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The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis ( ank/ank ) mice have a loss of function in the  Ank  gene, which codes for a regulator of PPi transport. In this study, we used these  ank/ank  mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging  in vivo .    Methods  Three age groups (8, 12, and 18 weeks) of  ank/ank  (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system.    Results  OsteoSense 750 signals in the paw joints were higher in  ank/ank  mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old  ank/ank  mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the  ank/ank  spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation.    Conclusions  Changes in joint pathology of  ank/ank  mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in  ank/ank  mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis.

Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice