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. 2017 Dec 7;12(12):e0188729.
doi: 10.1371/journal.pone.0188729. eCollection 2017.

Real-time visualization of thrombus formation at the interface between connectors and tubes in medical devices by using optical coherence tomography

Yuki Matsuhashi  1 , Kei Sameshima  1 , Yoshiki Yamamoto  2 , Mitsuo Umezu  1   2 , Kiyotaka Iwasaki  1   3
Affiliations

Real-time visualization of thrombus formation at the interface between connectors and tubes in medical devices by using optical coherence tomography

Yuki Matsuhashi et al. PLoS One. .

Abstract

Background: Blood-contacting devices have contributed to improving the treatment of patients. However, thrombus formation at the interface between a connector and tube is still a potential source of thrombus-related complications that induce stroke or myocardial infarction. We aimed to develop a non-blood-contacting real-time method for visualizing thrombus formation, and to experimentally investigate the time-dependent phenomenon of thrombus formation at the interface between a connector and a tube in a medical device.

Methods and findings: An optical coherence tomography device with a center wavelength of 1330 nm was used to visualize thrombus formation during porcine blood circulation for 50 min in a closed 50-mL circulation system isolated from ambient air. The thrombus formation sites at the interface between a tube and connector were visualized. The area of the thrombus formation at the interface between the inlet of the connector and the tube was found to be 0.012 ± 0.011 mm2. Conversely, at the interface between the outlet of the connector and the tube, the area was found to be 0.637 ± 0.306 mm2. Thus, significantly larger amounts of thrombus were formed at the outlet interface (p < 0.01). The thrombus formation area at the outlet interface increased over time. Conversely, the area of thrombus formation showed repeated increasing and decreasing behavior at the inlet interface. Flow visualization with particle image velocimetry showed the presence of a flow separated area in the minimal flow phase at the inlet interface and a large recirculating slow flow region at the outlet interface in the minimal flow phase. These data suggested that the recirculating stagnant flow region contributed to thrombus growth.

Conclusions: The method presented here was effective in quantitatively assessing time-dependent phenomena of thrombus formation at the connector-tube interface. The method may contribute to the assessment of thrombogenicity of a novel design of connector.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Schematic of a sequential visualization system for thrombus formation by using optical coherence tomography (OCT).
(a) Non-blood-contacting sequential visualization system of thrombus formation in a blood circulation system with OCT. (b) Flow and pressure waveforms in the blood circuit. (c) Connector used in this study. (d) Cross-sectional views at the interface between the connector and tube.
Fig 2
Fig 2. Thrombus formation at the connector interface.
(a) Cross-sectional view of the connector inlet. (b) Side view of the connector inlet. (c) Side view of the connector outlet. (d) Cross-sectional view of the connector outlet.
Fig 3
Fig 3. Signal intensity histograms.
(a) Signal intensity histogram of the original optical coherence tomography image. (b) Signal intensity histogram of the average of six time-differential images of seven consecutive frames.
Fig 4
Fig 4. Quantitative changes in the sequential thrombus formation area measured with optical coherence tomography.
(a) Thrombus formation at the interface between the connectors and the tube in the blood circulation test. The white arrow indicates the thrombus area, red lines represent the connectors, and yellow lines represent the location of the tube. The data represent one of the six tests shown with blue square plots in (b) and (c). (b) Thrombus formation area at the interface between the inlet of the connector and the tube. The tests were performed six times using porcine blood collected from six different individuals. (c) Thrombus formation area at the interface between the outlet of the connector and the tube. The right sides of (b) and (c) show the areas of thrombus formation detected by OCT after replacing blood with saline solution.
Fig 5
Fig 5. Light attenuation property of the optical coherence tomography due to the depth.
(a) The observation region was set from the lumen of the tube toward the depth direction up to 840 μm by each 120-μm interval. (b) Relationship between OCT signal intensities and depth away from the lumen of the tube.
Fig 6
Fig 6. Flow in the vicinity of the interface between the connector and tube.
Flow was visualized using particle image velocimetry. The white lines indicate the lumen of the tube and the edge of the connector.
See this image and copyright information in PMC

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