Subcutaneous injection of drug solution is widely used for continuous and low dose drug treatment. Although the drug injections have been administered for a long time, challenges in the design of injection devices are still needed to minimize the variability, pain, or skin disorder by repeated drug injections. To avoid these adverse effects, systematic study on the effects of injection conditions should be conducted to improve the predictability of drug effect. Here, the effects of injection conditions on the drug permeation in tissues were investigated using X-ray imaging technique which provides real-time images of drug permeation with high spatial resolution. The shape and concentration distribution of the injected drug solution in the porcine subcutaneous and muscle tissues are visualized. Dynamic movements of the wetting front (WF) and temporal variations of water contents in the two tissues are quantitatively analyzed. Based on the quantitative analysis of the experimental data, the permeability of drug solution through the tissues are estimated according to permeation direction, injection speed, and tissue. The present results would be helpful for improving the performance of drug injection devices and for predicting the drug efficacy in tissues using biomedical simulation.
X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2 microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measure in vivo blood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conducting in vivo X-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.
Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases.
Recently, the multi-needle drug injection has been adopted to overcome the shortcomes of conventional single-needle injection, enhancing the efficiency of drug delivery. However, the effect of needle array on the efficacy of drug delivery has not been fully elucidated. In this study, the interactions of drug analogous solution injected from a pair of needles were analyzed to examine the design criteria of effective multi-needle devices for drug delivery. Temporal and spatial variations of relative contents of the solution in the tissues were compared according to the distance between two adjacent needles (DN). As the DN increases from 5 to 20 D, where D is the needle diameter, the solution from each needle encounters 3.5 times faster, and 4.22 times more solution was accumulated. At the same time, the effective spreading area was continuously increased from 54.2 to 177.8 mm and RCS gradient decreases from 0.087 to 0.037, due to the overlapping effect of the spreading solution from neighboring needles. Finally, based on the experimental results, an optimal design criterion of needle array for effective drug delivery was proposed. The present results would be helpful in the design of multi-needle injection devices and eventually offer advantage to patients with effective drug delivery.
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