Download full text pdf

X Acoust. Imaging Sens. 2015; 1:32–35
Research Article
Open Access
Qi Weizhi, Cai Wei, Lu Xi, Rong Jian, and Huang Lin*
Imaging of myocardial infarction with
thermoacoustic tomography: An ex vivo study
DOI 10.1515/phto-2015-0003
Received December 1, 2014; accepted May 18, 2015
Abstract: In the present study, we evaluated the feasibility of thermoacoustic tomography (TAT) for imaging of ex
vivo mouse hearts with myocardial infarction. A circular
scanning TAT system with an unfocused transducer was
used to recover the dielectric property distribution of normal and myocardial infarcted mouse heart tissues. The applicability of this myocardial infarction imaging system
was validated using a model of myocardial infarction in
two Sprague-Dawley rats and verified through comparison
with magnetic resonance imaging (MRI). TAT results not
only indicated the location and ischemia and the extent of
myocardial ischemia (MI), but also showed good imaging
contrast between infarcted and normal myocardium without the use of contrast agent. The experimental results suggest that TAT may provide a unique opportunity to enable
real-time precision imaging to determine the site of injury
intraoperatively.
Keywords: MRI; Thermoacoustic tomography; Myocardial
ischemia
1 Introduction
Thermoacoustic tomography (TAT) is an imaging technique based on the thermoelastic effect, which occurs
when an acoustic wave is produced inside a sample due to
local heating and rapid expansion caused by short pulses
of microwave [1, 10]. This functional imaging method combines the advantages of good microwave imaging contrast
with the spatial resolution of ultrasound imaging [2]. In
TAT, the local absorption of microwave energy reveals dielectric properties of the tissue that are closely related to
its physiological and pathological state [3]. Tissues can be
imaged in TAT based on the differences in these dielectric properties. The noninvasive, high contrast and highresolution merits of this technique make it ideal for biological and clinical studies.
Myocardial ischemia (MI) is the lack of oxygen to heart
cells caused by the obstruction of blood flow in the coronary arteries and may result in significant tissue damage. For MI disease treatment, the timely and precise determination of the extent of tissue damage is critical. It
has been shown that ischemia, infarction and hypoxia
strongly affect the dielectric properties of myocardium [5,
11]. If changes in signal strength caused by different dielectric properties can be distinguished, a cardiac TAT may
have the ability to detect myocardial ischemic disease effectively [6].
In the current study, we investigated whether TAT can
produce images with appropriate contrast resolution to visualize MI in ex vivo rat hearts. The TAT results were compared to findings from magnetic resonance imaging (MRI)
and histology.
2 Methods and Materials
2.1 Animal model
*Corresponding Author: Huang Lin: School of Physical Electronics, University of Electronic Science and Technology of China,
Chengdu, 610054, China, E-mail: [email protected]
Qi Weizhi: (These authors contributed equally to this work.) School
of Physical Electronics, University of Electronic Science and Technology of China, Chengdu, 610054, China
Cai Wei: (These authors contributed equally to this work.) Department of radiology, Beijing Jishuitan hospital, Beijing, 100035, China
Lu Xi: The Fourth Affiliated Hospital of China Medical University,
Shenyang, 110032, China
Rong Jian: School of Physical Electronics, University of Electronic
Science and Technology of China, Chengdu, 610054, China
We used a rat myocardial infarction model. SpragueDawley rats weighing 280-300 g were first anesthetized
with sodium pentobarbital (50 mg/kg) intraperitoneally
and respiration was maintained using a rodent ventilator. Real time electrocardiogram (ECG, SA Instruments,
Inc. Stony Brook, NY 11790 USA) was used throughout
the surgery. A skin incision was made about 1 cm above
the apex beat area and blunt separation of the muscle
layers was required before the chest was opened at the
fourth intercostal space and the pericardium was stripped
© 2015 Qi Weizhi et al., licensee De Gruyter Open.
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
Unauthenticated
Download Date | 6/12/17 10:08 PM
Imaging of myocardial infarction with thermoacoustic tomography: An ex vivo study | 33
with forceps to expose the heart. A 6.0 suture was passed
underneath the left anterior descending coronary artery
(LAD) 1-2 mm proximal to the ostium of the coronary artery.
Coronary occlusion was achieved by tightening the suture around the artery. After the ligation, paleness was
observed at distal site of the left ventricular wall. The
occlusion was confirmed by the immediate changes in
ECG profiles, including a significant increase in the amplitude of the QRS complex and elevation of ST segment.
No surgery was performed in control normal rats. Animals
were treated according to the Guide for the Care and Use
of Laboratory Animals of the National Institutes of Health
and the ethics committee of the West China Hospital of
Sichuan University approved the study.
2.2 MRI protocol
MR imaging was conducted on a 7.0-T MRI (Bruker Biospec
70/30, Germany) for the normal group and 4 days after occlusion for the MI group at the same day. Rats were anesthetized and sedation was maintained with a mixture of
100% oxygen and isoflurane (1-3%) during the scan. The
animal was placed prone in a surface coil with the precordium positioned in the center of the coil. An ECG signal was obtained from two subcutaneous copper needles
loaded in the left forelimb and hind limb, and respiration
was monitored by a respiratory pillow (SA Instruments,
Inc. Stony Brook, NY 11790 USA) placed under the body.
