13 General introduction and outline of this thesis osteoarthritis-related costs for needed care was 1.1 billion euros, being 1.1% of total healthcare expenditure [5, 6]. The extent of the clinical and socio-economic burden frommusculoskeletal disease as a whole is, in short, substantial. Not every patient with (suspected) osteoarthritis will need medical imaging. In more challenging cases, however, for example in preparation of or in follow-up after orthopaedic surgical intervention for severe osteoarthritis (such as total knee arthroplasty, wrist surgery), or in painful tarsal coalition, medical imaging techniques will often play a central role. Patients with osteoarthritis of the knee, hand, and wrist and patients with tarsal coalitions under careful consideration for surgery, were studied in Part I of this thesis. In this setting, considerable potential costs for society are at stake as surgery is an expensive intervention. Studying the (potential) role of early accurate non-invasive medical imaging may aid in facilitating optimal and cost-effective care. Limitations in imaging benign peri-operative bone and joint disease of the extremities Although total knee arthroplasty in patients with (severe) osteoarthritis is mostly very successful, a considerable number of patients will experience persisting pain complaints, with an estimated 15-year failure of 7% [7, 8]. Persisting pain after knee surgery may have many different causes, one of the most notorious causes being loosening of the prosthesis material, with the consequence of possible revisional surgery at stake. Plain radiographs lack the sensitivity to adequately detect (aseptic) prosthesis loosening and are also less suitable for imaging three-dimensional (3D) structures, such as the knee, wrist or hind- and midfoot. In all patients with osteosynthesis material, hardware-induced artefacts still hamper computed tomography (CT) and magnetic resonance imaging (MRI), despite increasingly available high quality metal artefact reduction techniques. In patients after total knee arthroplasty, planar bone scintigraphy is known to have very high sensitivity for detecting loosening but lacks specificity and therefore falsepositive results limit definite diagnosis of loosening. Nuclear medicine uses radiopharmaceuticals for imaging as well as for radionuclide therapy and has a historically strong affinity with imaging of bone pathophysiology, first described in 1971 by Subramanian, et al. [9]. Bone scintigraphy is performed with diphosphonates (Technetium-99m-hydroxydiphosphonate abbreviated as [99mTc] Tc-HDP and Technetium-99m-methylene diphosphonate, [99mTc]Tc-MDP). As an improvement over planar scintigraphy, Single Photon Emission Tomography (SPECT), enables 3D cross-sectional visualization of the distribution of the radiopharmaceutical. 1