Myocardial contrast echocardiography and the transmural distribution of flow: A critical appraisal during myocardial ischemia not associated with infarction

AbstractObjectives. This study was undertaken to determine whether myocardial contrast echocardiography can be used to estimate the transmural distribution of flow.Background. Myocardial contrast echocardiography has been shown to reliably measure average transmural blood flow during myocardial ischemia. However, there is controversy regarding its ability to determine the transmural distribution of flow.Methods. The transmural distribution of flow was measured in 21 open chest anesthetized dogs with use of radiolabeled microspheres and sonicated albumin microbubbles (mean size 4.5 μm). In the 11 Group I dogs, myocardial contrast echocardiography was performed at baseline and during left anterior descending artery stenosis. In five of these dogs, it was also performed during left circumflex artery stenosis. In these dogs large (mean 12 μm) hand-agitated bubbles were also used. In the five Group II dogs, myocardial contrast echocardiography was performed before and 45 s after intracoronary injection of 6 mg of papaverine in the presence of a critical left circumflex artery stenosis. The five Group III dogs were studied during cardiopulmonary bypass at baseline and during left anterior descending artery stenosis. Off-line image analysis of the echocardiographic images was performed and timeintensity curves obtained from thess images were correlated with radiolabeled microsphere-derived flows.Results. The ratios of the parameters derived from the endocardium and epicardium during myocardial contrast echocardiography were found to correlate poorly (ranging from R2= 0 to R2= 0.35) with radiolabeled microsphere-derived endocardial/ epicardial flow ratios over a wide range of flow ratios (0.01 to 2.58). These results were not influenced either by the location of the regions of interest (left anterior descending vs. left circumflex artery bed) or by the size of the bubbles (4.5 vs. 12 μm).Conclusions. Myocardial contrast echocardiography cannot be used to assess the transmural distribution of flow during myocardial ischemia not associated with infarction

Ultrafast Microscopy Imaging of Acoustic Cluster Therapy Bubbles: Activation and Oscillation

Acoustic Cluster Therapy (ACT®) is a platform for improving drug delivery and has had promising pre-clinical results. A clinical trial is ongoing. ACT® is based on microclusters of microbubbles–microdroplets that, when sonicated, form a large ACT® bubble. The aim of this study was to obtain new knowledge on the dynamic formation and oscillations of ACT® bubbles by ultrafast optical imaging in a microchannel. The high-speed recordings revealed the microbubble–microdroplet fusion, and the gas in the microbubble acted as a vaporization seed for the microdroplet. Subsequently, the bubble grew by gas diffusion from the surrounding medium and became a large ACT® bubble with a diameter of 5–50 μm. A second ultrasound exposure at lower frequency caused the ACT® bubble to oscillate. The recorded oscillations were compared with simulations using the modified Rayleigh–Plesset equation. A term accounting for the physical boundary imposed by the microchannel wall was included. The recorded oscillation amplitudes were approximately 1–2 µm, hence similar to oscillations of smaller contrast agent microbubbles. These findings, together with our previously reported promising pre-clinical therapeutic results, suggest that these oscillations covering a large part of the vessel wall because of the large bubble volume can substantially improve therapeutic outcome.publishedVersio

Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection

Kerala’s COVID-19 response has gained international attention for its egalitarian approach. Ophira Gamliel reflects on how studying the Malayalam language provides insight into the culture that enables this success

In vivo PEG modification of vascular surfaces for targeted delivery

ObjectiveThrombosis and restenosis remain problematic for many intravascular procedures. Previously, it has been demonstrated that modifying an injured vascular surface with a protein-reactive polymer could block undesirable platelet deposition. As an added benefit, it would be advantageous if one could target therapeutics to the injured site. This study investigates a site-specific delivery system to target microspheres to vascular surfaces modified with a reactive polyethylene glycol tagged with biotin.MethodsRabbit femoral arteries were injured with a 2F embolectomy catheter. Modification of the vascular surface was achieved using a channeled balloon catheter or small-diameter tube. Microspheres were injected intravenously through catheterization of the ear vein. Polymer modification on the injured surface and delivery of microspheres was quantified using epifluorescence microscopy at 0, 24, 48, and 72 hours.ResultsPolymer modification of the vascular surface could be achieved using a channeled drug delivery catheter or small-diameter tube with similar results. Maximum polymer coverage occurred at 0 hours and decreased to 85% maximal at 24 hours, 72% at 48 hours, and 67% at 72 hours. The initial number of microspheres per mm2 binding to modified, injured arteries was 304 versus 141 for the unmodified, damaged control (P < .01). At subsequent times, the number of adherent microspheres to modified, injured arteries decreased by 50%, 70%, and 84% at 24, 48, and 72 hours, respectively; while nonspecific binding to unmodified, injured arteries quickly decreased by 93%. Initial microsphere binding to modified, healthy arteries was 153 microspheres/mm2 as opposed to 26 microspheres/mm2 for the unmodified, healthy controls (P < .01).ConclusionsChemical modification of injured vessels following intravascular procedures can be readily accomplished in vivo to create a substrate for targeted delivery systems. As a proof of concept, targeted microspheres preferentially adhered to polymer-modified surfaces as opposed to injured, unmodified, or healthy vascular surfaces.Clinical RelevanceClinical outcomes of intravascular procedures are often complicated by thrombosis and restenosis due to vascular injury. These results demonstrate the feasibility of providing site-specific recognition signals for delivery of agents to healthy and damaged vascular tissue, which could prove valuable in a variety of clinical settings where the localization of therapeutics is desirable. In particular, the delivery of antimitotic or antithrombotic particulate pharmaceuticals or carriers to arterial lumens following angioplasty or endarterectomy, or chemotherapeutic agents to tumor vasculature might be feasible