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(L) Page 127 to 137 Review Document Transcript

  • 1. 127 Review Nuclear Medicine imaging of infection and inflammation Part 3: Clinical applications Gnanasegaran G, Croasdale J, Buscombe JR Department of Nuclear Medicine, Royal Free Hospital, London NW3 2QG, U.K Abstract disability. This may be of particular concern in patients with diabetes where infections may be more severe and difficult Prompt localization of infection sites is essential for to treat. The diagnosis of musculoskeletal initiating appropriate therapeutic measures. There have infection/inflammation is based on clinical presentation, been major advances in the management of patients tissue culture, laboratory investigations and organ imaging. suffering from infective and/or inflammatory disorders as a Conventional radiography, ultrasound, magnetic resonance result of introduction of newer drugs with high sensitivity imaging (MRI), computed tomography (CT) and and specificity. However diagnosis of infection / radionuclide imaging procedures are selectively used to aid inflammation still remains a major clinical problem. in the diagnosi of infection and assessment of the extent of Although the typical signs of infection and inflammation bone involvement (Table-1). are useful in localizing the pathology at superficial sites, The major diagnostic difficulty in diabetic patients is infection and inflammation of internal structures are often distinguishing bone infection from non-infectious difficult to localize without the aid of imaging procedures. neuropathic bony lesion (1). Chronic infections can lead to Radionuclide imaging is an important diagnostic tool for contiguous bone infection and these infections are the evaluation of patho-physiological processes of potentially limb or life threatening. In general, imaging infection and inflammation. A spectrum of bone infection with nuclear medicine techniques is very radiopharmaceuticals and a number of imaging protocols sensitive either for whole body screening or local detection have been used in clinical practice. However every method of acute or exacerbated chronic infection/inflammation. differs in its potential to gather information at the cellular and molecular level. This review addresses some of the Osteomyelitis applications of radionuclide infection imaging procedures in musculoskeletal system, lymphatic system, in immuno- The organism most commonly responsible for compromised patients and in patients suffering from fever heamatogenous osteomyelitis is S. Aureus. Group B of unknown origin. streptococcal infection is seen more commonly in neonates Key words: Infection imaging, osteomyelitis, diabetic foot, (1, 2). Imaging techniques for the diagnosis of Fever of Unknown Origin, HIV osteomyelitis have a wide range of sensitivity, specificity and positive predictive values. Radiographic changes in World J Nuc Med 2005;4:127-137 early osteomyelitis are difficult to interpret and lag at least 2 weeks behind the time when scintigraphy becomes Introduction positive. About 90% of cases do not manifest the disease on planar X-ray until 3 to 4 weeks after the infective process In the previous article published in the October 2004 issue has set in (1). CT may show increased density within the of WJNM, we addressed the application of radionuclide marrow, but this may be difficult to appreciate. The overall infection imaging procedures in central nervous, sensitivity and specificity of MRI for the detection of acute respiratory, cardiovascular, Gastrointestinal, hepatic, osteomyelitis ranges from 92-100 %, and 89-100% hepatobiliary and genitor-urinarty systems. This part of the respectively (1, 3-9). Common nuclear medicine review will cover musculo-skeletal and lymphatic systems; techniques for the diagnosis of osteomyelitis include three as well as infection imaging in immuno-compromised or four-phase bone scans, Gallium-67 scintigraphy, patients and in patients with fever of unknown origin. radiolabeled white cell studies and leukoscan. Tc-99m MDP bone scan is highly sensitive for the diagnosis Musculoskeletal system of osteomyelitis and detects osteomyelitis 1 to 2 weeks Bone infections are complex and may result in significant before radiological changes are manifested (1) (Table 2). Three-phase bone imaging includes dynamic and static Correspondence: bone imaging (arterial, soft-tissue and cortical phases) is Dr. J.R.Buscombe MD useful. In osteomyelitis, all three phases demonstrate increased activity with the third phase showing focal uptake Consultant-Nuclear Medicine in the area of osteomyelitis (1). The 3-phase bone scan has a Royal Free Hospital reported sensitivity of 90-100% and a specificity of 70-95% London NW3 2QG, U.K for identification of osteomyelitis in non-violated bone. Email: j.buscombe@rfc.ucl.ac.uk World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 2. 