18 Chapter 1 as a result of the aforementioned osteoblast activity will only show after months of increased turnover. MRI has in general high sensitivity with especially precise imaging of soft tissues, but relatively low specificity for bone lesions and the imaging of the bony structures can be limited, especially in regions of avid bone marrow edema. Also, MRI is nearly always utilized to image limited parts of the body because of relatively long acquisition times with restricted field of view, which may be restricting in certain multifocal diseases, such as polyostotic FD/MAS. In order to assess the skeletal burden of FD/MAS, planar bone scintigraphy is currently frequently used. This modality is useful in clinical practice as an adjunct to determine the skeletal burden of FD/MAS, with the semiquantitative per-segment estimation using planar bone scintigraphy called Skeletal Burden Score (SBS), first postulated by Collins, et al. in 2005 [16] and without methodological changes thereafter. Although PET using sodium fluoride-18 (Na[18F]F-PET) was already introduced in 1962 by Blau, et al. [17] and approved by the FDA in 1972, its use is still limited because of (perceived) costs and availability of both the radiopharmaceutical and PET/CT-scanner capacity. Modern molecular imaging solutions in bone disease In the past decade, Na[18F]F-PET/CT is gaining popularity over bone scintigraphy because of improved recovery by modern PET/CT-scanners, better availability and reduced costs of the radiopharmaceutical and PET/CT-scanners, and thus meeting a growing demand for improved diagnostic accuracy. Na[18F]F-PET/CT images bone (patho-)physiology, mainly osteoblast activity. On a molecular physiological level, osteoblasts and osteoclasts perform their functional tasks of bone formation and resorption continuously and harmonically within all bones in healthy people. Bone pathology generally leads to a disbalance between the level of activity of osteoblasts and osteoclasts. From this perspective, bone disease can therefore be classified into osteoclastic, osteoblastic or combined phenotype. In most benign bone and joint diseases, the osteoblastic component is largely dominant. Bone scintigraphy including bone-SPECT/CT and Na[18F]F-PET/CT both sensitively image in vivo osteoblast activity by injection of a radiopharmaceutical. The uptake mechanism reflecting the young osteoblasts of both radiopharmaceuticals is slightly different, but both are influenced by regional bone perfusion and ultimately attach to the surface of hydroxyapatite crystals by chemisorption [18, 19]. Na[18F]F, being a much smaller compound, has favorable pharmacokinetics, with faster blood clearance and high first pass extraction, low non-specific protein binding, bone uptake via chemisorption [18].