In vivo quantification of arthritis-induced alterations of murine bones based on PET/CT image data

In vivo quantification of arthritis-induced alterations of murine bones based on PET/CT image data Bianca Hoffmann1,2, Carl-Magnus Svensson1, Maria Straßburger3, Hans Peter Saluz2,4 and Marc Thilo Figge1,2 1 Applied Systems Biology, Hans Knöll Institute, Jena, Germany 2 Friedrich Schiller University, Jena, Germany 3 Transfer Group Anti-infectives, Hans Knöll Institute, Jena, Germany 4 Cell and Molecular Biology, Hans Knöll Institute, Jena, Germany 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 • induced by glucose-6-phosphate isomerase (G6PI) [1] Longitudinal, in vivo Imaging (PET/CT) • 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 • roughness is significantly increased already at day 10 • variation of roughness radius r reveals differences between periosteal and endosteal cortical bone surface • combined PET/CT imaging allows for longitudinal, in vivo studies • 18F-fluoride is well suited to quantify pathological bone metabolism [4,5] • automated CT image analysis allows for fast and objective • • quantification of bone destruction [4,5,6] • roughness evaluation very sensitive for early bone erosion • revealed different dynamics of bone erosion at periosteal and • endosteal sites of cortical bone References: [1] Schubert et al., (2004) Immunization with glucose-6-phosphate isomerase induces T cell-dependent 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. [4] Irmler et al., (2014) 18F-fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis, Arthritis Res Ther 16(4), R155. [5] Hoffmann and Svensson et al., (2017) Automated quantification of early bone alterations and pathological bone turnover in experimental arthritis by in vivo PET/CT imaging, Sci Rep 7:2217. [6] Svensson and Hoffmann et al., (2017) Quantification of arthritic bone degradation by analysis of 3D micro-computed tomography data, Sci Rep 7:44434. This work was funded by the Bundesministerium für Bildung und Forschung (grant number: 0316040A) We thank Dr. I. M. Irmler and Prof. Dr. T. Kamradt for supporting the experimental setup and Dr. B. Gebser for preparation of PET tracers. 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 Contact: [email protected]