128 Gnanasegaran G, Croasdale J, Buscombe JR Indications Radiopharmaceuticals Musculoskeletal system (A-E, J, K, M, R) A. Tc-99m MDP Osteomyelitis Diabetic foot B. Tc-99m HMPAO labeled leukocytes Sternal infection Prosthesis infection C. In-111 oxine labeled leukocytes Disease activity in rheumatoid arthritis D. Gallium-67 Lymphatic system (D, I) E. Tc-99m Infecton Lymph node disease in hila, mediastinum Sarcoidosis F. Tc-99m DTPA Mycobacterial Infections G. Tc-99m pyrophosphate Miscellaneous H. In-111 antimyosin antibody Pyrexia/ fever of unknown (FUO/FUO) I. F-18 flurodeoxyglucose (FDG) (B, D, I, J) 1.Intra-thoracic disease J. Tc-99m/ In-111 HIG (human immunoglobin) Bronchiectasis Malignacies-lypmphoma K. Tc-99m Nanocolloid Infectious and non-infectious granulomatous disease-Tuberculosis, sarcoidosis L. Tc-99m Colloids Pulmonary vasculitis M. Tc-99m antigranulocyte antibody (Leukoscan) 2.Intra-abdominal disease Intraabdominal sepsis-subphrenic, intra-hepatic, N. In-111 Tropolonate labeled leukocytes intra-splenic , peri-renal, Free septic fluid in the peritoneal cavity. O. Tc-99m/In-111 Liposomes 3.Soft tissue sepsis P. I-123 IL2 (Interleukin 2) (Lymphocytes) 4.Post operative fever 5.Renal disease Q. Tc-99m IL8 (Interleukin 8) (Granulocytes) Non-functioning allograft Infected current or old access grafts R. In-111 pentetreotide (Octreoscan) Infection of catheter tunnel S .Tc-99m IDA (Iminodiacetic acid) Immunodeficiency syndrome / Human T. Tc-99m DMSA(dimercaptosuccinic acid) immunodeficiency virus (HIV) U. Tc-99m HMPAO infection (D, F, J) Vascular graft rejection (B, C, D, I) Table1. Indications of infection and inflammation imaging and radiopharmaceuticals Specificity drops to about 35% in patients with from 80 to 100%) (12). In-111 labeled leukocyte imaging is complicating bone conditions such as recent fracture, very sensitive (except in some cases of chronic trauma or surgery (1, 10). osteomyelitis), specific, and the method of choice for Gallium-67 scan can be positive as early as 4 hours after the diagnosing and localizing distal appendicular skeletal onset of infection, and it is usually positive by 24 hours osteomyelitis (13). (10). Gallium imaging lacks some specificity as there can Tc-99m labeled monoclonal antibody-Fab' fragments be increased uptake in metabolically active bone and bone (LeukoScan) is useful for detecting osteomyelitis. It is marrow. A normal Gallium scan virtually excludes the reported to have high sensitivity and specificity (14) diagnosis of acute osteomyelitis with a high degree of (Figure 1). The advantage of LeukoScan is that a result can certainty (negative predictive value 90-100%) (11). be obtained in few hours (1 to 2 hours) after injection (14) In-111 labeled leukocyte imaging has a higher sensitivity and is useful in the detection of spinal infections and and specificity for the diagnosis of acute osteomyelitis than infections at sites with normal bone marrow (15). combined bone/Gallium imaging (1). Schauwecker (12) Tc-99m nanocolloids have been used in patients with reported In- 111 labeled leukocyte imaging to have a osteomyelitis with reported sensitivity ranging from 87 to sensitivity of 90-95% in acute osteomyelitis for all bones in 95% and specificity between 77 and 100% (16). the body (overall sensitivity from various studies ranges World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 3. 129 Gnanasegaran G, Croasdale J, Buscombe JR Technique Advantages Drawbacks X-ray Least expensive 30% to 50% loss of bone density must Readily available. occur before a radiograph shows abnormality. It is often difficult to gauge the extent of infection. Sensitivity to detect osteomyelitis of the diabetic foot is low. Degenerative or Inflammatory arthritis and neuropathic joints generate false- positive results. Ultrasound Non-invasive, inexpensive, easy-to-use Diagnosis of osteomyelitis is limited to and devoid of radiation. the detection of soft tissue abnormalities Evaluates soft tissues and presence of around the bone. fluid accumulation next to prosthetic implants. CT Provides high spatial resolution images Differentiation of sequestra from osteoid and explicit cortical bony details. osteomas may be problematic. Displays anatomic detail to view end- Noninfectious hemorrhage, neoplasm, plate erosions and para-vertebral masses stress fracture, and/or radiation therapies in vertebral osteomyelitis. have similar CT-detected increases in Useful in guiding bone biopsy and intramedullary density as