APPLIED PHYSICS LETTERS 98, 023703 共2011兲
Magnetoacoustic imaging of human liver tumor with magnetic induction Gang Hu,1 Erik Cressman,2 and Bin He1,a兲 1
Department of Biomedical Engineering, University of Minnesota, Minnesota 55455, USA Department of Radiology, University of Minnesota, Minnesota 55455, USA
2
共Received 19 November 2010; accepted 27 December 2010; published online 13 January 2011兲 Magnetoacoustic tomography with magnetic induction 共MAT-MI兲 is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues. © 2011 American Institute of Physics. 关doi:10.1063/1.3543630兴 Electrical impedance imaging approaches have been widely explored for several decades, since changes in tissue’s electrical impedance provide useful physiological and pathological information about the biological tissues. Various imaging techniques have been employed to discern these conditions, including electrical impedance tomography,1,2 magnetic resonance electrical impedance tomography,3,4 magnetic induction tomography,5 magnetoacoustic tomography,6,7 Hall effect imaging,8 and the recently proposed magnetoacoustic tomography with magnetic induction 共MAT-MI兲.9–12 Among these methods, MAT-MI features excellent spatial resolution 共near to ultrasound imaging兲 as well as noncontact magnetic energy deposition. In MAT-MI, the sample is placed in a static magnetic field. Then, a timevarying magnetic field is applied to induce eddy currents in the conductive tissue volume. The Lorentz force is then generated, from the interaction between the eddy current and magnetic field, and causes mechanical vibration of the tissue. Acoustic waves are produced as a result of the vibration, and can be recorded by acoustic probes placed surrounding the object. Previous studies have already demonstrated that MAT-MI is capable and sensitive to imaging electrical conductivity contrast in gel phantoms,10 salted animal
tissues,11 and fresh animal tissues12 with a conductivity contrast around 0.4⬃ 0.6 S / m. In the present study, we conducted MAT-MI imaging of human liver tumor tissue samples to directly test the feasibility of distinguishing and imaging of cancerous tumor in human by means of MAT-MI. In MAT-MI, in order to deposit energy, an excitation coil is used to send out a pulsed magnetic stimulation B1共r , t兲 to a tissue sample 共see Fig. 1兲. Usually, the pulse duration is at microsecond scale for megahertz ultrasound generation. According to Faraday’s law, an electrical field E共r , t兲 will be induced in the space. If the object is conductive and with conductivity distribution 共r兲, we have the current density distribution J共r , t兲 in the object which can be determined by J共r , t兲 = 共r兲E共r , t兲. The quasistatic condition is satisfied in the MAT-MI problem, as the system working frequency is low. Because of the short duration of the magnetic stimulation, the current density J共r , t兲 can be approximated as the product of a pure spatial function J共r兲 and a delta function ␦共t兲. With a static magnetic field B0共r兲 and the corresponding Lorentz force J共r兲 ⫻ B0共r兲, the acoustic pressure distribution p共r⬘ , t兲 at spatial point r⬘ in the acoustically homogenous medium will follow the wave equation,9
FIG. 1. 共Color online兲 Schematic of MAT-MI for tumor imaging.
a兲
Author to whom correspondence should be addressed. Electronic mail:
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© 2011 American Institute of Physics
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Appl. Phys. Lett. 98, 023703 共2011兲
Hu, Cressman, and He
FIG. 2. 共Color online兲 共a兲 Photography of a well-controlled phantom consisting of a human liver tumor tissue and a normal tissue. Two portions are from the identical sample. The feature points at tissue interface and boundary are labeled with letters. 共b兲 Reconstructed MAT-MI image in 共a兲. 共c兲 Photography of a phantom consisting of two pieces of normal pork liver tissues for a control experiment. 共d兲 Reconstructed image of the phantom in 共c兲. No significant MAT-MI signals were observed corresponding to the tissue contact interface from point b to e in 共c兲.
