Controlled radio-frequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by¹H,²³Na and³¹P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma

Abstract

A magnetic resonance (MR) technique is developed to produce controlled radio-frequency (RF) hyperthermia (HT) in subcutaneously-implanted 9L-gliosarcoma in Fisher rats using an MR scanner and its components; the scanner is also simultaneously used to monitor the tumour temperature and the metabolic response of the tumour to the therapy. The method uses the (1)H chemical shift of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (TmDOTA(-)) to monitor temperature. The desired HT temperature is achieved and maintained using a feedback loop mechanism that uses a proportional-integral-derivative controller. The RF HT technique was able to heat the tumour from 33 degrees to 45 degrees C in approximately 10 min and was able to maintain the tumour temperature within +/-0.2 degrees C of the target temperature (45 degrees C). Simultaneous monitoring of the metabolic changes with RF HT showed increases in total tissue and intracellular Na(+) as measured by single-quantum and triple-quantum filtered (23)Na MR spectroscopy (MRS), respectively, and decreases in intra- and extracellular pH and cellular bioenergetics as measured by (31)P MRS. Monitoring of metabolic response in addition to the tumour temperature measurements may serve as a more reliable and early indicator of therapy response. In addition, such measurements during HT treatment will enhance our understanding of the tumour response mechanisms during HT, which may prove valuable in designing methods to improve therapeutic efficiency.

Increased Temperature Enhances the Antimicrobial Effects of Daptomycin, Vancomycin, Tigecycline, Fosfomycin, and Cefamandole on Staphylococcal Biofilms

“…However, to create heat, an alternating current might be applied to the implant at an appropriate frequency. Other physical measures that could be used to create heating at the implant surface could be microwaves or lasers, both at appropriate frequencies, or, as described recently, magnetic resonance scanning (26). However, as evidence of clinical safety is not yet available, the increase in the temperature to 45°C, particularly for a prolonged period, may be associated with thermal burn injuries.…”

From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers

“…Mild hyperthermia, the heating of tumors to 40–42°C, [62] has a long history of clinical use, whereby localized heating is achieved by focused ultrasound, microwaves, or radiowaves. [63] Mild hyperthermia can be used to influence accumulation in tumors by controlling the in situ behavior of temperature-responsive drug carriers as they circulate in the tumor vasculature. The lower critical solution temperature (LCST) phase-transition behavior of elastin-like polypeptides (ELPs), within a precisely tuned thermal window of 39–42°C, can be exploited in vivo, as local heating triggers the transition of ELPs from a soluble state into insoluble micrometer-scale aggregates within the tumor vasculature.…”

An integrated platform for small-animal hyperthermia investigations under ultra-high-field MRI guidance

“…In smaller animals, such as rodents, which are often used for pre-clinical investigations, surface applicators may be suitable for heating both superficial and deep-seated targets [28]. James et al, developed a dual-mode radiofrequency coil for delivering inductive hyperthermia, while also serving as an MRI receive coil [30].…”