infectious detecting very small sequestra, cortical inflammation does. abnormalities, soft tissue extension, hyper Scatter phenomenon, which occurs when attenuation and constriction of the metal is present in or near the area of medullary cavity, destruction of cortical bone infection. bone, and new bone formation. Not Cost-effective. MRI MRI displays greater resolution for soft High cost. tissue abnormalities than CT scans or Lack of universal availability. radiographs and greater anatomical detail Imaging interference caused by metal than radionuclide scans. implants, and lower resolution of MRI is a useful modality for calcified bone structures and the cortex. differentiating between bone and soft Differentiation of infection from tissue infection. Trauma, infarct, ischemia, or neoplastic Extremely useful in patients with process may be difficult. These may vertebral osteomyelitis and has a resemble osteomyelitis in MRI. sensitivity of 96% and specificity of 92% Three-phase Three-phase Tc-99m MDP scans are very High false-positive rates have occurred in Tc-99m MDP sensitive in the detection of osteomyelitis, patients with soft tissue infections such as bone scan (sensitivity of 92% and specificity of 94% the diabetic foot, decubitus ulcer in non-violated bone) infections, septic arthritis and non- Least expensive infectious Inflammatory bone disease. Readily available. False-negative bone scans occur and apparently do not correlate with the onset of disease, antibiotic therapy, causative organism, or radiographic changes. Table 2. Imaging osteomyelitis (3-9) Diabetic foot negative rods and anaerobes (18). Charcot's In patients with diabetes, osteomyelitis of the foot is a osteoarthropathy may also occur in the diabetic foot (19). It common and serious problem (17). Infections usually is important to distinguish this from other conditions, such appear in foot ulcers, which are associated with neuropathy, as osteomyelitis (19) (Figure 2). Sella et al have reported vasculopathy, and various metabolic disturbances (18). that a three-phase bone scan alone is not specific enough to Aetiologic agents are usually aerobic gram-positive cocci, distinguish between Charcot's and osteomyelitis in the mid- but chronic or serious infections often contain gram- foot (19). Additional four-phase scan or gallium does not World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 4. 130 Gnanasegaran G, Croasdale J, Buscombe JR Figure 1. Diabetic man with distal tibial osteomyelitis. SPECT bone scan shows abnormal intense focal radiotracer uptake in the distal end of left tibia (Left). On the other hand the 4 hour Tc-99m leukoscan SPECT (Right) shows concentra- tion of radiotracer at the site of infection (arrow), as well as in the cortical sequestrum (arrow) seem to improve specificity significantly (19). Combined Prosthesis infection leukocyte scans and sulfur colloid marrow scans have been Infection around hip and knee arthroplasties is a major reported to improve the specificity and distinguish problem in orthopaedic surgery (21). The presence of Charcot's from osteomyelitis. Sella et al have reported that, infection changes the management drastically (21). combined leukocyte scans and bone marrow imaging are Generally, the causes for pain in hip prosthesis are the gold standard for evaluating the diabetic foot infection mechanical and biological (21). The mechanical causes and distinguishing it from osteoarthropathy (19). However, include the distal load transfer and the periprostheic bone other groups working in this area have not confirmed these resorption (21). The biological causes include aseptic finding. Although, X-ray is less sensitive than other loosening (polyethylene debris reaction) and septic imaging modalities it should be used as the initial loosening (infection) (21). Radionuclide imaging plays a diagnostic procedure in suspected osteomyelitis in the very valuable role in detecting infection around hip and diabetic patients as it may show morphological changes, knee arthroplasties. The three-phase Tc-99m MDP bone which may explain some of the nonspecific abnormalities scan has a high sensitivity but low specificity. However, a on the radionuclide studies (20). normal study is a strong indicator against prosthetic Figure 2. Tc-99m HIG scan in a patient of diabetes with osteomyelitis of right foot. Please note intense radiotracer uptake in the lesion. World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 5. 