Body temperature was monitored with a rectal temperature probe while a heating blanket covered the rat to keep
the body temperature at 37°C.
Scout imaging was first acquired using gradient-echo
sequence to localize the coronal images at the proper level
of the left ventricle (LV). Late gadolinium enhancement
(LGE) imaging was performed by fast imaging with steady
precession (FISP) cine (TR/TE = 5.2 ms/1.8 ms, Flip angle =
25°, matrix size = 256 × 256, FOV = 50 × 50 mm, slice thickness = 1.5 mm, 25 frames for each slice) 10 minutes after an
injection of the contrast agent Gd-DTPA (Magnevist, Bayer
Health Care Pharmaceuticals, 0.15 mmol/kg).
Figure 1: Experimental setup for thermoacoustic tomography.
tion. For all experiments, the actual averaged microwave
power density at the specimen surface was far below the
safety standard [7] (20 mW/cm2 at 3 GHz), which is noninvasive and clinically acceptable. An unfocused immersion
transducer with a central frequency of 2.25 MHz (V323-SU,
Olympus) was used to collect the TA signals in a circular
scanning mode. The transducer-received signals were amplified by an amplifier (Preamp2-D, US Ultratek, Inc. USA)
and converted into digital signal by a computer controlled
data acquisition card.
After 1 day of MRI acquisition, to insure that the MRI
used contrast agent was cleared out, rats were sacri?ced
and hearts were excised. The excised hearts were immediately placed horizontally on a holder and immersed into
coupling medium (transform oil) for TAT.
2.4 MRI analysis
Using the LGE image, the signal intensity from the infarcted myocardium was defined in areas where the signal
intensity >5 SD at the distal site of left ventricle within a
0.08 cm2 region of interest (ROI). Signal intensity of normal tissue was also measured in a remote area of myocardium. The signal intensity ratio of infarcted and normal myocardium was measured. All the calculations were
made using code written in MATLAB (MathWorks, Massachusetts, USA).
2.3 TAT imaging
2.5 TAT analysis
The TAT system has been described previously by our
group [8, 9] and a schematic of the TAT scanner is shown in
Fig. 1. A 3.0 GHz custom-designed pulsed microwave generator transmitted out short microwaves with 0.75 µs pulse
duration. Pulsed microwaves were coupled into the specimen via a horn antenna (114 × 144 mm2 ) for TA stimula-
TAT images were reconstructed by a delay and sum algorithm implemented in MATLAB. A region of interest (ROI)
with the same shape and size were drawn in infarct and remote normal myocardium areas for comparison of the signal intensity ratios. In the control group, ROIs correspond-
Unauthenticated
Download Date | 6/12/17 10:08 PM
34 | Qi Weizhi et al.
ing to the same areas as in the MI group were drawn to
evaluate the change of signal intensity due to the LAD occlusion.
3 Results
3.1 MRI result
Figure 3: MRI images from the myocardium of infarcted rats.
In both MI rats in this experiment, regional wall-motion
abnormalities of the affected vascular territory were seen
on cine images. Transmural delayed hyperenhancement
was seen in the myocardium along the distribution of the
involved coronary artery, including the septal, anterior,
and lateral wall or apex (Fig. 3). The signal intensity ratio
of infarcted and normal myocardium was 2.097 and 2.062,
respectively.
Figure 4: TAT images of MI rats (A and B) compared to the normal rat
(C).
3.2 TAT result
4 Discussion and Conclusion
TAT images clearly displayed the outline of the left ventricle in normal rats. The partly blood-?lled left ventricle
gave the strongest signal while the myocardium presented
a relatively lower signal as indicated in Fig. 4. The infarct
regions in multiple continuous slices from MI rats were
characterized by increased signal intensity compared to
the surrounding normal muscle tissues, which are shown
in Fig. 3. The mean TA signal intensity ratio of infarcted
and normal myocardium in MI group was 5.739 and 5.794,
respectively, whereas the signal intensity ratio of corresponding areas in the normal control rat was just 2.42.
We also used an H&E staining, a histological gold standard, to detect the infarct size. The infarcted areas were
stained in blue due to the acidophilic components in nuclear pyknosis and karyolysis. The comparative slices determined on the basis of typical anatomical landmarks,
the size and position of infarction detected by TAT and
MRI corresponded well to each other and was confirmed
by H&E staining.
Figure 2: Photographs of excised rat hearts after MI with markers (A
and B) and a normal rat heart with markers (C).
Our current results clearly demonstrate the feasibility of
TAT for MI ex vivo detection. To our knowledge, this is the
first study to compare the relatively new method of TAT
with MRI.
