Catheterization and cardiovascular diagnosis, 1994
To test the hypothesis that coronary sinus retroperfusion would preserve regional myocardial func... more To test the hypothesis that coronary sinus retroperfusion would preserve regional myocardial function during either left anterior descending or circumflex occlusion, sonomicrometer crystals were implanted in the midmyocardium of five chronically instrumented dogs. Regional fractional shortening was measured during 5 min of coronary occlusion with and without retroperfusion. Percent fractional shortening in the left anterior descending region fell from 18% at baseline to -4%(dyskinesis) after 3 min of left anterior descending occlusion. With coronary sinus retroperfusion, the percent fractional shortening declined from 16% at baseline to 0 (akinesis) during occlusion. A modest but significant improvement in percent fractional shortening in the ischemic region during left anterior descending occlusion occurred with retroperfusion (p < .05). By contrast, no amelioration of ischemic dysfunction occurred with retroperfusion during circumflex occlusion. Coaxial flow into the great card...
2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2009
Large lipid core is common in rupture-prone atherosclerotic plaques. Detection of the location an... more 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 multiwavelength 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.
Photons Plus Ultrasound: Imaging and Sensing 2011, 2011
Carotid atherosclerosis has been identified as a potential risk factor for cerebrovascular events... more 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
Photons Plus Ultrasound: Imaging and Sensing 2010, 2010
Using contrast agents with desired targeting moiety and optical absorption, intravascular photoac... more Using contrast agents with desired targeting moiety and optical absorption, intravascular photoacoustic imaging may be used to identify various biomarkers expressed during the progression of atherosclerotic lesions. In this paper, we present intravascular photoacoustic imaging of macrophages in the atherosclerotic lesions using bio-conjugated gold nanoparticles as the contrast agent. Atherosclerotic lesions were created in the aorta of a New Zealand
Proceedings of SPIE - The International Society for Optical Engineering, 2006
ABSTRACT Intravascular ultrasound (IVUS) imaging ,has emerged ,as an ,imaging ,technique to evalu... more ABSTRACT Intravascular ultrasound (IVUS) imaging ,has emerged ,as an ,imaging ,technique to evaluate ,coronary artery diseases including vulnerable plaques. However, in addition to the morphological characteristics provided by IVUS imaging, there is a need for functional imaging capability that could identify the composition of vulnerable plaques. Intravascular photoacoustic (IVPA) imaging, in conjunction with clinically available IVUS imaging, may be such a technique allowing,vulnerable plaque ,characterization and ,differentiation. We ,have ,developed ,an integrated ,intravascular ultrasound and photoacoustic imaging,system to visualize clinically relevant structural and functional properties of the coronary arteries. The performance,of the combined,IVUS and IVPA imaging,system was evaluated through images of arterial phantoms. Experiments were performed using high frequency IVUS imaging catheters operating at 20 MHz, 30 MHz and 40 MHz. The IVPA imaging ,was ,successful in highlighting ,inclusions based on differential ,optical absorption while these lesions did not have sufficient contrast in the IVUS images. Finally, initial IVUS and IVPA imaging studies were performed,on ex vivo samples of a rabbit artery using the 40 MHz IVUS imaging catheter. Results ofthe above studies demonstrate the feasibility of combining intravascular ultrasound and photoacoustic imaging and suggest clinical utility of the developed imaging system in interventional cardiology. Keywords: Photoacoustic imaging, ultrasound imaging, intravascular imaging, atherosclerosis, vulnerable plaque, optoacoustic imaging, coronary arteries, catheter, IVUS, interventional cardiology. 1.,INTRODUCTION Cardiovascular disease is the leading cause of mortality inthe Unites States. The American Heart Association estimates an annual mortality of greater than 1 million [1]. The disease of the heart is a huge health problem and a major economic
Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2007
Diagnosis and treatment of atherosclerosis necessitates the detection and differentiation of rupt... more Diagnosis and treatment of atherosclerosis necessitates the detection and differentiation of rupture prone plaques. In principle, intravascular photoacoustic (IVPA) imaging has the ability to simultaneously visualize the structure and composition of atherosclerotic plaques by utilizing the difference in optical absorption. Extensive studies are required to validate the utility of IVPA imaging in detecting vulnerable plaques and address issues associated with the clinical implementation of the technique. In this work, we performed ex vivo imaging studies using a rabbit model of atherosclerosis. The intravascular photoacoustic (IVPA) and ultrasound (IVUS) images of the normal aorta and aorta with plaque were obtained and compared with histological slices of the tissue. The results indicate that IVPA imaging is capable of detecting plaques and showed potential in determining the composition. Furthermore, we initially addressed several aspects of clinical implementation of the IVPA imaging. Specifically, the configuration of combined IVPA and IVUS catheter was investigated and the effect of the optical absorption of the luminal blood on the IVPA image quality was evaluated. Overall, this study suggests that IVPA imaging can become a unique and important clinical tool.