131 Gnanasegaran G, Croasdale J, Buscombe JR prosthesis. The sensitivity and specificity of Tc-99m/In-111 labeled leukocytes are reported to be high (Figure 3). The published results on the accuracy of radiolabelled leukocytes are variable. The interpretation of radiolabelled leukocyte images entails a comparison of uptake/activity in the region of interest to activity/uptake in some reference points. Increased activity compared to the reference point is interpreted as positive for infection (22-30). The combination of Tc-99m MDP with Tc-99m /In-111 labeled leukocytes improves the diagnostic efficacy (23, 31). Radiolabelled leukocytes may also accumulate in the bone marrow, which remains around any prosthesis, often presenting as small islands of activity, which could be mis- read as focal infection. This can be overcome by bone marrow imaging with sulphur colloid (22). Both radiolabeled leukocytes and sulphur colloid accumulate in the bone marrow, but only radiolabeled leukocytes accumulate at the site of infection (22). Therefore if the distribution of the two agents is congruent, infection is less likely than if it is non-congruent, with labeled white cells being present but no bone marrow activity on the marrow abnormality. The overall reported accuracy of a Tc-99m scan. The reported accuracy of combined MDP bone scan in the evaluation of a painful prosthetic leukocyte/marrow imaging is about 90% (22, 32). joint is only about 50-70% (22). The reason for this could be Orthopaedic infection can also be successfully imaged with because of variable patterns in the peri-prosthetic uptake. Tc-99m antigranulocyte antibody Fab' fragments There are different types of prosthesis, which have not been (Leukoscan). LeukoScan is reported to have a high studied in detail in terms of normal evolution of peri- sensitivity in diagnosing bone infection in patients with prosthetic uptake patterns (23). diabetic foot and joint prosthesis or other peripheral bone Sequential bone and gallium imaging has also been used to implants (33). In our experience SPECT improves both the evaluate painful joint prosthesis. The overall reported visualization and localization of infection around the accuracy of this technique is about 70-80% (22) (Table 3). prosthetic knee. Gallium uptake in general is related to inflammation and Current data also indicate that Tc-99m ciprofloxacin is a not to infection. So this technique is not suited for useful method for imaging hip prosthesis infection (34). differentiating infection and inflammation (24). Tc-99m ciprofloxacin imaging showed diagnostic Radiolabelled leukocytes are useful for imaging the joint sensitivity of 86% and a specificity of 78% for correctly classifying the presence of infection in patients with knee Tracers Sensitivity Specificity 67 Ga/bone 66 % 81% 99m Tc-nanocolloid 100% 82% 111 In-HIG 100% 100% 111 In-leukocyte/bone 88% 95% 111 In-leukocyte/marrow 100% 97% 99m Tc-leukocyte 97% 89% 99m Tc-LeukoScan 85% 77% 99m Tc-ciprofloxacin 92% 91% Table 3 Sensitivity and specificity of various radiopharmaceuticals in knee and hip prosthesis imaging (22,25-31,34,35) Diagnosis Gallium-67 Thallium-201 Pulmonary infection Positive Negative Kaposi's sarcoma Negative Positive Mycobacterial infection Strongly positive Weakly positive Table 4 . Patterns of uptake in lungs in patients with AIDS (60) World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 6. 132 Gnanasegaran G, Croasdale J, Buscombe JR Figure 4. A classical Ga-67 citrate scan in a patient suffering from sarcoidosis, anterior (left) and posterior (right) views showing lacrimal, nasal and parotid uptake (Panda sign), mediastinal and hilar lyphadanopathy (lambda sign). In addition there is also uptake in the groin lymph nodes. prosthesis (34, 35). (38). Although these scans are sensitive, it is difficult to Reports suggest that F-18 FDG is useful in detecting delineate the joint structures. This could be improved by infected joint prosthesis. However, in spite of high performing a SPECT study of the joint. In-111 labeled sensitivity, it cannot differentiate aseptic loosening from leukocyte scan is reported to be positive in 60% of cases infection (22, 36, 37). (38). False-positive results occur in patients with synovitis Sternal infection secondary to active osteoarthritis (38). Sternal split for cardiac surgery (coronary artery bypass graft) is usually the cause of fever. The incidence of strenal Rheumatoid arthritis infection ranges from 0.4% to 8-9% and with complications Rheumatoid arthritis is an autoimmune disease that causes such as mediastinitis the mortality is reported to be high chronic inflammation of the joints. Traditional method of (23). It is important to distinguish superficial and deep- monitoring the joint disease of patients with rheumatoid seated sternal wound infection (23). Radiolabelled arthritis is x-rays. MRI has been found to be sensitive as an leukocyte imaging is