Magnetic Resonance Thermometry During Hyperthermia for Human High-Grade Sarcoma

doi:10.1016/S0360-3016(97)00855-9

International Journal of Radiation OncologyBiologyPhysics

Volume 40, Issue 4, 1 March 1998, Pages 815-822

https://doi.org/10.1016/S0360-3016(97)00855-9 Get rights and content

Abstract

Purpose: To determine the feasibility of measuring temperature noninvasively with magnetic resonance imaging during hyperthermia treatment of human tumors.

Methods: The proton chemical shift detected using phase-difference magnetic resonance imaging (MRI) was used to measure temperature in phantoms and human tumors during treatment with hyperthermia. Four adult patients having high-grade primary sarcoma tumors of the lower leg received 5 hyperthermia treatments in the MR scanner using an MRI-compatible radiofrequency heating applicator. Prior to each treatment, an average of 3 fiberoptic temperature probes were invasively placed into the tumor (or phantom). Hyperthermia was applied concurrent with MR thermometry. Following completion of the treatment, regions of interest (ROI) were defined on MR phase images at each temperature probe location, in bone marrow, and in gel standards placed outside the heated region. The median phase difference (compared to pretreatment baseline images) was calculated for each ROI. This phase difference was corrected for phase drift observed in standards and bone marrow. The observed phase difference, with and without corrections, was correlated with the fiberoptic temperature measurements.

Results: The phase difference observed with MRI was found to correlate with temperature. Phantom measurements demonstrated a linear regression coefficient of 4.70° phase difference per ° Celsius, with an R² = 0.998. After human images with artifact were excluded, the linear regression demonstrated a correlation coefficient of 5.5° phase difference per ° Celsius, with an R² = 0.84. In both phantom and human treatments, temperature measured via corrected phase difference closely tracked measurements obtained with fiberoptic probes during the hyperthermia treatments.

Conclusions: Proton chemical shift imaging with current MRI and hyperthermia technology can be used to monitor and control temperature during treatment of large tumors in the distal lower extremity.

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.

References (27)

J Overgaard et al.
Randomized trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma
Lancet
(1995)
P.K Sneed et al.
Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost + hyperthermia for glioblastoma multiformeProceedings of the 38th Annual Astro Meeting (Abstr.)
Int. J. Radiat. Oncol. Biol. Phys.
(1996)
C.C Vernon et al.
Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trialsInternational Collaborative Hyperthermia Group
Int. J. Radiat. Oncol. Biol. Phys.
(1996)
J De Poorter et al.
The proton-resonance-frequency-shift method compared with molecular diffusion for quantitative measurement of two-dimensional time-dependent temperature distribution in a phantom
J. Magn. Res.
(1994)
R Vadagni et al.
Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV head and neck patients
Int. J. Radiat. Oncol. Biol. Phys.
(1994)
G.M Hahn
H Cline et al.
MR temperature mapping of focused ultrasound surgery
Magn. Reson. Med.
(1994)
L Dubois et al.
Non-invasive microwave multifrequency radiometry used in microwave hyperthermia for bidimensional reconstruction of temperature patterns
Int. J. Hyperthermia
(1993)
K Hynynen et al.
MRI-guided noninvasive ultrasound surgery
Med. Phys.
(1993)
D.A McRae et al.
Noninvasive, in vivo electrical impedance of EMT-6 tumours during hyperthermiacorrelation with morphology and tumour-growth-delay
Int. J. Hyperthermia
(1997)

K.D Paulsen et al.

Initial in vivo experience with EIT as a thermal estimator during hyperthermia

Int. J. Hyperthermia

(1996)

T Samulski et al.

Noninvasive thermometry using magnetic resonance diffusion imagingPotential for application in hyperthermic oncology

Int. J. Hyperthermia

(1992)

R Seip et al.

Noninvasive real-time multipoint temperature control for ultrasound phased array treatments

IEEE Trans. UFFC

(1996)

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Clinical InvestigationsMagnetic Resonance Thermometry During Hyperthermia for Human High-Grade Sarcoma

Abstract

Introduction

Section snippets

MR Imaging

MR-Hyperthermia Systems

Results

Discussion

Acknowledgements

Lancet

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

J. Magn. Res.

Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV head and neck patients

Int. J. Radiat. Oncol. Biol. Phys.

MR temperature mapping of focused ultrasound surgery

Magn. Reson. Med.

Non-invasive microwave multifrequency radiometry used in microwave hyperthermia for bidimensional reconstruction of temperature patterns

Int. J. Hyperthermia

MRI-guided noninvasive ultrasound surgery

Med. Phys.

Noninvasive, in vivo electrical impedance of EMT-6 tumours during hyperthermiacorrelation with morphology and tumour-growth-delay

Int. J. Hyperthermia

Initial in vivo experience with EIT as a thermal estimator during hyperthermia

Int. J. Hyperthermia

Noninvasive thermometry using magnetic resonance diffusion imagingPotential for application in hyperthermic oncology

Int. J. Hyperthermia

Noninvasive real-time multipoint temperature control for ultrasound phased array treatments

IEEE Trans. UFFC

Clinical Investigations
Magnetic Resonance Thermometry During Hyperthermia for Human High-Grade Sarcoma