MicroPET-compatible, small animal hyperthermia ultrasound system (SAHUS) for sustainable, collimated and controlled hyperthermia of subcutaneously implanted tumours

Abstract

An external ultrasound system was developed for the heating of subcutaneously implanted tumours in small animals. This small animal hyperthermia ultrasound system (SAHUS) was designed to be compatible with a microPET (small animal positron emission tomography) scanner to facilitate studies of hyperthermia effects on tumour hypoxia. Collimation and localization of energy deposition, a specific goal for the new device to avoid regional and/or systemic heating of small animals, was demonstrated using thermoradiography following high-power short-time heating of a layered gel phantom. The in vivo heating capabilities of the SAHUS were tested using PC3 cell line tumours (2000-2700 mm(3)) grown in the lateral proximal thighs of Nu-/Nu- nuBR nude mice. Intratumour temperatures were recorded during heating trials with deep and superficial interstitial thermocouples. The experimental data showed that the SAHUS could produce hyperthermia in 8 +/- 2 mm diameter tumours in small animals to a target temperature of 41.5 degrees C and maintain it within a narrow temperature range (+/- 0.3 degrees C) for up to 4 h without raising the core temperature of the animals. PET imaging studies, data to be published separately, were conducted before and during SAHUS-induced hyperthermia. Both devices performed as expected and there was no significant decrease in image quality. In this paper, the new SAHUS is described and data from phantom and in vivo experiments presented.

Localized versus regional hyperthermia: Comparison of xenotransplants treated with a small animal ultrasound system and waterbath limb immersion

“…Of note, achieving a threshold minimum temperature dose-duration combination in the clinical setting may make the difference between successful or unsuccessful tumour control [27]. Furthermore, specific absorption rate (SAR) measurements performed via subtraction thermoradiographs in a phantom demonstrated ultrasonic attenuation of the beam with depth into the phantom [19]. To address this, a feedback loop from the intra-tumoural probe was placed mid-tumour at central axis to the SAHUS power unit to provide a method of ensuring adequate heating at the point of probe placement.…”

“…The development of SAHUS has provided an opportunity to explore ultrasound-based hyperthermia in xenotransplants [19]. We therefore compared ultrasound vs the traditional waterbath immersion hyperthermia methods for tumour growth delay and the basis for the differences in the tumour growth delay.…”

“…Intra-tumoural temperatures were recorded both in heated and non-heated contralateral tumours during treatment. Temperature was controlled via a feedback loop between the thermometry unit and a personal computer running customized software [19]. Thermometry was performed with clinical-grade, 20-gauge needle thermocouples (Labthermics Technologies, Champagne, IL).…”

“…Recently, however, Singh et al [19] devised a model to analyse the effects of hyperthermia for in vivo studies utilizing a small animal ultrasound system (SAHUS). This system represents a significant advance as it is compatible with small bore imaging devices such as microPET, provides power delivery in a feedback control loop, has rapid fall-off of thermal temperature outside the transducer and maintains temperature within a narrow range.…”

Monitoring the effect of mild hyperthermia on tumour hypoxia by Cu-ATSM PET scanning

“…The optimal session might also be one that is extremely short and has a very transitory effect on tumour oxygenation. For example, radiation and hyperthermia can be given simultaneously [39][40][41]. If it proves to be the case that the oxygenation improvement from a very short session reverses shortly after cessation of hyperthermia/radiation, then inter-treatment repopulation among hypoxic but viable cells will be less than if they remained oxygenated between treatments-a potential therapeutic advantage.…”