Abstract
Abstract: :
Purpose: To describe an improved method for the injection of well defined quantities of thrombolytic drugs into occluded retinal veins and arteries while minimizing collateral tissue damage and reflux leakage. We present a new technique, based upon modification of the vapor bubble-driven injection previously described by us, that allows for the creation of a pulsed liquid flow of larger volume with well-defined radial dimensions, axial velocity and duration. Methods: A mobile magnet is enclosed in a glass capillary surrounded by an electromagnetic coil. A millisecond pulse of electric current applied to the coil accelerates the magnet to a velocity of up to 10 m/s. As soon as the magnet hits a piston it pushes the liquid through a micronozzle generating a pulsed liquid jet with velocities of up to 100 m/s. If a pulse of current in the coil continues after the engagement of the magnet with the piston, the injection continues at lower speed - up to 30 m/s during the same pulse. This second phase of the injection at lower speed allows for delivery of larger amounts of liquid without increasing the chance of perforation of the distal wall of the blood vessel. Time-resolved imaging of injection dynamics was performed on an inverted microscope using fast shadow photography and fluorescence. Histological sections of the blood vessel were performed after in-vivo injection. Results: A pulsed liquid jet driven by a flying magnet through a micronozzle of 12 µm in diameter reaches peak flow velocities of up to 100 m/s with total ejected volumes of up to 1 µL during an ejection time of several milliseconds. Injection into blood vessels performed in-vitro and in-vivo has demonstrated the capability of forming a 20 µm perforation in the proximal wall of the vessel with no damage to its distal wall. Hemorrhage from the vessel treated in-vivo stopped after a few seconds due to the self-sealing nature of the microperforation. Conclusions: A pulsed liquid microjet can be utilized to inject up to 1 µL of fluid directly into small blood vessels with minimal collateral vascular damage. Possible applications may include injection of well-defined quantities of thrombolytic drugs into occluded blood vessels for fragmentation of vascular clots. The instrument may also be modified for trans-cutaneous drug delivery without needles with either a single probe or an array of micronozzles.
Keywords: 615 vascular occlusion/vascular occlusive disease • 554 retina • 436 injection