Geert Springeling

Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis

Abstract. 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.

Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second

Lipid deposition can be assessed with combined intravascular photoacoustic/ultrasound (IVPA/US) imaging. To date, the clinical translation of IVPA/US imaging has been stalled by a low imaging speed and catheter complexity. In this paper, we demonstrate imaging of lipid targets in swine coronary arteries in vivo, at a clinically useful frame rate of 20 s-1. We confirmed image contrast for atherosclerotic plaque in human samples ex vivo. The system is on a mobile platform and provides real-time data visualization during acquisition. We achieved an IVPA signal-to-noise ratio of 20 dB. These data show that clinical translation of IVPA is possible in principle.

Photoacoustic imaging of carotid artery atherosclerosis

Abstract. We introduce a method for photoacoustic imaging of the carotid artery, tailored toward detection of lipid-rich atherosclerotic lesions. A common human carotid artery was obtained at autopsy, embedded in a neck mimicking phantom and imaged with a multimodality imaging system using interstitial illumination. Light was delivered through a 1.25-mm-diameter optical probe that can be placed in the pharynx, allowing the carotid artery to be illuminated from within the body. Ultrasound imaging and photoacoustic signal detection is achieved by an external 8-MHz linear array coupled to an ultrasound imaging system. Spectroscopic analysis of photoacoustic images obtained in the wavelength range from 1130 to 1250 nm revealed plaque-specific lipid accumulation in the collagen structure of the artery wall. These spectroscopic findings were confirmed by histology.

Intravascular photoacoustic imaging of human coronary atherosclerosis

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. We specifically imaged lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction. An integrated intravascular photoacoustics (IVPA) and ultrasound (IVUS) catheter with an outer diameter of 1.25 mm was developed. The catheter comprises an angle-polished optical fiber adjacent to a 30 MHz single-element transducer. The ultrasonic transducer was optically isolated to eliminate artifacts in the PA image. We performed measurements on a cylindrical vessel phantom and isolated point targets to demonstrate its imaging performance. Axial and lateral point spread function widths were 110 μm and 550 μm, respectively, for PA and 89 μm and 420 μm for US. We imaged two fresh human coronary arteries, showing different stages of disease, ex vivo. Specific photoacoustic imaging of lipid content, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm.

An intravascular photoacoustic imaging catheter

We developed an integrated intravascular photoacoustic (IVPA) and ultrasound (IVUS) catheter to image atherosclerotic plaque structure and composition, which are important determinants of plaque vulnerability. Our catheter comprises an angle-polished optical fiber and a 30 MHz single-element piezoelectric transducer. The ultrasonic transducer was optically isolated to eliminate artifacts in the photoacoustic (PA) image. We showed its imaging performance using a vessel phantom and quantified its imaging characteristics by doing measurements on isolated point targets. The axial and lateral point spread function widths were 110 µm and 550 µm respectively for IVPA imaging and 89 µm and 420 µm respectively for IVUS imaging. The signal to noise ratios were 50 dB (PA) and 54 dB (US).

Impact of device geometry on the imaging characteristics of an intravascular photoacoustic catheter

A basic requirement for intravascular photoacoustic (IVPA) imaging catheters is that the delivery of light lies within the ultrasonic field of view. Size and manufacturing constraints favor probe designs with offset optical and acoustic beams. This noncollinear dual beam arrangement leads to a curved PA point spread function (PSF). In this work, we characterize the three-dimensional shape of the PSF for IVPA imaging in clear and optically scattering media. We show that the product of the two beam profiles can accurately model the measured peak response in clear and scattering media. We discuss the impact of the PSF shape and its relation to probe construction. We test the imaging capability of the catheter on a phantom and a human artery ex vivo.

Heartbeat OCT and Motion-Free 3D in Vivo Coronary Artery Microscopy

Intravascular optical coherence tomography (IV-OCT) has gained widespread use over the past few years, offering highly detailed images of coronary artery pathologies and interventions [(1)][1]. In contrast to the cross-sectional view, longitudinal sections and 3-dimensional (3D) renderings are

A Broadband Polyvinylidene Difluoride-Based Hydrophone with Integrated Readout Circuit for Intravascular Photoacoustic Imaging

Intravascular photoacoustic (IVPA) imaging can visualize the coronary atherosclerotic plaque composition on the basis of the optical absorption contrast. Most of the photoacoustic (PA) energy of human coronary plaque lipids was found to lie in the frequency band between 2 and 15 MHz requiring a very broadband transducer, especially if a combination with intravascular ultrasound is desired. We have developed a broadband polyvinylidene difluoride (PVDF) transducer (0.6 × 0.6 mm, 52 μm thick) with integrated electronics to match the low capacitance of such a small polyvinylidene difluoride element (<5 pF/mm(2)) with the high capacitive load of the long cable (∼100 pF/m). The new readout circuit provides an output voltage with a sensitivity of about 3.8 μV/Pa at 2.25 MHz. Its response is flat within 10 dB in the range 2 to 15 MHz. The root mean square (rms) output noise level is 259 μV over the entire bandwidth (1-20 MHz), resulting in a minimum detectable pressure of 30 Pa at 2.25 MHz.

Compressive 3D ultrasound imaging using a single sensor

Compressive 3D ultrasound imaging is possible with only one sensor and a simple aperture coding mask. Three-dimensional ultrasound is a powerful imaging technique, but it requires thousands of sensors and complex hardware. Very recently, the discovery of compressive sensing has shown that the signal structure can be exploited to reduce the burden posed by traditional sensing requirements. In this spirit, we have designed a simple ultrasound imaging device that can perform three-dimensional imaging using just a single ultrasound sensor. Our device makes a compressed measurement of the spatial ultrasound field using a plastic aperture mask placed in front of the ultrasound sensor. The aperture mask ensures that every pixel in the image is uniquely identifiable in the compressed measurement. We demonstrate that this device can successfully image two structured objects placed in water. The need for just one sensor instead of thousands paves the way for cheaper, faster, simpler, and smaller sensing devices and possible new clinical applications.

Catheter design optimization for practical intravascular photoacoustic imaging (IVPA) of vulnerable plaques

Intravascular photoacoustic/ultrasound imaging (IVPA/US) can image the structure and composition of atherosclerotic lesions identifying lipid-rich plaques ex vivo and in vivo. In the literature, multiple IVPA/US catheter designs were presented and validated both in ex-vivo models and preclinical in-vivo situations. Since the catheter is a critical component of the imaging system, we discuss here a catheter design oriented to imaging plaque in a realistic and translatable setting. We present a catheter optimized for light delivery, manageable flush parameters and robustness with reduced mechanical damage risks at the laser/catheter joint interface. We also show capability of imaging within sheath and in water medium.