Intravascular Imaging
High mortality in coronary heart disease is mainly attributed to the rupture of a vulnerable atherosclerotic plaque. These high-risk arterial plaques often remain clinically silent and the first and only manifestation of the disease could result in death. Generally, the high cholesterol levels in the blood trigger several molecular events in the arterial vessel wall with the subsequent development of lipid-rich inflammatory lesions. The advantages in biological research and understanding of vulnerable plaques have not yet translated into improved clinical outcomes. Among several reasons is the inability for current clinical imaging techniques to simultaneously visualize plaque morphology and composition. Although screening of plaques non-invasively is preferable, structural and functional invasive imaging of plaques during coronary interventions is also required.
The overall goal of the intravascular imaging project is to develop an advanced in-vivo catheter-based imaging technology capable of morphological and functional assessment of vulnerable plaques to guide coronary interventions.
Intravascular Photoacoustic (IVPA) Imaging
Photoacoustic imaging relies on the detection of acoustic waves generated by the absorption of sub-ablation threshold nanosecond laser pulses. We perform intravascular photoacoustic (IVPA) imaging using a custom-built prototype system. The imaging system consists of a 5-ns pulsed laser, motion control system, IVUS catheter, ultrasound pulser/receiver, data acquisition and a digital delay generator. The laser excitation upon absorption produces photoacoustic response in the sample. The IVPA response is detected using a 40 MHz IVUS imaging catheter and digitized at 200 MS/sec. The IVUS catheter in the system also allows us to perform pulse-echo IVUS imaging simultaneously. We tested our prototype imaging system using tissue phantom and ex vivo rabbit aorta imaging studies. Results from our phantom studies presented in Figure 1 indicate the advantage of performing combined IVUS and IVPA imaging. In the IVUS image of the phantom, the inclusion was not visible. However, the graphite filled inclusion produced photoacoustic signals and was clearly visible in the IVPA image. Therefore, both the structure and the content of the vessel phantom were imaged using the combined IVUS/IVPA imaging.
Figure 1. Arterial vessel phantom studies illustrating the synergism of combined IVUS and IVPA imaging [1]
In ex vivo aorta studies, the presence of plaque was indicated by intimal thickening visualized on the IVUS image. However, the extent and composition of the lesion are not clear. In contrast, the IVPA image showed regions with low optical absorption at 532 nm (lipids) and normal to high IVPA response from the rest of the plaque containing collagen and blood. The results indicate the ability of IVPA imaging to detect and demarcate specific regions of the plaque (Figure 2).
Figure 2. IVUS and IVPA image from the same cross-section of rabbit aorta. Corresponding histology shows an advanced fibro-cellular inflammatory plaque containing macrophages, lipids and collagen.
Spectroscopic IVPA Imaging
Figure 3. (a) IVPA signal from wavelength 680nm to 900nm. (b) IVPA signal variation between 680nm and 900nm wavelength. (c) IVPA signal variation in different areas from 680nm to 900nm wavelength.
The studies presented in Figure 2 were performed at a laser excitation wavelength of 532 nm which is not suitable for intravascular imaging through blood. Furthermore, IVPA imaging at a single wavelength restricts the ability to differentiate between diverse types of plaques and other lipids. Therefore, we introduce spectroscopic IVPA imaging where photoacoustic imaging is performed at multiple wavelengths. The change in the IVPA signal was observed in the IVPA images obtained at different wavelengths in the optical tissue diagnostic range of 680 nm – 900 nm. We plotted the spectroscopic image by computing the slope of the change in the IVPA response with wavelength. The spectroscopic IVPA image presented in Figure 3 suggests the ability to simultaneously differentiate the lipids, collagen types I and III, as well as blood. By comparing the IVPA response to the known optical absorption spectra of various plaque constituents, the composition of the plaque can be obtained.
Molecular IVPA Imaging
Gold nanoparticles can be used as contrast agent for photoacoustic imaging. The optical property of gold nanoparticles can be tuned by manipulating their shape. These nanoparticles can enhance the optical absorption of targeted molecular or cellular specific components of the plaques at various stages of atherosclerosis development. With the help of the nanoparticles, IVPA can be used to perform molecular imaging.
Figure 4. Possible targets in atherosclerotic plaques.
Phantom studies have been done with murine macrophages and 50 nm spherical gold nanoparticles. By the non-specific uptake of macrophages, after incubating macrophages with nanoparticles, gold nanoparticles will be in aggregated state in the vehicles of macrophages. Because of plasma resonance coupling, the optical property of aggregated gold nanoparticles is different from the non-aggregated particles (Figure 5). IVPA images at 680 nm wavelength of the phantom showed high contrast enhancement in the compartment that contains macrophages loaded with nanoparticles (Figure 6).
References:
S. Sethuraman, S. Aglyamov, J. Amirian, R. Smalling, S. Emelianov, “Intravascular photoacoustic imaging using an IVUS imaging catheter,” IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 54(5), 978-986 (2007)
S. Sethuraman, S. Mallidi, S.R. Aglyamov, J.H. Amirian, R.W. Smalling, S.Y. Emelianov, “Intravascular photoacoustic imaging of atherosclerotic plaques - ex vivo study,” Proceedings of the 2007 SPIE Photonics West Symposium: Photons Plus Ultrasound: Imaging and Sensing, volume 6437, 29:1-9 (2007)
S. Sethuraman, S. Mallidi, S.R. Aglyamov, R.W. Smalling, S.Y. Emelianov, “Intravascular photoacoustic imaging of macrophage rich plaques,” Abstract of the 24nd Annual Houston Conference on Biomedical Engineering Research, The Houston Society for Engineering in Medicine and Biology, 8-9 February 2007, Houston, TX, 95 (2007)
S. Sethuraman, S. Aglyamov, J. Amirian, R. Smalling, S. Emelianov, “Intravascular photoacoustic imaging to detect and differentiate atherosclerotic plaques,” Proceedings of the 2005 IEEE Ultrasonics Symposium, 133-136 (2005)
S. Sethuraman, S.R. Aglyamov, J. Amirian, R. Smalling, and S.Y. Emelianov, “An integrated ultrasound-based intravascular imaging of atherosclerosis,” Proceedings of the Fourth International Conference on the Ultrasonic Measurement and Imaging of Tissue Elasticity, 69 (2005)
R. P. Choudhury, V. Fuster, Z. A. Fayad, “Molecular, cellular and functional imaging of atherothrombosis,” Nature Reviews, 3, 913-925 (2004)
B. Wang, E. Yantsen, T. Larson, S. Sethuraman, K. Sokolov, S. Emelianov, “Intravascular photoacoustic imaging with gold nanoparticles,” Proceedings of the 2007 IEEE Ultrasonics Symposium, 848-851 (2007)
Patrick M. Winter, Anne M. Morawski, Shelton D. Caruthers, Ralph W. Fuhrhop, Huiying Zhang, Todd A. Williams, John S. Allen, Elizabeth K. Lacy, J. David Robertson, Gregory M. Lanza, Samuel A. Wickline, “Molecular imaging of angiogenesis in early-stage atherosclerosis with avß3-integrin-targeted nanoparticles,” Circulation 108, 2270–2274 (2003).