reported to be useful in these indicator of early rheumatoid joint destruction, but it is very infections (23). expensive. Tc-99m MDP bone scans are very sensitive in Septic arthritis detecting reactive bone oedema associated with Septic arthritis is infection of a joint. It is commonly due to osteoarthritis. Differentiation of a septic arthritis from a pyogenic organisms. Large joints such as the hip and knee non-infectious synovial inflammation is not possible by are most usually involved (38). Radionuclide scans are scintigraphy. Tc-99m MDP will demonstrate increased reported to be of limited use in patients with septic arthritis tracer activity at the sites of inflammation. Gallium-67 and (38). However, reports suggest that Gallium-67 and In-111 In-111 labeled leukocytes will also accumulate at these labeled scans can be used to localize the sites of infection sites of inflammation. World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 7. 133 Gnanasegaran G, Croasdale J, Buscombe JR predictive value for the detection of bone and joint infection, it may not always discriminate between infected and aseptic osteoarticular diseases in symptomatic patients referred for surgery (41). Appelboom et al reported that Infectonscans could be an additional method of imagingthe inflammatory synovial process in arthritis (42). It is also reported that In-111 pentetreotide accumulates at the inflammatory sites and could be useful in imaging arthritis (43). Further studies are necessary. The use of PET scans with C-11 choline is reported to be a promising tracer for quantitative imaging of proliferative arthritis changes (44). But further evaluation is necessary and this technique is expensive. Vascular graft rejection/infection Vascular graft infection is a common and serious complication of reconstructive surgery. It is reported to occur in 2% of patients (45). The successful management of vascular graft infection depends on correct diagnosis and evaluation of the extent (46). Various radiopharmaceuticals are used in imaging vascular graft infections (Gallium- 67/Tc-99m HMPAO labeled leukocytes, In-111 oxine Figure 5. Tc-99m leukoscan in a patient with fever of unknown origin. Posterior view. Note a small area of increased focal uptake near the spleen, which turned out to be a psoas abscess. On a 3-phase bone scan the inflamed joint will demonstrate diffusely increased flow and blood pool activity. Delayed images usually demonstrate increased activity within the bone on either side of the joint. However, Tc-99m MDP bone scan is of limited value in the evaluation of juvenile rheumatoid arthritis. The prominent uptake of tracer within the growth plates often obscures increased peri-articular tracer uptake, especially in small joints. Tc-99m polyclonal immunoglobulin-G has been shown to be a successful agent in the depiction of active inflammation in rheumatoid arthritis (RA). The detection rate of active joint inflammation with Tc-99m HIG is reported to be much higher than that with Tc-99m MDP (39). However, it is not the method that should be applied in all patients. Tc-99m IgG-scintigarphy is well suited for follow-up of patients under treatment with persistent complaints (40). Though Tc-99m Ciprofloxacin (Infecton) scintigraphy is Figure 6. Ga-67 citrate scan in a patient with AIDS and reported to have good sensitivity and a high negative pneumocystis carinii pneumonia, showing intense lung uptake. World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 8. 134 Gnanasegaran G, Croasdale J, Buscombe JR labeled leukocytes, Tc-99m/ In-111 HIG and In-111/Tc-99m labeled leukocytes are useful to identify antigranulocyte monoclonal antibody). Delgado et al. occult infections. The probability of successful reported that the radiolabeled leukocyte scan is more useful localization using a radiolabeled leukocyte scan is higher if than Tc-99m HIG (47). According to Prats et al, Tc-99m the clinical scenario is pointing towards a pyogenic HMPAO labeled leukocytes is the radiopharmaceutical of infection. Successful imaging with radiolabeled leukocytes choice for the evaluation of vascular grafts. Tc-99m requires an inflammatory process involving neutrophils HMPAO labeled leukocytes have an overall sensitivity and predominantly (56). However, most cases of FUO may specificity greater than 85-90% (45,48). The commonly have lesions with predominant monocytic or lymphocytic advocated protocol is to image the vascular (Flow) phase, infiltrations, which are unlikely to give a positive scan with 5-minute, 30 minute, and 3 hour over the region of interest. In-111/Tc-99m labeled leukocytes (56). However occult Whole body images should also be acquired at 3 hours and