Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction

ObjectivesWe sought to determine if intravenously injected microbubbles would be retained by the carotid arteries (CAs) in the setting of endothelial dysfunction (ED) using a linear transducer equipped with a low mechanical index pulse sequence scheme (PSS).BackgroundMicrobubbles normally pass freely through large and small vessels but are retained in regions with ED. New high-frequency low mechanical index PSS can potentially be utilized to image these retained microbubbles.MethodsIntravenous albumin- and lipid-encapsulated microbubbles were administered in seven pigs while imaging the CAs before and after a 20% intralipid infusion to induce hypertriglyceridemia. The degree of microbubble retention was quantified by measuring endothelial acoustic intensity (AI) after clearance of free-flowing microbubbles. Microbubble adherence was also evaluated after selective balloon injury of the CAs. The CA diameter responses to acetylcholine were quantified.ResultsAfter induction of hypertriglyceridemia, adherence of albumin-encapsulated microbubbles was visually evident in all CAs, and endothelial AI increased significantly (p < 0.001 compared with baseline). The CA responses to acetylcholine went from vasodilation at baseline to vasoconstriction during hypertriglyceridemia. Endothelial AI also increased in the balloon-stretched vessels (p < 0.01 compared with uninjured vessels) after albumin-encapsulated microbubble injection, with a ring of microbubbles selectively adhering to the injured segment. This retention was not observed with lipid-encapsulated microbubbles. Scanning electron microscopy confirmed that albumin-coated microbubbles adhered to endothelial cells.ConclusionsRetention of intravenously injected albumin microbubbles occurs in the setting of both global and regional ED in large vessels and can be noninvasively imaged with high-frequency low mechanical index PSS

Pressure-Enabled Drug Delivery Approach in the Pancreas with Retrograde Venous Infusion of Lipiodol with Ex Vivo Analysis.

PurposeTo determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach.MethodsUtilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands.ResultsA total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5-2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p &lt; 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia.ConclusionsPEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study

Pressure-Enabled Drug Delivery Approach in the Pancreas with Retrograde Venous Infusion of Lipiodol with Ex Vivo Analysis.

PurposeTo determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach.MethodsUtilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands.ResultsA total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5-2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p &lt; 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia.ConclusionsPEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study