Biomed Opt Express. 2015 Nov 1; 6(11): 4557-4566. DOI: 10.1364/BOE.6.004557.
High-speed Intravascular Photoacoustic Imaging at 1.7 μm with a KTP-based OPO
Jie Hui1,8, Qianhuan Yu2,3,8, Teng Ma4,8, Pu Wang5, Yingchun Cao5, Rebecca S. Bruning6, Yueqiao Qu7, Zhongping Chen7, Qifa Zhou4, Michael Sturek6, Ji-Xin Cheng5,*, and Weibiao Chen2,*
1 Department of Physics and Astronomy, Purdue University, West Lafayette, IN, 47906
2 Key Laboratory of Space Laser Communication and Detection Technology, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800, China
3 University of Chinese Academy of Science, Beijing 100049, China
4 Department of Biomedical Engineering, NIH Ultrasonic Transducer Resource Center, University of Southern California, Los Angeles, CA, 90089
5 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47906
6 Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202
7 Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92612
8 These authors contributed equally to this work
Lipid deposition inside the arterial wall is a hallmark of plaque vulnerability. Based on overtone absorption of C-H bonds, intravascular photoacoustic (IVPA) catheter is a promising technology for quantifying the amount of lipid and its spatial distribution inside the arterial wall. Thus far, the clinical translation of IVPA technology is limited by its slow imaging speed due to lack of a high-pulse-energy high-repetition-rate laser source for lipid-specific first overtone excitation at 1.7 μm. Here, we demonstrate a potassium titanyl phosphate (KTP)-based optical parametric oscillator with output pulse energy up to 2 mJ at a wavelength of 1724 nm and with a repetition rate of 500 Hz. Using this laser and a ring-shape transducer, IVPA imaging at speed of 1 frame per sec was demonstrated. Performance of the IVPA imaging system’s resolution, sensitivity, and specificity were characterized by carbon fiber and a lipid-mimicking phantom. The clinical utility of this technology was further evaluated ex vivo in an excised atherosclerotic human femoral artery with comparison to histology.
Recently, a novel fast intravascular phototacoustic/ultrasound imaging device has been developed and validated ex vivo through imaging diseased human artery by Dr. Ji-Xin Cheng’s lab at Purdue University. This technology has unique advantages for accurate detection of “bad” plaques and thus, holds the great potential to be used as a life-saving device in the clinic for accurate diagnosis of cardiovascular disease.
Why accurate diagnosis of ‘bad’ plaques is so important?
As is widely known, cardiovascular disease is the No.1 cause of deaths both in U.S. and worldwide . Over 80 million adults in the States suffered from cardiovascular disease in 2006 alone and with an increasing trend in years afterwards. The cost associated is estimated to be over $470 billion per year only in U.S. Pathophysiological studies have demonstrated that the majority of fatal acute coronary syndromes are due to ‘bad’ plaques . These plaques are more prone or ‘vulnerable’ to rupture and thrombosis and have been characterized by large lipid cores covered by a thin fibrous cap. Currently, no clinically available imaging devices can reliably and accurately diagnose vulnerable plaques . Intravascular optical coherence tomography as an emerging modality lacks the chemical selectivity to identify plaque compositions and does not have enough imaging depth to accurately map the overall plaque distribution in the arterial wall.
Why this imaging device can be the potential solution?
Catheter-based intravascular photoacoustic/ultrasound (IVPA/US) imaging has been considered as a promising hybrid method to meet the aforementioned need. Combining nanosecond pulsed laser excitation with ultrasonic detection, IVPA catheter maps the lipid deposition, the key hallmark for vulnerable plaque . The photoacoustic signal arises endogenously from the overtone absorption of C-H bond [4,5,6]. Fig. 1(A) depicts the intravascular photoacoustic/ultrasound imaging scenario. In photoacoustic image, lipid deposition in the plaque area has strongest absorption at the wavelength of ~1.7 μm, thus provides the highest and distinctive contrast, when compared with other components in the artery. The IVUS image provides the information of artery structure. When these two channels are combined together as shown in the Fig. 1(B), researchers can get the complementary information of diseased artery wall, which can be used for accurate identification of the “bad” plaques.
Why a fast imaging speed is so important?
The traditionally used lasers operate at pulse repetition rate of 10-20 Hz. Such a low repetition rate translates to a speed of 50 s to get a cross-sectional image. With such a slow speed, it is impossible for the device to get a good image of the highly dynamic artery in live animals or human patients. In our work, with a lab-built 500 Hz fast laser source with an output wavelength of 1.7 μm, the imaging speed has been dramatically improved to 1 cross-sectional image per sec, which is nearly two orders of magnitude larger than the imaging speed by using the transitionally used low repetition rate lasers. This speed is fast enough for a preclinical evolution of this technology in live animal models, like Ossabaw swine. The clinical data from live human patients can be expected to come in not far future!
Figure 1. (A) Schematic of high-speed intravascular photoacoustic/ultrasound imaging. (B) High-speed intravascular photoacoustic/ultrasound image of diseased human artery with lipid-laden plaque. The merged image composed of photoacoustic image (green) and ultrasound image (black and white) gives complementary information (lipid depositions marked with white arrows and artery structure) of the artery wall for the identification of “bad” plaques.
Dr. Ji-Xin Cheng, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907; Tel: (765)-494-4335; Email: email@example.com
 S. Yusuf, S. Reddy, S. Ounpuu, and S. Anand, “Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 104(22), 2746-2753 (2001).
 P. Libby, “Inflammation in atherosclerosis,” Nature 420, 868–874 (2002).
 R. Puri, E. M. Tuzcu, S. E. Nissen, and S. J. Nicholls, “Exploring coronary atherosclerosis with intravascular imaging,” Int. J. Cardiol. 168(2), 670–679 (2013).
 H. W. Wang, N. Chai, P. Wang, S. Hu, W. Dou, D. Umulis, L. V. Wang, M. Sturek, R. Lucht, and J.X. Cheng, “Label-free bond-selective imaging by listening to vibrationally excited molecules,” Phys. Rev. Lett. 106(23), 238106 (2011).
 J. Hui, R. Li, E. H. Phillips, C. J. Goergen, M. Sturek, and J. X. Cheng, “Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves”, Photoacoustics 4(1), 11-21 (2016).
 P. Wang, T. Ma, M. N. Slipchenko, S. Liang, J. Hui, K. K. Shung, S. Roy, M. Sturek, Q. Zhou, Z. Chen, and J. X. Cheng, “High-speed intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque enabled by a 2-kHz barium nitrite raman laser,” Sci. Rep. 4, 6889 (2014).