Combined [18F]-Fluoride Imaging in Experimental Arthritis

1 Cell and Molecular Biology, Hans Knöll Institute, Jena, Germany 2 Applied Systems Biology, Hans Knöll Institute, Jena, Germany 3 Friedrich Schiller University, Jena, Germany 4 Molecular and Applied Microbiology, Hans Knöll Institute, Jena, Germany 5 Institute of Immunology, Jena, Germany Contact: [email protected] Combined [18F]-Fluoride Imaging in Experimental Arthritis Bianca Hoffmann1,2,3, Carl-Magnus Svensson2, Maria Straßburger4, Björn Gebser1, Ingo Irmler5, Thomas Kamradt5, Hans Peter Saluz1,3 and Marc Thilo Figge2,3 Rheumatoid Arthritis (RA) • one of the most common autoimmune diseases • leads to joint swelling, bone erosion, loss of joint function Experimental Arthritis • used to study RA and arthritic processes • glucose-6-phosphate isomerase(G6PI) induced [1] Longitudinal, in vivo Imaging • combined positron emission tomography/computed tomography 1. Prepare volumes of interest (VOIs) 2. Reconstruct surface • extract parts of image stack • marching cubes algorithm [2] • that contain the hind paws vr• triangulated surface mesh 3. Calculate local roughness [3] 4. Calculate global roughness [3] • for each facet normal • composite histogram • average angle between r• sum of frequencies of • facet normals angles above threshold PET image analysis • manually place regions of interest • around paws • calculate standard uptake value (SUV) PET imaging results: • increased uptake of [18F]-fluoride • in arthritic animals • distribution of the tracer is • visualized by PET/CT image • fusion • accumulates predominantly in • metatarsophalangeal and tarso- • crural joint regions CT imaging results: • arthritic animals show increased • bone roughness in hind paws • already at day 10 roughness is • significantly increased • roughness is declining in late remitting phase of experimental arthritis • variation of roughness radius r reveals differences between outer and • inner cortical bone surface • at outer surface roughness appears on a smaller spatial scale with a • turnover to larger spatial scales at day 35 • combined PET/CT imaging allows longitudinal, in vivo studies • [18F]-fluoride is well suited to quantify pathological bone metabolism • fully automated CT image analysis pipeline for roughness evaluation • very sensitive to early anatomical changes of the bones • revealed different dynamics of bone erosion at periosteal and • endosteal sites of the cortical bone References: [1] Schubert et al., (2004) Immunization with Glucose-6-Phosphate Isomerase Induces T CellDependent Peripheral Polyarthritis in Genetically Unaltered Mice, J Immunol 172(7), 4503–4509. [2] Lorensen and Cline, (1987) Marching cubes: A high resolution 3D surface construction algorithm, ACM Siggraph Comput Graph 21(4), 163-169. [3] Silva et al., (2006) Application of surface roughness analysis on micro-computed tomographic images of bone erosion: examples using a rodent model of rheumatoid arthritis., Mol Imaging 5(4), 475–84. This work was funded by the Bundesministerium für Bildung und Forschung (grant number: 0316040A) Methods Background Results Conclusion threshold ii threshi iVOI aaf afR angleoffrequency)( )( 180    Fore paw Hind paw Cortical Bone Bone Marrow Outer bone surface Inner bone surface