Jimmy L. Su

Plasmonic Intravascular Photoacoustic Imaging for Detection of Macrophages in Atherosclerotic Plaques

To detect macrophages in atherosclerotic plaques, plasmonic gold nanoparticles are introduced as a contrast agent for intravascular photoacoustic imaging. The phantom and ex vivo tissue studies show that the individual spherical nanoparticles, resonant at 530 nm wavelength, produce a weak photoacoustic signal at 680 nm wavelength while photoacoustic signal from nanoparticles internalized by macrophages is very strong due to the plasmon resonance coupling effect. These results suggest that intravascular photoacoustic imaging can assess the macrophage-mediated aggregation of nanoparticles and therefore identify the presence and the location of nanoparticles associated with macrophage-rich atherosclerotic plaques.

Detection of lipid in atherosclerotic vessels using ultrasound-guided spectroscopic intravascular photoacoustic imaging

Lipid is a common constituent in atherosclerotic plaques. The location and area of the lipid region is closely related to the progression of the disease. Intravascular photoacoustic (IVPA) imaging, a minimally invasive imaging modality, can spatially resolve the optical absorption property of arterial tissue. Based on the distinct optical absorption spectrum of fat in the near infrared wavelength range, spectroscopic IVPA imaging may distinguish lipid from other water-based tissue types in the atherosclerotic artery. In this study, a bench-top spectroscopic IVPA imaging system was used to ex-vivo image both atherosclerotic and normal rabbit aortas. By combing the spectroscopic IVPA image with the intravascular ultrasound (IVUS) image, lipid regions in the aorta were identified. The results demonstrated that IVUS-guided spectroscopic IVPA imaging is a promising tool to differentiate lipid in atherosclerosis.

Intravascular Photoacoustic Imaging

Intravascular photoacoustic (IVPA) imaging is a catheter-based, minimally invasive, imaging modality capable of providing high-resolution optical absorption map of the arterial wall. Integrated with intravascular ultrasound (IVUS) imaging, combined IVPA and IVUS imaging can be used to detect and characterize atherosclerotic plaques building up in the inner lining of an artery. In this paper, we present and discuss various representative applications of combined IVPA/IVUS imaging of atherosclerosis, including assessment of the composition of atherosclerotic plaques, imaging of macrophages within the plaques, and molecular imaging of biomarkers associated with formation and development of plaques. In addition, imaging of coronary artery stents using IVPA and IVUS imaging is demonstrated. Furthermore, the design of an integrated IVUS/IVPA imaging catheter needed for in vivo clinical applications is discussed.

Photoacoustic imaging of clinical metal needles in tissue

The ability to visualize and track temporarily or permanently implanted metal devices is important in many applications ranging from diagnosis to therapy. Specifically, reliable imaging of metal needles is required in todays clinical settings. Currently, ultrasound is utilized to image a needle inserted into tissue in real time. However, the diagnostic value and tracking ability of these images depends highly on the orientation of the needle, and also its proximity to regions of interest in the tissue. We examine the use of photoacoustic imaging combined with current ultrasound imaging methods to obtain high-contrast images of commonly used needles in the body. Experiments were performed using 21 G and 30 G needles inserted into ex vivo porcine tissue and tissue-mimicking phantoms. The needles and surrounding tissue were imaged using an ultrasound imaging system interfaced with the pulsed laser source necessary for photoacoustic imaging. The results suggest that photoacoustic imaging, combined with ultrasound imaging, is capable of real-time, high-contrast, and high-spatial-resolution visualization of metal implants within anatomical landmarks of the background tissue.

Photoacoustic imaging of coronary artery stents

Coronary stents are the most commonly used treatment in the United States to repair narrowed or weakened arteries. The ability to visualize the stent during the stenting procedure and post-surgery is crucial to correctly place the stent with respect to the vessel stenosis, and to identify its position within the vessel wall. Current imaging modalities suffer from low contrast, resolution and/or unfavorable artifacts that can inhibit correct visualization of the stent in the artery. We demonstrated the effectiveness of a combined intravascular photoacoustic and intravascular ultrasound imaging method for high resolution and sufficient contrast imaging of commercial stents with respect to the vessel wall.

Photoacoustic imaging of prostate brachytherapy seeds.

Brachytherapy seed therapy is an increasingly common way to treat prostate cancer through localized radiation. The current standard of care relies on transrectal ultrasound (TRUS) for imaging guidance during the seed placement procedure. As visualization of individual metallic seeds tends to be difficult or inaccurate under TRUS guidance, guide needles are generally tracked to infer seed placement. In an effort to improve seed visualization and placement accuracy, the use of photoacoustic (PA) imaging, which is highly sensitive to metallic objects in soft tissue, was investigated for this clinical application. The PA imaging properties of bare (i.e., embedded in pure gelatin) and tissue-embedded (at depths of up to 13 mm) seeds were investigated with a multi-wavelength (750 to 1090 nm) PA imaging technique. Results indicate that, much like ultrasonic (US) imaging, an angular dependence (i.e., seed orientation relative to imaging transducer) of the PA signal exists. Despite this shortcoming, however, PA imaging offers improved contrast, over US imaging, of a seed in prostate tissue if sufficient local fluence is achieved. Additionally, although the PA signal of a bare seed is greatest for lower laser wavelengths (e.g., 750 nm), the scattering that results from tissue tends to favor the use of higher wavelengths (e.g., 1064 nm, which is the primary wavelength of Nd:YAG lasers) when the seed is located in tissue. A combined PA and US imaging approach (i.e., PAUS imaging) shows strong potential to visualize both the seed and the surrounding anatomical environment of the prostate during brachytherapy seed placement procedures.

