Real-Time Neutron Imaging to Detect Origin of Blocking in Drug Injection Devices

Nondestructive testing is a common method for root cause investigations of malfunction of mechanical devices, for example, medical devices for drug dose delivery. Radiography is a method that has the advantage that it is possible to see through the sample. In this work we are using neutron radiography to observe drug distribution in drug injection devices during the injection process and as post-injection examination. Using neutrons it is possible to show small amounts of liquid in capillaries, and foam bubbles are shown with great contrast compared to metal and glass. The investigation has two parts optimized for high spatial and high temporal resolution, respectively. Using high spatial resolution it is possible to resolve the thin films of drug product in foam and even to detect the drug residues in the injection needle. Switching to high temporal resolution we demonstrate that it is possible to follow the injection process. Spatio-temporal data sets of the injection process were acquired using remotely triggered injection devices and a camera allowing sub-second frame rates.The motion analysis required the application of an edge-preserving spatio-temporal denoising filter to improve the signal-to-noise ratio. After filtering it is possible to detect relevant edges and extract motion curves from the spatio-temporal data.

Neutron imaging is a nondestructive method based on radiography using neutrons and is suitable for detecting small amounts of aqueous liquids even in metallic casing/sheath/tubing. This property has here been used to visualize the distribution of a drug product in a syringe needle of a drug injection device. In the static case the method clearly showed the difference between needles that were empty, full, or contained a mix of gas and liquid. A second investigation was aimed to visualize the dynamic behavior of an auto-injector device. In this experiment the imaging method was capable of following the injection phase of the device. By analyzing the acquired images in time and space it is possible to measure the injection velocity curves of the piston and drug, respectively.