Photons Plus Ultrasound: Imaging and Sensing 2012, 2012
ABSTRACT Combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging ... more ABSTRACT Combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging has been previously established as a viable means for imaging atherosclerotic plaques using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of an atherosclerotic rabbit aorta following injection of gold nanorods (AuNR) with peak absorbance within the tissue optical window was performed. Ex-vivo imaging results revealed high photoacoustic signal from localized AuNR. Corresponding histological cross-sections and digital photographs of the artery lumen confirmed the presence of AuNR preferentially located at atherosclerotic regions and in agreement with IVPA signal. Furthermore, an integrated IVUS/IVPA imaging catheter was used to image the AuNR in the presence of luminal blood. The results suggest that AuNR allow for IVPA imaging of exogenously labeled atherosclerotic plaques with a comparatively low background signal and without the need for arterial flushing.
We previously demonstrated a method to perform simultaneous intravascular photoacoustic (IVPA) an... more We previously demonstrated a method to perform simultaneous intravascular photoacoustic (IVPA) and ultrasound (IVUS) imaging using an IVUS imaging catheter. During photoacoustic imaging, the energy fluence of optical irradiation was maintained low to conform to laser safety standards for medical imaging applications. However, the maximum permissible exposure for intravascular imaging is not yet well established and it is essential to address general safety issues of IVPA imaging. Hence, there is a need to monitor the temperature dynamics following laser excitation in IVPA imaging to estimate the maximum temperature increase and to insure thermal safety. In this paper, we present an ultrasound technique to monitor the temporal behavior of temperature in a tissue mimicking phantom and in an excised sample of arterial tissue after either a single laser pulse or during multiple laser pulses. The results of our study suggest that it is possible to monitor temperature and insure safety during the combined intravascular ultrasound and photoacoustic imaging.
Intravascular photoacoustic (IVPA) imaging has the potential to detect atherosclerotic plaques. P... more Intravascular photoacoustic (IVPA) imaging has the potential to detect atherosclerotic plaques. Previously, we obtained IVPA images using a 532 nm pulsed laser and a 40 MHz intravascular ultrasound (IVUS) imaging catheter. The optical absorption of light by the plaque components was used as a contrast mechanism helpful in detecting the plaque. However, plaque differentiation requires a method to remotely assess plaque composition. We hypothesized that plaque characterization can be performed by monitoring the changes in photoacoustic response with the change in laser excitation wavelength. In this preliminary study, we performed spectroscopic IVPA imaging to analyze the change in the photoacoustic response of the aortic tissue (a rabbit aorta with plaque and a control aorta) using different laser excitation wavelengths. Specifically, we perform IVPA imaging at multiple wavelengths within 680-900 nm range. The slope of the spectral change in photoacoustic response was computed between selected wavelengths to produce a spectroscopic IVPA image. The results of our study suggest the ability of the multi-wavelength IVPA imaging to identify and differentiate the fibrous, lipid and blood components of the atherosclerotic plaque.
