Microbubble Cavitation Imaging

Ultrasound cavitation of microbubble contrast agents has a potential for therapeutic applications such as sonothrombolysis (STL) in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (moderate oscillations, stable cavitation, and inertial cavitation) and activity level in and around a treatment area. Acoustic passive cavitation detectors (PCDs) have been used to this end but do not provide spatial information. This paper presents a prototype of a 2-D cavitation imager capable of producing images of the dominant cavitation state and activity level in a region of interest. Similar to PCDs, the cavitation imaging described here is based on the spectral analysis of the acoustic signal radiated by the cavitating microbubbles: ultraharmonics of the excitation frequency indicate stable cavitation, whereas elevated noise bands indicate inertial cavitation; the absence of both indicates moderate oscillations. The prototype system is a modified commercially available ultrasound scanner with a sector imaging probe. The lateral resolution of the system is 1.5 mm at a focal depth of 3 cm, and the axial resolution is 3 cm for a therapy pulse length of 20 mu s. The maximum frame rate of the prototype is 2 Hz. The system has been used for assessing and mapping the relative importance of the different cavitation states of a microbubble contrast agent. In vitro (tissue-mimicking flow phantom) and in vivo (heart, liver, and brain of two swine) results for cavitation states and their changes as a function of acoustic amplitude are presented

Effects Of Attenuation And Thrombus Age On The Success Of Ultrasound And Microbubble-Mediated Thrombus Dissolution

The purpose of this study was to examine the effects of applied mechanical index, incident angle, attenuation and thrombus age on the ability of 2-D vs. 3-D diagnostic ultrasound and microbubbles to dissolve thrombi. A total of 180 occlusive porcine arterial thrombi of varying age (3 or 6 h) were examined in a flow system. A tissue-mimicking phantom of varying thickness (5 to 10 cm) was placed over the thrombosed vessel and the 2-D or 3-D diagnostic transducer aligned with the thrombosed vessel using a positioning system. Diluted lipid-encapsulated microbubbles were infused during ultrasound application. Percent thrombus dissolution (%TD) was calculated by comparison of clot mass before and after treatment. Both 2-D and 3-D-guided ultrasound increased %TD compared with microbubbles alone, but %TD achieved with 6-h-old thrombi was significantly less than 3-h-old thrombi. Thrombus dissolution was achieved at 10 cm tissue-mimicking depths, even without inertial cavitation. In conclusion, diagnostic 2-D or 3-D ultrasound can dissolve thrombi with intravenous nontargeted microbubbles, even at tissue attenuation distances of up to 10 cm. This treatment modality is less effective, however, for older aged thrombi. (E-mail: [email protected]) (C) 2011 World Federation for Ultrasound in Medicine & Biology

Diagnostic Ultrasound Induced Inertial Cavitation To Non-Invasively Restore Coronary And Microvascular Flow In Acute Myocardial Infarction

Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery. Pigs were then randomized to either a) 1/2 dose tissue plasminogen activator (0.5 mg/kg) alone; or same dose plasminogen activator and an intravenous microbubble infusion with either b) guided high mechanical index short pulse (2.0 MI; 5 usec) therapeutic ultrasound impulses; or c) guided 1.0 mechanical index long pulse (20 usec) impulses. Passive cavitation detectors indicated the high mechanical index impulses (both long and short pulse duration) induced inertial cavitation within the microvasculature. Epicardial recanalization rates following randomized treatments were highest in pigs treated with the long pulse duration therapeutic impulses (83% versus 59% for short pulse, and 49% for tissue plasminogen activator alone; p \u3c 0.05). Even without epicardial recanalization, however, early microvascular recovery occurred with both short and long pulse therapeutic impulses (p \u3c 0.005 compared to tissue plasminogen activator alone), and wall thickening improved within the risk area only in pigs treated with ultrasound and microbubbles. We conclude that although short pulse duration guided therapeutic impulses from a diagnostic transducer transiently improve microvascular flow, long pulse duration therapeutic impulses produce sustained epicardial and microvascular re-flow in acute myocardial infarction

Computational Simulations for Aortic Coarctation: Representative Results From a Sampling of Patients