ⵜ2 p共r⬘,t兲 −
1 2 p共r⬘,t兲 = ⵜ · 关J共r兲 ⫻ B0共r兲兴 · ␦共t兲, c2 t2
共1兲
where the c is the acoustic speed. The acoustic source distribution at the right hand side of Eq. 共1兲 can be computed using the time reversal method9,13 ⵜ · 关J共r兲 ⫻ B0共r兲兴 ⬇ −
1 2c3
− r兩/c兲,
冕冕
⌺
dSd
n · 共rd − r兲 p⬙共rd,兩rd 兩rd − r兩2 共2兲
where rd is the detection point on the surface ⌺ and p⬙ is the second time derivative of the pressure. If the object has electrically piecewise homogeneous distribution, the conductivity distribution can be obtained by applying a median filter to the acoustic source map when the wide-bandwidth MAT-MI signals are available,14 or by using a multi-excitation method.15 The left hand side of Eq. 共2兲 is divergence of Lorentz force which represents acoustic source responsible for the acoustic signals recorded by a probe. For this experiment, we used an experimental system with a circular measurement configuration 共Fig. 1兲. Both the sample and the transducer were immersed under distilled water for acoustic signal coupling. The flat transducer was mounted on a holder driven by a step motor for mechanical rotation in the XY plane. This transducer had a diameter of 25 mm and a peak sensitivity frequency close to 0.5 MHz. For higher detection sensitivity in acoustic measurements, the transducer was custom fabricated using piezocomposite technology. Piezoelectric signals collected by the transducer were amplified with a low-noise ultrasound amplifier with
90 dB voltage gain before the data digitalization. In order to improve signal-to-noise ratio, a customized magnetic stimulator was employed to deliver strong yet safe magnetic energy to the object.12 The magnetic coil with outer diameter of 70 mm was placed under the water tank. The coil driver was equipped with an adjustable high-voltage source, a capacitor, and a solid state switch for handling large currents. Fast discharge of the internal capacitor produced stimulation with a pulse width of 1.6 s. When the charging voltage was set at peak voltage 共24 kV兲, the magnetic stimulator was able to induce an average electrical field of 550 V/m at the bottom of the sample. To build a static magnetic field, two permanent magnets with diameter of 75 mm were placed on the top and bottom of the sample. The separation between the two magnets was adjustable according to the sample thickness. The produced magnetic flux density was 0.2⬃ 0.3 T. A data acquisition system was used for trigger control, signal synchronization and data transferring. For each channel, 2048 data points were collected with a 5 MHz sampling rate. All experimental studies have been approved by the Institutional Review Board 共IRB兲 for Human Research at the University of Minnesota. An excised fresh liver sample with original size of 30⫻ 40⫻ 12 mm3 was obtained from a patient having previously undergone surgical removal of liver tumor. Pathology study of the liver tumor samples confirmed that the tumor sample was a cancerous tumor. The tumor site in the sample was located approximately at the center, presenting an irregular shape with maximum diameter of roughly 1.5 cm. We built a phantom consisting tissues with regular shape for this experiment. The tumor site was excised from the surrounding normal tissue. Direct conductivity measurements were performed for both tumor tissue and the surrounding tissue in ten different points 共five for tumor tissue and five for normal tissue兲 at 0.5 MHz before and after the excision by using a four-electrode probe.16 The probe constant was precalibrated with standard solutions 共Oakton Inc.兲 of varying nominal conductivity values of 0.26, 0.83, and 1.19 S/m at an experimental temperature of 21 ° C. The calibrated results indicated good measurement linearity for a conductivity range from 0.20 to 1.20 S/m, which was comparable to that of fresh soft tissues. No significant changes in the electrical conductivity had been observed by the tumor excision. The tumor tissue had conductivity of 0.65–0.70 S/m, while the normal tissue characterized a lower conductivity of 0.25–0.28 S/m. Following conductivity measurements, the tumor and normal tissue samples were diced into rectangular shapes with sizes of 11⫻ 4.5⫻ 8 and 11⫻ 5 ⫻ 8 mm3, respectively. Lastly, a tumor phantom was composed by pressing the two tissue portions together as shown in Fig. 2共a兲. In the imaging experiments, the transducer collected the MAT-MI ultrasound signals with angular step of 2°. At each view point, 200 times data averaging was used. We reconstructed the acoustic source distribution by using the twodimensional discrete form of Eq. 共2兲. Figure 2共b兲 shows the reconstructed acoustic source image, which illustrates contours being consistent with the boundaries between the tumor and normal tissue, as well as the tissues with the surrounding gel 关Fig. 2共a兲兴. Some feature points at the tissue interface and outer boundary were marked for the comparison. Both the location and the size of the sample were well distinguished and imaged. For a comparison, we did a control experiment on a phantom, which was made by pushing two pieces of
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Appl. Phys. Lett. 98, 023703 共2011兲
Hu, Cressman, and He
cause the biological tissues have soft structure, which usually exhibits nonuniform distribution along the Z direction, while the photograph in Fig. 3共a兲 was taken only from the top. However, In Fig. 3共b兲, the normal-pathological interface still can be resolved as indicated by an arrow. The upper part of the interface is not well imaged because an existing air gap greatly attenuated the MAT-MI signals at that region. Further, the overall imaging quality is reduced by the relative thinness 共2 mm兲 of the sample. For this sample, no direct conductivity measurements were made, because the probe tip length 共1.5–1.8 mm兲 was comparable to the sample thickness, which would generate inaccurate conductivity results. The real liver tumor tissue sample 关Fig. 3共a兲兴 may represent a much more complex structure than the sample tumor phantom we created 关Fig. 2共a兲兴. Such irregular shape makes it difficult to image. In addition, the transition zone from normal tissue to tumor in some cases can be broad, which makes the tumor-normal interface difficult to discern. This ambiguous interface also contributed to the reduced imaging quality because the recorded ultrasound signal intensity is theoretically proportional to the tissue conductivity gradient. Despite these challenges, Fig. 3 indicates the feasibility for imaging real human liver cancerous tumor in an in vitro setting by means of the MAT-MI. In conclusion, we demonstrate that the MAT-MI imaging method is able to distinguish with high spatial resolution the small electrical conductivity contrast formed by liver tumor tissues and normal tissues. Further investigation may establish MAT-MI as an important technique for imaging and earlier detection of cancers in a clinical setting. FIG. 3. 共Color online兲 共a兲 Photograph of a real human liver tumor sample, which retains the naturally formed tissue structure. Several markers were added at feature points at tissue interface and boundary for image comparison. 共b兲 Reconstructed MAT-MI image of the sample shown in 共a兲.