Atherosclerosis is a systemic disease characterized by the development of a plaque leading to sev... more Atherosclerosis is a systemic disease characterized by the development of a plaque leading to several acute coronary syndromes. Imaging of plaque structure and composition is important in diagnosing the disease and further guiding coronary interventions. Currently, there is no clinical imaging technique capable of providing comprehensive morphological and functional information of the plaques. Several emerging techniques including palpography and thermography are under investigation for intravascular imaging of atherosclerosis. In this paper we present photoacoustic imaging as a means to assess the composition of plaques based on the optical properties of tissue.
We present a preliminary study demonstrating the capability of ultrasound-guided intravascular ph... more We present a preliminary study demonstrating the capability of ultrasound-guided intravascular photoacoustic (IVPA) imaging to visualize the depth-resolved distribution of lipid deposits in atherosclerotic plaques in vivo. Based on the characteristic optical absorption of lipid in the near infrared wavelength range, IVPA imaging at a single, 1720 nm, wavelength was used to provide a spatially-resolved, direct measurement of lipid content in atherosclerotic arteries. By overlaying an IVPA image with a spatially co-registered intravascular ultrasound (IVUS) image, the combined IVPA/IVUS image was used to visualize lipid distribution within the vessel wall. Ultrasound-guided IVPA imaging was performed in vivo in the abdominal aorta of a Watanabe heritable hyperlipidemic (WHHL) rabbit. Subsequently, the excised rabbit aorta filled with a solution of red blood cells (RBC) was then imaged ex vivo, and histology was obtained in the section adjacent to the imaged cross-section. To demonstrate the potential for future clinical application of IVPA/IVUS imaging, a sample of diseased human right coronary artery (RCA) was also imaged. Both in vivo and ex vivo IVPA images clearly showed the distribution of lipid in the atherosclerotic vessels. In vivo IVPA imaging was able to identify diffuse, lipid-rich plaques in the WHHL rabbit model of atherosclerosis. Furthermore, IVPA imaging at a single wavelength was able to identify the lipid core within the human RCA ex vivo. Our results demonstrate that ultrasound-guided IVPA imaging can identify lipid in atherosclerotic plaques in vivo. Importantly, the IVPA/IVUS images were obtained in presence of luminal blood and no saline flush or balloon occlusion was required. Overall, our studies suggest that ultrasound-guided IVPA imaging can potentially be used for depth-resolved visualization of lipid deposits within the anatomical context of the vessel wall and lumen. Therefore, IVUS/IVPA imaging may become an important tool for the detection of rupture-prone plaques.
Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on... more Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.
The assessment of plaque composition is one of the important steps in the interventional manageme... more The assessment of plaque composition is one of the important steps in the interventional management of atherosclerosis. The difference in the optical absorption between the arterial wall and plaque constituents could be utilized to obtain high resolution photoacoustic images. Therefore, intravascular photoacoustic (IVPA) imaging has the potential to play a major role in the detection and differentiation of atherosclerotic lesions. Using a rabbit model of atherosclerosis, we performed ex vivo imaging studies to evaluate the ability of IVPA imaging to detect the presence of inflammation in the plaque. Specifically, the difference in the magnitude of the photoacoustic response from the free lipids, macrophage foam cells, blood and the rest of the arterial wall were used in detecting the fibrocellular inflammatory plaque. The constituents identified in the IVPA images were confirmed by the results from histology.
Lipid is a common constituent in atherosclerotic plaques. The location and area of the lipid regi... more 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.
