Selective infarct zone imaging with intravenous acoustically activated droplets.

BACKGROUND: Microbubbles (MB) can be compressed to nanometer-sized droplets and reactivated with diagnostic ultrasound; these reactivated MB possess unique imaging characteristics. OBJECTIVE: We hypothesized that droplets formed from compressing Definity MB may be used for infarct-enhancement imaging. METHODS: Fourteen rats underwent ligation of their left anterior descending (LAD) artery, and five pigs underwent 90 minute balloon occlusions of their mid LAD. At 48 hours in rats, transthoracic ultrasound was performed at two and four minutes following 200 µL intravenous injections (IVI) of Definity droplets (DD), at which point the MI was increased from 0.5 to 1.5 to assess for a transient contrast enhancement zone (TEZ) within akinetic segments. In pigs, 1.0 mL injections of DD were administered and low frame rate (triggered end systolic or 10 Hz) imaging 2-4 minutes post iVI to selectively activate and image the infarct zone (IZ). Infarct size was defined by delayed enhancement magnetic resonance imaging (DE-MRI) and post-mortem staining (TTC). RESULTS: Increasing MI to 1.5 (at two or four minutes after IVI) resulted in a TEZ in rats, which correlated with infarct size (r = 0.94, p<0.001). A TEZ was not seen at 2-4 minutes in any rat (n = 8) following Definity MB injections. Fluorescent staining confirmed DD presence within the infarct zone 10 minutes after intravenous injection. In pigs, selective enhancement within the IZ was achieved by using a low frame rate single pulse harmonic mode; IZ size matched the location seen with DE-MRI and correlated with TTC defect size (r = 0.90, p<0.05). CONCLUSION: DD formulated from commercially available MB can be acoustically activated for selective infarct enhancement imaging.

Review of emerging surgical robotic technology.

BACKGROUND: The use of laparoscopic and robotic procedures has increased in general surgery. Minimally invasive robotic surgery has made tremendous progress in a relatively short period of time, realizing improvements for both the patient and surgeon. This has led to an increase in the use and development of robotic devices and platforms for general surgery. The purpose of this review is to explore current and emerging surgical robotic technologies in a growing and dynamic environment of research and development. METHODS: This review explores medical and surgical robotic endoscopic surgery and peripheral technologies currently available or in development. The devices discussed here are specific to general surgery, including laparoscopy, colonoscopy, esophagogastroduodenoscopy, and thoracoscopy. Benefits and limitations of each technology were identified and applicable future directions were described. RESULTS: A number of FDA-approved devices and platforms for robotic surgery were reviewed, including the da Vinci Surgical System, Sensei X Robotic Catheter System, FreeHand 1.2, invendoscopy E200 system, Flex® Robotic System, Senhance, ARES, the Single-Port Instrument Delivery Extended Research (SPIDER), and the NeoGuide Colonoscope. Additionally, platforms were reviewed which have not yet obtained FDA approval including MiroSurge, ViaCath System, SPORT™ Surgical System, SurgiBot, Versius Robotic System, Master and Slave Transluminal Endoscopic Robot, Verb Surgical, Miniature In Vivo Robot, and the Einstein Surgical Robot. CONCLUSIONS: The use and demand for robotic medical and surgical platforms is increasing and new technologies are continually being developed. New technologies are increasingly implemented to improve on the capabilities of previously established systems. Future studies are needed to further evaluate the strengths and weaknesses of each robotic surgical device and platform in the operating suite.

Acoustic Behavior of a Reactivated, Commercially Available Ultrasound Contrast Agent.

