Pickhardt Perry J, Halberg Richard B, Taylor Andrew J, Durkee Ben Y, Fine Jason, Lee Fred T, Weichert Jamey P
Department of Radiology, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA.
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3419-22. doi: 10.1073/pnas.0409915102. Epub 2005 Feb 22.
This study was initiated to evaluate the efficacy of negative contrast-enhanced microcomputed tomography (microCT) colonography for the noninvasive detection of colonic tumors in living mice. After colonic preparation, 20 anesthetized congenic mice were scanned with high-resolution microCT. Images were displayed by using commercial visualization software and interpreted by two gastrointestinal radiologists, who were unaware of tumor prevalence and findings at gross pathology. Two-dimensional multiplanar images were assessed by using a five-point scale to distinguish colonic tumors (polyps) from fecal pellets (5 = definitely a tumor, 4 = probably a tumor, 3 = indeterminate, 2 = probably not a tumor, 1 = definitely not a tumor). Gross pathologic evaluation of excised mouse colons served as the reference standard. Data analysis included dichotomizing results, with 1-2 indicating no tumor and 3-5 indicating tumor and also receiver operator characteristic curve analysis with area under the curve for threshold-independent assessment. A total of 41 colonic polyps in 18 of the 20 mice were identified at gross examination on necropsy, of which 30 measured 2-5 mm and 11 measured <2 mm in size. The pooled per-polyp sensitivity for lesions >2 mm was 93.3% (56/60). The pooled per-mouse sensitivity for polyps >2 mm was 97.1% (33/34). Pooled specificity for distinguishing fecal pellets from tumor was 98.5% (65/66). The combined area under the curve from receiver operator characteristic curve analysis was 0.810 +/- 0.038 (95% confidence interval, 0.730-0.890). These findings indicate that accurate noninvasive longitudinal monitoring of colon tumor progression or response to various therapies is now technically feasible in live mice by using this microCT colonography method.
本研究旨在评估阴性对比增强微型计算机断层扫描(microCT)结肠成像技术在活体小鼠中无创检测结肠肿瘤的效果。结肠准备完成后,对20只麻醉的同基因小鼠进行高分辨率microCT扫描。使用商业可视化软件显示图像,并由两名胃肠放射科医生解读,他们对肿瘤患病率和大体病理学检查结果不知情。通过五点量表评估二维多平面图像,以区分结肠肿瘤(息肉)和粪便颗粒(5 = 肯定是肿瘤,4 = 可能是肿瘤,3 = 不确定,2 = 可能不是肿瘤,1 = 肯定不是肿瘤)。切除的小鼠结肠的大体病理学评估作为参考标准。数据分析包括将结果二分法,1 - 2表示无肿瘤,3 - 5表示有肿瘤,还包括进行受试者操作特征曲线分析并计算曲线下面积以进行独立于阈值的评估。在尸检的大体检查中,20只小鼠中有18只共发现41个结肠息肉,其中30个大小为2 - 5毫米,11个大小小于2毫米。对于大小>2毫米的病变,每个息肉的合并敏感性为93.3%(56/60)。对于大小>2毫米的息肉,每只小鼠的合并敏感性为97.1%(33/34)。区分粪便颗粒和肿瘤的合并特异性为98.5%(65/66)。受试者操作特征曲线分析的合并曲线下面积为0.810±0.038(95%置信区间,0.730 - 0.890)。这些发现表明,通过这种microCT结肠成像方法,在活体小鼠中对结肠肿瘤进展或对各种治疗的反应进行准确的无创纵向监测在技术上现在是可行的。