The Journal of Thoracic and Cardiovascular Surgery, 2008
The aim of this study was to test the hypothesis that after an acute myocardial infarction, endot... more The aim of this study was to test the hypothesis that after an acute myocardial infarction, endothelin-1 release with subsequent calcium overload is a mediator of myocardial reperfusion injury, which can be inhibited, in part, by left ventricular unloading immediately before reperfusion. We recently have reported that left ventricular unloading before reperfusion reduces infarct size after acute myocardial infarction. However, the biologic mechanisms of infarct salvage in unloaded hearts subjected to ischemia/reperfusion remain undefined. Twelve pigs were subjected to 1 hour of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. A left ventricular assist device was initiated 15 minutes before reperfusion and maintained during reperfusion (assist device group, n = 6). A control group (n = 6) was subjected to reperfusion alone. Infarct size, endothelin-1 plasma levels, intracellular calcium levels, and apoptosis were analyzed in both groups. At reperfusion, left ventricular unloading significantly decreased left ventricular end-diastolic and end-systolic pressures. Infarct size, expressed as a percentage of zone at risk, was also significantly reduced by 54% in the group with the left ventricular assist device compared with controls. Support with a left ventricular assist device reduced endothelin-1 release from the heart at 15 minutes, 30 minutes, and 1 hour of reperfusion. Myocardial release of endothelin-1 was significantly correlated with infarct size at 15 minutes of reperfusion (r = 0.79; P = .008). Left ventricular unloading caused a significant reduction of calcium overload and of the percentage of apoptotic cells in the ischemic region. Our findings suggest that endothelin-1 release and calcium overload are important mediators of reperfusion injury and that they can be significantly reduced by left ventricular unloading before coronary artery reperfusion during myocardial infarction.
Journal of the American College of Cardiology, 2003
with death or Ml). We then validated this model in a pre-specified subgroup of patients from the ... more with death or Ml). We then validated this model in a pre-specified subgroup of patients from the GRACE registry who met criteria for inclusion in the TIMI 116 trial (n=ll505).
The Journal of the Acoustical Society of America, 2009
There is a need for an imaging technique that can reliably identify and characterize the vulnerab... more 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.
The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the dise... more The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.
Catheterization and cardiovascular diagnosis, 1994
To test the hypothesis that coronary sinus retroperfusion would preserve regional myocardial func... more To test the hypothesis that coronary sinus retroperfusion would preserve regional myocardial function during either left anterior descending or circumflex occlusion, sonomicrometer crystals were implanted in the midmyocardium of five chronically instrumented dogs. Regional fractional shortening was measured during 5 min of coronary occlusion with and without retroperfusion. Percent fractional shortening in the left anterior descending region fell from 18% at baseline to -4%(dyskinesis) after 3 min of left anterior descending occlusion. With coronary sinus retroperfusion, the percent fractional shortening declined from 16% at baseline to 0 (akinesis) during occlusion. A modest but significant improvement in percent fractional shortening in the ischemic region during left anterior descending occlusion occurred with retroperfusion (p < .05). By contrast, no amelioration of ischemic dysfunction occurred with retroperfusion during circumflex occlusion. Coaxial flow into the great card...
2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2009
Large lipid core is common in rupture-prone atherosclerotic plaques. Detection of the location an... more 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 multiwavelength 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.
