Local identifiability of a receptor-binding radiopharmacokinetic system having measured parameters of known uncertainty.
Local identifiability of a receptor-binding radiopharmacokinetic system having measured parameters of known uncertainty.
复制标题
具有已知不确定性的测量参数的受体结合放射性药物动力学系统的局部可识别性。
DOI：
10.1109/10.312097
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Stadalnik,RC
中科院分区：
文献类型：
--
作者：
Vera,DR;Scheibe,PO;Banin,Y;Stadalnik,RC
局部可识别性被确定为受体结合的放射性药代动力学系统，包括测量参数的已知不确定度。采用[/sup 99m/Tc]半乳糖糖白蛋白（TcNGA）检测健康人及重度肝病患者。在30分钟动态成像研究期间，测量包括肝脏和心脏的计数率，注射TcNGA的量L/sub /，每升采样血浆中注射剂量的分数f~。这些测量的典型相对标准偏差分别为1%、0.2%和5%。然后，利用描述肝脏和血浆时间-活性数据的四态非线性模型计算受体浓度[R]/sub 0/、tcnga -受体前向结合率常数k/sub b/、肝外血浆体积V/sub e/、肝血浆体积V/sub h/、考虑到L/sub 0/和f~的测量不确定度，对参数[R]/sub 0/、k/sub b/、V/sub e/、V/sub h/和f的标准误差没有显著增加。当L/sub 0/和f~的相对误差增加到40%时，Se（p/sub j/）的变化范围在10 ~ 100%之间，其中参数V/sub h/最敏感。例外是se(k/sub i/)，其增幅小于1%。通常与肝病患者相关的影像学研究[R]/sub 0/降低，除了se（k/sub b/）的增幅较低外，所有估计参数误差的增幅都较大。最后，通过模拟参数/spl sigma//sub 12/和/spl sigma//sub 13/的相对标准差从0到40%的变化，研究了直接测量肝脏观测系数/spl sigma//sub 12/和/spl sigma//sub 13/所带来的误差传播。健康受试者的影像学检查显示se未增加（p/sub j/）。使用肝脏疾病患者的TcNGA成像数据进行局部可识别性计算导致参数估计精度较低；当/spl sigma//sub 12/和/spl sigma//sub 1/3的相对标准偏差达到40%时，标准误差增加了3倍
Local identifiability was determined for a receptor-binding radiopharmacokinetic system that included measured parameters of known uncertainty. Healthy subjects and patients with severe liver disease were studied with [/sup 99m/Tc] galactosylneoglycoalbumin (TcNGA). Measurements during the 30-min dynamic imaging study included the count rate over liver and heart, the quantity of TcNGA injected L/sub 0/, and the fraction-of-injected dose per liter of sampled plasma f~. Typical relative standard deviations for these measurements were 1, 0.2, and 5 percent, respectively. A four-state nonlinear model describing the hepatic and plasma time-activity data was then used to calculate the standard error se(p/sub j/) for model parameters representing receptor concentration [R]/sub 0/, the TcNGA-receptor forward binding rate constant k/sub b/, extrahepatic plasma volume V/sub e/, hepatic plasma volume V/sub h/, and hepatic plasma flow F. Accounting for the measurement uncertainties of L/sub 0/ and f~ did not significantly increase the standard errors for parameters [R]/sub 0/, k/sub b/, V/sub e/, V/sub h/ and F. When the relative errors of L/sub 0/ and f~ were increased to 40%, the change in Se(p/sub j/) ranged from 10 to 100%, with parameter V/sub h/ being the most sensitive. The exception was se(k/sub i/), the increase of which was less than 1%, Imaging studies with reduced [R]/sub 0/, typically associated with patients with liver disease, resulted in greater increases in all estimated parameter errors except se(k/sub b/) which had a lower increase. Lastly, the error propagation introduced by direct measurement of the liver observational coefficients /spl sigma//sub 12/ and /spl sigma//sub 13/ was investigated by simulating changes in the relative standard deviation in parameters /spl sigma//sub 12/ and /spl sigma//sub 13/ from 0 to 40%. Imaging studies from healthy subjects showed no increase in se(p/sub j/). Local identifiability calculations using TcNGA imaging data from patients with liver disease resulted in parameter estimates of lower precision; standard errors increased by a factor of three when the relative standard deviation of /spl sigma//sub 12/ and /spl sigma//sub 1/3 reached 40%.<>