- Email: [email protected]
Role of acoustic interface layer during high intensity focused ultrasound therapeutics
आऋऑऎऊࣽईࣜऋंࣜ उँऀअࣿࣽईࣜ ࣿऋईईँःँएࣜऋंࣜऌईࣽ Journal of Medical Colleges of PLA 23 (2008) 223–227 www.elsevier.com/locate/jmcpla
Role of acoustic interface layer during high intensity focused ultrasound therapeuticsƿ Li Quanyi, Fu Liyuan, Qin Yan, Li Faqi*,Wang Zhibiao Sate Key Laboratory of Medical Ultrasound Engineering Co-founded by Chongqing and Ministry of Science and Technology, Institute of Ultrasound Engineering, Department of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China Received 28 March 2008; accepted 10 May 2008
Abstract After interface layer was simulated by the magnetic nano-particles in the egg white phantom, high intensity focused ultrasound (HIFU) at the same dosage was introduced to radiate the phantom in different depths to blow the acoustic interface layer to mimic “point” exposure. The results showed that the volumes of biological focal region (BFR) were enlarged when the acoustic focal region (AFR) is close with interface layer. This meant that the magnetic nano-particles enhanced the therapeutic efficiency of HIFU. When the distance of the AFR from the interface layer was 10 mm, the size and shape of the BFR were similar with those of the control group, but a larger lesion at the interface, which was harmful for treatment, was observed. When the distance of the AFR to the interface layer increased to 30 mm, the size and shape of the BFR were also similar to those of the control group. When the thickness of the interface layer diminished, the utility of enhancement decreased. Continuous increase of the safe area for treatment and decrease of the utility of enhancement were observed along with the abatement of the thickness of the interface layer Keywords: Magnetic nano-particles; Interface layer; Biological focal region; High intensity focused ultrasound
1. Introduction ƿ Supported by the Development Plan for Innovation Teams of Ministry of Education (2005-33), the National Natural Science Foundation of China (30471653), and the Natural Science Foundation of Chongqing (2006BA5020) * Corresponding author. E-mail address: [email protected](Li F.)
High intensity focused ultrasound (HIFU), as a new method [1–3] , has been used to treat solid tumor in clinical practice for years. In 1998, Wang et al [4] defined the punctiform coagulative necrosis region which was induced by HIFU as biological focal region (BFR), and also considered BFR as the basic unit of HIFU-caused tumor
224
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227
ablation. Because of the complexity of biological tissues, the acoustic interface layer is formed among different tissues when ultrasound transmits in multilayered tissues. Ultrasound will be reflected and refracted by this interface layer, and the distribution of the energy is affected in the target region, so it is very important to study the effects of acoustic interface layer on BFR. The acoustic environment in tissue (AET) was defined as the biological structure, functional status and acoustic properties in tissue during exposure to HIFU; and suggested an ideal AET condition should include the following 2 aspects: Firstly, there should be enough energy deposition in the target tissue; Secondly, it would be better to have a reflecting interface behind the target region. In order to study the effects of interface layer on HIFU-induced BFR, interface layers were simulated by nano-particles ( compatible with biological tissue; easily-tobe-used and controlled in magnetic field in vitro) in egg white phantom in this paper.
2. Materials and methods
2.1. Materials
Egg white phantom (storage time less than 24 h) was self-made. The magnetic nano-particles, 80–90 nm in diameter, which were modified on the surface and were compatible with biological tissues, were purchased from Beijing Zhongjianlong &o. Ltd., China.
2.2. Experimental system
A JC HIFU tumor therapeutic system (Chongqing Haifu Technology Co. Ltd., China), comprised an ultrasonic therapeutic unit and an
ultrasonic diagnostic unit, was employed. The therapeutic transducer with a diameter of 110 mm and focal length of 150 mm was mounted at the bottom of the tank filled with degassed water and beams of ultrasound pointed upwards. A diagnostic transducer was located at the centre of the therapeutic transducer in order to guide the HIFU treatment and to monitor the therapeutic effects in real time. The ultrasound beam with a frequency of 1.60 MHz was adopted in the present study (Fig. 1).
