Multimodality cardiovascular molecular imaging technology

Abstract

Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine.

FIGURE 1

Photochemical model of endothelial injury.

FIGURE 2

(A and B) Transverse photoacoustic images. Intensity after injury (B) is about 10–12 dB higher. (C) Longitudinal photoacoustic image. Intensity at injury spot (dashed circle) is about 10 dB higher.

FIGURE 3

All-optical intravascular photoacoustic–ultrasound system in guidewire. PDMS = poly(dimethylsiloxane); ROUT = resonant optical ultrasound transducer.

FIGURE 4

Pictures of console room and inside magnet room (seen on LCD screen in front of operator) during swine experiment. Real-time display is directly in front of surgeon. Operator responds to voice commands through voice-activated microphone to change scan plane views.

FIGURE 5

Targeting and visualization of intramyocardial injections. Each image is single frame from continuous real-time MRI movie. (A) Injection catheter in position with distal tip against myocardium. (B) Test injection, with interactive saturation applied, shows contrast entering myocardium. (C) Injection of labeled cells; dark signals show presence of cells.

FIGURE 6

Three slices obtained in interleaved fashion showing position of valve delivery device in left ventricle. Top left view shows trochar entering apex of left ventricle; just below that view we can see guidewire (green signal) passing beyond aortic annulus, and in view on top we can see aortic annulus in short-axis orientation, with valve positioned in its center. 3D viewer shows relationship of short-axis slice and anatomic markers on long-axis view. Axial image provided feedback when valve was rotated to align commissures of valve between coronary ostia (cyan dots) before deployment.

FIGURE 7

Selected frames from real-time MR images displayed within scan room, showing deployment of prosthetic valve. (A) Guidewire is advanced through trocar across native aortic valve. (B) Prosthetic valve is advanced to end of trocar. (C) Prosthetic valve is advanced into position in left ventricular outflow track. (D) Prosthetic valve is inserted across native valve and aligned with coronary ostia and aortic annulus. (E) Balloon filled with dilute gadolinium-diethylenetriaminepentaacetic acid MRI contrast agent is used to expand prosthetic valve. (F) Interactive saturation is used to enhance visualization of extent of balloon inflation. (G) Balloon is taken down and pulled back through trocar. (H) Guidewire is removed. (I) Delivery device is removed from trochar. Total time of this sequence of pictures is 77 s. (Reprinted with permission of (19).)

FIGURE 8

¹⁸F intravascular radiation detector. (Reprinted with permission of (37).)

FIGURE 9

Representative cases with TCFA and intracoronary thrombus. (Left) Case of TCFA; thickness of fibrous cap is 50 μm. (Right) Intracoronary thrombus protruding into vessel lumen from surface of vessel wall. (Reprinted with permission of (51).)

FIGURE 10

Distribution of broken fibrous cap thickness in patients with plaque rupture. Analysis of distribution shows 2 peaks. Around 70% of patients presented with thickness less than 70 μm. (Reprinted with permission of (51).)

FIGURE 11

OCT, using flush-only technique, images entire culprit coronary artery from distal bifurcation to ostium in ACS patient. Angiogram shows severe lesion in mid portion of right coronary artery and moderate stenosis in distal vessel. (A) Additional TCFA in proximal site; shoulder of fibrous cap is its thinnest part (40 μm, arrows). (B) Proximal TCFA. Center of fibrous cap is cap’s thinnest section (60 μm, arrows). (C) Proximal end of culprit TCFA. Thinnest point is shoulder of cap (50 μm, arrows). (D) Culprit plaque rupture. Cavity formation is clearly visible (arrow). (E) Representative culprit thrombus. OCT clearly shows mass protruding into vessel lumen from surface of vessel wall (arrows). (F) Three layers of arterial wall and branch. (G) Distal lesion. Thick fibrous cap can be observed at 4-o’clock position (240 μm, arrows). (Reprinted with permission of (52).)

FIGURE 12

(A) Raw OCT images of fibroatheroma with density of macrophages within fibrous cap. (B) Raw OCT images of fibroatheroma with high density of macrophages within fibrous cap. (C) Corresponding histology for A (CD68 immunoperoxidase; ×100). (D) Corresponding histology for B (CD68 immunoperoxidase; ×100). Macrophages (arrows in C and D) could be observed as punctate, highly reflecting regions (arrows in A and B) in raw OCT images. (Reprinted with permission of (62).)

FIGURE 13

OFDI images of left anterior descending artery. (A) Right anterior oblique angiogram after stent deployment, showing stent sites (s) and 4.2-cm OFDI pullback segment (ps). Maximum-intensity projection (B) and cutaway views (C) of 3D volume-rendered OFDI dataset, showing scattered calcium deposits and large lipid-rich lesion at distal portion of ps (arrowhead). Color scale for B and C: red = artery wall; green = macrophages; yellow = lipid pool; blue = stent; white = calcium; gray = guidewire. Scale bars in B and C, 5.0 mm. (Reprinted with permission of (48).)

FIGURE 14

Frequency of no-reflow phenomenon and lipid arc. Frequency of no-reflow phenomenon increases according to lipid arc at culprit plaque. Although all patients without lipid plaques (34/34 [100%]) achieved good reflow, 46% of patients with lipid-rich plaque (13/28 [46%]) presented no-reflow phenomenon after percutaneous coronary intervention. (Reprinted with permission of (65).)