Biomedical subjects

C T W Moonen

Publications and source records attributed to C T W Moonen.

3 recordsLinked to original sources

PubMed2005

Magnetic resonance temperature imaging.

Continuous, real-time, 3D temperature mapping during a hyperthermic procedure may provide (i) enhanced safety by visualizing temperature maps in and around the treated region, (ii) improved efficiency by adapting local energy deposition with feedback coupling algorithms and (iii) therapy end-points based on the accumulated thermal dose. Non-invasive mapping of temperature changes can be achieved with MRI and may be based on temperature dependent MRI parameters. The excellent linearity of the temperature dependency of the proton resonance frequency (PRF) and its near-independence with respect to tissue type make the PRF-based methods the preferred choice for many applications, in particular at mid- to-high field strength (> or =0.5 T). The PRF methods employ RF-spoiled gradient echo imaging methods and incorporate fat suppression techniques for most organs. A standard deviation of less than 1 degrees C, for a temporal resolution below 1 s and a spatial resolution of approximately 2 mm is feasible for immobile tissues. Special attention is paid to methods for reducing artifacts in MR temperature mapping caused by intra-scan and inter-scan motion and motion and temperature-induced susceptibility effects in mobile tissues. Real-time image processing and visualization techniques, together with accelerated MRI acquisition techniques, are described because of their potential for therapy guidance.

Humans↗

PubMed2003

Spatial and temporal control of transgene expression in vivo using a heat-sensitive promoter and MRI-guided focused ultrasound.

BACKGROUND: Among the techniques used to induce and control gene expression, a non-invasive, physical approach based on local heat in combination with a heat-sensitive promoter represents a promising alternative but requires accurate temperature control in vivo. MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control allows automatic execution of a predefined temperature-time trajectory. The purpose of this study was to demonstrate temporal and spatial control of transgene expression based on a well-defined local hyperthermia generated by MRI-FUS. METHODS: Expression of the green fluorescent protein (GFP) marker gene was used. Two cell lines were derived from C6 glioma cells. The GFP expression of the first one is under the control of the CMV promoter, whereas it is under the control of the HSP70 promoter in the second one and thus inducible by heat. Subcutaneous tumours were generated by injection in immuno-deficient mice and rats. Tumours were subjected to temperatures varying from 42 to 50 degrees C for 3 to 25 min controlled by MRI-FUS and analyzed 24 h after the heat-shock. Endogenous HSP70 expression and C6 cell distribution were also analyzed. RESULTS: The results demonstrate strong expression at 50 degrees C applied during a short time period (3 min) without affecting cell viability. Induced expression was also clearly shown for temperature in the range 44-48 degrees C but not at 42 degrees C. CONCLUSIONS: Heating with MRI-FUS allows a tight and non-invasive control of transgene expression in a tumour.

Animals↗

PubMed2003

Image-guided control of transgene expression based on local hyperthermia.

Spatial and temporal control of transgene expression is one of the major prerequisites of efficient gene therapy. Recently, a noninvasive, physical approach has been presented based on local heat in combination with a heat-sensitive promoter. This strategy requires tight temperature control in vivo. Here, we use MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control on a whole-body clinical MRI system for a completely automatic execution of a predefined temperature-time trajectory in the focal point. Feasibility studies on expression control were carried out on subcutaneously implanted rat tumors. A stable modified C6 glioma cell line was used carrying a fused gene coding for thymidine kinase (TK) and green fluorescent protein (GFP) under control of the human heat-shock protein 70 (HSP70) promoter. In vitro studies showed strong induction of the TK-GFP gene expression upon heat shock under various conditions and localization of the protein product in the nucleus. In vivo tumors were subjected to a 3-min temperature elevation using MRI-FUS with a constant temperature, and were analysed 24 hr after the heat shock with respect to GFP fluorescence. Preliminary results showed strong local induction in regions heated above 40 degrees C, and a good correspondence between temperature maps at the end of the heating period and elevated expression of TK-GFP.

Animals↗