The first treatment control system that explicitly and automatically balances the efficacy and safety goals of noninvasive thermal therapies is described, and its performance is evaluated in phantoms and in vivo using ultrasound heating with a fixed, focused transducer. The treatment efficacy is quantified in terms of thermal dose delivered to the target. The developed feedback thermal dose controller has a cascade structure with the main nonlinear dose controller continuously generating the reference temperature trajectory for the secondary, constrained, model predictive temperature controller. The control system ensures thermal safety of the normal tissue by automatically complying with user-specified constraints on the maximum allowable normal tissue temperatures. To reflect hardware limitations and to prevent cavitation, constraints on the maximum transducer power can also be imposed. It is shown that the developed controller can be used to achieve the minimum-time delivery of the desired thermal dose to the target without violating safety constraints, which is a novel and clinically desirable feature. The developed controller is model based, and requires patient- and site-specific models for its operation. These models were obtained during pre-treatment identification experiments. In our implementation, predictive models, internally used by the automatic treatment controller, are dynamically updated each time new temperature measurements become available. The adaptability of internal models safeguards against adverse effects of modelling errors, and ensures robust performance of the control system in the presence of a priori unknown treatment disturbances. The successful validation with two experimental models of considerably different thermal and ultrasound properties suggests the applicability of the developed treatment control system to different anatomical sites.

The problem of controlling noninvasive thermal therapies is formulated as the problem of directly controlling thermal dose of the target. To limit the damage to the surrounding normal tissue, the constraints on the peak allowable temperatures in the selected spacial locations are imposed. The developed controller has a cascade structure with a linear, constrained, model predictive temperature controller in the secondary loop. The temperature controller manipulates the intensity of the ultrasound transducer with saturation constraints, which noninvasively heats the spatially distributed target. The main nonlinear thermal dose controller dynamically generates the reference temperature trajectories for the temperature controller. The thermal dose controller is designed to force the treatment progression at either the actuation or temperature constraints, which is required to minimize the treatment time. The developed controller is applicable to high and low-intensity treatments, such as thermal ablation and thermoradiotherapy. The developed approach is tested using computer simulations for a one-dimensional model of a tumor with constraints on the maximum allowable temperature in the normal tissue and a constrained power output of the ultrasound transducer. The simulation results demonstrate that the proposed approach is effective at delivering the desired thermal dose in a near minimum time without violating constraints on the maximum allowable temperature in healthy tissue, despite significant plant-model mismatch introduced during numerical simulation. The results of in vitro and in vivo validation are reported elsewhere.

A model-predictive controller (MPC) of the thermal dose in hyperthermia cancer treatments has been developed and evaluated using simulations with one-point and one-dimensional models of a tumor. The developed controller is the first effort in: 1) the application of feedback control to pulsed, high-temperature hyperthermia treatments; 2) the direct control of the treatment thermal dose rather than the treatment temperatures; and 3) the application of MPC to hyperthermia treatments. Simulations were performed with different blood flow rates in the tumor and constraints on temperatures in normal tissues. The results demonstrate that 1) thermal dose can be controlled in the presence of plant-model mismatch and 2) constraints on the maximum allowable temperatures in normal tissue and/or the pulsed power magnitude can be directly incorporated into MPC and met while delivering the desired thermal dose to the tumor. For relatively high blood flow rates and low transducer surface intensities--factors that limit the range of temperature variations in the tumor, the linear MPC, obtained by piece-wise linearization of the dose-temperature relationship, provides an adequate performance. For large temperature variations, the development of nonlinear MPC is necessary.

A thermal therapy feedback control approach to control thermal dose using a moving power deposition field is developed and evaluated using simulations. A normal tissue safety objective is incorporated in the controller design by imposing constraints on temperature elevations at selected normal tissue locations. The proposed control technique consists of two stages. The first stage uses a model-based sliding mode controller that dynamically generates an 'ideal' power deposition profile which is generally unrealizable with available heating modalities. Subsequently, in order to approximately realize this spatially distributed idealized power deposition, a constrained quadratic optimizer is implemented to compute intensities and dwell times for a set of pre-selected power deposition fields created by a scanned focused transducer. The dwell times for various power deposition profiles are dynamically generated online as opposed to the commonly employed a priori-decided heating strategies. Dynamic intensity and trajectory generation safeguards the treatment outcome against modelling uncertainties and unknown disturbances. The controller is designed to enforce simultaneous activation of multiple normal tissue temperature constraints by rapidly switching between various power deposition profiles. The hypothesis behind the controller design is that the simultaneous activation of multiple constraints substantially reduces treatment time without compromising normal tissue safety. The controller performance and robustness with respect to parameter uncertainties is evaluated using simulations. The results demonstrate that the proposed controller can successfully deliver the desired thermal dose to the target while maintaining the temperatures at the user-specified normal tissue locations at or below the maximum allowable values. Although demonstrated for the case of a scanned focused ultrasound transducer, the developed approach can be extended to other heating modalities with moving deposition fields, such as external and interstitial ultrasound phased arrays, multiple radiofrequency needle applicators and microwave antennae.

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