Photons Plus Ultrasound: Imaging and Sensing 2011, 2011
Carotid atherosclerosis has been identified as a potential risk factor for cerebrovascular events... more 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
Photons Plus Ultrasound: Imaging and Sensing 2010, 2010
Using contrast agents with desired targeting moiety and optical absorption, intravascular photoac... more Using contrast agents with desired targeting moiety and optical absorption, intravascular photoacoustic imaging may be used to identify various biomarkers expressed during the progression of atherosclerotic lesions. In this paper, we present intravascular photoacoustic imaging of macrophages in the atherosclerotic lesions using bio-conjugated gold nanoparticles as the contrast agent. Atherosclerotic lesions were created in the aorta of a New Zealand
Proceedings of SPIE - The International Society for Optical Engineering, 2006
ABSTRACT Intravascular ultrasound (IVUS) imaging ,has emerged ,as an ,imaging ,technique to evalu... more ABSTRACT Intravascular ultrasound (IVUS) imaging ,has emerged ,as an ,imaging ,technique to evaluate ,coronary artery diseases including vulnerable plaques. However, in addition to the morphological characteristics provided by IVUS imaging, there is a need for functional imaging capability that could identify the composition of vulnerable plaques. Intravascular photoacoustic (IVPA) imaging, in conjunction with clinically available IVUS imaging, may be such a technique allowing,vulnerable plaque ,characterization and ,differentiation. We ,have ,developed ,an integrated ,intravascular ultrasound and photoacoustic imaging,system to visualize clinically relevant structural and functional properties of the coronary arteries. The performance,of the combined,IVUS and IVPA imaging,system was evaluated through images of arterial phantoms. Experiments were performed using high frequency IVUS imaging catheters operating at 20 MHz, 30 MHz and 40 MHz. The IVPA imaging ,was ,successful in highlighting ,inclusions based on differential ,optical absorption while these lesions did not have sufficient contrast in the IVUS images. Finally, initial IVUS and IVPA imaging studies were performed,on ex vivo samples of a rabbit artery using the 40 MHz IVUS imaging catheter. Results ofthe above studies demonstrate the feasibility of combining intravascular ultrasound and photoacoustic imaging and suggest clinical utility of the developed imaging system in interventional cardiology. Keywords: Photoacoustic imaging, ultrasound imaging, intravascular imaging, atherosclerosis, vulnerable plaque, optoacoustic imaging, coronary arteries, catheter, IVUS, interventional cardiology. 1.,INTRODUCTION Cardiovascular disease is the leading cause of mortality inthe Unites States. The American Heart Association estimates an annual mortality of greater than 1 million [1]. The disease of the heart is a huge health problem and a major economic
Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2007
Diagnosis and treatment of atherosclerosis necessitates the detection and differentiation of rupt... more Diagnosis and treatment of atherosclerosis necessitates the detection and differentiation of rupture prone plaques. In principle, intravascular photoacoustic (IVPA) imaging has the ability to simultaneously visualize the structure and composition of atherosclerotic plaques by utilizing the difference in optical absorption. Extensive studies are required to validate the utility of IVPA imaging in detecting vulnerable plaques and address issues associated with the clinical implementation of the technique. In this work, we performed ex vivo imaging studies using a rabbit model of atherosclerosis. The intravascular photoacoustic (IVPA) and ultrasound (IVUS) images of the normal aorta and aorta with plaque were obtained and compared with histological slices of the tissue. The results indicate that IVPA imaging is capable of detecting plaques and showed potential in determining the composition. Furthermore, we initially addressed several aspects of clinical implementation of the IVPA imaging. Specifically, the configuration of combined IVPA and IVUS catheter was investigated and the effect of the optical absorption of the luminal blood on the IVPA image quality was evaluated. Overall, this study suggests that IVPA imaging can become a unique and important clinical tool.
Photons Plus Ultrasound: Imaging and Sensing 2012, 2012
ABSTRACT Combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging ... more ABSTRACT Combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging has been previously established as a viable means for imaging atherosclerotic plaques using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of an atherosclerotic rabbit aorta following injection of gold nanorods (AuNR) with peak absorbance within the tissue optical window was performed. Ex-vivo imaging results revealed high photoacoustic signal from localized AuNR. Corresponding histological cross-sections and digital photographs of the artery lumen confirmed the presence of AuNR preferentially located at atherosclerotic regions and in agreement with IVPA signal. Furthermore, an integrated IVUS/IVPA imaging catheter was used to image the AuNR in the presence of luminal blood. The results suggest that AuNR allow for IVPA imaging of exogenously labeled atherosclerotic plaques with a comparatively low background signal and without the need for arterial flushing.
