An automatic occlusion device for remote control of tumor tissue ischemia

Abstract

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multimodal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics.

Figure 1

The prototype of the automatic occlusion device. The device comprises a flexible cannula encasing a shape memory alloy wire and a control box encasing a rotary switch, a solid state relay, and a driver circuit board connected to a computer. The distal end of the automatic occlusion device is connected to a surgical suture.

Figure 2

Schematic of the control circuit for the automatic occlusion device. The computer is used to control the digital output of a data acquisition card to activate the solid state relay. The rotary switch allows for the selection of five resistors corresponding to different occlusion voltage levels.

Figure 3

Experimental setup for benchtop validation of the automatic occlusion device. The enlarged sketch shows how the silicon tube and the surrounding tissue simulating material are ligated by the surgical suture that is connected to the distal end of the occlusion device.

Figure 4

Experimental setup for femoral vessel ligation on a black male C57BL/6 mouse.

Figure 5

Simultaneous monitoring of tumor oxygen and blood flow dynamics during reversible tumor ischemia on a xenograft nude mouse.

Figure 6

Correlation between the occlusion voltage applied to the automatic occlusion device and the resulting blood flow rate in a vessel simulator.

Figure 7

Tissue oxygenation measured on the right leg of a black male C57BL/6 mouse during the successive femoral vessel ligation. The top figure shows the tissue oxygenation history during repetitive ligation. The grey data points in the background are actual oxygenation measurements and the thick solid line in the foreground is the 12^th order least square polynomial fitting of the experimental data. The bottom figure shows the ligation status. “On” represents the status that the occlusion voltage was applied. “Off” represents no ligation. At the “on” status, the vessel ligation caused tissue ischemia and the reduction of tissue oxygenation. At the “off” status, tissue oxygenation resumes back to its original level.

Figure 8

Relative changes of tumor tissue oxygenation, blood flow, and oxygen tension during ischemia and reperfusion on the xenograft nude mouse. The Student's paired t-Test shows that ligation significantly reduced tumor tissue oxygenation, blood flow, and oxygen tension (P <0.001).