BACKGROUND: Commercially available microbubbles such as Definity contain octafluoropropane encapsulated in a lipid shell. This perfluorocarbon can be compressed into liquid nanodroplets at room temperatures and activated with transthoracic diagnostic ultrasound. The aim of this study was to determine the size range and acoustic characteristics of Definity nanodroplets (DNDs) compared with Definity microbubbles (DMBs). METHODS: An in vitro flow system was used with a diagnostic ultrasound transducer (S5-1, iE33). DMBs were prepared using package insert instructions. DNDs were prepared by cooling DMBs in a -10°C to -15°C isopropyl alcohol bath before hand-pressurizing the solution. The formed DNDs were sized, diluted to 1% solutions, and infused continuously into a phosphate-buffered saline solution running within Silastic tubing. Acoustic intensity (AI) was compared with equivalent dilutions of DMBs at different mechanical indices (MIs) ranging from 0.2 to 1.4 (n = 6 comparisons at each MI) using real-time 56-Hz and triggered 2-Hz frame rates (FRs). A 3-cm-thick tissue-mimicking phantom was used to simulate transthoracic attenuation. In vivo transthoracic studies were performed in four normal pigs infused with 10% intravenous infusions of DMBs or DNDs at real-time and triggered end-systolic FRs to compare differences in myocardial and left ventricular cavity AI. RESULTS: DNDs were smaller than DMBs and ranged in size from 50 to 1,000 nm. In vitro studies revealed that at an MI of 0.2 and an FR of 56 Hz, DMBs had high AI (37 ± 2 dB), but AI dropped to 25 ± 2 dB at an MI of 1.0 (P < .001, analysis of variance). In comparison, DNDs had virtually no AI at MIs of 0.2 to 0.6 at both triggered and 56-Hz FRs (1 ± 0 dB), but AI increased to 34 ± 2 dB at an MI of 1.4 using an FR of 56 Hz (P < .001 vs MI of 0.2). AI also persisted longer at 56 Hz with DNDs when using higher MIs. In vivo studies demonstrated higher myocardial AI for DNDs at higher MIs when using real-time FR, most likely from microvascular nanodroplet activation. CONCLUSION: These data indicate significant differences in acoustic responses of the commercially available DMBs when administered as an equivalent number of DNDs. The DND formulation may render them more useful for high-MI real-time imaging and other targeted transthoracic diagnostic applications.

Utilization of diagnostic ultrasound and intravenous lipid-encapsulated perfluorocarbons in non-invasive targeted cardiovascular therapeutics.

Diagnostic ultrasound (DUS) pressures have the ability to induce inertial cavitation (IC) of systemically administered microbubbles; this bioeffect has many diagnostic and therapeutic implications in cardiovascular care. Diagnostically, commercially available lipid-encapsulated perfluorocarbons (LEP) can be utilized to improve endocardial and vascular border delineation as well as assess myocardial perfusion. Therapeutically, the liquid jets induced by IC can alter endothelial function and dissolve thrombi within the immediate vicinity of the cavitating microbubbles. The cavitating LEP can also result in the localized release of any bound therapeutic substance at the site of insonation. DUS-induced IC has been tested in pre-clinical studies to determine what effect it has on acute vascular and microvascular thrombosis as well as nitric oxide (NO) release. These pre-clinical studies have consistently shown that DUS-induced IC of LEP is effective in restoring coronary vascular and microvascular flow in acute ST segment elevation myocardial infarction (STEMI), with microvascular flow improving even if upstream large vessel flow has not been achieved. The initial clinical trials examining the efficacy of short pulse duration DUS high mechanical index impulses in patients with STEMI are underway, and preliminary studies have suggested that earlier epicardial vessel recanalization can be achieved prior to arriving in the cardiac catheterization laboratory. DUS high mechanical index impulses have also been effective in pre-clinical studies for targeting DNA delivery that has restored islet cell function in type I diabetes and restored vascular flow in the extremities downstream from a peripheral vascular occlusion. Improvements in this technique will come from three dimensional arrays for therapeutic applications, more automated delivery techniques that can be applied in the field, and use of submicron-sized acoustically activated LEP droplets that may better permeate the clot prior to DUS activation and cavitation. This article will focus on these newer developments for DUS therapeutic applications.