2.3. Methods The egg white phantom was made according to the reference [5]. Interface layer was simulated by the 80- to 90-nm-diametered magnetic nano-particles which was controlled by a magnet field as required (Fig. 2). The magnetic nanoparticles formed a layer (to mimic interface layer) in the phantom with 42 mm to the surface of the phantom (near from acoustic source) and 8–10 mm to the other surface of the phantom. Control group was formed in the same way as the experiment group except no interface layer was included. In order to study the effects of interface layer on the “lesion” (BFR) induced by HIFU, HIFU was carried out as point exposure with the power of 175 W, the exposure time of 10 s and repeated for 6 times at interval of 1 s. The exposure depths were 10 , 30 and 40 mm, respectively. Water tank
B model
Phantom Treat bed Treaat bed
HIFU transducer
B model image
Fig. 1. Illustration of experimental system. B model: Ultrasonic detector.
225
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227 MNP-layer 8–10 mm 42 mm
Phantom
A
B
C
D
E
F
G
Fig. 2. Interface layer of magnetic nano-particles (MNP-layer) in the egg white phantom. A˖Illustration of egg white phantom; B, D, F: Interfaces with the thickness of 0.27, 1.01 and 1.67 nm respectively; C, E, G: The thickness of the interfaces under a microscope with the magnification of 100, 100 and 40 respectively.
3. Results and discussion The acoustic energy decayed exponentially when it was propagating in tissue [6]. The volume of BFR induced by HIFU was decreased with the increase of the exposure depth when the power was at the same dosage. The BFR ZDV reduced significantly when the exposure depth increased by 20 mm [7]. Fig. 3 shows the BFR in the control phantom. Because the ultrasound will be reflected and transmitted at the interface of 2 different media, and the energy allocation dependV on the acoustic impedance characteristics of the media, the higher degree of the mismatching of impedance characteristicV of biological tissue is, the more easily the temperature rises. When the reflection of
A ƽ
B ƽ
C ƽ
Fig. 3. Phantom of control group after HIFU radiation. A– C: 7he depth of exposure were 10, 30 and 40 mm respectively.
superimposed on the target tissue, the energy will increased, thus, the efficiency of HIFU treatment will be enhanced. If the interface thickness was 1.67, 1.01 and 0.27 mm respectively, the treatment depth was 40 mm, and the distance from the interface layer to the sound source was 42 mm, the volume of the focal which focused on margin and the interfacial layer of the surface was about 1.1 mm×2.1 mm×3.2 mm. The results showed that the volume of HIFU BFR was increased significantly, but it was decreased with the decreasH of the thickness of interfacial layer. The shape of the BFR changed from “trumpet” into “inverted triangle”, as showed in Fig. 4–6. The results were consistent with the viewpoint brought forward by Wang [4]: The existence of the interface can improve the efficiency of HIFU treatment.
A ƽ
B ƽ
C ƽ
Fig. 4. Phantom of the interface of 1.67 mm in thickness after HIFU radiation. A–C: The depth of exposure were 10, 30 and 40 mm respectively. ķ indicates the lesion in the focus and ĸ the one in the interface.
226
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227
A ƽ
B ƽ
C ƽ
Fig. 5. Phantom of the interface of 1.01 mm in thickness after HIFU radiation. A, B (Vertical view), C: the depth of exposure were 10, 30 and 40 mm respectively. ķ indicates the lesion in the focus and ĸ the one in the interface.
When the exposure depth was 30 mm (the distance from the focus to interface was about 10 mm), there were 2 observed lesions in the phantom. One was destroyed in the focus (in B ķ of Fig. 4–6), the other was necrotized out the focus, but in the interface (in B ĸ of Fig. 4–6). The volume and the shape of the necrosis in the focus were similar with those of the control group. While the thickness of the interface layer decreased gradually, so did the volume of the necrosis in the interface. Because the protein gel phantom could not completely absorb ultrasonic sound, some of the ultrasound transmitted through the focal to the surface of nano-magnetic particles interface layer. Due to the high thermal conductivity of nano-magnetic particles, the energy could deposit in the interface to cause the damage there. The thicker the interface layer was, the more energy could deposit, and the larger necrosis was in the interface. This negative effects was detrimental for HIFU treatment and should be avoided in order to improve the safety of HIFU. The size of BFR induced by HIFU was similar with that of the control group when the exposure depth was 10 mm, but the effect of the interface layer reduced with the decreasing of the exposure depth, and no lesion was found at interface layer.
A ƽ
B ƽ
C ƽ
Fig. 6. Phantom of the interface of 0.27 mm in thickness after HIFU radiation. A–C: The depth of exposure were 10, 30 and 40 mm respectively. ķ indicates the lesion in the focus and ĸ the one in the interface.
