Endograft exclusion of the false lumen restores local hemodynamics in a model of type B aortic dissection.

OBJECTIVE: Endovascular intervention in uncomplicated type B dissection has not been shown conclusively to confer benefit on patients. The hemodynamic effect of primary entry tear coverage is not known. Endovascular stent grafts were deployed in a model of aortic dissection with multiple fenestrations to study these effects. It is hypothesized that endograft deployment will lead to restoration of parabolic true lumen flow as well as elimination of false lumen flow and transluminal jets and vortices locally while maintaining distal false lumen canalization. METHODS: Thoracic stent grafts were placed in silicone models of aortic dissection with a compliant and mobile intimal flap and installed in a flow loop. Pulsatile fluid flow was established with a custom positive displacement pump, and the models were imaged by four-dimensional flow magnetic resonance imaging. Full flow fields were acquired in the models, and velocities were extracted to calculate flow rates, reverse flow indices, and oscillatory shear index, the last two of which are measures of stagnant and disturbed flows. RESULTS: Complete obliteration of the false lumen was achieved in grafted aorta, with normal parabolic flow profiles in the true lumen (maximal velocity, 30.4 ± 8.4 cm/s). A blind false lumen pouch was created distal to this with low-velocity (5.8 ± 2.7 cm/s) and highly reversed (27.9% ± 13.9% reverse flow index) flows. In distal free false lumen segments, flows were comparable to ungrafted conditions with maximal velocities on the order of 7.0 ± 2.1 cm/s. Visualization studies revealed forward flow in these regions with left-handed vortices from true to false lumen. Shear calculations in free false lumen regions demonstrated reduced oscillatory shear index. CONCLUSIONS: Per the initial hypothesis, endovascular grafting improved true lumen hemodynamics in the grafted region. Just distally, a prothrombotic flow regimen was noted in the false lumen, yet free false lumen distal to this remained canalized. Clinically, this suggests a need for advancing endovascular intervention beyond sole entry tear coverage to prevent further false lumen canalization through uncovered fenestrations.

Development and testing of a silicone in vitro model of descending aortic dissection.

BACKGROUND: Stanford type B dissection of the descending aorta is a potentially fatal condition that is poorly understood. Limited scientific understanding of the role of current interventional techniques, as well as heterogeneity in the condition, contributes to lack of consensus as to the most effective treatment strategy. This study introduces an anatomically accurate model for investigating aortic dissection in a laboratory setting. MATERIALS AND METHODS: A silicone model was fabricated and filled with fluid to mimic human blood. Flow was established, and the model was scanned using a four-dimensional flow magnetic resonance imaging protocol. On analysis, luminal flow rates were quantified by multiplying local velocity by included area. RESULTS: The upstream total flow was compared with the sum of the flow in the true and false lumens. The two values were within the margin of error. Furthermore, flow rates matched with the relative areas of each compartment. CONCLUSIONS: These results validate our model as a novel and unique system that mimics a type B aortic dissection and will allow for more sophisticated analysis of dissection physiology in future studies.

Intermediate fenestrations reduce flow reversal in a silicone model of Stanford Type B aortic dissection.

Pulsatile, three-dimensional hemodynamic forces influence thrombosis, and may dictate progression of aortic dissection. Intimal flap fenestration and blood pressure are clinically relevant variables in this pathology, yet their effects on dissection hemodynamics are poorly understood. The goal of this study was to characterize these effects on flow in dissection models to better guide interventions to prevent aneurysm formation and false lumen flow. Silicone models of aortic dissection with mobile intimal flap were fabricated based on patient images and installed in a flow loop with pulsatile flow. Flow fields were acquired via 4-dimensional flow MRI, allowing for quantification and visualization of relevant fluid mechanics. Pulsatile vortices and jet-like structures were observed at fenestrations immediately past the proximal entry tear. False lumen flow reversal was significantly reduced with the addition of fenestrations, from 19.2 ±â€¯3.3% in two-tear dissections to 4.67 ±â€¯1.5% and 4.87 ±â€¯1.7% with each subsequent fenestration. In contrast, increasing pressure did not cause appreciable differences in flow rates, flow reversal, and vortex formation. Increasing the number of intermediate tears decreased flow reversal as compared to two-tear dissection, which may prevent false lumen thrombosis, promoting persistent false lumen flow. Vortices were noted to result from transluminal fluid motion at distal tear sites, which may lead to degeneration of the opposing wall. Increasing pressure did not affect measured flow patterns, but may contribute to stress concentrations in the aortic wall. The functional and anatomic assessment of disease with 4D MRI may aid in stratifying patient risk in this population.