Cells in the MI region may undergo pathophysiological changes due to hypoxic injury. Damage to the membrane structure may cause the cell contents and organelles
to be released into the extracellular space, which can induce a rising of local colloid osmotic pressure, and further result in interstitial swelling. The physiological effect
of MI on dielectric properties has been extensively investigated and the correlation has been confirmed by previous
studies [11]. A decrease in myocardial resistance and an increase of dielectric properties, which can induce high TA
signal amplitude, have been observed in MI. In the present
study, enhanced signal intensity from MI using the TAT
method agreed with its dielectric properties, and may be
explained mostly by an increase in interstitial fluid volume.
In this study, we validated our TAT findings with results from two well-established diagnostic methods: MRI
and histology. The LGE MRI has high sensitivity for identifying MI, as infarcted nonviable myocardium has a delayed enhanced signal intensity compared with that of
healthy myocardium. This effect results from the altered
wash-in and washout kinetics of contrast material in infarcted myocardium due to leakage into the interstitial
Unauthenticated
Download Date | 6/12/17 10:08 PM
Imaging of myocardial infarction with thermoacoustic tomography: An ex vivo study | 35
Table 1: Signal intensity ratio of MRI and TAT.
Normal
Myocardium infarcted
Ratio of MI and Normal
MRI
(with contrast agent)
2.062
2.097
1.016
space caused by myocyte death, membrane disintegration
and microvascular damage [12].
Many characteristics of TAT make it a competitive
imaging method for diagnosis of MI in the future. In our
study, the ratio between infarct and normal myocardium
was approximately 5.7 in the two samples without contrast
agent. This high signal contrast suggests TAT is more sensitive to tissue condition changes than MRI and may be better at distinguishing super-acute ischemic myocardium.
Additionally, TAT requires the use of less contrast agent
and may greatly reduce the risk of contrast agent toxicity. TAT also has a very small data acquisition time (millisecond range) due to multiple receiving antennas, which
makes it suitable for intraoperative real-time imaging.
Combined with other advantages including cost efficiency
and safety, it is expected that this technology might be
used for more sophisticated analyses of cardiac function
and viability of myocardial tissue.
In conclusion, our study confirmed the ability of TAT
to identify MI in rat hearts ex vivo; the noninvasive imaging method could be a potential tool for evaluation of myocardial ischemia in future.
Acknowledgement: This research was partially supported
by the International cooperation project of Sichuan
Province Science and Technology Agency (2014HH0037 to
Rong Jian).
TAT
(without contrast agent)
2.42
5.739
2.371
on, 45(9), 1163-1172.
Pham, T., Beigie, C., Park, Y., & Wong, J. Y. (2014). Microbubbles
as Theranostics Agents. In Nano-Oncologicals (pp. 329-350).
Springer International Publishing.
[5] Ogunlade, O., & Beard, P. (2014, March). Electric and magnetic
properties of contrast agents for thermoacoustic imaging. In
SPIE BiOS (pp. 89432V-89432V). International Society for Optics and Photonics.
[6] Osepchuk, J. M., & Petersen, R. C. (2001). Safety standards for
exposure to RF electromagnetic fields. Microwave Magazine,
IEEE, 2(2), 57-69.
[7] Huang, L., Yao, L., Liu, L., Rong, J., & Jiang, H. (2012). Quantitative thermoacoustic tomography: Recovery of conductivity maps of heterogeneous media. Applied Physics Letters,
101(24), 244106.
[8] Huang, L., Liu, L., Lu, K., Zhong, X., Li, T., Chen, B., & Jiang, H. 3
GHz Thermoacoustic Tomography System.
[9] Nikolova, N. K. Microwave Biomedical Imaging. Wiley Encyclopedia of Electrical and Electronics Engineering.
[10] Janse, M. J., & Wit, A. L. (1989). Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev, 69(4), 1049-1169.
[11] Serguei Y. S., Alexander E. B., Vitaly G. P., Yuri E. S., Thomas C.
W., Alexander E. S. (2003). Microwave Tomography for Detection/Imaging of Myocardial Infarction. I. Excised Canine Hearts.
Annals of Biomedical Engineering, 31(3), 262-270.
[12] Rajiah P., Desai M. Y., Kwon D., Flamm S. D. (2013). MR imaging
of myocardial infarction. Sep-Oct, 33(5), 1383-412.
[4]
References
[1]
[2]
[3]
Lou, C., & Xing, D. (2010). Temperature monitoring utilising
thermoacoustic signals during pulsed microwave thermotherapy: a feasibility study. International Journal of Hyperthermia,
26(4), 338-346.
Nie, L., Xing, D., Zhou, Q., Yang, D., & Guo, H. (2008).
Microwave-induced thermoacoustic scanning CT for highcontrast and noninvasive breast cancer imaging. Medical
physics, 35(9), 4026-4032.
Zhu, L., Xu, L. X., & Chencinski, N. (1998). Quantification of
the 3-D electromagnetic power absorption rate in tissue during transurethral prostatic microwave thermotherapy using
heat transfer model. Biomedical Engineering, IEEE Transactions
Unauthenticated
Download Date | 6/12/17 10:08 PM