Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology

Abstract

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

Keywords: Coronary atherosclerosis; Hybrid imaging; Intravascular imaging.

Figure 1

Centreline methodology proposed to reconstruct coronary anatomy from X-ray and intravascular imaging data acquired during a conventional cardiac catheterization. The luminal centreline is detected in two angiographic projections and then it is extruded perpendicularly to its plane forming two surfaces (A). The intersection of the two surfaces is a 3D curve that corresponds to the backbone of the vessel. The side branches are identified in the intravascular ultrasound or the optical coherence tomography images and vectors are drawn to mark their direction (Panels 1, 2, 3, 4). These vectors and the luminal borders detected in the remaining frames are placed perpendicularly onto the extracted luminal centreline and their relative axial twist is estimated using the sequential triangulation algorithm. The first intravascular ultrasound or optical coherence tomography frame is rotated around the luminal centreline, the reconstructed lumen is projected onto the angiographic images and the direction of the vectors indicating the side branches in intravascular images are compared with the origin of the corresponding branches in X-ray projections (B and E). The rotation angle of the first frame at which the best matching is achieved corresponds to the correct absolute orientation of the first frame (C–F). The final intravascular ultrasound - and optical coherence tomography-based models are shown in panels (D–G). The data for the design of this figure were kindly provided by Jang.

Figure 2

Combined near infrared spectroscopy—intravascular ultrasound catheter. (A) The tip of the catheter incorporates a rotating intravascular ultrasound transducer operating at 50 MHz with extended bandwidth, and two near infrared spectroscopy fibres that transmit and collect the near infrared light. (B) The chemogram is the output of the near infrared spectroscopy catheter (bottom right), is co-registered with the intravascular ultrasound data creating hybrid images that allow assessment of lumen, outer vessel wall, and plaque dimensions including plaque burden and simultaneous evaluation of the longitudinal and circumferential distribution of the lipid component. Panel B was reprinted with permission from Madder et al.

Figure 3

Dual mode intravascular ultrasound—optical coherence tomography catheter. The prototype has a diameter of 3 Fr with the optical coherence tomography component being integrated to the intravascular ultrasound probe (A and B). This design allows a collinear alignment of the two transducers (C), and thus accurate co-registration of the intravascular ultrasound (D) and optical coherence tomography (E) images (the asterisk indicates the presence of red thrombus).

Figure 4

Serial optical coherence tomographic—near infrared fluoresence imaging of plaque inflammation with the ProSenseVM110, a molecular sensor for cathepsin protease activity. Atheroma was induced in the rabbit aorta by mechanical balloon injury and hypercholesterolaemic diet. Serial in vivo optical coherence tomographic—near infrared fluoresence and intravascular ultrasound imaging was performed at 8 and 12 weeks after injury, 24 h after intravenous injection of ProSenseVM110. (A) Longitudinal co-registered near infrared fluorescence and intravascular ultrasound imaging at 8 and 12 weeks. (B) Axial optical coherence tomographic—near infrared fluorescence fusion image (yellow/white = high near infrared fluorescence; blue/black = low near infrared fluorescence) at the location of the white dotted line in (A), second row (near infrared fluorescence, 12 weeks). Matched cross-sectional fluorescence microscopy (red = ProSense VM110; green = autofluorescence) and histopathology demonstrates increased ProSense VM110 NIRF signal within a moderate fibrofatty atheroma (H&E) associated with cathepsin B immunostain. Scale bars, 1 mm. Figure courtesy of Dr Eric Osborn and Dr Giovanni Ughi.

Figure 5

Schematic representation of the combined optical coherence tomography—near infrared spectroscopy catheter (A). Optical coherence tomography—near infrared spectroscopy images of human cadaver plaques that appear similar by optical coherence tomography. The optical coherence tomography microstructural image is surrounded by the near infrared spectroscopy absorption spectrum at each angle of rotation of the catheter, where yellow indicates high absorption (B and C). The plaque in (B) does not exhibit significant near infrared spectroscopy absorption, whereas the lesion in (C) does. These near infrared spectroscopy datasets indicate that the plaque in (B) is fibrocalcific, whereas in (C) is a lipid-rich plaque. Reprinted with permission from Fard et al.

Figure 6

Intravascular ultrasound - intravascular photoacoustic imaging. (A) Sketch of a catheter tip, showing the ultrasound transducer (yellow) aligned with the tip of a side-looking optical fibre on a flexible drive shaft. (B) Microphotograph of an experimental catheter device (figure provided by M. Wu and G. Springeling unpublished), with a red pointer laser indicating the optical channel, in a polymer sheath (outer diameter 1.1 mm). (C) Lipid imaging of a human atherosclerotic plaque ex vivo, wavelength = 1710 nm. Conventional intravascular ultrasound is shown in greyscale, with intravascular photoacoustic lipid signal in red-orange overlay. Comparison with histology (D; Oil Red O stain) shows high intravascular photoacoustic signal in lipid-rich areas. (E) Stent imaging with intravascular ultrasound in an atherosclerotic vessel with highly echogenic plaque. The stent struts provide very limited contrast. (F) The high intravascular photoacoustic signal generated by the metal stent struts allows accurate assessment of stent apposition (J. Su, unpublished).

Figure 7

Schematic representation (A) and picture (B) of the bi-modal intravascular ultrasound-fluorescence lifetime imaging catheter used for the imaging of the coronary arteries. Co-registered fluorescence lifetime imaging-intravascular ultrasound data acquired using a bimodal catheter from an ex vivo human coronary artery. Fluorescence lifetime imaging data correspond to lifetime values from 390/40 nm wavelength band. (C) Fluorescence lifetime imaging-intravascular ultrasound data in 3D with select intravascular ultrasound frames. (D) En-face lifetime map. (E) Cross-sectional fluorescence lifetime imaging-intravascular ultrasound data (i) with corresponding (ii) CD68 stained and (iii) elastin-Masson's Trichrome histology sections. Red arrow head points to a region identified as fibrotic (collagen rich) plaque while the orange arrow head points to a region identified as thin-cap fibroatheroma plaque with macrophages (CD68+). Thin-cap fibroatheromas shows lower lifetime when compared with collagen rich areas. Scale bars are 1 mm.