Positron emission tomography scans for distinguishing between osteomyelitis and infarction in sickle cell disease

Abstract

In a recently published review on bone involvement in sickle cell disease Almeida and Roberts (2005) reported that differentiation between bone infarction and osteomyelitis in sickle cell patients remains a diagnostic problem. Differentiation is essential because of the risk of the under-treatment of osteomyelitis. The clinical features of vaso-occlusive crisis are often comparable to osteomyelitis. In both vaso-occlusive crises and osteomyelitis, patients complain of pain and tenderness on palpation of the involved bone. A periosteal reaction resulting in swelling and erythema can occur in both conditions. Differentiation is usually not possible solely on clinical signs. When osteomyelitis is suspected, imaging of the affected area could help to support the diagnosis. Nuclear imaging, such as bone scintigraphy with 99mTc-labelled methylene diphosphonate, is highly sensitive for many active benign and malignant bone disorders. Therefore, it plays an important role in the evaluation of osteomyelitis, especially in acute osteomyelitis. In chronic osteomyelitis, the uptake of bone-seeking tracers is rather poor and non-specific. Radiolabelled white blood cells are commonly used to visualise infection or inflammation. In sickle cell disease, however, it has been shown that leucocyte scans cannot reliably discriminate between sickle cell vaso-occlusive crises and osteomyelitis. Magnetic resonance imaging (MRI) can display abnormal periosteal swelling but also fails to discriminate between infarction and infection. In a recent effort to discriminate between vaso-occlusive crises and osteomyelitis of the mandible in a known sickle cell patient, a three-phase bone scan was performed. The patient's complaints were pain in the mandibular angle with tenderness on palpation on the left side and a numb left lower lip for more than 3 weeks. These clinical signs were highly suspicious of a vaso-occlusive crisis or osteomyelitis. The bone scan showed slightly increased uptake in the left mandible area and some inhomogeneous uptake in the skull. A leucocyte scan could not be completed because the in vitro separation procedure of leucocytes from red blood cells and platelets before labelling from the patient's blood sample was not successful. Since the complaints of the patient did not resolve, further attempts were made to determine the nature of his complaints. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to establish the presence of inflammation. In areas of inflammation or infection, a high glucose metabolism is present, which results in an accumulation of the glucose analogue FDG. The FDG-PET showed a remarkably high intensive hot spot in the left mandible and no other hot spots in the rest of the skull (Fig 1). The intensity of this spot did not correspond to the intensity of the spot on the bone scan. To verify the finding of the FDG-PET scan a second PET scan was performed using 18F-NaF. This type of PET scan displays bone remodelling processes comparable to bone scans, but with a higher spatial resolution. The 18F-NaF is incorporated in hydroxyapatite of the bone and its accumulation is dependent on the regional blood flow and the osteoblastic activity (Cook & Fogelman, 2002). The 18F-NaF PET scan showed multiple inhomogeneous spots in the skull, mainly in concurrence with the bone scan. An intense hot spot was seen in the left mandible, the intensity of which was comparable to the 18F-FDG PET scan. The findings on the PET scans supported the diagnosis of osteomyelitis. One week after with the commencement of antibiotics an abscess developed at the painful site of the mandible. Various scan results of the patient. (A) 99mTc bone scan with increased uptake at the mandible. (B) 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showing a single hot spot at the left mandible. Frontal (C) and lateral (D) views of a NaF PET scan showing multiple areas of infarction/remodelling in the skull and one intense hot spot in the left mandible corresponding to the single hot spot in FDG-PET scan, as depicted in B. In this particular case, PET scans helped to discriminate between infarction and inflammation or infection. It is therefore suggested that, when a distinction between infarction and infection is required and bone scintigraphy or a leucocyte scan is not conclusive, FDG-PET imaging could be considered.