4.2 Robust (H ∞ ) Control
4.2.4 Robust Control With Sensitivity Analysis
In this subsection I will present the results of robust control which was designed using sensitivity analysis. These results are not only my own results. In the current subsection I will describe only partial results which are closely connected to my Thesis group 1, not the whole controller design methods and full simulation results will be discussed.
The aim is to investigate how the designed controller reacts to parametric changes, viz.
robustness of the controller.
The current robust control was designed for the tumor growth model under angiogenic inhibition described in (3.4-3.6), and it was carried out with sensitivity analysis in order to determine the uncertainty weighting matrix, and to investigate the effect of parametric perturbation on the closed-loop system. The tumor growth model was linearized at the x10= 100 mm3 operation point similarly as in Subsection 4.2.1. Results were published in A. Szeles, J. S´api, et al.2012; A. Szeles, D. A. Drexler, et al.2014; L Kov´acs, A Szeles, et al. 2014.
Starting from the formal definition of the multiplicative uncertainty, parametric sensitivity analysis was performed on the nonlinear model to determineWunc. The idea was partially adapted and modified from (L Kov´acs, Kulcs´ar, et al. 2011; Liu and Zeng 2012) in order to incorporate uncertain parameters into the design process. Ranges are associated to these selected parameters. By taking every single extremal combination of the parameters, linearization is performed. Finally, the frequency content of the perturbed and linearized model is compared and relative difference is computed. Instead of using the extremal values, a gridding technique is proposed. Consequently, we consider the combination of the selected parameters in a multiplicative manner.
A ±5% variability of the Lewis lung carcinoma parameters and a ±10% variability of the vascular inactivation rate was assumed (Hahnfeldt et al. 1999). For the Lewis lung carcinoma parameters, factorsf1, f2 and f3 were chosen from a (+5%, +2.5%, 0,−2.5%,
−5%) grid, and for the vascular inactivation rate, factor f4 was taken from a (+10%, +5%,−5%, −10%) grid. The perturbed nonlinear model is:
0.0010 0.01 0.1 1 10 100 0.2
0.4 0.6 0.8 1 1.2
1.4 Sensitivity analysis
Multiplicative magnitude error
Figure 4.13: Relative modeling error functions (perturbed system compared to the nom-inal model) in frequency domain and uncertainty upper bound (dashed line).
x˙1(t) = −λ1x1(t) log x1(t) x2(t)
(4.66) x˙2(t) = bx1(t)−dx1(t)2/3x2(t)−ex2(t)u(t) (4.67)
y = x1, (4.68)
where λ1 = (1 +f1)λ1, b = (1 +f2)b, d = (1 +f3)d and e = (1 +f4)e. For each possible combination, the nonlinear model was linearized at thex10= 100 mm3 operation point, and the obtained linear model was used to determine parametric sensitivity by determiningsupWrel of the relative uncertainty relation:
where Gp stands for the perturbed model and Gn for the nominal model. The frequency
0 5 10 15 20 25 30 35 40
Figure 4.14: Characteristics of tumor regression and control input in case of different perturbation scenarios – parameters change between the 5th and 10th day (blue), the 10th and 15th day (red) and the 15th and 20th day (green), each
model parameter is perturbed independently with a variability of±25%.
domain of interest wasω∈[0.001 100] rad/day. The determined parametric sensitivity was upper bounded (Figure4.13):
supWrel= 0.47s+ 8
s+ 2. (4.70)
The results of the sensitivity analysis show that in lower frequency domain, ω ∈ [0.001 0.1] rad/day, the model is less sensitive for parameter perturbation than in higher frequency domain, ω ∈ [0.01 100] rad/day. In the low frequency domain which is characteristic for tumor growth dynamics, the uncertainty upper bound allows 125%
deviation in the gain of the transfer function relative to the nominal transfer function (Figure4.13) instead of the 65% deviation resulted from the perturbation of the parameters.
This means that significantly larger variance of the parameters is allowed in the low frequency domain, regardless of their dynamical characteristics.
The obtained uncertainty weighting function W should work as a high pass filter to
reduce disturbance at low frequency, and to avoid strong restrictions at high frequency:
Wunc= 0.01s+ 2
s+ 8. (4.71)
Sensor noise, as a wide-band signal, can be modeled with a constant value. During the design process,Wnanticipates 5% measurement noise for volume measurements. This is in accordance with the measurement noise used in (Hahnfeldt et al. 1999).
Wn= 0.05. (4.72)
The control input is penalized by the weighting function Wu, wchich was chosen to
Wu = 0.01. (4.73)
The zero of the weighting function was chosen based on the uncertainty weighting function to form the desired ”cone” shape in frequency domain. The amplification was set to compensate the amplification of the model-matching function and to minimize oscillation in constant reference signal tracking:
Wperf = 6.5·10−7s+ 2
s+ 8. (4.74)
Effect of Parametric Perturbation on the Closed-Loop System
Effect of parametric perturbation on the closed-loop system was investigated. In this case, there is no measurement noise, and the measurements are taken continuously. The parameters are perturbed independently (b, d,λ1, e) with a variability of ±25% in three different time intervals:
• between the 5th and 10th day,
• between the 10th and 15th day,
• between the 15th and 20th day.
Parameter perturbation does not affect tumor regression before the 5th day because of the applied saturation. After the 20th day, steady state is achieved and the tumor volume is nearly minimal; thus, perturbations do not change significantly the performance of the controller.
If the condition of the patient changes after the 10th day of the therapy, the speed of tumor regression does not change remarkably, total inhibitor inlet varies between 815.8
5−10 10−15 15−20 700
750 800 850 900 950
1000 Total inhibitor inlet in case of transient behavior
Total inhibitor inlet (mg/kg)
Days of transient
Figure 4.15: The total inhibitor inlet in case of different perturbation scenarios – param-eters change between the 5th and 10th day (blue), the 10th and 15th day (red) and the 15th and 20th day (green), each model parameter is perturbed
independently with a variability of±25%.
mg/kg and 916.4 mg/kg (Figure4.15). Parameter perturbation between the 5th and 10th day can cause both deterioration and amelioration in terms of speed of tumor regression, daily and total inhibitor inlet (Figure 4.14). The total inhibitor inlet varies between 742.9 mg/kg and 964.9 mg/kg (Figure 4.15). In the figure each cross represents a total inhibitor inlet value for a perturbed parameter, e.g. one cross means the total inhibitor inlet if the tumor growth rate (λ1) is perturbed with +25%. One can see from the figure that the effect of the perturbation decreases as the treatment time increases.
These simulations demonstrated that the designed controller reacts to parametric changes very pliantly, as expected from robust control methodology.