First published online November 12, 2007
British Journal of Radiology (2008) 81, 69-72
© 2008 British Institute of Radiology
doi: 10.1259/bjr/41820699
Implant hyperthermia resonant circuit produces heat in response to MRI unit radiofrequency pulses
T Niwa, MD1,3,
Y Takemura, PhD2,
T Inoue, MD1,
N Aida, MD3,
H Kurihara, MD1 and
T Hisa, RT1
1 Department of Radiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, 2 Department of Electrical and Computer Engineering, Graduate School of Engineering, Yokohama National University, 79-1, Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, 3 Depatment of Radiology, Kanagawa Children's Medical Centre, 2-138-4 Mutsukawa, Minami-ku, Yokohama, 232-8555, Japan
Correspondence: Tetsu Niwa, MD, Department of Radiology, Kanagawa Children Medical Centre, 2-138-4 Mutsukawa, Minami-ku, Yokohama, 232-8555, Japan. E-mail: tniwa{at}kcmc.jp
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Abstract
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A small resonant circuit was investigated for its potential for producing hyperthermia to treat cancer. Implant hyperthermia has been performed using tiny elements implanted inside the body that are heated by an external energy source. We assessed the effect on heat generation of a resonant circuit used as an implant hyperthermia device by MRI unit radiofrequency (RF) pulses with different imaging sequences. The resonant circuit used as a heating device consisted of a closed connection between a coil and a capacitor. The resonant frequency was set to 63.9 MHz so that the circuit would react and generate heat in response to the RF pulses of a 1.5 T MRI unit. The resonant circuit was placed in the MRI unit with an optical thermometer enclosed by insulating material, and the temperature rise was monitored during imaging sequences. Standard imaging MRI sequences —fast low angle shot gradient echo (FLASH), T1 weighted spin echo image (T1WI) and rapid acquisition with refocused echoes (RARE) — were used to produce RF pulses that affected the resonant circuit. This circuit was gradually heated during all MRI sequences. The temperature rise ranged from 7.2°C to 12.6°C. The highest temperature rise was obtained with RARE, followed by FLASH and T1WI. Thus, this apparatus may have potential for implant hyperthermia, which could provide minimally invasive anticancer therapy.
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Introduction
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Hyperthermia is known to be cytotoxic at temperatures of 40–45°C. This temperature may be selectively lethal to cancer cells, especially in the hypoxic, nutrient-deprived, low pH conditions that are present in malignant tumours [1]. Most normal tissues are not damaged at temperatures below 44°C. Various heating methods can be used for hyperthermia therapy. Implant hyperthermia has been performed using tiny elements implanted inside the body that are heated by an external energy source. This process was introduced as it can locally heat the cancerous tissue and reduce adverse effects on normal tissue. It can treat tissues that are difficult to heat from an external source owing to the presence of bone or air, or because they are either in a deep location or in highly mobile areas of the body. Previous reports have shown the effectiveness of implant hyperthermia for brain and liver tumours in animal models [2, 3] and for tongue, brain, breast and prostate tumours in humans [4–7]. Several implant hyperthermia devices have been reported, including hot water tubes, electrically heated rods, inductively heated ferromagnetic implants, magnetic nanoparticles and magnesium ferrite complex powder [2–5, 8, 9]. The disadvantage of these methods is that additional equipment with a high power supply or a relatively high magnetic field is required.
To overcome these problems, we considered the use of a resonant circuit as an implant hyperthermia device that can be excited by the radiofrequency (RF) pulses from a MRI unit [10]. The resonant circuit consists of a closed connection between a coil and a capacitor, which is heated by applying an alternating current (AC) magnetic field at the resonant frequency. Even small AC magnetic fields can heat the resonant circuit when the AC magnetic field matches the resonant frequency. The RF pulses of the MRI unit were used as the AC magnetic field source to induce current in the resonant circuit. If adequate heating could be obtained by the small resonant circuit with MRI unit RF pulses, then this could be used as a minimally invasive anticancer therapy and a simultaneous imaging analysis system. In this study, the heat generation of the resonant circuit in response to RF pulses from a 1.5 T MRI unit with different imaging sequences was assessed.
