**7. Brief considerations and limitations regarding anatomic imaging modalities**

Radiograph or plain films are almost always the initial imaging study for diagnosing and assessing osteomyelitis. Finding on plain films to suggest or support infectious process include periosteal elevation or thickening, cortical thickening, irregularity with loss of trabecular architecture, sclerosis, osteolysis, and new bone formation. It is however important to note that these changes may not be evident at least until 5-7 days in children and 10-14 days in adults. Plain films show lytic changes only after at least 50%-75% of the bone matrix is destroyed.

Ultra-sonography is mostly utilized in evaluation and diagnosing of fluid collections, involvement of the periosteum, along with assessing surrounding soft tissue abnormalities. It may provide guidance for diagnostic or therapeutic aspirations, subsequent drainage and/or tissue biopsy.

Anatomic imaging modalities including CT and MR imaging provide excellent structural resolution for the detection and characterization of infectious or inflammatory conditions. These provide a high-quality assessment of infection related structural abnormalities. However, the limitation is that these techniques rely solely on structural changes and,

Radionuclide Infection Imaging: Conventional to Hybrid 93

antimicrobial peptides, fluconazole and chitin targeting agents that have been studied to image fungal infection in mice. There is a limitation of difficulty in differentiating bacterial and fungal infections. However, radiolabelled fluconazole has the ability to distinguish

Tc-99m ubiquicidin (Tc-99m UBI29-41), Tc-99m labelled lactoferrin (hLF1-11), Tc-99m fluconazole and I-123 labelled chitinase are being further studied at the moment. Tc-99m UBI29-41 was clinically tested in trial setting as human infection imaging agent (Akhtar et al., 2005) with promising results. They suggested an optimal imaging time of 30 minutes post injection for this agent. Another team (Salber et al., 2008) assessed and compared Tc-99m ubiquicidin and F-18 ubiquicidin autoradiography to anti-Staphylococcus aureus immunofluorescence in rat muscles abscesses. However, most recently, (Assadi et al., 2011) assessed the diagnostic accuracy of Tc-99m UBI29-41 scintigraphy for osteomyelitis making a comparison to Tc-99m MDP Bone scan and MR imaging. The authors concluded that for fast imaging with high accuracy, Tc-99m UBI29-41 is suitable for detection of osteomyelitis. In this most recent study the accuracy for Tc-99m UBI29-41 for detection of infection was observed to be 100% as compared to 90% for Tc-99m MDP bone scan. MR imaging was done in more than half of these cases and showed an accuracy of 75% for detecting osteomyelitis. Further in another most recent preliminary study by (Nazari et al., 2011) evaluated the role and ability of Tc-99m UBI29-41 to assess response to antibiotic therapy in orthopedic infections with quantitative analysis. With these recent encouraging reports, Tc-99m UBI29-

N-formyl products (fMLF or fMLP) labelled with Tc-99m are also being studied in rabbits for localization of infection. Tc-99m labelled Interleukin-8 (IL-8) seems another promising agent for the future as after initial animal model experiments it has been tried in humans

Radionuclide imaging plays a significant role in infection detection and localization. Currently the selection of infection imaging agent depends upon the availability and local expertise especially in cases of labelling leukocytes which require time consuming labelling procedures. SPECT-CT provides essential anatomical localization especially in cases of vertebral osteomyelitis, diabetic foot, and infected prosthesis, cardiovascular, abdominal and pulmonary infections. Gallium scintigraphy can be replaced with FDG PET where available. FDG PET is a preferred procedure of choice for pyrexia of unknown origin, vasculitis, sarcoidosis, infected grafts and inflammatory bowel disease, moreover quantitative FDG PET analysis appears another promising further advance. Finally, with the progress in hybrid imaging the diagnostic power of conventional scintigraphy in detection and localization of infection has greatly augmented and the development of newer infection

The authors would like to acknowledge and thank Dr AbdulRedha A. Esmail and Dr Fahad Marafi for their contribution of the PET/CT images. We would also like to extend our thanks to our colleagues and staff of Departments of Nuclear Medicine and PET Unit, Al-

Jahra Hospital and Kuwait Cancer Control Centre for their help and contribution.

seeking agents pave the way for improved patient management in future.

Candida albicans infection from bacterial infections/sterile inflammation.

41 seems a novel agent of the future for infection imaging.

with promising initial results.

**10. Acknowledgment** 

**9. Conclusion** 

therefore, differentiation between active and structural but indolent alterations following surgery or other interventions is difficult to differentiate and these modalities are generally of limited value in detecting early disease regardless of the cause. In evaluation of infectious process CT scans may assist in the assessment of disruption of the bony cortex and softtissue involvement. Furthermore, CT may also reveal edema, intra-osseous fistula and cortical defects that lead to soft tissue sinus tracts.

CT is better suited for an evaluation of cortical bone, whereas MR imaging is more useful for the evaluation of internal architecture of structures such as the bone marrow, muscles, tendons, ligaments, cartilage etc. MR imaging has high accuracy in the acute osteomyelitis evaluation and detection primarily delineating adjacent soft tissue infection; particularly when no prior alterations in osseous or soft structure are present. However, in patients who have undergone previous surgical intervention, MR imaging may not be able to clearly distinguish signal abnormality secondary to bone marrow edema or enhancement related to a reactive phenomenon and that related to infection. Similarly, the diagnostic accuracies of both CT and MR imaging to evaluate osteomyelitis generally decrease in the presence of metallic implants due to streak and susceptibility artefacts.

MR imaging has a higher sensitivity and specificity than plain films and CT. Further findings become positive earlier in the disease process with MR than with plain films. MR imaging is particularly better at depicting bone marrow abnormalities with sensitivity of 82%-100% and specificity of 75%-95%. Vertebral osteomyelitis is one condition where MR has a characteristic pattern of confluent vertebral body and disk involvement; the diagnostic accuracy in such cases amount to 90%. MR imaging findings in osteomyelitis usually are related 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. A decreased intensity on T1-weighted images with no change on T2-weighted images may indicate surgical or post-traumatic scarring of bone marrow. The MR imaging limitations are primarily due to the reason that findings of osteomyelitis are nonspecific, and similar changes may occur as a result of fractures, tumours, and a number of various intramedullary or juxtamedullary processes that result in bone marrow edema.