infection may also be associated with neutrophilic occasionally 24-hour images are helpful (45,49-51). The infiltration. (56). Reports suggest that pure neutrophils and common causes for false positive of Tc-99m HMPAO mixed leukocytes perform equally well in FUO (57). There labeled leukocyte scans are perigraft haematoma, graft is also an ongoing debate as to which radionuclide to use. In thrombosis, bleeding, pseudo aneurysms and scans general Tc-99m has many useful characteristics of an ideal performed in the first days after surgery (45,49-51). agent but could be less useful in FUO, the reason being that, undiagnosed fevers are usually low grade and chronic in Lymphatic system nature, which would call for a delayed imaging at 24-48 hours. Tc-99m has a shorter half-life with decreased The major parts of the lymphatic system are the bone stability in labeled cells and non-specific bowel activity marrow, spleen, thymus, lymph nodes and the tonsils. Other limits its use at 24 hours (58). organs like lungs, intestines, liver and skin also contain Tc-99m HIG is also used to investigate undiagnosed fever lymphatic tissue. The lymphatic system branches through since it is a marker of increased endothelial permeability most of the parts of the body; it can be involved in a wide and accumulates at sites of pathology as a result of non- range of conditions. Lymphadenopathy might be the result specific leakage into the interstitial space (56). However, of an infection and swelling of the lymph nodes can be due more studies with comparison with other agents are to an infiltration of cancerous cells. Generalized warranted. Antibodies such as Tc-99m Leukoscan have a lymphadenopathy usually indicates systemic disease. less defined role at present (Figure 5). Lymph node disease There has been some indication that PET may be of use in Lymph node disease in hila of lungs and mediastinum may this patient group, but at present there is very little represent reactive changes due to infection within the lung consistent evidence to show that PET, at least using F-18 or from other granulomatous disease (Sarcoid, FDG, will be of great value in such patients, though there Mycobacterial Infections) (52). Radionuclides like are a few anecdotal evidence of efficacy (54). Gallium-67 and F-18 FDG can be used in the assessment of lymphadenopathy (Figure 4). A combination of Gallium-67 Immunodeficiency syndrome / Human and Thallium-201 is used to differentiate between the immunodeficiency virus (HIV) infection inflammatory and malignant nature of lymphadenopathy (52). Most recently work with F-18 FDG PET has These patients may have an increased exposure to invasion suggested that this technique can also be used to monitor the by many organisms, which would normally, only colonise progression of viral disease with both HIV and flu virus those patients who have normal immunity. It may be (53-55). possible for them to have more than one infection and as the host's immune response is reduced to present with Fever of unknown (FUO) attenuated clinical symptoms. The causes of the patient's immunosupression may be congenital, due to drugs, either Pyrexia of unknown origin is described as fever lasting at chemotherapy or anti-transplant rejection drugs or due to least 28 days with 7 days of in-patient investigations infection such as HIV. It is not unusual for patients to suffer failing to find the causative agent. unusual infections not seen in normal patients, for example Gallium-67, In-111/Tc-99m labeled leukocytes and pulmonary infection with Pnemocystitis carinii (PCP) polyclonal HIG are the most commonly used agents for remains a major cause of death and morbidity in patients detection of FUO (30). Gallium-67 is reported to be the with AIDS (59). agent of choice in FUO and occult infection greater than 2 Gallium-67 citrate scanning of the chest was recognized as weeks (56). Gallium-67 is not used to make a diagnosis, but a more sensitive means of detecting PCP than plain chest to localize the site, which can then be further investigated radiographs before the advent of AIDS (Figure 6) (Table 4). by conventional modalities like CT/MRI. Increased Kramer et al reported high sensitivity of 98 % for Gallium- Gallium-67 uptake in seen in both infectious and 67 scanning for detection of PCP. Reports suggest that inflammatory conditions (pyogenic abscess, tuberculosis, specificity for PCP is increased in patients with scans sarcoidosis and vasculitis). Diagnosing abdominal showing diffuse uptake of Gallium-67 particularly when pathology with Gallium-67 could be difficult due to non- the pattern is heterogeneous (60-63). Localization of specific bowel activity. Gallium-67 uptake is also useful in directing the World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