Pulsatile Flow Leads to Intimal Flap Motion and Flow Reversal in an In Vitro Model of Type B Aortic Dissection.

Understanding of the hemodynamics of Type B aortic dissection may improve outcomes by informing upon patient selection, device design, and deployment strategies. This project characterized changes to aortic hemodynamics as the result of dissection. We hypothesized that dissection would lead to elevated flow reversal and disrupted pulsatile flow patterns in the aorta that can be detected and quantified by non-invasive magnetic resonance imaging. Flexible, anatomic models of both normal aorta and dissected aorta, with a mobile intimal flap containing entry and exit tears, were perfused with a physiologic pulsatile waveform. Four-dimensional phase contrast magnetic resonance (4D PCMR) imaging was used to measure the hemodynamics. These images were processed to quantify pulsatile fluid velocities, flow rate, and flow reversal. Four-dimensional flow imaging in the dissected aorta revealed pockets of reverse flow and vortices primarily in the false lumen. The dissected aorta exhibited significantly greater flow reversal in the proximal-to-mid dissection as compared to normal (21.1 ± 3.8 vs. 1.98 ± 0.4%, p < 0.001). Pulsatility induced unsteady vortices and a pumping motion of the distal intimal flap corresponding to flow reversal. Summed true and false lumen flow rates in dissected models (4.0 ± 2.0 L/min) equaled normal flow rates (3.8 ± 0.1 L/min, p > 0.05), validated against external flow measurement. Pulsatile aortic hemodynamics in the presence of an anatomic, elastic dissection differed significantly from those of both steady flow through a dissection and pulsatile flow through a normal aorta. New hemodynamic features including flow reversal, large exit tear vortices, and pumping action of the mobile intimal flap, were observed. False lumen flow reversal would possess a time-averaged velocity close to stagnation, which may induce future thrombosis. Focal vortices may identify the location of tears that could be covered with a stent-graft. Future correlation of hemodynamics with outcomes may indicate which patients require earlier intervention.

Thermally multiplexed polymerase chain reaction.

Amplification of multiple unique genetic targets using the polymerase chain reaction (PCR) is commonly required in molecular biology laboratories. Such reactions are typically performed either serially or by multiplex PCR. Serial reactions are time consuming, and multiplex PCR, while powerful and widely used, can be prone to amplification bias, PCR drift, and primer-primer interactions. We present a new thermocycling method, termed thermal multiplexing, in which a single heat source is uniformly distributed and selectively modulated for independent temperature control of an array of PCR reactions. Thermal multiplexing allows amplification of multiple targets simultaneously-each reaction segregated and performed at optimal conditions. We demonstrate the method using a microfluidic system consisting of an infrared laser thermocycler, a polymer microchip featuring 1 µl, oil-encapsulated reactions, and closed-loop pulse-width modulation control. Heat transfer modeling is used to characterize thermal performance limitations of the system. We validate the model and perform two reactions simultaneously with widely varying annealing temperatures (48 °C and 68 °C), demonstrating excellent amplification. In addition, to demonstrate microfluidic infrared PCR using clinical specimens, we successfully amplified and detected both influenza A and B from human nasopharyngeal swabs. Thermal multiplexing is scalable and applicable to challenges such as pathogen detection where patients presenting non-specific symptoms need to be efficiently screened across a viral or bacterial panel.