Treatments for coarctation of the aorta (CoA) can alleviate blood pressure (BP) gradients(D), but long-term morbidity still exists that can be explained by altered indices of hemodynamics and biomechanics. We introduce a technique to increase our understanding of these indices for CoA under resting and nonresting conditions, quantify their contribution to morbidity, and evaluate treatment options. Patient-specific computational fluid dynamics (CFD) models were created from imaging and BP data for one normal and four CoA patients (moderate native CoA: D12 mmHg, severe native CoA: D25 mmHg and postoperative end-to-end and end-to-side patients: D0 mmHg). Simulations incorporated vessel deformation, downstream vascular resistance and compliance. Indices including cyclic strain, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were quantified. Simulations replicated resting BP and blood flow data. BP during simulated exercise for the normal patient matched reported values. Greatest exercise-induced increases in systolic BP and mean and peak DBP occurred for the moderate native CoA patient (SBP: 115 to 154 mmHg; mean and peak DBP: 31 and 73 mmHg). Cyclic strain was elevated proximal to the coarctation for native CoA patients, but reduced throughout the aorta after treatment. A greater percentage of vessels was exposed to subnormal TAWSS or elevated OSI for CoA patients. Local patterns of these indices reported to correlate with atherosclerosis in normal patients were accentuated by CoA. These results apply CFD to a range of CoA patients for the first time and provide the foundation for future progress in this area

Platelet-activating factor acetylhydrolase and haemophagocytosis in the sepsis syndrome.

Sepsis syndrome (SS) is associated with depressed PAF acetylhydrolase, the enzyme responsible for the degradation of platelet activating factor. PAF acetylhydrolase is in a large part produced by macrophages, whose inadequate activation with haemophagocytosis is frequent in patients with SS. The aim of this study was to test the hypothesis that PAF acetylhydrolase levels could be affected in these critically ill patients, because of the large amounts produced by activated macrophages in vitro and in vivo in animal models. The levels of serum PAF acetylhydrolase were assessed in 90 SS patients, who were divided into three groups: patients with (n = 34) or without haemophagocytosis (n = 31), and patients without thrombocytopenia (n = 25) who were used as a control group. The number of organ dysfunctions was matched between patients with haemophagocytosis and controls. Normal reference values were obtained in 59 randomly selected blood donors. Circulating levels of PAF acetylhydrolase were significantly (p = 0.0001) decreased in patients with SS (57+/-3 nmol/ml/min, n = 90) when compared with healthy subjects (69+/-3 nmol/ml/min, n = 59). PAF acetylhydrolase levels were greater in the presence of a haemophagocytosis but without statistical significance (64.2+/-6.5 vs. 50.1+/-2.8:p = 0.25). Despite the fact that macrophagic activation stimulates the in vitro release of PAF acetylhydrolase, no difference was found between patients with or without haemophagocytosis. The mechanism and the role of the PAF acetylhydrolase reduction in SS patients remain to be determined

Computational simulations demonstrate altered wall shear stress in aortic coarctation patients previously treated by resection with end-to-end anastomosis

Background.  Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity. Methods.  Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility. Results.  The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch. Conclusions.  Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies

Role of superantigenic strains in the prognosis of community-acquired methicillin-susceptible Staphylococcus aureus bacteraemia

ABSTRACTMethicillin-susceptible Staphylococcus aureus (MSSA) strains can produce superantigenic toxins that may trigger a massive release of pro-inflammatory cytokines, which are involved in the onset of septic shock. This 1-year prospective pilot study assessed the role of the production of superantigenic toxins in the outcome of immunocompetent patients hospitalised for community-acquired MSSA bacteraemia. Thirty-seven patients were enrolled, of whom 14 died in hospital. Fourteen patients had septic shock, and the mortality rate in this subgroup was 56%. Twenty-seven (73%) isolates produced at least one superantigenic toxin, but this did not influence the rate of occurrence of septic shock or death

Diagnostic Ultrasound High Mechanical Index Impulses Restore Microvascular Flow In Peripheral Arterial Thromboembolism

We sought to explore mechanistically how intermittent high-mechanical-index (MI) diagnostic ultrasound impulses restore microvascular flow. Thrombotic microvascular obstruction was created in the rat hindlimb muscle of 36 rats. A diagnostic transducer confirmed occlusion with low-MI imaging during an intravenous microbubble infusion. This same transducer was used to intermittently apply ultrasound with an MI that produced stable or inertial cavitation (IC) for 10 min through a tissue-mimicking phantom. A nitric oxide inhibitor, L-Nω-nitroarginine methyl ester (L-NAME), was pre-administered to six rats. Plateau microvascular contrast intensity quantified skeletal microvascular blood volume, and postmortem staining was used to detect perivascular hemorrhage. Intermittent IC impulses produced the greatest recovery of microvascular blood volume (p \u3c 0.0001, analysis of variance). Nitric oxide inhibition did not affect the skeletal microvascular blood volume improvement, but did result in more perivascular hemorrhage. IC inducing pulses from a diagnostic transducer can reverse microvascular obstruction after acute arterial thromboembolism. Nitric oxide may prevent unwanted bio-effects of these IC pulses

On Coupling a Lumped Parameter Heart Model and a Three-Dimensional Finite Element Aorta Model

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure–volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions