Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS–paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.
Purpose: The goal of this study was to develop an ex vivo system capable of rapidly evaluating arterial drug levels in living, isolated porcine carotid arteries.Methods: A vascular bioreactor system was developed that housed a native porcine carotid artery under physiological flow conditions. The ex vivo bioreactor system was designed to quantify the acute drug transfer of catheter-based drug delivery devices into explanted carotid arteries. To evaluate our ex vivo system, a paclitaxel-coated balloon and a perfusion catheter device delivering liquid paclitaxel were utilized. At 1-h post-drug delivery, arteries were removed, and paclitaxel drug levels measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Parallel experiments were performed in a pig model to validate ex vivo measurements.Results: LC-MS/MS analysis demonstrated arterial paclitaxel levels of the drug-coated balloon-treated arteries to be 48.49 ± 24.09 ng/mg and the perfusion catheter-treated arteries to be 25.42 ± 9.74 ng/mg at 1 h in the ex vivo system. Similar results were measured in vivo, as arterial paclitaxel concentrations were measured at 59.23 ± 41.27 ng/mg for the drug-coated balloon-treated arteries and 23.43 ± 20.23 ng/mg for the perfusion catheter-treated arteries. Overall, no significant differences were observed between paclitaxel measurements of arteries treated ex vivo vs. in vivo.Conclusion: This system represents the first validated ex vivo pulsatile system to determine pharmacokinetics in a native blood vessel. This work provides proof-of-concept of a quick, inexpensive, preclinical tool to study acute drug tissue concentration kinetics of drug-releasing interventional vascular devices.
The purpose of this pilot study was to investigate the feasibility of a perfusion catheter to deliver liquid paclitaxel into arterial segments. A clinically relevant rabbit ilio-femoral injury model was utilized to determine the impact of liquid paclitaxel delivered locally into the vessel wall using a perfusion catheter at 1 h to 14 days. Treatment by two clinically available forms of liquid paclitaxel, a solvent-based (sb) versus an albumin-bound (nab), along with a control (uncoated balloons), were investigated. Pharmacokinetic results demonstrated an increase in the retention of the sb-paclitaxel versus the nab-paclitaxel at 1 h; however, no other differences were observed at days one, three, and seven. Histological findings at 14 days showed significantly less neointimal area in the sb-paclitaxel treated arteries as compared with the nab-paclitaxel and the uncoated balloon-treated arteries. Additionally, percent area stenosis was significantly less in the sb-paclitaxel group. These results support the concept of local liquid delivery of paclitaxel into the arterial segments.
which was pretrained on 1.2 million everyday color images. Real-time data-augmentation was performed, including rotations, translation, shearing, and zoom. Six window-level settings were used for each slice. Data were split into training (30 patients: 15 with and 15 without dissection; 4235 images), validation (10 patients: 5 with and 5 without dissection; 1295 images) and test (40 patients: 20 with and 20 without dissection; 3423 images). A 2D network was used that analyzed three slices at a time. Receiver operating characteristic (ROC), area-underthe-curves (AUC) on the test data, and sensitivity and specificity of the algorithms were performed. Results: On the test set, the algorithm had a patient-level AUC of 0.97 (95% CI: 0.91-1.00), sensitivity of 100.0% (20/20) and specificity of 90.0% (18/20) for distinguishing aortic dissection from controls. There were two false positive cases, which included one with eccentric mural thrombus and another with an endovascular stent. Conclusions: Deep learning shows tremendous promise in identifying acute aortic dissection on thoracic CT.
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