A rotating cerium anode X-ray system allows visualization of intramural coronary vessels after cardiac stem cell therapy for myocardial infarction

Abstract

Conventional angiography is insufficient for evaluating the therapeutic effect of cardiac regeneration therapy. A microangiographic X-ray system using a cerium anode was developed. Cerium has a characteristic X-ray with a peak at 34.6 keV, which allows visualization of tiny amounts of iodine. The performance of the cerium anode X-ray system was evaluated in two excised normal canine hearts and in excised ischemic canine hearts treated with c-kit-positive cardiac stem cells (5 canines) or without cells (5 control canines). In the normal canines, branches penetrating from the left anterior descending artery into the myocardium were visualized, down to third-order branches. In just the treated hearts treated with stem cells, small vessels characterized by irregular vessel walls were observed. The cerium anode X-ray system allowed visualization of microvessels in excised ischemic canine hearts, and may evaluate the effect of cardiac stem cell therapy.

Keywords: C-kit-positive cardiac stem cells; Canine models; Cerium anode; Microangiography; Myocardial infarction.

Fig. 1

A new microangiographic X-ray system using a cerium anode. The cerium anode X-ray system is sufficiently small to be utilized in hospitals

Fig. 2

An excised heart irradiated by the cerium anode X-ray system. a The image was obtained by the cerium anode X-ray system set at 100 kV, 50 mA, and 100 ms of tube voltage, current, and exposure time, respectively. A guide wire with a diameter of 100 μm (black arrow in Fig. 3a) is used for calibration to measure the vessel diameters. b This is a magnified image of (a). It shows many IMCAs from EPCA down to the third-order branches as indicated by the white delta symbol

Fig. 3

An excised heart irradiated by the conventional X-ray system. a The image was obtained by the conventional X-ray system set at 100 kV, 50 mA, and 100 ms of tube voltage, current, and exposure time, respectively. b This is a magnified image of (a). The IMCA second-order branches were visualized as indicated by the white delta symbol

Fig. 4

An excised heart irradiated by the cerium anode X-ray system with a 20-cm-thick acrylic plate. a The image was obtained by the rotating cerium anode X-ray system set at 100 kV, 50 mA, and 1000 ms of tube voltage, current, and exposure time, respectively, after placing a 20-cm-thick acrylic plate between the X-ray tube and the excised heart. b This is a magnified image of (a). The third-order branches were sufficiently visualized as indicated by the white arrow

Fig. 5

An excised heart irradiated by the conventional X-ray system with a 20-cm-thick acrylic plate. a The image was obtained by the conventional X-ray system set at 100 kV, 50 mA, and 1000 ms of tube voltage, current, and exposure time, respectively, after placing a 20-cm-thick acrylic plate between the X-ray tube and the excised heart. b This is a magnified image of (a). The IMCA third-order branches from EPCA were poorly visualized as indicated by the white arrow

Fig. 6

Cardiac stem cells (CSCs) stained with the anti-c-kit antibody. c-kit-positive CSCs were stained in red. The nuclei were stained in blue with 4′,6-diamidino-2-phenylindole

Fig. 7

An excised heart of a canine not treated with CSCs (control group). a The excised canine heart of the control group was exposed by the cerium anode X-ray system. b This is a magnified image of (a). An avascular bed at the heart apex (indicated by black arrows) and interrupted arteries in the border zone of the ischemic area (indicated by white arrows) were visualized in the control group

Fig. 8

An excised heart of a canine treated with c-kit-positive cardiac stem cells (CSC group). a The excised canine heart of the CSCs group was exposed by the cerium anode X-ray system. b This is a magnified image of (a). Numerous microvessels were visualized at the ischemic area in all canines in the CSC group. These newly formed vessels are characterized by irregularities as indicated by white arrows