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Methods and materials
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The resonant circuit used in this study consisted of a closed connection between a coil (2.07 µH) and a capacitor (3.0 pF). The coil had six turns and a diameter of 12 mm (Figure 1
). The resonant circuit had a resonant frequency of 63.9 MHz, which is equal to the central frequency of a 1.5 T MRI unit-modulated RF magnetic field. The quality factor (Q factor) of the resonance circuit was 275. The magnetic flux densities of commercial high magnetic field MRI units are 1.0 T, 1.5 T and 3.0 T. Each MRI scanner has its own corresponding resonant frequency for the RF pulse. By adjusting the resonant frequency of the resonant circuit to the resonant frequency of each MRI scanner, heating should be obtained. An MRI unit generally consists of three different coil systems. One coil system produces a large static magnetic field, the second produces a RF pulse, and the third produces a gradient magnetic field. The RF pulse of the MRI unit consists of a sinc waveform. In a 1.5 T MRI unit, the RF pulse is modulated approximately in the range of 63.9±0.25 MHz to match the proton resonant frequency in the gradient magnetic field, so that a specific cross section can be selected for the process of imaging data acquisition. The gradient magnetic field coils, which are used to obtain spatial information, produce a much smaller magnetic field than does the RF coil; therefore, we assumed that their effect on the resonant circuit was negligible. Although the static magnetic field of the MRI unit is strong, it has no effect with respect to heating of the resonant circuit.
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Figure 1. The resonant circuit used in this study. This consists of a closed connection between a coil and a capacitor. The diameter of the device is 12 mm.
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The resonant circuit was placed in the centre of a commercially available 1.5 T MRI unit (Harmony; Siemens, Erlangen, Germany) together with an optical thermometer protected by insulating material; the thermometer was not affected by the high-frequency magnetic field. The resonant circuit was aligned so that the MRI RF pulse penetrated the coil of the resonant circuit. Because the device was small, loading of the RF coil used for transmission was insufficient unless appropriately sized water bottles were placed around the hyperthermia device. MRI scanning was performed with the standard imaging sequences: fast low angle shot gradient echo (FLASH), T1 weighted spin echo image (T1WI), and rapid acquisition with refocused echoes (RARE). Each scan was continuously performed to produce RF pulses that affected the resonant circuit; the temperature rise was monitored during each imaging sequence. In our previous experimental study, the temperature rise was diminished based on the difference between the resonant frequency of the resonant circuit and the AC magnetic field [10]. Thus, we set each of the parameters for each sequence to produce the central frequency of the magnetic field; that is, the parameters were set to obtain the central slice in the magnetic field, which was to be as thin as possible. As the MRI unit's RF pulses are generated at intervals according to the sequence chosen and are of low energy, imaging parameters were set to produce RF pulses optimally (shortest possible echo time and a large flip angle) with respect to pick-up in the resonant circuit. To compare the differences in the temperature rise between narrow and relatively wide spectrum RF pulses, the temperature rise with single- and multi-slice scanning on FLASH sequences was compared. The imaging parameters used in this study are shown in Table 1. For each imaging sequence, the temperature rise was monitored for 5 min; the initial temperature was room temperature (23°C).
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Results
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The resonant circuit was heated gradually during each sequence. The small resonant circuit for implant hyperthermia had an adequate temperature rise for hyperthermia in response to the weak RF pulses of the MRI unit. The greatest temperature rise was obtained with the RARE sequence (12.6°C), followed by the FLASH with one centre slice scanning (Figure 2). The RARE sequence produces more RF pulses over a short period of time than do the other sequences. With the FLASH sequence, a higher temperature rise was obtained with one centre slice scanning compared with multi-slice scanning. The multi-slice sequence uses several resonant frequencies along with the gradient magnetic field to target the imaging slice; this is not efficient with respect to heating of the resonant circuit. A lower temperature rise (>7°C) was obtained with T1WI and FLASH with multi-slice sequence scanning.
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Figure 2. The temperature rise of the resonant circuit for each imaging sequence. RARE, rapid acquisition with refocused echoes; FLASH, fast low angle shot gradient echo. The highest temperature rise was achieved with the RARE sequence.