fresh pork liver tissue together as in Fig. 2共c兲. The size of each piece was 15⫻ 5.5⫻ 5 mm3. The two pieces had nearly the same conductivity value. No significant signals from that contact interface are observed in the reconstructed image shown in Fig. 2共d兲, which demonstrates that the tiny mechanical discontinuities contribute little to MAT-MI signals. Hence, such vertical line and other boundary lines represent acoustic source distribution when there is change in electrical conductivity.17 This result suggests that the MAT-MI is able to differentiate the tumor tissue and the normal tissue by using conductivity differences as a means for contrast. In the second experiment, we used a sample retaining the naturally formed liver tumor and normal tissue structure as shown in Fig. 3共a兲. This sample had a nearly trapezoidal shape with maximum side lengths of 16 mm, and an approximate width of 12 mm. The reconstruction of acoustic source distribution was accomplished according to Eq. 共2兲. Figure 3共b兲 shows the processed acoustic source image of the sample. We also marked several feature points on both sample photograph and reconstructed image for the comparison. Small deformations at outer boundary are observed be-
This work was supported in part by NIH Grant No. R21EB006070 and NSF Grant No. BES-0602957. 1
K. Paulson, W. Lionheart, and M. Pidcock, IEEE Trans. Med. Imaging 12, 681 共1993兲. 2 P. Metherall, D. C. Barber, R. H. Smallwood, and B. H. Brown, Nature 共London兲 380, 509 共1996兲. 3 M. Joy, G. Scott, and M. Henkelman, Magn. Reson. Imaging 7, 89 共1989兲. 4 O. Kwon, E. Woo, J. Yoon, and J. K. Seo, IEEE Trans. Biomed. Eng. 49, 160 共2002兲. 5 A. J. Peyton, Z. Z. Yu, G. Lyon, S. Al-Zeibak, J. Ferreira, J. Velez, F. Linhares, A. R. Borges, H. L. Xiong, N. H. Saunders, and M. S. Beck, Meas. Sci. Technol. 7, 261 共1996兲. 6 B. C. Towe and M. R. Islam, IEEE Trans. Biomed. Eng. 35, 892 共1988兲. 7 B. J. Roth, P. J. Basser, and J. P. Jr Wikswo, IEEE Trans. Biomed. Eng. 41, 723 共1994兲. 8 H. Wen, J. Shah, and R. S. Balaban, IEEE Trans. Biomed. Eng. 45, 119 共1998兲. 9 Y. Xu and B. He, Phys. Med. Biol. 50, 5175 共2005兲. 10 X. Li, Y. Xu, and B. He, J. Appl. Phys. 99, 066112 共2006兲. 11 R. Xia, X. Li, and B. He, Appl. Phys. Lett. 91, 083903 共2007兲. 12 G. Hu, X. Li, and B. He, Appl. Phys. Lett. 97, 103705 共2010兲. 13 Y. Xu and L. V. Wang, Phys. Rev. Lett. 92, 033902 共2004兲. 14 X. Li, Y. Xu, and B. He, IEEE Trans. Biomed. Eng. 54, 323 共2007兲. 15 X. Li and B. He, IEEE Trans. Med. Imaging 29, 1759 共2010兲. 16 J. Z. Tsai, J. A. Will, S. Hubbard-Van Stelle, H. Cao, S. Tungjitkusolmun, Y. B. Choy, D. Haemmerich, V. R. Vorperian, and J. G. Webster, IEEE Trans. Biomed. Eng. 49, 472 共2002兲. 17 Q. Ma and B. He, IEEE Trans. Biomed. Eng. 55, 813 共2008兲.
