Optimal design of experiments for estimating arterial wall transport parameters

Abstract

Atherosclerosis is associated with an accumulation of low-density lipoprotein (LDL) in the arterial wall. To quantify transport processes involved in this phenomenon, tracer experiments are performed by exposing the arterial wall to labeled LDL. Distributed mathematical models are needed to describe the resulting LDL profiles in the tissue. Parameter values can be estimated by fitting model-generated profiles to experimental data. The authors believe that in vivo parameter estimates can be made more practical through the application of optimal experiment design analysis. Their analysis was based on an examination of the sensitivity coefficients and the Hessian matrix. Two experiment designs were considered. The findings indicate that it is possible to improve the precision of the estimates of in vivo transport parameters by designing experiments which use a labeled LDL tracer and a distinguishable, labeled LDL, chemically modified with tyramine-cellobiose.<>