Advances in Clinical and Biomedical Applications of Photoacoustic Imaging

IMPORTANCE OF THE FIELD: Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring. AREAS COVERED IN THIS REVIEW: This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions. WHAT THE READER WILL GAIN: Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm. TAKE HOME MESSAGE: Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting.

Methodical Study on Plaque Characterization using Integrated Vascular Ultrasound, Strain and Spectroscopic Photoacoustic Imaging

Carotid atherosclerosis has been identified as a potential risk factor for cerebrovascular events, but information about its direct effect on the risk of recurrent stroke is limited due to incomplete diagnosis. The combination of vascular ultrasound, strain rate and spectroscopic photoacoustics could improve the timely diagnosis of plaque status and risk of rupturing. Current ultrasound techniques can noninvasively image the anatomy of carotid arteries. The spatio-temporal variation in displacement of different regions within the arterial wall can be derived from ultrasound radio frequency data; therefore an ultrasound based strain rate imaging modality can be used to reveal changes in arterial mechanical properties. Additionally, spectroscopic photoacoustic imaging can provide information on the optical absorption properties of arterial tissue and it can be used to identify the location of specific tissue components, such as lipid pools. An imaging technique combining ultrasound, strain rate and spectroscopic photoacoustics was tested on an excised atherosclerotic rabbit aorta. The ultrasound image illustrates inhomogeneities in arterial wall thickness, the strain rate indicates the arterial segment with reduced elasticity and the spectroscopic photoacoustic image illustrates the accumulation of lipids. The results demonstrated that ultrasound, strain rate and spectroscopic photoacoustic imaging are complementary. Thus the integration of the three imaging modalities advances the characterization of atherosclerotic plaques.

Intravascular ultrasound and photoacoustic imaging

There is a need for an imaging technique that can reliably identify and characterize the vulnerability of atherosclerotic plaques. Catheter-based intravascular ultrasound (IVUS) is one of the imaging tools of the clinical evaluation of atherosclerosis. However, histopathological information obtained with IVUS imaging is limited. We present and discuss the applicability of a combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging approach to assess both vessel structure and tissue composition thus identifying rupture-prone atherosclerotic plaques. Photoacoustic (or optoacoustic and, generally, thermoacoustic) imaging relies on the absorption of electromagnetic energy, such as light, and the subsequent emission of an acoustic wave. Therefore, the amplitude and temporal characteristics of the photoacoustic signal is primarily determined by optical absorption properties of different types of tissues and can be used to differentiate the lipid, fibrous and fibro-cellular components of an inflammatory lesion. Simultaneous IVUS and IVPA imaging studies were conducted using 40 MHz clinical IVUS imaging catheter interfaced with a pulsed laser system. The performance of the IVPA/IVUS imaging was assessed using phantoms with point targets and vessel-mimicking phantoms. To detect the lipids in the plaque, ex-vivo IVPA imaging studies of a normal and an atherosclerotic rabbit aorta were performed at a 532 nm wavelength. To assess plaque composition, multi-wavelength (680–950 nm) spectroscopic IVPA imaging studies were carried out. Finally, molecular and cellular IVPA imaging was demonstrated using plasmonic nanoparticles. Overall, our studies suggest that plaque detection and characterization can be improved using the combined IVPA/IVUS imaging.

On the possibility to detect lipid in atherosclerotic plaques using intravascular photoacoustic imaging

Large lipid core is common in rupture-prone atherosclerotic plaques. Detection of the location and distribution of lipid in the atherosclerotic plaques can greatly benefit the diagnosis and treatment of vulnerable plaques. Recently introduced intravascular photoacoustic (IVPA) imaging - a technique to image the optical absorption property of tissue - can be used to detect and differentiate atherosclerotic plaques. In this work, we further investigated the ability of using spectroscopic IVPA imaging to visualize the lipid in atherosclerotic plaques. IVPA imaging was performed on an ex-vivo rabbit aorta in the 1200 – 1230 nm wavelength range. In the lipid-rich plaques, the photoacoustic signal strength within this spectral range behaved similar to the optical absorption spectrum of fatty tissue. To distinguish lipid from other types of tissue, correlation analysis was used. Specifically, intraclass correlation between the IVPA signals and the absorption spectrum of lipid reconstructed from multi-wavelength IVPA images was conducted on a pixel-by-pixel basis. The resulted correlation map showed the distribution of lipid in the atherosclerotic plaques. The distribution of lipid is further confirmed by histopathological analysis of tissue. The results of our study suggest that spectroscopic IVPA imaging, together with correlation analysis, may be used to detect lipid in atherosclerotic plaques.