early identification and localization of spine infection is necessary for adequate therapeutic strategy. To localize the precise site of infection we evaluated In-111 Biotin SPECT/CT versus planar and SPECT imaging. Methods: Seventy-two consecutive patients were enrolled and underwent SPECT/CT and planar imaging 2 to 4 hours post i.v. injection of In-111 Biotin. Final diagnosis was based on bacterial cultures and/or clinical/imaging follow-up for at least 1 year. We evaluated the diagnostic performance of planar, SPECT, and SPECT/CT In-111 Biotin scintigraphy. Results: In-111 Biotin SPECT/CT and SPECT showed similar values of sensitivity (93.5% vs. 92.1%) and the same specificity (92.3%), planar imaging showed 80.4% of sensitivity and 69.2% of specificity. In 16 patients SPECT/CT correctly localized the infection site (bone, soft tissue, or both bone and soft tissue). Conclusions: SPECT/CT enhances the impact of In-111 Biotin scintigraphy on the clinical management of patients, allowing the exact site of infection to be localized to select the appropriate therapy.