Abstract

Mild hyperthermia has been successfully employed to induce reversible physiological changes that can directly treat cancer and enhance local drug delivery. In this approach, temperature monitoring is essential to avoid undesirable biological effects that result from thermal damage. For thermal therapies, Magnetic Resonance Imaging (MRI) has been employed to control real-time Focused Ultrasound (FUS) therapies. However, combined ultrasound imaging and therapy systems offer the benefits of simple, low-cost devices that can be broadly applied. To facilitate such technology, ultrasound thermometry has potential to reliably monitor temperature. Control of mild hyperthermia was previously achieved using a proportional-integral-derivative (PID) controller based on thermocouple measurements. Despite accurate temporal control of heating, this method is limited by the single position at which the temperature is measured. Ultrasound thermometry techniques based on exploiting the thermal dependence of acoustic parameters (such as longitudinal velocity) can be extended to create thermal maps and allow an accurate monitoring of temperature with good spatial resolution. However, in vivo applications of this technique have not been fully developed due to the high sensitivity to tissue motion. Here, we propose a motion compensation method based on the acquisition of multiple reference frames prior to treatment. The technique was tested in the presence of 2-D and 3-D physiological-scale motion and was found to provide effective real-time temperature monitoring. PID control of mild hyperthermia in presence of motion was then tested with ultrasound thermometry as feedback and temperature was maintained within 0.3°C of the requested value.

Highlights

  • Non-invasive treatments based on mild temperature elevation have shown promising results in enhancing local drug delivery using temperature sensitive liposomes (TSL) [1,2,3] or for heat-activated gene delivery [4]

  • Magnetic Resonance Imaging (MRI)-guided focused ultrasound (MRgFUS) is currently undergoing clinical trials for a broad range of ablative applications and mild hyperthermia was investigated under MR guidance [15, 16]

  • Accurate estimation of temperature elevation was achieved in a tissue-mimicking phantom in the presence of motion

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Summary

Introduction

Non-invasive treatments based on mild temperature elevation (hyperthermia) have shown promising results in enhancing local drug delivery using temperature sensitive liposomes (TSL) [1,2,3] or for heat-activated gene delivery [4]. Thermal strain imaging is based on the time shift estimation of backscattered echoes induced by a local change in tissue temperature [24, 25, 38]. Temperature dependence of the speed of sound (SOS) and thermal expansion of the tissue are the two phenomena at the origin of the echo time shift. These combined effects lead to local speckle modification in ultrasound images when a temperature change occurs. The relationship between temperature change and thermal strain is expressed as: k

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