International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationsMagnetic Resonance Thermometry During Hyperthermia for Human High-Grade Sarcoma
Introduction
Hyperthermia has been shown to improve tumor control in randomized clinical trials 1, 2, 3, 4. Several mechanisms of action provide a rationale for using hyperthermia to improve the therapeutic ratio in cancer treatment, including direct cell kill, radiation sensitization, and chemosensitization [5]. However, optimizing delivery of hyperthermia has historically been restricted by limitations in heating technology and treatment planning, and an inability to fully characterize temperature distributions in tissue. With regard to the latter, a major drawback has been the necessity to use invasive probes to monitor and control temperatures. Temperature distributions obtained in clinical treatment are nonuniform and generally unpredictable. Treatment personnel are unable to characterize these nonuniform temperature distributions from just one or two invasively placed catheters. An appealing alternative would be a means of noninvasively measuring temperature, even if it involves a loss of measurement resolution relative to current invasive techniques. Consequently, there has been long-term, and recently, renewed interest in the development of noninvasive thermometry for clinical hyperthermia 6, 7, 8, 9, 10, 11, 12, 13, 14.
One of the technologies being investigated for noninvasive thermometry is magnetic resonance imaging (MRI). Magnetic resonance relaxation times are temperature-dependent and have been considered for thermometric image parameters [15]. Also, the diffusion coefficient of water and chemical shift of water or other agents have been proposed as thermal parameters measurable via MRI 11, 13, 16, 17, 18. In particular, the chemical shift of water has a temperature coefficient of approximately 0.01 parts per million (ppm) per ° Celsius 19, 20, 21. This resonance shift, measured as a phase change in gradient-echo images, has been shown to be effective for temperature mapping in tissue-equivalent phantoms and in vivo 14, 22, 23. This technique has also been used as a means to target tissue for ablation using focused ultrasound and high-intensity lasers 6, 8, 22, 24, 25. These reports, demonstrating a correlation between the MR measured parameters and temperature, clearly indicate potential for noninvasively mapping temperature 3-dimensionally (3D). Further development of these techniques will provide valuable thermal dosimetry information that could be used to optimize hyperthermia treatments, hardware design, and mathematical models of dose distribution. Noninvasive thermometry will likely also have additional applications in medicine, research, and industry.
In this work, we investigated the feasibility of using noninvasive MR chemical-shift thermometry in humans. We report the difficulties encountered in treating humans and propose techniques for addressing these problems.
Section snippets
MR Imaging
Imaging was performed at 1.5 T in a whole-body clinical MRI unit1 dedicated to research studies. Magnitude and phase images were extracted from gradient-echo pulse-sequence acquisitions. Typical pulse-sequence acquisition parameters were: TR (repetition time) = 34 ms; TE (echo time) = 20 ms; FOV (field of view) = 240 mm; slice thickness = 10 mm; BW (full band width) = ± 16 kHz; acquisition matrix = 256 × 256; number of excitations (NEX) = 1.
MR-Hyperthermia Systems
In a previous work, we described a technique that
Results
Fig. 1 is a plot of phase difference vs. time observed at several ROIs in the phantom, including external reference standards, in a mock treatment setup that did not involve heating. These data demonstrate the stability of phase measurement with the Signa system over time periods that are relevant to conventional hyperthermia treatments (30–90 min). The total drift on average is approximately 20 degrees of phase for this 90-min measurement period. In repeated experiments, there is a consistent
Discussion
In this work, we demonstrate the feasibility of using MRI to monitor temperature during hyperthermia therapy for patients with sarcoma in the distal lower extremity. The MR technique measures the chemical shift of the proton resonance frequency associated with temperature via a phase-difference image. This experience revealed several technical difficulties that required modification to our procedure as the human studies evolved. Consequently, the quality of thermal images improved for the more
Acknowledgements
Thanks to staff members Janye Blivin and Phil Antoine for their support in this work, and Jane Hoppenworth and Jeanne Forrest for their assistance in preparation of this manuscript. We also thank patients MJ, BM, WB, and LO for volunteering for these studies. Support of this research was provided in part by NIH/NCI grant number 2PO1 CA42745, and RO1 CA62618.
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