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Discussion
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In our previous study, it was found that the temperature rise was much smaller when there were greater differences between the resonant frequency of the resonant circuit and the applied AC magnetic field. The temperature rise was reduced by 50% when the frequency of the applied pulse varied by 1 MHz from the resonant frequency of the resonance circuit [10]. Therefore, for heat generation, it is necessary to match the resonant frequency of the resonant circuit and the AC magnetic field. The MRI imaging parameters were set to obtain one central slice with the smallest possible thickness and the smallest bandwidth. We also set the imaging parameters to produce strong effective pulses. The magnetic field of the MRI RF pulses depends on various parameters, including the type of sequences, the flip angle, the echo time and the echo spacing. In the standard MRI sequence for imaging, RF pulses are generated at intervals, according to the sequence, with relatively low energy. Although interaction occurs, the temperature rise of the resonance circuit with standard imaging sequences should be much smaller.
Several implant methods for hyperthermia have been developed. For example, metal can be heated in a magnetic field, and a MRI unit's RF pulse can cause heating of metal. However, there have been several reports of heating or burns related to relatively long (>1 m in length) metal loops that form an antenna [11, 12]. As the MRI unit's RF pulses are produced intermittently and its RF magnetic field is very small, a small metal device would have almost no toxicity during imaging sequences [13–15]. It would be almost impossible for overheating to develop with a small metal implant device used with an MRI unit. Inductively heated ferromagnetic implants and a magnesium ferrite complex powder have been used as implant materials, and are affected by a magnetic field (250 kHz and 100 kHz, respectively) [4, 9]. These materials can be heated by specific energy sources, such as coils and strong power supply units. We estimated that these materials require much stronger magnetic fields than those obtained with an MRI unit to obtain heating. Conversely, resonant circuits can be effectively heated by the small RF magnetic field of a MRI unit. It would be advantageous to use a resonant circuit with an MRI unit for hyperthermia, because MRI units are widely used in medical practice and could become a useful source of external energy source for implant hyperthermia therapy. Although the resonance circuit for implant causes artefacts on imaging, this system — because of its imaging capability — would make it possible to assess the device's location and the status of the surrounding tissue, as well as the temperature, with MRI thermometry just after hyperthermia therapy; repeated therapy would be possible if residual or recurrent tumour were identified. It was speculated that the resonance circuit might cause artefacts in a relatively wide area on images with interaction of RF pulses of MRI. Although we have not studied in detail the image artefact resulting from the resonance circuit, we assume that any artefact will be in a limited area, leaving the surrounding tissue accessible for assessment (Figure 3).
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Figure 3. The image of the resonance circuit implanted in the porcine muscle. AT1 weighted spin echo image shows that the resonance circuit causes relatively limited artefact (arrow). It is thus possible to assess the surrounding tissue.
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The current system has several problems that need to be resolved. Firstly, the production of heat by the resonant circuit depends on the direction of the magnetic field. In this study, the resonant circuit was positioned so that the AC magnetic field could penetrate the resonant circuit's coil. However, it would be difficult to place the device in one direction in vivo. Possible solutions may include using coils placed in various directions within the implant device, or aligning the system with the MRI unit's static magnetic field. Secondly, the resonant circuit used in this study was a relatively large prototype (12 mm in diameter). Its diameter could be reduced to 1 mm so that it could be delivered with a needle or catheter. Thirdly, the temperature rise was monitored in the static field. In biological tissue, heat diffusion and local vessel perfusion may reduce local heating. The penetration of RF pulses to the coil would be lower for real tissue, resulting in a reduction in the effectiveness of heating. The water bottles used to simulate human tissue were not adequate to demonstrate the reduced penetration that might be expected in vivo. The number of resonance circuits required for hyperthermia would depend on the size and characteristics of the tumour. In the future, the position and number of implants required in biological tissue will have to be assessed. Finally, the resonance circuit for implantation causes imaging artefacts. These may be decreased by reducing the size or changing the material of the resonance circuit.
In conclusion, the resonant circuit increased in temperature in response to the MRI unit's RF pulse. The highest temperature rise was achieved with the RARE sequence. This system has the potential to be used as a method of implant hyperthermia that provides minimally invasive anticancer therapy.
This study was partly supported by Grants-in-Aid for Scientific Research of the Japanese Society for the Promotion of Science.
Received for publication January 23, 2007.
Revision received June 20, 2007.
Accepted for publication June 26, 2007.
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Abstract
Introduction
