Application of ex vivo micro-computed tomography for assessment of in vivo fluorescence and plain radiographic imaging for monitoring bone metastases and osteolytic lesions.

The intracardiac injection model is a commonly used in vivo model to test therapeutic response in bone metastases. However, few studies have critically compared the performance of different imaging methods in terms of sensitivity and quantitative assessment of osteolytic lesions. We performed in vivo optical and plain radiographic imaging of bone metastases followed by high-sensitivity ex vivo micro-computed tomography (micro-CT) imaging. This approach allowed for quantitative assessment of in vivo imaging techniques using fluorescence and plain radiography. Comparison of lesions detected in vivo by fluorescent optical imaging with ex vivo micro-CT revealed that the limited spatial resolution of fluorescent optical imaging may underestimate the number of bone metastases. Radiography was compared with micro-CT for the detection of osteolytic lesions. When using dichotomous yes/no grading, there was a 64% agreement in detection of osteolytic lesions. When subjective semiquantitative grading methods were used to assess the extent of osteolytic lesions, a positive association between the micro-CT grades and the square root of the radiography-based grades was observed (p < 0.05). Micro-CT also showed a significant association with fluorescent optical values; however, no such association was observed between lesion scores based on radiographs and those based on fluorescent imaging. The findings reveal an approximate two-fold sensitivity for micro-CT compared to plain radiography in the detection of osteolytic lesions. Significant associations between micro-CT-based osteolytic lesion grade and tumor growth characterized by increased fluorescent area document the value of these two techniques for the assessment of osteolytic bone metastases.