  • 9. 135 Gnanasegaran G, Croasdale J, Buscombe JR bronchoscopy for transbronchial biopsy leading to a with additional bone marrow imaging provides the best diagnosis of PCP. In cases with very intense heterogeneous method for localizing disease. In patients with fever of uptake of Ga-67 throughout the lungs and a negative chest unknown origin Gallium-67 is still the first choice, though X-ray, one should have a high suspicion for PCP. PET may have more use in the future. In most of these Lung Tc-99m DTPA transfer/permeability has been widely patients nuclear medicine provides both unique and used to assess the integrity of the lung alveolar-capillary clinically useful information. interface (52,64). Pneumocystis carinii pneumonia (PCP) is the most common cause of pneumonia in HIV antibody Acknowledgements positive patients. The presence of a biphasic, rapid transfer Dr. Gopinath Gnanasegaran was funded by the Special curve indicates severe extensive alveolar damage and is Trustees of the Royal Free Hospital, London, United seen in PCP or legionella pneumonia (65). Tc-99m DTPA Kingdom. transfer/permeability measurement is a rapid, easy method of evaluating patients with HIV disease (52,64). Polyclonal human immunoglobulin (HIG) is a non-specific agent. Tc-99m HIG has been used to image patients with References AIDS and it was found to be inferior to Gallium in imaging chest and abdomen (66). This was thought to be due to 1. Wegener WA, Alavi A. Diagnostic imaging of increased blood pool, which was found to be significant musculoskeletal infection. Roentgenography; gallium, even at 24 hours post injection (66). In direct comparison indium-labeled white blood cell, gammaglobulin, bone with Ga-67 in 25 patients with AIDS presenting with fever scintigraphy; and MRI. Orthop Clin North Am. 1991; the sensitivity of Tc-99m HIG was only 55% and 8 positive 22(3):401-18. Review sites detected by Ga-67 was found to be negative with Tc- 2. Shirtliff ME, Mader JT. Acute septic arthritis. Clin 99m HIG (66). Microbiol Rev 2002; 15(4):527-44 In-111 labeled leukocytes may be used for the detection of 3. Shirtliff ME, Mader JT. Current Treatment Options in pulmonary infections or inflammatory conditions in AIDS. Infectious Diseases 2003; 5:323335, Current Science Ga-67 citrate, however, is more sensitive (100%) for Inc.ISSN 1523-3820 diffuse processes showing greater uptake than In-111 4. Butt WP. The radiology of infection. Clin Orthop 1973, labeled leukocytes (sensitivity 40%) in patients with PCP 96:2030. (67). Goldenberg et al reported a sensitivity of 85 % and 5. Cardinal E, Bureau NJ, Aubin B, Chhem RK. Role of specificity of 86.7% for PCP using a Tc-99m labeled Fab ultrasound in musculoskeletal infections. Radiol Clin fragment of a murine monoclonal antibody to PCP (68). In North Am 2001, 39:191201. general, radionuclide techniques are sensitive for the 6. Tehranzadeh J, Wong E, Wang F, Sadighpour M. detection of PCP, especially Ga-67 scans; however, they Imaging of osteomyelitis in the mature skeleton. Radiol lack in specificity for PCP. Clin North Am 2001, 39:223250. Patients with HIV could suffer from a dementia type illness 7. Modic MT, Feiglin DH, Piraino DW et al. Vertebral related to low-grade encephalopathy (HIV osteomyelitis: assessment using MR. Radiology 1985, encephalopathy). Cerebral perfusion studies with Tc-99m 157:157166. HMPAO (SPECT) and F-18 FDG are reported to be useful 8. Erdman WA, Tamburro F, Jayson HT et al. (69). With both these agents a marked reduction of cerebral Osteomyelitis: characteristics and pitfalls of diagnosis perfusion is seen in the medial temporal lobes, followed by with MR imaging. 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Osteomyelitis of the foot in diabetic Conclusion patients. Clin Infect Dis. 1997; 25: 1318-26. 13. Al-Sheikh W, Sfakianakis GN, Mnaymneh W et al. In bone and joint diseases radionuclide imaging remains as Subacute and chronic bone infections: diagnosis using an effective and accurate method of diagnosis. The use of In-111, Ga-67 and Tc-99m MDP bone scintigraphy, and three-phase bone scans followed by a specific infection radiography. Radiology 1985; 155: 501-506 imaging study enables most patients to be correctly 14. Von Rothenburg T, Schaffstein J, Ludwig J, Vehling D, diagnosed. In the suspected prosthetic joint the use of Koster O, Schmid G. Imaging osteomyelitis with Tc- radiolabeled leukocytes, Infecton and leukoscan, possibly 99m-labeled antigranulocyte antibody Fab' fragments. World Journal of Nuclear Medicine, Volume 4, Number 2, April 2005
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