The acoustic wave transmitted along the direction of convergence angle, as the distance from focal to the interface layer was 30 mm, so the acoustic energy deposition reduced in the interface layer (compared with treatment depth of 30 mm), enable to induce the egg white phantom lesion. It indicated that the safety treatment region enlarges with decreasing of the interface layer’s thickness.
4. Conclusion Therapeutic efficiency of HIFU can be enhanced when the focus is near the interface layer, but when the acoustic focus is at some region below this layer, negative impact on HIFU safety is observed. The safe region below the interface is decided by the interface layer’s thickness and therapeutic dosage. Our results indicate that the safe therapy region is 30 mm from the interface layer at the power of 175 W. In a word, the middle interface layer has severe influence on the BFR. It is very important for the safety and efficiency of HIFU clinical practice. In other words, we should choose therapeutic dosage carefully in clinical practice when there is an interface layer behind target region.
227
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227
References
resection with high intensity focused ultrasound. J Acoust Soc Am 1998; 103 (5): 2869.
1. Wu F, Wang ZB, Chen WZ, et al. Extracorporeal high
5. Li FQ, Ma P, Kou XQ, et al. A Transparent
intensity focused ultrasound ablation in the treatment
tissue-mimicking phantom for evaluating the focusing
of 1038 patients with solid carcinomas in China: an
performance of HIFU. Zhongguo Yi Xue Ying Xiang
overview. Ultrason Sonochem 2004; 11 (3–4): 149–
Ji Shu 2006; 22 (8): 1262–1265. (In Chinese)
154. 2. Thüroff
S,
Chaussy
C,
Vallancien
G,
et
al.
High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European
6. Feng R. Manual for ultrasonography. Nanjing: Publisher of Nanjing University, 1999: 657–717. (In Chinese)
multicentric study. J Endourol 2003; 17 (8): 673–677.
7. Wang ZB, Bai J, Li FQ, et al. Development of
3. Stewart E, Gedroyc W, Tempany C, et al. Focused
biological focal field of high-intensity focused
ultrasound treatment of uterine fibroids: safety and
untrasoud. Zi Ran Ke Xue Jin Zhan, 2002, 12 (4):
feasibility of a noninvasive thermoablative technique.
423–425. (In Chinese)
Am J Obstet Gynecol, 2003; 189 (1): 48–54. 4. Wang ZB,Wu F,Wang ZL, et al. Concept of biological focal field and its importance in tissue
(Editor Guo Jianxiu)
Role of acoustic interface layer during high intensity focused ultrasound therapeuticsƿ Li Quanyi, Fu Liyuan, Qin Yan, Li Faqi*,Wang Zhibiao Sate Key Laboratory of Medical Ultrasound Engineering Co-founded by Chongqing and Ministry of Science and Technology, Institute of Ultrasound Engineering, Department of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China Received 28 March 2008; accepted 10 May 2008
Abstract After interface layer was simulated by the magnetic nano-particles in the egg white phantom, high intensity focused ultrasound (HIFU) at the same dosage was introduced to radiate the phantom in different depths to blow the acoustic interface layer to mimic “point” exposure. The results showed that the volumes of biological focal region (BFR) were enlarged when the acoustic focal region (AFR) is close with interface layer. This meant that the magnetic nano-particles enhanced the therapeutic efficiency of HIFU. When the distance of the AFR from the interface layer was 10 mm, the size and shape of the BFR were similar with those of the control group, but a larger lesion at the interface, which was harmful for treatment, was observed. When the distance of the AFR to the interface layer increased to 30 mm, the size and shape of the BFR were also similar to those of the control group. When the thickness of the interface layer diminished, the utility of enhancement decreased. Continuous increase of the safe area for treatment and decrease of the utility of enhancement were observed along with the abatement of the thickness of the interface layer Keywords: Magnetic nano-particles; Interface layer; Biological focal region; High intensity focused ultrasound
1. Introduction ƿ Supported by the Development Plan for Innovation Teams of Ministry of Education (2005-33), the National Natural Science Foundation of China (30471653), and the Natural Science Foundation of Chongqing (2006BA5020) * Corresponding author. E-mail address: [email protected](Li F.)
