Cellular Changes in Response to Embedded Fragments: An Animal Surveillance Model

Abstract

Background: Explosive munitions have wounded approximately 50,000 service members in the Global War on Terrorism. Medical surveillance programs use traditional x-ray as a method of monitoring embedded metal fragments in the body. X-ray replicates a two-dimensional image of bone and air filled structures, it does not display the soft tissue. Tomographic imaging allows specific measured slices of the subject to be obtained in a quantitative manner to display anatomic structures like tumors. Purpose: The purpose of this pilot study was to determine the sensitivity and specificity of small animal Positron Emission Tomography - Computed Tomography (PET-CT) in identifying metabolic changes in muscle tissue surrounding a heavy metal tungsten alloy and compare this imaging to traditional x-ray images. Methods: In the first experiment Fischer 344 male rats were randomly assigned to three groups (implanted with heavy metal tungsten alloy (HMTA) pellets, tantalum (Ta) pellets as the control metal or Sham control without pellet implantation). One rat was in each category for the first experiment. Animals received a series of x-rays and 18F-fluoro-2-deoxy-D-glucose (FDG) and18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET-CT scans over 16 weeks. The second experiment used a larger sample of (2 Sham, 15 Ta, 15 HMTA) animals and FDG PET-CT scans. Tracer uptake was quantified using the standard unit value (SUV). Imaging data were compared between groups and over time. Sensitivity and specificity were determined. Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) were calculated. Histopathology was assessed by a pathologist, blinded to treatment group. Results: Increased FDG uptake was associated with an aggressive malignancy in the HMTA implanted rats. A significant difference in FDG uptake between the Ta and HMTA animals and a significant change in tracer uptake over the sixteen weeks for the HMTA animals was found. PET-CT imaging had a sensitivity of 86% and specificity of 100% and the area under the curve (AUC) .938. Conclusion: PET-CT imaging provided information on metabolic changes occurring at the site of the implanted metals not available from x-rays. PET-CT imaging and can be a useful tool in the surveillance of toxic embedded fragments.