We previously demonstrated a method to perform simultaneous intravascular photoacoustic (IVPA) an... more We previously demonstrated a method to perform simultaneous intravascular photoacoustic (IVPA) and ultrasound (IVUS) imaging using an IVUS imaging catheter. During photoacoustic imaging, the energy fluence of optical irradiation was maintained low to conform to laser safety standards for medical imaging applications. However, the maximum permissible exposure for intravascular imaging is not yet well established and it is essential to address general safety issues of IVPA imaging. Hence, there is a need to monitor the temperature dynamics following laser excitation in IVPA imaging to estimate the maximum temperature increase and to insure thermal safety. In this paper, we present an ultrasound technique to monitor the temporal behavior of temperature in a tissue mimicking phantom and in an excised sample of arterial tissue after either a single laser pulse or during multiple laser pulses. The results of our study suggest that it is possible to monitor temperature and insure safety during the combined intravascular ultrasound and photoacoustic imaging.
Intravascular photoacoustic (IVPA) imaging has the potential to detect atherosclerotic plaques. P... more Intravascular photoacoustic (IVPA) imaging has the potential to detect atherosclerotic plaques. Previously, we obtained IVPA images using a 532 nm pulsed laser and a 40 MHz intravascular ultrasound (IVUS) imaging catheter. The optical absorption of light by the plaque components was used as a contrast mechanism helpful in detecting the plaque. However, plaque differentiation requires a method to remotely assess plaque composition. We hypothesized that plaque characterization can be performed by monitoring the changes in photoacoustic response with the change in laser excitation wavelength. In this preliminary study, we performed spectroscopic IVPA imaging to analyze the change in the photoacoustic response of the aortic tissue (a rabbit aorta with plaque and a control aorta) using different laser excitation wavelengths. Specifically, we perform IVPA imaging at multiple wavelengths within 680-900 nm range. The slope of the spectral change in photoacoustic response was computed between selected wavelengths to produce a spectroscopic IVPA image. The results of our study suggest the ability of the multi-wavelength IVPA imaging to identify and differentiate the fibrous, lipid and blood components of the atherosclerotic plaque.
Atherosclerosis is a systemic disease characterized by the development of a plaque leading to sev... more Atherosclerosis is a systemic disease characterized by the development of a plaque leading to several acute coronary syndromes. Imaging of plaque structure and composition is important in diagnosing the disease and further guiding coronary interventions. Currently, there is no clinical imaging technique capable of providing comprehensive morphological and functional information of the plaques. Several emerging techniques including palpography and thermography are under investigation for intravascular imaging of atherosclerosis. In this paper we present photoacoustic imaging as a means to assess the composition of plaques based on the optical properties of tissue.
We present a preliminary study demonstrating the capability of ultrasound-guided intravascular ph... more We present a preliminary study demonstrating the capability of ultrasound-guided intravascular photoacoustic (IVPA) imaging to visualize the depth-resolved distribution of lipid deposits in atherosclerotic plaques in vivo. Based on the characteristic optical absorption of lipid in the near infrared wavelength range, IVPA imaging at a single, 1720 nm, wavelength was used to provide a spatially-resolved, direct measurement of lipid content in atherosclerotic arteries. By overlaying an IVPA image with a spatially co-registered intravascular ultrasound (IVUS) image, the combined IVPA/IVUS image was used to visualize lipid distribution within the vessel wall. Ultrasound-guided IVPA imaging was performed in vivo in the abdominal aorta of a Watanabe heritable hyperlipidemic (WHHL) rabbit. Subsequently, the excised rabbit aorta filled with a solution of red blood cells (RBC) was then imaged ex vivo, and histology was obtained in the section adjacent to the imaged cross-section. To demonstrate the potential for future clinical application of IVPA/IVUS imaging, a sample of diseased human right coronary artery (RCA) was also imaged. Both in vivo and ex vivo IVPA images clearly showed the distribution of lipid in the atherosclerotic vessels. In vivo IVPA imaging was able to identify diffuse, lipid-rich plaques in the WHHL rabbit model of atherosclerosis. Furthermore, IVPA imaging at a single wavelength was able to identify the lipid core within the human RCA ex vivo. Our results demonstrate that ultrasound-guided IVPA imaging can identify lipid in atherosclerotic plaques in vivo. Importantly, the IVPA/IVUS images were obtained in presence of luminal blood and no saline flush or balloon occlusion was required. Overall, our studies suggest that ultrasound-guided IVPA imaging can potentially be used for depth-resolved visualization of lipid deposits within the anatomical context of the vessel wall and lumen. Therefore, IVUS/IVPA imaging may become an important tool for the detection of rupture-prone plaques.
Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on... more Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.
The assessment of plaque composition is one of the important steps in the interventional manageme... more The assessment of plaque composition is one of the important steps in the interventional management of atherosclerosis. The difference in the optical absorption between the arterial wall and plaque constituents could be utilized to obtain high resolution photoacoustic images. Therefore, intravascular photoacoustic (IVPA) imaging has the potential to play a major role in the detection and differentiation of atherosclerotic lesions. Using a rabbit model of atherosclerosis, we performed ex vivo imaging studies to evaluate the ability of IVPA imaging to detect the presence of inflammation in the plaque. Specifically, the difference in the magnitude of the photoacoustic response from the free lipids, macrophage foam cells, blood and the rest of the arterial wall were used in detecting the fibrocellular inflammatory plaque. The constituents identified in the IVPA images were confirmed by the results from histology.
Lipid is a common constituent in atherosclerotic plaques. The location and area of the lipid regi... more 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.
The Journal of Thoracic and Cardiovascular Surgery, 2008
The aim of this study was to test the hypothesis that after an acute myocardial infarction, endot... more The aim of this study was to test the hypothesis that after an acute myocardial infarction, endothelin-1 release with subsequent calcium overload is a mediator of myocardial reperfusion injury, which can be inhibited, in part, by left ventricular unloading immediately before reperfusion. We recently have reported that left ventricular unloading before reperfusion reduces infarct size after acute myocardial infarction. However, the biologic mechanisms of infarct salvage in unloaded hearts subjected to ischemia/reperfusion remain undefined. Twelve pigs were subjected to 1 hour of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. A left ventricular assist device was initiated 15 minutes before reperfusion and maintained during reperfusion (assist device group, n = 6). A control group (n = 6) was subjected to reperfusion alone. Infarct size, endothelin-1 plasma levels, intracellular calcium levels, and apoptosis were analyzed in both groups. At reperfusion, left ventricular unloading significantly decreased left ventricular end-diastolic and end-systolic pressures. Infarct size, expressed as a percentage of zone at risk, was also significantly reduced by 54% in the group with the left ventricular assist device compared with controls. Support with a left ventricular assist device reduced endothelin-1 release from the heart at 15 minutes, 30 minutes, and 1 hour of reperfusion. Myocardial release of endothelin-1 was significantly correlated with infarct size at 15 minutes of reperfusion (r = 0.79; P = .008). Left ventricular unloading caused a significant reduction of calcium overload and of the percentage of apoptotic cells in the ischemic region. Our findings suggest that endothelin-1 release and calcium overload are important mediators of reperfusion injury and that they can be significantly reduced by left ventricular unloading before coronary artery reperfusion during myocardial infarction.
Journal of the American College of Cardiology, 2003
with death or Ml). We then validated this model in a pre-specified subgroup of patients from the ... more with death or Ml). We then validated this model in a pre-specified subgroup of patients from the GRACE registry who met criteria for inclusion in the TIMI 116 trial (n=ll505).
The Journal of the Acoustical Society of America, 2009
There is a need for an imaging technique that can reliably identify and characterize the vulnerab... more 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.
The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the dise... more The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.
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Papers by James Amirian