High intensity focused ultrasound (HIFU), as a new method [1–3] , has been used to treat solid tumor in clinical practice for years. In 1998, Wang et al [4] defined the punctiform coagulative necrosis region which was induced by HIFU as biological focal region (BFR), and also considered BFR as the basic unit of HIFU-caused tumor
224
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227
ablation. Because of the complexity of biological tissues, the acoustic interface layer is formed among different tissues when ultrasound transmits in multilayered tissues. Ultrasound will be reflected and refracted by this interface layer, and the distribution of the energy is affected in the target region, so it is very important to study the effects of acoustic interface layer on BFR. The acoustic environment in tissue (AET) was defined as the biological structure, functional status and acoustic properties in tissue during exposure to HIFU; and suggested an ideal AET condition should include the following 2 aspects: Firstly, there should be enough energy deposition in the target tissue; Secondly, it would be better to have a reflecting interface behind the target region. In order to study the effects of interface layer on HIFU-induced BFR, interface layers were simulated by nano-particles ( compatible with biological tissue; easily-tobe-used and controlled in magnetic field in vitro) in egg white phantom in this paper.
2. Materials and methods
2.1. Materials
Egg white phantom (storage time less than 24 h) was self-made. The magnetic nano-particles, 80–90 nm in diameter, which were modified on the surface and were compatible with biological tissues, were purchased from Beijing Zhongjianlong &o. Ltd., China.
2.2. Experimental system
A JC HIFU tumor therapeutic system (Chongqing Haifu Technology Co. Ltd., China), comprised an ultrasonic therapeutic unit and an
ultrasonic diagnostic unit, was employed. The therapeutic transducer with a diameter of 110 mm and focal length of 150 mm was mounted at the bottom of the tank filled with degassed water and beams of ultrasound pointed upwards. A diagnostic transducer was located at the centre of the therapeutic transducer in order to guide the HIFU treatment and to monitor the therapeutic effects in real time. The ultrasound beam with a frequency of 1.60 MHz was adopted in the present study (Fig. 1).
2.3. Methods The egg white phantom was made according to the reference [5]. Interface layer was simulated by the 80- to 90-nm-diametered magnetic nano-particles which was controlled by a magnet field as required (Fig. 2). The magnetic nanoparticles formed a layer (to mimic interface layer) in the phantom with 42 mm to the surface of the phantom (near from acoustic source) and 8–10 mm to the other surface of the phantom. Control group was formed in the same way as the experiment group except no interface layer was included. In order to study the effects of interface layer on the “lesion” (BFR) induced by HIFU, HIFU was carried out as point exposure with the power of 175 W, the exposure time of 10 s and repeated for 6 times at interval of 1 s. The exposure depths were 10 , 30 and 40 mm, respectively. Water tank
B model
Phantom Treat bed Treaat bed
HIFU transducer
B model image
Fig. 1. Illustration of experimental system. B model: Ultrasonic detector.
225
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227 MNP-layer 8–10 mm 42 mm
Phantom
A
B
C
D
E
F
G
Fig. 2. Interface layer of magnetic nano-particles (MNP-layer) in the egg white phantom. A˖Illustration of egg white phantom; B, D, F: Interfaces with the thickness of 0.27, 1.01 and 1.67 nm respectively; C, E, G: The thickness of the interfaces under a microscope with the magnification of 100, 100 and 40 respectively.
3. Results and discussion The acoustic energy decayed exponentially when it was propagating in tissue [6]. The volume of BFR induced by HIFU was decreased with the increase of the exposure depth when the power was at the same dosage. The BFR ZDV reduced significantly when the exposure depth increased by 20 mm [7]. Fig. 3 shows the BFR in the control phantom. Because the ultrasound will be reflected and transmitted at the interface of 2 different media, and the energy allocation dependV on the acoustic impedance characteristics of the media, the higher degree of the mismatching of impedance characteristicV of biological tissue is, the more easily the temperature rises. When the reflection of
A ƽ
B ƽ
C ƽ
Fig. 3. Phantom of control group after HIFU radiation. A– C: 7he depth of exposure were 10, 30 and 40 mm respectively.
superimposed on the target tissue, the energy will increased, thus, the efficiency of HIFU treatment will be enhanced. If the interface thickness was 1.67, 1.01 and 0.27 mm respectively, the treatment depth was 40 mm, and the distance from the interface layer to the sound source was 42 mm, the volume of the focal which focused on margin and the interfacial layer of the surface was about 1.1 mm×2.1 mm×3.2 mm. The results showed that the volume of HIFU BFR was increased significantly, but it was decreased with the decreasH of the thickness of interfacial layer. The shape of the BFR changed from “trumpet” into “inverted triangle”, as showed in Fig. 4–6. The results were consistent with the viewpoint brought forward by Wang [4]: The existence of the interface can improve the efficiency of HIFU treatment.
