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

Abstract

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.

A new multiple trauma model of the mouse

“…The CT scan was performed at the Molecular Imaging North Competence Center (Am Botanischen Garten 14, 24,118 Kiel). Micro computed tomography in Kiel has been applied previously to mice in several studies [ 25 , 26 ]. Two radiologists planed every scan.…”

Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT)

“…34 Mouse models with osteogenesis imperfecta have demonstrated improved bone architecture with haematopoietic stem cell transplant therapy 35 and characterization of osseous tumour infiltration have been combined with bioluminescence imaging techniques in prostate cancer mouse models in vivo to better assess tumour growth and response. 19,36 There are few studies of micro-CT assessment of muscle fibre characterization and disease, although its feasibility and benefits over diffusion tensor imaging have been reported. 37 Micro-CT has been used to test the effectiveness of uptake of implant materials within muscle tissue "dead space" postdebridement in mice.…”

Preclinical evaluation of Sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases

“…Fluorescent tumor area was determined as this parameter has been reported to have a better correlation with micro-CT-based osteolytic lesion grade than fluorescent intensity [32]. The fluorescent area of metastatic tumors was measured when tumors were first detected at 4 weeks following tumor cell inoculation and again one week later.…”