Huang Wei, Li Xin, Morris Elizabeth A, Tudorica Luminita A, Seshan Venkatraman E, Rooney William D, Tagge Ian, Wang Ya, Xu Jingang, Springer Charles S
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17943-8. doi: 10.1073/pnas.0711226105. Epub 2008 Nov 12.
The pharmacokinetic analysis of dynamic-contrast-enhanced (DCE) MRI data yields K(trans) and k(ep), two parameters independently measuring the capillary wall contrast reagent transfer rate. The almost universally used standard model (SM) embeds the implicit assumption that equilibrium transcytolemmal water exchange is effectively infinitely fast. In analyses of routine DCE-MRI data from 22 patients with suspicious breast lesions initially ruled positive by institutional screening protocols, the SM K(trans) values for benign and malignant lesions exhibit considerable overlap. A form of the shutter-speed model (SSM), which allows for finite exchange kinetics, agrees with the SM K(trans) value for each of the 15 benign lesions. However, it reveals that the SM underestimates K(trans) for each of the seven malignant tumors in this population. The fact that this phenomenon is unique to malignant tumors allows their complete discrimination from the benign lesions, as validated by comparison with gold-standard pathology analyses of subsequent biopsy tissue samples. Likewise, the SM overestimates k(ep), particularly for the benign tumors. Thus, incorporation of the SSM into the screening protocols would have precluded all 68% of the biopsy/pathology procedures that yielded benign findings. The SM/SSM difference is well understood from molecular first principles.
动态对比增强(DCE)MRI数据的药代动力学分析可得出K(trans)和k(ep)这两个参数,它们独立测量毛细血管壁造影剂的转移速率。几乎普遍使用的标准模型(SM)隐含了这样一个假设,即跨细胞膜水交换达到平衡的速度实际上是无限快的。在对22例最初经机构筛查方案判定为阳性的可疑乳腺病变患者的常规DCE-MRI数据进行分析时,良性和恶性病变的SM K(trans)值存在相当大的重叠。一种考虑了有限交换动力学的快门速度模型(SSM),与15例良性病变中的每一例的SM K(trans)值相符。然而,它表明该人群中7例恶性肿瘤的SM均低估了K(trans)。这一现象仅在恶性肿瘤中出现,这一事实使得可以将它们与良性病变完全区分开来,后续活检组织样本的金标准病理分析验证了这一点。同样,SM高估了k(ep),尤其是对于良性肿瘤。因此,将SSM纳入筛查方案将避免所有68%产生良性结果的活检/病理程序。从分子第一原理可以很好地理解SM/SSM差异。