A ƽ
B ƽ
C ƽ
Fig. 4. Phantom of the interface of 1.67 mm in thickness after HIFU radiation. A–C: The depth of exposure were 10, 30 and 40 mm respectively. ķ indicates the lesion in the focus and ĸ the one in the interface.
226
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227
A ƽ
B ƽ
C ƽ
Fig. 5. Phantom of the interface of 1.01 mm in thickness after HIFU radiation. A, B (Vertical view), C: the depth of exposure were 10, 30 and 40 mm respectively. ķ indicates the lesion in the focus and ĸ the one in the interface.
When the exposure depth was 30 mm (the distance from the focus to interface was about 10 mm), there were 2 observed lesions in the phantom. One was destroyed in the focus (in B ķ of Fig. 4–6), the other was necrotized out the focus, but in the interface (in B ĸ of Fig. 4–6). The volume and the shape of the necrosis in the focus were similar with those of the control group. While the thickness of the interface layer decreased gradually, so did the volume of the necrosis in the interface. Because the protein gel phantom could not completely absorb ultrasonic sound, some of the ultrasound transmitted through the focal to the surface of nano-magnetic particles interface layer. Due to the high thermal conductivity of nano-magnetic particles, the energy could deposit in the interface to cause the damage there. The thicker the interface layer was, the more energy could deposit, and the larger necrosis was in the interface. This negative effects was detrimental for HIFU treatment and should be avoided in order to improve the safety of HIFU. The size of BFR induced by HIFU was similar with that of the control group when the exposure depth was 10 mm, but the effect of the interface layer reduced with the decreasing of the exposure depth, and no lesion was found at interface layer.
A ƽ
B ƽ
C ƽ
Fig. 6. Phantom of the interface of 0.27 mm in thickness after HIFU radiation. A–C: The depth of exposure were 10, 30 and 40 mm respectively. ķ indicates the lesion in the focus and ĸ the one in the interface.
The acoustic wave transmitted along the direction of convergence angle, as the distance from focal to the interface layer was 30 mm, so the acoustic energy deposition reduced in the interface layer (compared with treatment depth of 30 mm), enable to induce the egg white phantom lesion. It indicated that the safety treatment region enlarges with decreasing of the interface layer’s thickness.
4. Conclusion Therapeutic efficiency of HIFU can be enhanced when the focus is near the interface layer, but when the acoustic focus is at some region below this layer, negative impact on HIFU safety is observed. The safe region below the interface is decided by the interface layer’s thickness and therapeutic dosage. Our results indicate that the safe therapy region is 30 mm from the interface layer at the power of 175 W. In a word, the middle interface layer has severe influence on the BFR. It is very important for the safety and efficiency of HIFU clinical practice. In other words, we should choose therapeutic dosage carefully in clinical practice when there is an interface layer behind target region.
227
Li Quanyi et al. / Journal of Medical Colleges of PLA 23 (2008) 223–227
References
resection with high intensity focused ultrasound. J Acoust Soc Am 1998; 103 (5): 2869.
1. Wu F, Wang ZB, Chen WZ, et al. Extracorporeal high
5. Li FQ, Ma P, Kou XQ, et al. A Transparent
intensity focused ultrasound ablation in the treatment
tissue-mimicking phantom for evaluating the focusing
of 1038 patients with solid carcinomas in China: an
performance of HIFU. Zhongguo Yi Xue Ying Xiang
overview. Ultrason Sonochem 2004; 11 (3–4): 149–
Ji Shu 2006; 22 (8): 1262–1265. (In Chinese)
154. 2. Thüroff
S,
Chaussy
C,
Vallancien
G,
et
al.
High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European
6. Feng R. Manual for ultrasonography. Nanjing: Publisher of Nanjing University, 1999: 657–717. (In Chinese)
multicentric study. J Endourol 2003; 17 (8): 673–677.
7. Wang ZB, Bai J, Li FQ, et al. Development of
3. Stewart E, Gedroyc W, Tempany C, et al. Focused
biological focal field of high-intensity focused
ultrasound treatment of uterine fibroids: safety and
untrasoud. Zi Ran Ke Xue Jin Zhan, 2002, 12 (4):
feasibility of a noninvasive thermoablative technique.
423–425. (In Chinese)
Am J Obstet Gynecol, 2003; 189 (1): 48–54. 4. Wang ZB,Wu F,Wang ZL, et al. Concept of biological focal field and its importance in tissue
(Editor Guo Jianxiu)